75 results on '"Rahime Şimşek"'
Search Results
2. Synthesis, characterization, crystal structure and Hirshfeld surface analysis of isobutyl 4-[4-(difluoromethoxy)phenyl]-2,6,6-trimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate
- Author
-
Sema Öztürk Yıldırım, Mehmet Akkurt, Gökalp Çetin, Rahime Şimşek, Ray J. Butcher, and Ajaya Bhattarai
- Subjects
crystal structure ,1,4-dihydropyridine ring ,cyclohexene ring ,quinoline ring system ,van der waals interactions ,hirshfeld surface analysis ,Crystallography ,QD901-999 - Abstract
In the title compound, C24H29F2NO4, which crystallizes in the orthorhombic Pca21 space group with Z = 4, the 1,4-dihydropyridine ring adopts a distorted boat conformation, while the cyclohexene ring is in a distorted half-chair conformation. In the crystal, the molecules are linked by N—H...O and C—H...O interactions, forming supramolecular chains parallel to the a axis. These chains pack with C—H...π interactions between them, forming layers parallel to the (010) plane. The cohesion of the crystal structure is ensured by van der Waals interactions between these layers. Hirshfeld surface analysis shows the major contributions to the crystal packing are from H...H (56.9%), F...H/H...F (15.7%), O...H/H...O (13.7%) and C...H/H...C (9.5%) contacts.
- Published
- 2023
- Full Text
- View/download PDF
3. Synthesis, crystal structure and Hirshfeld surface analysis of tert-butyl 4-[4-(difluoromethoxy)phenyl]-2,7,7-trimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate
- Author
-
Ezgi Pehlivanlar, Sema Öztürk Yıldırım, Rahime Şimşek, Mehmet Akkurt, Ray J. Butcher, and Ajaya Bhattarai
- Subjects
crystal structure ,hydrogen bonds ,van der waals forces ,c—h...f interactions ,hirshfeld surface analysis ,Crystallography ,QD901-999 - Abstract
The 1,4-dihydropyridine ring of the title compound, C24H29F2NO4, adopts a distorted boat conformation, while the cyclohexene ring is in an almost twist-boat conformation. In the crystal, N—H...O and C—H...O hydrogen bonds as well as C—H...π interactions connect molecules, forming layers parallel to the (100) plane. These layers are linked by van der Waals forces and C—H...F interactions, which consolidate the crystal structure. Hirshfeld surface analysis shows the major contributions to the crystal packing are from H...H (54.1%), F...H/H...F (16.9%), O...H/H...O (15.4%) and C...H/H...C (12.6%) contacts.
- Published
- 2023
- Full Text
- View/download PDF
4. Crystal structure and Hirshfeld surface analysis of isopropyl 4-[2-fluoro-5-(trifluoromethyl)phenyl]-2,6,6-trimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate
- Author
-
Sema Öztürk Yıldırım, Mehmet Akkurt, Gökalp Çetin, Rahime Şimşek, Ray J. Butcher, and Ajaya Bhattarai
- Subjects
crystal structure ,1,4-dihydropyridine ring ,cyclohexene ring ,quinoline ring system ,van der waals interactions ,hirshfeld surface analysis ,Crystallography ,QD901-999 - Abstract
In the title compound, C23H25F4NO3, the 1,4-dihydropyridine ring adopts a distorted boat conformation, while the cyclohexene ring is almost showing a half-chair conformation. In the crystal, intermolecular N—H...O hydrogen bonds connect the molecules into chains with graph-set motif C(6) parallel to the a-axis. These chains are linked together by C—H...O and C—H...F interactions, forming a three-dimensional network. In addition, C—H...π interactions link the molecules into layers parallel to the (100) plane. A Hirshfeld surface analysis was performed to further investigate the intermolecular interactions.
- Published
- 2023
- Full Text
- View/download PDF
5. Synthesis, characterization, crystal structure and Hirshfeld surface analysis of a hexahydroquinoline derivative: tert-butyl 4-([1,1′-biphenyl]-4-yl)-2,6,6-trimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate
- Author
-
Sema Öztürk Yıldırım, Mehmet Akkurt, Gökalp Çetin, Rahime Şimşek, Ray J. Butcher, and Ajaya Bhattarai
- Subjects
crystal structure ,1,4-dihydropyridine ring ,cyclohexene ring ,quinoline ring system ,van der waals interactions ,hirshfeld surface analysis ,disorder ,Crystallography ,QD901-999 - Abstract
The title compound, C29H33NO3, crystallizes with three molecules (A, B and C) in the asymmetric unit. They differ in the twist of the phenyl and benzene rings of the 1,1′-biphenyl ring with respect to the plane of the 1,4-dihydropyridine ring. In all three molecules, the 1,4-dihydropyridine ring adopts a distorted boat conformation. The cyclohexene ring has an envelope conformation in molecules A and B, while it exhibits a distorted half-chair conformation for both the major and minor components in the disordered molecule C. In the crystal, molecules are linked by C—H...O and N—H...O hydrogen bonds, forming layers parallel to (100) defining R14(6) and C(7) graph-set motifs. Additional C—H...π interactions consolidate the layered structure. Between the layers, van der Waals interactions stabilize the packing, as revealed by Hirshfeld surface analysis. The greatest contributions to the crystal packing are from H...H (69.6% in A, 69.9% in B, 70.1% in C), C...H/H...C (20.3% in A, 20.6% in B, 20.3% in C) and O...H/H...O (8.6% in A, 8.6% in B, 8.4% in C) interactions.
- Published
- 2022
- Full Text
- View/download PDF
6. Ethyl 2,7,7-trimethyl-4-(1-methyl-1H-indol-3-yl)-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate
- Author
-
Cihat Şafak, Rahime Şimşek, Ahmed El-Khouly, Miyase Gözde Gündüz, Ray J. Butcher, and Sema Öztürk Yildirim
- Subjects
Crystallography ,QD901-999 - Abstract
In the title molecule, C24H28N2O3, the cyclohexene ring is in a sofa conformation and the 1,4-dihydropyridine ring is in a slight boat conformation. In the indole ring system, the pyrrole and benzene rings form a dihedral angle of 2.63 (7)°. In the crystal, N—H...O hydrogen bonds connect the molecules into C(6) chains parallel to the b axis and pairs of weak C—H...O hydrogen bonds link inversion-related chains into a ladder motif through R22(18) rings. A weak intramolecular C—H...O hydrogen bond is also observed.
- Published
- 2013
- Full Text
- View/download PDF
7. Ethyl 4-(5-bromo-1H-indol-3-yl)-2,6,6-trimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate
- Author
-
Miyase Gözde Gündüz, Ray J. Butcher, Sema Öztürk Yildirim, Ahmed El-Khouly, Cihat Şafak, and Rahime Şimşek
- Subjects
Crystallography ,QD901-999 - Abstract
The title compound, C23H25BrN2O3, crystallizes with two independent molecules in the asymmetric unit (Z′ = 2) which differ in the twist of the 5-bromo-1H-indole ring with respect to the plane of the 4-methyl-1,4,5,6,7,8-hexahydroquinoline ring [dihedral angles of 78.55 (9) and 89.70 (8)° in molecules A and B, respectively]. The indole ring is planar in both molecules [maximum deviations = 0.021 (3) and −0.020 (3) Å for the N atom] while the cyclohexene ring has adopts a sofa conformation. In the crystal, molecules are linked by pairs of N—H...O hydrogen bonds, forming dimers with R12(6) ring motifs. These dimers are connected by N—H...O hydrogen bonds, generating chains along [110]. A C—H...O contact occurs between the independent molecules.
- Published
- 2012
- Full Text
- View/download PDF
8. Neurological Effects of SARS-CoV-2 and Neurotoxicity of Antiviral Drugs Against COVID-19
- Author
-
Rahime Şimşek, Selinay Başak Erdemli Köse, Pinar Erkekoglu, Büşra Ünlü, and Anıl Yirün
- Subjects
Pharmacology ,SARS-CoV-2 ,business.industry ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,fungi ,Encephalopathy ,Neurotoxicity ,COVID-19 ,General Medicine ,Disease ,medicine.disease_cause ,medicine.disease ,Antiviral Agents ,COVID-19 Drug Treatment ,Mechanism of action ,Drug Discovery ,Immunology ,Pandemic ,medicine ,Animals ,Humans ,medicine.symptom ,business ,Hiccups ,Coronavirus - Abstract
Abstract: Severe Acute Respiratory Syndrome (SARS) is caused by different SARS viruses. In 2020, novel coronavirus (SARS-CoV-2) led to an ongoing pandemic, known as “Coronavirus Disease 2019 (COVID-19)”. The disease can spread among individuals through direct (via saliva, respiratory secretions, or secretion droplets) or indirect (through contaminated objects or surfaces) contact. The pandemic has spread rapidly from Asia to Europe and later to America. It continues to affect all parts of the world at an increasing rate. There have been over 92 million confirmed cases of COVID-19 by mid-January 2021. The similarity of homological sequences between SARS-CoV-2 and other SARSCoVs is high. In addition, clinical symptoms of SARS-CoV-2 and other SARS viruses show similarities. However, some COVID-19 cases show neurologic signs like headache, loss of smell, hiccups and encephalopathy. The drugs used in the palliative treatment of the disease also have some neurotoxic effects. Currently, there are approved vaccines for COVID-19. However, there is a need for specific therapeutics against COVID-19. This review will describe the neurological effects of SARS-CoV-2 and the neurotoxicity of COVID-19 drugs used in clinics. Drugs used in the treatment of COVID-19 will be evaluated by their mechanism of action and their toxicological effects.
- Published
- 2022
9. Adverse Effects of COVID-19 Treatments: A Special Focus on Susceptible Populations
- Author
-
Beyza Nur Küçük, Rahime Şimşek, Selinay Başak Erdemli Köse, Anil Yirun, and Pinar Erkekoglu
- Subjects
SARS-CoV-2 ,Health, Toxicology and Mutagenesis ,Humans ,General Medicine ,Toxicology ,Antiviral Agents ,Pandemics ,Pathology and Forensic Medicine ,COVID-19 Drug Treatment - Abstract
On December 2019, the world faced a new pandemic caused by a novel type of coronavirus, namely severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This disease is named as "coronavirus disease 2019 (COVID-19)." This RNA virus infected millions of people around the world causing millions of deaths. It takes approximately 8-10 years to develop a new drug and it seems hard to have a specific pharmaceutical agent against COVID-19. So far, there is only one drug that has applied for registration. The drugs used in clinics against COVID-19 were approved for malaria, human immunodeficiency syndrome (HIV), influenza A and B, and other viral diseases. All these drugs for COVID-19 treatment are being applied according to "drug repurposing (drug repositioning)" strategy. However, they could cause some severe adverse effects on susceptible populations. In some cases, patients can survive after disease. However, the adverse effects of these drugs may lead to morbidity and mortality later. In this review, drugs used against COVID-19 in clinics, their mechanisms of action and possible adverse effects on susceptible populations will be discussed.
- Published
- 2022
10. Synthesis, characterization, crystal structure and Hirshfeld surface analysis of a hexa-hydro-quinoline derivative
- Author
-
Sema Öztürk, Yıldırım, Mehmet, Akkurt, Gökalp, Çetin, Rahime, Şimşek, Ray J, Butcher, and Ajaya, Bhattarai
- Abstract
The title compound, C
- Published
- 2022
11. Synthesis and biological evaluation of substituted hexahydroquinoline derivatives
- Author
-
Gökalp Çetin and Rahime Şimşek
- Subjects
Chemistry ,Materials Chemistry ,Combinatorial chemistry ,Biological evaluation - Published
- 2019
12. Synthesis and Crystal Structure of Benzyl 4-(2-fluoro-4-(trifluoromethyl)phenyl)- 2,6,6-trimethyl-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate and Its DFT Analysis Combined with Bond Order Modeling in Terms of The Bond Critical Point Quantities
- Author
-
Ray J. Butcher, Gökalp Çetin, Sema Öztürk Yildirim, Rahime Şimşek, and Zeki Büyükmumcu
- Subjects
Crystallography ,chemistry.chemical_compound ,Trifluoromethyl ,Materials science ,chemistry ,Critical point (thermodynamics) ,Bond ,Carboxylate ,Crystal structure ,Bond order - Abstract
Inflammation is the underlying cause of many diseases such as cardiovascular diseases, cancer and autoimmune diseases. Recently 1,4-dihydropyridine (1,4-DHP) compounds were found effective to reduce inflammation which contributes to development of inflammation associated diseases. Based on these data we synthesized to investigate this type of action of annulated 1,4-DHP molecule, benzyl 4-(2-fluoro-4-(trifluoromethyl)phenyl)-2,6,6-trimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate and proved the structure of this molecule by IR, 1H-NMR, 13C-NMR, HMRS and X-ray crystallography.X-ray analyses were conducted to find out the exact 3D structure of the mentioned molecule. The molecular structure crystallizes in triclinic space group, P-1, with a = 7.0889(11) Å, b = 12.4861(18) Å, c = 14.338(2) Å, α = 66.899(4)°, β = 89.025(4)°, γ = 85.101(4)° and V = 1162.9(3) Å3. In the title molecule, C27H25F4NO3, the cyclohexene ring is in a sofa conformation and the 1,4-dihydropyridine ring is in a slight boat conformation. In the 2-fluoro phenyl and benzyl rings form a dihedral angle of 13.6(1)°. In the crystal structure stabilized by the intra- and intermolecular N—H···O, C—H···O and C—H···F interactions. The molecules are linked together to form a dimer by N(1)—H(1N) ···O(1)i and C(2)—H(2A) ···O(1)i hydrogen bonds [symmetry code: (i) x+1,y,z ], producing two R12(6) rings.Natural charge, QTAIM, bond order, molecular planarity and molecular surface analyses have been performed on the optimized geometry by DFT. Considering the quantities obtained at the bond critical poins, the chemical bonds are discussed for classification. The correlation between bond critical point quantities and the bond orders based on different definitions have been explored considering different bond order models from the literature. The Laplacian Bond Order (LBO) gives best correlation for four of five bond order models. All the bond order models with an exception of the model with parameter G have approximately same correlation degree for C-C bonds. For C-H bonds, only bond model with parameters of electron density and the principle curvatures for LBO gives relatively good correlation with R2 value of 0.943. The two phenyl rings of the structure have aromaticity comparable to benzene as deduced from QTAIM quantities and molecular planarity metrics. As a result of molecular surface analysis, the mass density, molecular polarity index, v (the measure of charge balance), σ2tot .v (measure of intermolecular interactions) were calculated and compared with literature values.
- Published
- 2021
13. Synthesis and Characterization of New Hexahydroquinoline Derivatives, In Silico Determination of Their Inhibitory Effects on Transforming Growth Factor Beta (TGF-β) and Their Effects on Oxidative Stress In Vitro
- Author
-
Didem Oral, Gökalp Çetin, Aylin Balci, Pınar Erkekoglu, and Rahime Şimşek
- Subjects
Pharmaceutical Science ,General Medicine - Published
- 2021
14. Synthesis, structural characterization and density functional studies of ethyl 4-(biphenyl-4-yl)-2,6,6-trimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate A non-merohedral twinned structure
- Author
-
Cihat Şafak, Sema Öztürk Yıdırım, Ray J. Butcher, Gökalp Çetin, Zeki Büyükmumcu, and Rahime Şimşek
- Subjects
Biphenyl ,010405 organic chemistry ,Hydrogen bond ,Calcium channel ,Organic Chemistry ,Biological activity ,010402 general chemistry ,01 natural sciences ,Medicinal chemistry ,0104 chemical sciences ,Analytical Chemistry ,Inorganic Chemistry ,chemistry.chemical_compound ,chemistry ,Proton NMR ,Moiety ,Molecule ,Carboxylate ,Spectroscopy - Abstract
1,4-Dihydropyridine (1,4-DHP) derivatives have the reducing effect of extracellular Ca2+ ions influx on the L-type calcium channel. Because of this effect many 1,4-DHP derivatives are potent calcium channel blockers and antihypertensive agents. The biphenyl group is present in the structures of the most biologically active compounds and thus is an important group. By introducing this moiety into the structure of various compounds, active compounds are obtained. Thus, pharmacologically active structures can be condensed with the biphenyl structure to achieve novel biologically active compounds or compounds with increased activity. In this study, to achieve an active calcium channel blocker compound, the biphenyl group was introduced into the 1,4-DHP structure. The structure of the compound is proved by IR, 1H NMR, Mass spectroscopy, X-ray crystallography and elemental analysis. The cytotoxic activity assays have continued and positive results have been obtained. The phenyl rings [C16–C21 and C22–C27] make dihedral angles of 84.4 (1) and 87.5 (1)°, respectively, with the 1,4-dihydropyridine ring [N1/C1/C4–C9]. In the crystal, adjacent molecules are linked by N H … O and C H … O hydrogen bonds into chains parallel to [010].
- Published
- 2018
15. Synthesis, crystal structure and antimycobacterial activities of 4-indolyl-1,4-dihydropyridine derivatives possessing various ester groups
- Author
-
Vagolu Siva Krishna, Cihat Şafak, Miyase Gözde Gündüz, Rahime Şimşek, Dharmarajan Sriram, Ray J. Butcher, Sema Öztürk Yıldırım, and Ece Baydar
- Subjects
chemistry.chemical_classification ,Molecular model ,010405 organic chemistry ,INHA ,Ligand ,Stereochemistry ,medicine.drug_class ,General Chemistry ,010402 general chemistry ,Condensation reaction ,Antimycobacterial ,01 natural sciences ,0104 chemical sciences ,chemistry ,medicine ,Moiety ,Alkyl ,Isopropyl - Abstract
The present study reports the synthesis of a series of alkyl 4-(5/6-bromo-1H-indole-3-yl)-2,6,6/2,7,7-trimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate derivatives by a simple, rapid and convenient modified Hantzsch condensation reaction under microwave irradiation. The structure elucidation of the target compounds was carried out by different spectral techniques including IR, 1H-NMR, COSY, 13C-NMR, and mass analysis. Additionally, the proposed structure of compound 3 was proved by single crystal X-ray analysis. In vitro anti-tubercular activity of the compounds was evaluated against Mycobacterium tuberculosis H37Rv. The obtained results indicated that some compounds exhibited moderate antimycobacterial activity with weak cytotoxicity. Among them, compounds carrying ethyl or isopropyl groups in their ester moiety were found to be the most active compounds in this series. Molecular modeling studies were carried out to gain an idea about the mechanism of action of the active compounds. According to the results, the interactions were found quite similar with the co-crystalized ligand of M. tuberculosis enoyl reductase (InhA).
- Published
- 2017
16. Synthesis of fused 1,4-dihydropyridines as potential calcium channel blockers
- Author
-
Rahime Şimşek, Alper B. Iskit, Ahmed El-Khouly, Miyase Gözde Gündüz, Erdem Kamil Ozer, Cihat Şafak, and Yildirim Sara
- Subjects
0301 basic medicine ,03 medical and health sciences ,030104 developmental biology ,010405 organic chemistry ,Chemistry ,Calcium channel ,Biochemistry (medical) ,Clinical Biochemistry ,Biophysics ,01 natural sciences ,Molecular Biology ,Biochemistry ,0104 chemical sciences - Abstract
Objective The aim of this study was to synthesize ten 1,4-dihydropyridine (DHP) derivatives in which substituted cyclohexane rings were fused to the DHP ring and to determine how different ester groups and the benzoyl substituent introduced in 4-phenyl ring affected their calcium channel blocking activity. Methods A microwave-assisted one-pot method was applied for the synthesis of compound 1–5 according to a modified Hantzsch reaction. The benzoyl moiety was introduced in the 4-phenyl ring of these dihydropyridines by refluxing with benzoyl chloride in acetone in the presence of anhydrous potassium carbonate. Synthesized products were characterized by elemental analysis, IR, 1H-NMR and 13C-NMR spectroscopy. The inhibitory actions of compounds 1–10 on calcium channel blocking activity were tested on isolated rat aorta preparations. Results The obtained pharmacological results showed that although all compounds are potent relaxing agents on isolated rat aorta smooth muscle, introduction of a benzoyloxy substitiuent on the phenyl ring (compound 6–10) decreased the relaxant effect of these compunds. Conclusion The reported 1,4-DHP derivatives have calcium channel blocking activity on rat aorta smooth muscle.
- Published
- 2017
17. Theoretical and experimental study of the ground and excited states of 1,4-dihydropyridine based hexahydroquinoline derivatives achieved by microwave irradiation
- Author
-
Cláudia de Brito da Silva, Cihat Şafak, Fabiano Severo Rodembusch, Gabriel Modernell Zanotto, Josene M. Toldo, Miyase Gözde Gündüz, Rahime Şimşek, and Paulo Fernando Bruno Gonçalves
- Subjects
010405 organic chemistry ,Chemistry ,Substituent ,Charge density ,General Chemistry ,010402 general chemistry ,Photochemistry ,01 natural sciences ,Fluorescence ,Catalysis ,0104 chemical sciences ,Solvent ,chemistry.chemical_compound ,Wavelength ,Excited state ,Materials Chemistry ,Absorption (electromagnetic radiation) ,Maxima - Abstract
In this article, the photophysical characterisation in solution of a series of hexahydroquinoline derivatives is described using UV-Vis absorption and steady-state fluorescence emission spectroscopies. The compounds were obtained from one-pot four component synthesis via Hantzsch reaction using microwave irradiation. These compounds present absorption maxima located at around 350 nm and fluorescence emission maxima in the UV-violet-blue region. The Lippert–Mataga correlation indicates an ICT character in the excited state for the studied compounds since a linear relation of the fluorescence maxima versus the solvent polarity function was found. Theoretical calculations were also performed in order to study the geometry and charge distribution of these compounds in their ground and excited electronic states. No significant changes in absorption and emission maximum wavelength were found by changing the solvent or substituent groups attached to the hexahydroquinoline structure.
- Published
- 2017
18. Electrochemical detection of antioxidant activities of 4-indolyl-5-oxo-6,6 (or 7,7)- dimethyl-1,4,5,6,7,8-hexahydroquinoline derivatives
- Author
-
Cihat Şafak, İncilay Süslü, Rahime Şimşek, and Sevilay Erdoğan Kablan
- Subjects
Antioxidant ,Chemistry ,medicine.medical_treatment ,medicine ,Electrochemical detection ,Combinatorial chemistry - Published
- 2021
19. Photodegradation studies of 1,4-dihydropyridine compounds by MCR analysis on UV spectral data
- Author
-
Cihat Şafak, Giuseppina Ioele, Miyase Gözde Gündüz, Rita Muzzalupo, Rahime Şimşek, Gaetano Ragno, and Michele De Luca
- Subjects
Dihydropyridines ,Light ,Analytical chemistry ,chemistry.chemical_element ,DHPS ,02 engineering and technology ,Ring (chemistry) ,Photochemistry ,01 natural sciences ,chemistry.chemical_compound ,Drug Stability ,Spectrophotometry ,Drug Discovery ,Pyridine ,medicine ,Chlorine ,Photodegradation ,Pharmacology ,Photolysis ,medicine.diagnostic_test ,Chemistry ,010401 analytical chemistry ,Photodissociation ,Aromatization ,021001 nanoscience & nanotechnology ,0104 chemical sciences ,Kinetics ,Molecular Medicine ,Spectrophotometry, Ultraviolet ,0210 nano-technology - Abstract
Background: 1,4-Dihydropyridines (DHPs) are well-known light-sensitive compounds. Photostability studies are necessary to ensure safety in therapy. Materials & Methods: Photodegradation experiments on 15 condensed DHP derivatives were made according to the International Conference on Harmonization rules. Degradation profiles were monitored by spectrophotometry and the data were processed by multivariate curve resolution analysis. Results: The analysis of the spectral data showed the formation of a single photoproduct from two DHPs, due to the aromatization of the pyridine ring. Traces of a second photoproduct were revealed in 12 DHPs and a third photoproduct was verified only in one case. Conclusion: DHPs showed high stability when fluorine was in the position R1 of the phenyl ring or simultaneously present in R1 and R2 positions. In contrast, the presence of chlorine in R1 or R2 strongly increased the degradation.
- Published
- 2016
20. Synthesis and spectroscopic characterization and DFT study of benzyl 4-([1,1’-biphenyl]-4-yl)-2,6,6-trimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate
- Author
-
Rahime Şimşek, Ray J. Butcher, Zeki Büyükmumcu, Sema Öztürk Yıdırım, and Gökalp Çetin
- Subjects
010405 organic chemistry ,Hydrogen bond ,Organic Chemistry ,Carbon-13 NMR ,010402 general chemistry ,01 natural sciences ,0104 chemical sciences ,Analytical Chemistry ,Inorganic Chemistry ,chemistry.chemical_compound ,Crystallography ,chemistry ,Intramolecular force ,Proton NMR ,Molecule ,Carboxylate ,Single crystal ,Spectroscopy ,Monoclinic crystal system - Abstract
Calcium channel blocker compounds act on L-type calcium channels and reducing the influx of extracellular calcium ions into the cell. These are divided into three main groups, one of which is 1,4-dihydropyridine derivatives. In this study, a new compound bearing the hexahydroquinoline ring analogous to 1,4-dihydropyridine structure was synthesized and its structure proved by instrumental techniques such as mass spectroscopy, H-1 NMR, C-13 NMR, IR and elemental analysis. In addition to the spectral methods used, X-ray study has been carried out to realize advanced studies on the structure of the mentioned compound. The analyses of single crystal X-ray diffraction show that the title compouns crystallized in the monoclinic system with space group P 21/n. Lattice constants are a = 7.1231(3) angstrom, b = 30.0033(19) angstrom, c = 11.8361(7) angstrom, beta = 95.698(4)degrees, Z = 4. Crystallographic studies also show that the molecular structure was stabilized by intramolecular, intermolecular hydrogen bonds. (C) 2019 Elsevier B.V. All rights reserved.
- Published
- 2020
21. Experimental and molecular modeling investigation of isopropyl 4-(biphenyl-4-Yl)-2,6,6-trimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate
- Author
-
Rahime Şimşek, Gökalp Çetin, Sema Öztürk Yıldırım, Cihat Şafak, Özlem Savaş Pekdur, Ray J. Butcher, and Zeki Büyükmumcu
- Subjects
Biphenyl ,endocrine system ,chemistry.chemical_compound ,Molecular model ,chemistry ,Molecule ,Biological activity ,Crystal structure ,Carboxylate ,Medicinal chemistry ,Isopropyl ,Monoclinic crystal system - Abstract
The most important effect of 1,4-dihydropyridine (1,4-DHP) derivatives with various biological activities is to reduce the influx of extracellular Ca2+ ions. Because of this feature, many 1,4-DHP derivatives have been identified as potent calcium channel blockers and have been included in the treatment as antihypertensive agents. On the other hand, the biphenyl group is an important group in the molecule of biologically active compounds. The active compounds are obtained by introducing the biphenyl group into the structure of various compounds. In this study, the biphenyl group was introduced into the 1,4-DHP ring to reach to hexahydroquinoline (HHQ) derivative as an active calcium channel blocker compound. The structure of the compound was proved by IR, 1H-NMR, Mass spectroscopy, X-ray crystallography and elemental analysis. The cytotoxic properties of the compound has been determined, and biological activity assays continue. The crystal structure of C28H31NO3 was determined by single crystal X-ray diffraction: monoclinic, space group C c, a = 11.9713(3) A, b = 18.7893(5) A, c = 10.7358(3) A, β = 102.411(4)°, Z = 4. The title molecule is twisted with the dihedral angle between two phenyl rings being 50.86(10)°. The optimized geometries of the title compound have been obtained employing DFT method. The calculated geometrical parameters were found to be in agreement with the experimental data.The most important effect of 1,4-dihydropyridine (1,4-DHP) derivatives with various biological activities is to reduce the influx of extracellular Ca2+ ions. Because of this feature, many 1,4-DHP derivatives have been identified as potent calcium channel blockers and have been included in the treatment as antihypertensive agents. On the other hand, the biphenyl group is an important group in the molecule of biologically active compounds. The active compounds are obtained by introducing the biphenyl group into the structure of various compounds. In this study, the biphenyl group was introduced into the 1,4-DHP ring to reach to hexahydroquinoline (HHQ) derivative as an active calcium channel blocker compound. The structure of the compound was proved by IR, 1H-NMR, Mass spectroscopy, X-ray crystallography and elemental analysis. The cytotoxic properties of the compound has been determined, and biological activity assays continue. The crystal structure of C28H31NO3 was determined by single crystal X-ray diffr...
- Published
- 2018
22. Synthesis and Biological Evaluation of New Tricyclic Dihydropyridine Based Derivatives on Potassium Channels
- Author
-
Miyase Gözde, Gündüz, Yesim, Kaya, Rahime, Şimşek, Inci, Sahin-Erdemli, and Cihat, Şafak
- Subjects
4-Dihydropyridine ,Pinacidil ,Original Article ,Potassium channel ,Docking - Abstract
The present study reports a microwave-assisted method for the synthesis of twelve novel tricyclic 1,4-dihydropyridine derivatives in which dimethyl-substituted cyclohexane and / or tetrahydrothiophene rings are fused to the DHP ring. The structures of the compounds were confirmed by spectral methods and elemental analysis. The potassium channel opening effects of the compounds were determined on rat mesenteric arteries and urinary bladders. The obtained results indicated that some compounds produced mesenteric artery-selective relaxant properties and the effects of these compounds were mediated through ATP-sensitive potassium channels. The replacement of the second tetrahydrothiophene ring with dimethyl-substituted cyclohexane ring led to more active compounds. Docking studies were carried out to understand the interactions of the compounds with the active site of potassium channel. The unsubstituted nitrogen atom on the 1,4-dihydropyridine ring and one of the sulfonyl oxygens were found to be important for the formation of hydrogen bonds to stabilize the compound in the center of the cavity. The nature and position of phenyl ring substituents were also effective on the activity of the compounds. Finally, a theoretical study was established to predict the ADME of the most active compounds.
- Published
- 2017
23. Synthesis and photodegradation studies of analogues of muscle relaxant 1,4-dihydropyridine compounds
- Author
-
Ahmed El-Khouly, Cihat Şafak, Miyase Gözde Gündüz, Fatma Isli, Rahime Şimşek, Şeniz Yıldırım, Gaetano Ragno, Michele De Luca, Gökçe Sevim Öztürk Fincan, Giuseppina Ioele, and Fedora Grande
- Subjects
Dihydropyridines ,Light ,medicine.drug_class ,1,4-dihydropyridine compounds ,drug design ,Pharmaceutical Science ,DHPS ,02 engineering and technology ,In Vitro Techniques ,photostability ,01 natural sciences ,Medicinal chemistry ,chemistry.chemical_compound ,Structure-Activity Relationship ,Pyridine ,medicine ,Structure–activity relationship ,Moiety ,Organic chemistry ,Animals ,Photodegradation ,Pharmaceutical industry ,Pharmacology ,Photolysis ,010405 organic chemistry ,Chemistry ,Dihydropyridine ,Muscle relaxant ,Muscle, Smooth ,General Medicine ,structure activity relationship ,021001 nanoscience & nanotechnology ,0104 chemical sciences ,muscle relaxant ,MCR analysis ,mcr analysis ,Neuromuscular Agents ,Rabbits ,HD9665-9675 ,0210 nano-technology ,Derivative (chemistry) ,medicine.drug - Abstract
This paper describes the synthesis of 1,4-dihydropyridine compounds (DHPs) endowed with good muscle relaxant activity and stability to light. Six new condensed DHPs were synthesized by the microwave irradiation method. A long-chain ester moiety [2-(methacryloyloxy)ethyl] and various substituents on the phenyl ring were demonstrated to affect the muscle relaxant activity occurring in isolated rabbit gastric fundus smooth muscle strips. Forced photodegradation conditions were applied to the molecules according to the ICH rules. The degradation profile of the drugs was monitored by spectrophotometry coupled with the multivariate curve resolution technique. Formation of the oxidized pyridine derivative was observed for all the studied DHPs, except for one compound, which showed very fast degradation and formation of a second photo-product. Pharmacological tests on the molecules showed a good muscle relaxing effect, with a mechanism similar to that of nifedipine, however, proving to be more stable to light.
- Published
- 2017
24. Microwave-assisted synthesis and myorelaxant activity of 9-indolyl-1,8-acridinedione derivatives
- Author
-
Miyase Gözde Gündüz, Ray J. Butcher, Ahmed El-Khouly, Gökçe Sevim Öztürk Fincan, Fatma Isli, Rahime Şimşek, Cihat Şafak, Yusuf Sarioglu, Sema Öztürk Yildirim, and Şeniz Yıldırım
- Subjects
Potassium Channels ,Stereochemistry ,Muscle Relaxation ,Crystallography, X-Ray ,Medicinal chemistry ,Molecular Docking Simulation ,chemistry.chemical_compound ,Drug Discovery ,Animals ,Microwaves ,Pharmacology ,Indole test ,biology ,Chemistry ,Pinacidil ,Organic Chemistry ,Active site ,Muscle, Smooth ,General Medicine ,Potassium channel ,Muscle relaxation ,Docking (molecular) ,Acridine ,biology.protein ,Acridines ,Rabbits - Abstract
In this study a microwave-assisted method was applied for the synthesis of novel 9-(substituted indolyl)-3,4,6,7-tetrahydroacridine-1,8-(2H,5H,9H,10H)-dione derivatives. The structures of the compounds were confirmed by spectral methods including X-ray studies and elemental analysis. The Emax and pD2 values of the compounds and pinacidil were determined on noradrenaline precontracted tissues of isolated strips of rabbit gastric fundus smooth muscle. The obtained results indicated that some compounds and pinacidil produced concentration-dependent relaxation on the strips. The efficacy of compound 9 was higher than pinacidil. Docking studies were carried out to understand the interactions of the compounds with the active site of potassium channel. Methyl substituents on the acridine backbone and bromine atom on the indole ring led to more active compounds.
- Published
- 2014
25. Synthesis and Evaluation of 1,4-Dihydropyridine Derivatives with Calcium Channel Blocking Activity
- Author
-
Miyase Gözde Gündüz, Rahime Şimşek, Chris Bladen, Gerald W. Zamponi, and Cihat Şafak
- Subjects
Dihydropyridines ,Calcium Channels, L-Type ,Voltage-dependent calcium channel ,Physiology ,Stereochemistry ,Chemistry ,Calcium channel ,Clinical Biochemistry ,Dihydropyridine ,DHPS ,Calcium Channel Blockers ,Rats ,Calcium Channels, T-Type ,Structure-Activity Relationship ,HEK293 Cells ,Physiology (medical) ,medicine ,Animals ,Humans ,Moiety ,Structure–activity relationship ,Pharmacophore ,Selectivity ,medicine.drug - Abstract
1,4-Dihydropyridines (DHPs) are an important class of L-type calcium channel blockers that are used to treat conditions such as hypertension and angina. Their primary target in the cardiovascular system is the Cav1.2 L-type calcium channel isoform, however, a number of DHPs also block low-voltage-activated T-type calcium channels. Here, we describe the synthesis of a series of novel DHP derivatives that have a condensed 1,4-DHP ring system (hexahydroquinoline) and report on their abilities to block both L- and T-type calcium channels. Within this series of compounds, modification of a key ester moiety not only regulates the blocking affinity for both L- and T-type channels, but also allows for the development of DHPs with 30-fold selectivity for T-type channels over the L-type. Our data suggest that a condensed dihydropyridine-based scaffold may serve as a pharmacophore for a new class of T-type selective inhibitors.
- Published
- 2013
26. Microwave-Assisted Synthesis and Spasmolytic Activity of 4-Indolylhexahydroquinoline Derivatives
- Author
-
Ray J. Butcher, Cihat Şafak, Ahmed El-Khouly, S. Öztürk Yıldırım, Rahime Şimşek, Ç. Çengelli, Kevser Erol, and Miyase Gözde Gündüz
- Subjects
Male ,chemistry.chemical_classification ,Indole test ,Dihydropyridines ,Parasympatholytics ,Calcium channel blockade ,General Medicine ,Calcium Channel Blockers ,Ring (chemistry) ,Microwave assisted ,Rats ,Structure-Activity Relationship ,chemistry.chemical_compound ,chemistry ,Ileum ,Drug Discovery ,Animals ,Moiety ,Organic chemistry ,Female ,Methanol ,Microwaves ,Ammonium acetate ,Alkyl - Abstract
In the present study a microwave-assisted one-pot method was applied for the synthesis of 18 novel condensed 1,4-dihydropyridines carrying the indole moiety. The compounds were achieved by the reaction of appropriate 1,3-cyclohexanedione, substituted indole carboxaldehyde derivative, alkyl acetoacetate and ammonium acetate in methanol, according to a modified Hantzsch reaction. The structure elucidation of the compounds was carried out by spectral methods including X-ray studies. Their spasmolytic activities through calcium channel blockade were assayed on isolated rat ileum. The obtained results indicated that the introduction of the brom atom on the indole ring altered the mentioned activity positively.
- Published
- 2013
27. ESR study of some gamma irradiated amino acids and condensed 1,4-dihydropyridines
- Author
-
Y. Emre Osmanoğlu, Cihat Şafak, Rahime Şimşek, Murat Aydin, and Miyase Gözde Gündüz
- Subjects
chemistry.chemical_classification ,Chemistry ,Hydrochloride ,Radical ,Organic Chemistry ,Photochemistry ,Analytical Chemistry ,law.invention ,Amino acid ,Inorganic Chemistry ,Paramagnetism ,chemistry.chemical_compound ,Unpaired electron ,law ,Organic chemistry ,Amine gas treating ,Electron paramagnetic resonance ,Hyperfine structure ,Spectroscopy - Abstract
L -alanine methyl ester hydrochloride, 2-aminoisobutyric acid and some condensed 1,4-dihydropyridine derivatives (Compounds R1–R4) were gamma irradiated, the induced free radicals was investigated at room temperature by electron spin resonance techniques. The observed paramagnetic species of amino acids compounds were attributed to the CH 3 ĊHCOOCH 3 and (CH 3 ) 2 ĊCOOH radicals, respectively. The observed spectra of the 1,4-dihydropyridine derivatives interpreted in terms of some type of amine radical fragments. The spectra were computer simulated and the g values of the radicals and the hyperfine structure constants of the unpaired electron with nearby protons and 14 N nucleus were determined. In this study, the observed paramagnetic species were found to be stable at room temperature more than 2 months.
- Published
- 2013
28. Synthesis and photodegradation studies of analogues of muscle relaxant 1,4-dihydropyridine compounds
- Author
-
MIYASE GÖZDE GÜNDÜZ, GAETANO RAGNO, RAHIME ŞIMŞEK, MICHELE DE LUCA, CIHAT ŞAFAK, FEDORA GRANDE, AHMED EL-KHOULY, FATMA İŞLI, ŞENIZ YILDIRIM, GÖKÇE SEVIM ÖZTÜRK FINCAN, GIUSEPPINA IOELE, MIYASE GÖZDE GÜNDÜZ, GAETANO RAGNO, RAHIME ŞIMŞEK, MICHELE DE LUCA, CIHAT ŞAFAK, FEDORA GRANDE, AHMED EL-KHOULY, FATMA İŞLI, ŞENIZ YILDIRIM, GÖKÇE SEVIM ÖZTÜRK FINCAN, and GIUSEPPINA IOELE
- Abstract
This paper describes the synthesis of 1,4-dihydropyridine compounds (DHPs) endowed with good muscle relaxant activity and stability to light. Six new condensed DHPs were synthesized by the microwave irradiation method. A long-chain ester moiety [2-(methacryloyloxy)ethyl] and various substituents on the phenyl ring were demonstrated to affect the muscle relaxant activity occurring in isolated rabbit gastric fundus smooth muscle strips. Forced photodegradation conditions were applied to the molecules according to the ICH rules. The degradation profile of the drugs was monitored by spectrophotometry coupled with the multivariate curve resolution technique. Formation of the oxidized pyridine derivative was observed for all the studied DHPs, except for one compound, which showed very fast degradation and formation of a second photoproduct. Pharmacological tests on the molecules showed a good muscle relaxing effect, with a mechanism similar to that of nifedipine, however, proving to be more stable to light.
- Published
- 2017
29. Synthesis, structural characterization and myorelaxant activity of 4-naphthylhexahydroquinoline derivatives containing different ester groups
- Author
-
Miyase Gözde Gündüz, Ray J. Butcher, Emine Albayrak, Cihat Şafak, Yusuf Sarioglu, Rahime Şimşek, Fatma Isli, Şeniz Yıldırım, Gökçe Sevim Öztürk Fincan, Sema Öztürk Yıldırım, and Kırıkkale Üniversitesi
- Subjects
chemistry.chemical_classification ,crystal structure ,Gastric fundus ,synthesis ,010405 organic chemistry ,Chemistry ,Stereochemistry ,structure elucidation ,myorelaxant activity ,General Chemistry ,Crystal structure ,010402 general chemistry ,01 natural sciences ,0104 chemical sciences ,lcsh:Chemistry ,lcsh:QD1-999 ,Smooth muscle ,1,4-dihydropyridine ,Moiety ,Mass analysis ,Long chain ,Two-dimensional nuclear magnetic resonance spectroscopy ,Alkyl - Abstract
Gunduz, Miyase Gozde/0000-0002-2287-9509; Bayram, Cem/0000-0001-8717-4668; SARIOGLU, YUSUF/0000-0002-9227-365X WOS: 000382175400001 The present study reports the synthesis, structural characterization and myorelaxant activity evaluation of a series of 16 novel 4-naphthylhexahydroquinoline derivatives. The compounds were achieved by one-pot microwave-assisted method via a modified Hantzsch reaction. The structures of the compounds were confirmed by various spectral methods, such as IR, 1D and 2D NMR techniques and mass analysis. X-Ray studies of compound 10 provided further evidence for the proposed structure. To evaluate their myorelaxant activities, the E-max and pD(2) values of the compounds and nifedipine were determined on isolated rabbit gastric fundus smooth muscle strips. The obtained results indicated that the introduction of long chain alkyl groups, such as the 2-methoxyethyl or 2-(methacryloyloxy)ethyl moiety, to the ester group led to the most active compounds. Scientific Research Fund of Hacettepe University, TurkeyHacettepe University [013.D03.301.001]; NSF-MRI programNational Science Foundation (NSF)NSF - Office of the Director (OD) [CHE-0619278] The authors gratefully acknowledge the financial support provided by the Scientific Research Fund of Hacettepe University, Turkey through Project 013.D03.301.001.; RJB wishes to acknowledge the NSF-MRI program (grant CHE-0619278) for funds to purchase the diffractometer and the Howard University Nanoscience Facility for access to liquid nitrogen.
- Published
- 2016
30. Synthesis and Myorelaxant Activity of Fused 1,4-Dihydropyridines on Isolated Rabbit Gastric Fundus
- Author
-
Cihat Şafak, Fatma Isli, Miyase Gözde Gündüz, Yusuf Sarioglu, Rahime Şimşek, Anthony Linden, Şeniz Yıldırım, Gökçe Sevim Öztürk Fincan, and Sevil Ozger Ilhan
- Subjects
chemistry.chemical_compound ,Smooth muscle ,Cyclohexane ,Gastric fundus ,Chemistry ,Stereochemistry ,Calcium channel ,Drug Discovery ,Moiety ,chemistry.chemical_element ,Calcium ,Cyclopentane - Abstract
Strategy, Management and Health Policy Preclinical Research In the present study, 25 novel condensed 1,4-dihydropyridine (DHP) derivatives bearing cyclopentane, cyclohexane, or tetrahydrothiopene ring with a bulky and lipophilic moiety (3-pyridylmethyl) in the ester group were synthesized via a modified Hantzsch reaction, and their calcium channel modulator activities were assayed on isolated rabbit gastric fundus smooth muscle strips. To evaluate the myorelaxant effects of the compounds, the maximum relaxant response (Emax) and pD 2 values were calculated. The results indicated that all compounds produced concentration-dependent relaxation and the introduction of five- or six-membered rings to the DHP nucleus and 3-pyridiylmethyl moiety to the ester group led to potent calcium antagonists.
- Published
- 2012
31. Studies on Calcium Antagonist Activities of 2-Ethyl-3-carbmethoxy-4-aryl-5-oxo-6,6-dimethyl-1,4,5,6,7,8-hexahydroquinoline Derivatives
- Author
-
Başar Sirmagül, Kevser Erol, Rahime Şimşek, and Cihat Şafak
- Subjects
Male ,Magnetic Resonance Spectroscopy ,Spectrophotometry, Infrared ,Barium Compounds ,Nicardipine ,chemistry.chemical_element ,Ileum ,In Vitro Techniques ,Quinolones ,Calcium ,Biology ,Medicinal chemistry ,Mass Spectrometry ,Muscle, Smooth, Vascular ,Structure-Activity Relationship ,chemistry.chemical_compound ,Chlorides ,Drug Discovery ,Mole ,medicine ,Animals ,Sheep ,Aryl ,Antagonist ,Biological activity ,Anatomy ,Calcium Channel Blockers ,In vitro ,Rats ,Carotid Arteries ,medicine.anatomical_structure ,chemistry ,Female ,Chromatography, Thin Layer ,medicine.drug - Abstract
In this study, 23 new compounds having 2-ethyl-3-carbmethoxy-4-aryl-5-oxo-6,6-dimethyl-1,4,5,6,7, 8-hexahydroquinoline structure have been synthesised and screened for their calcium antagonistic activities. The structure of the compounds were characterised by IR, 1H-NMR, 13C-NMR, mass spectroscopy and elemental analyses. The calcium antagonistic activities of the compounds were determined by the tests performed on isolated rat ileum and lamb carotid artery. Although none of the synthesized compounds were as active as nicardipine in isolated rat ileum, the compounds 9, 10 and 19 have shown high activity. In screening studies on lamb carotid artery, compounds 10, 14 and 19 have been found active at a concentration of 10(-4) mol/l.
- Published
- 2011
32. Investigation of myorelaxant activity of 9-aryl-3,4,6,7-tetrahydroacridine-1,8-(2H,5H,9H,10H)-diones in isolated rabbit gastric fundus
- Author
-
Cihat Şafak, Gökçe Sevim Öztürk Fincan, Ismail Mert Vural, Yusuf Sarioglu, Miyase Gözde Gündüz, and Rahime Şimşek
- Subjects
Gastric fundus ,Stereochemistry ,Aryl ,Organic Chemistry ,Rabbit (nuclear engineering) ,Nuclear magnetic resonance spectroscopy ,Mass spectrometry ,chemistry.chemical_compound ,chemistry ,Pinacidil ,Methanol ,General Pharmacology, Toxicology and Pharmaceutics ,Ammonium acetate ,Nuclear chemistry - Abstract
In this study, twelve compounds having 9-aryl-3,4,6,7-tetrahydroacridine-1,8-(2H,5H,9H,10H)-dione structure were synthesized by reaction of 5-methyl-1,3-cyclohexanedione, the appropriate aromatic aldehydes, and ammonium acetate in methanol. The structures of the compounds were elucidated by infrared, H-1- and C-13-nuclear magnetic resonance spectroscopy (-NMR), mass spectroscopy, and elemental analysis. The maximum relaxant effects (E (max)) and pD2 values of the compounds 3a-l and pinacidil were tested on isolated strips of rabbit gastric fundus smooth muscle.
- Published
- 2011
33. Substituted 9-aryl-1,8-acridinedione derivatives and their effects on potassium channels
- Author
-
Rahime Şimşek, Ali Evrim Dogan, Cihat Şafak, Miyase Gözde Gündüz, and Kevser Erol
- Subjects
chemistry.chemical_classification ,Aryl ,Organic Chemistry ,Inorganic chemistry ,Mass spectrometry ,Aldehyde ,Medicinal chemistry ,Potassium channel ,chemistry.chemical_compound ,chemistry ,Pinacidil ,Potassium channel opener ,Methanol ,General Pharmacology, Toxicology and Pharmaceutics ,Ammonium acetate - Abstract
In this study, 12 new 3,6-dimethyl-9-aryl-3,4,6,7-tetrahydroacridine-1,8(2H,5H,9H,10H)-diones derivatives were synthesized. Synthesis of the compounds was realized by the reaction of 5-methyl-1,3-cyclohexanedione, the appropriate aromatic aldehyde, and ammonium acetate in methanol. The structure of the compounds was elucidated by infrared (IR), 1H-nuclear magnetic resonance (NMR), 13C-NMR, mass spectroscopy, and elemental analysis. Functional effects of the compounds on vascular potassium channels and mechanism of phenylephrine-induced contractile responses were investigated in isolated rat aorta rings. Pinacidil was used as a standard potassium channel opener.
- Published
- 2008
34. Evaluation of myorelaxant activity of 7-substituted hexahydroquinoline derivatives in isolated rabbit gastric fundus
- Author
-
Gökçe Sevim Öztürk, Cihat Şafak, Yusuf Sarioglu, Ismail Mert Vural, Rahime Şimşek, and Miyase Gözde Gündüz
- Subjects
medicine.drug_class ,Stereochemistry ,Muscle Relaxation ,Drug Evaluation, Preclinical ,In Vitro Techniques ,Pharmacology ,Inhibitory postsynaptic potential ,Norepinephrine ,chemistry.chemical_compound ,Drug Discovery ,medicine ,Animals ,Gastric Fundus ,Lagomorpha ,biology ,Pinacidil ,Organic Chemistry ,Muscle, Smooth ,Muscle relaxant ,Biological activity ,General Medicine ,biology.organism_classification ,In vitro ,Potassium channel ,chemistry ,Quinolines ,Potassium channel opener ,Rabbits - Abstract
In this article, 16 new methyl(ethyl) 4-(dichlorophenyl)-2,7-dimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylates and methyl(ethyl) 2-methyl-4-(dichlorophenyl)-5-oxo-7-phenyl-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate derivatives have been synthesized by the Hantzsch reaction and screened for their myorelaxant and potassium channel opening activities. The maximum relaxant effects (E-max) and pD(2) values on exogenous noradrenaline precontracted tissues and inhibitory effects on cholinergic neurotransmission of the compounds and pinacidil were determined on isolated strips of rabbit gastric fundus smooth muscle. Obtained results indicated that some compounds and pinacidil produced concentration-dependent relaxation on rabbit gastric fundus smooth muscle strips in the two test conditions. (c) 2007 Elsevier Masson SAS. All rights reserved.
- Published
- 2008
35. Structure-Activity Relationships of Receptor Binding of 1,4-Dihydropyridine Derivatives
- Author
-
Shizuo Yamada, Luvsandorj Oyunzul, Shinya Uchida, Daiki Takahashi, Miyase Gözde Gündüz, Yoshihiko Ito, Chiat Safak, Satomi Onoue, and Rahime Şimşek
- Subjects
Dihydropyridines ,endocrine system ,Stereochemistry ,Potassium ,Pharmaceutical Science ,chemistry.chemical_element ,Receptors, Nicotinic ,Rats, Sprague-Dawley ,Radioligand Assay ,Structure-Activity Relationship ,chemistry.chemical_compound ,KATP Channels ,Nifedipine ,medicine ,Animals ,Phenyl group ,Rats, Wistar ,Receptor ,IC50 ,Pharmacology ,Binding Sites ,Calcium channel ,Aryl ,Receptors, Purinergic ,Antagonist ,Brain ,General Medicine ,Calcium Channel Blockers ,Rats ,Receptors, Adrenergic ,chemistry ,Calcium Channels ,Protein Binding ,medicine.drug - Abstract
The present study was undertaken to investigate binding activity of synthesized 1,4-dihydropyridine (1,4-DHP) derivatives (Compounds 1--124) to 1,4-DHP calcium channel antagonist receptors in rat brain. Sixteen 1,4-DHP derivatives inhibited specific (+)-[3H]PN 200-110 binding in rat brain in a concentration-dependent manner with IC50 value of 0.43 to 3.49 microM. Scatchard analysis revealed that compounds 54, 69, 85, like nifedipine, caused a significant increase in apparent dissociation constant (Kd) for (+)-[3H]PN 200-110, while compounds 68, 69 and 80 caused a significant decrease in maximal number of bindings sites (Bmax). These data suggest that compounds 68, 69 and 80 exert longer-acting antagonistic effects of 1,4-DHP receptors than compounds 54, 69 and 85. The structure-activity relationship study has revealed that 1) ester groups in 3- and 5-positions are the most effective, 2) the aryl group in the 4-position of 1,4-DHP ring is the basic requirement for optimal activity, 3) position and type of electron-withdrawing groups on phenyl group at position 4 would affect the receptor-binding activity. Furthermore, compound 58 exerted alpha1 receptor binding activity, being 1.6 times greater than 1,4-DHP receptors. Compounds 81, 84, 91, 94, 106, 108 and 109 showed significant binding of ATP-sensitive potassium (K ATP) channel, and the binding activities of compounds 81, 84, 108 and 109 were 1.6--3.8 times greater than the binding activity for 1,4-DHP receptors. Compounds 91 and 106 had similar binding activity for K ATP channel and 1,4-DHP receptors. In conclusion, the present study has shown that novel 1,4-DHP derivatives exert relatively high binding affinity to 1,4-DHP receptors and has revealed new aspect of structure-activity relationships of 1,4-DHP derivatives, especially hexahydroquinoline derivatives.
- Published
- 2008
36. Microwave-assisted synthesis of condensed 1,4-dihydropyridines as potential calcium channel modulators
- Author
-
Osman Cihat Şafak, Rahime Şimşek, Mehmet Yildirim Sara, Alper B. Iskit, Ahmed El-Khouly, Miyase Gözde Gündüz, Erdem Kamil Ozer, Selçuk Üniversitesi, and Farmasötik Kimya
- Subjects
chemistry.chemical_classification ,Ethanol ,Voltage-dependent calcium channel ,synthesis ,Stereochemistry ,medicine.drug_class ,Calcium channel ,Relaxation (NMR) ,1,4-Dihydropyridine,hexahydroquinoline,synthesis,calcium channel ,General Chemistry ,Calcium channel blocker ,hexahydroquinoline ,Medicinal chemistry ,chemistry.chemical_compound ,Chemistry ,Engineering ,chemistry ,Nifedipine ,medicine ,calcium channel ,1,4-Dihydropyridine ,Ammonium acetate ,Alkyl ,medicine.drug - Abstract
WOS: 000359063900017, This study reports the design, synthesis, and calcium channel modulatory activity evaluation of a series of 14 novel fused 1,4-dihydropyridine derivatives. The molecular design of the compounds was based on modifications of nifedipine, which is a calcium channel blocker. The compounds were achieved by one-pot microwave-assisted reaction of 4,4-dimethyl-1,3-cyclohexanedione, 5-chlorosalicylaldehyde/3,5-dichlorosalicylaldehyde, an appropriate alkyl acetoacetate, and ammonium acetate in ethanol according to a modified Hantzsch reaction. The structures of the compounds were confirmed by spectral methods and elemental analysis. To evaluate their relaxant activities, the maximum relaxant response (E-max) and pD(2) values of the compounds and nifedipine were determined on isolated rat aorta rings. The obtained results indicated that all compounds produced concentration-dependent relaxation on the rings possibly due to the blockade of calcium channels. The E-max values (a measure of efficacy) of five compounds were higher than those of nifedipine., Turkish Academy of SciencesTurkish Academy of Sciences [EA-TUBA-GEBIP/2001-2-11], Alper B. Iskit has been supported by the Turkish Academy of Sciences, in the framework of the Young Scientist Award Program (EA-TUBA-GEBIP/2001-2-11).
- Published
- 2015
37. Analgesic effect of a broad-spectrum dihydropyridine inhibitor of voltage-gated calcium channels
- Author
-
Miyase Gözde Gündüz, Chris Bladen, Lina Chen, Fang Xiong Zhang, Vinicius M. Gadotti, Gerald W. Zamponi, Rahime Şimşek, and Cihat Şafak
- Subjects
Analgesics ,Dihydropyridines ,P-type calcium channel ,Voltage-dependent calcium channel ,Physiology ,business.industry ,Calcium channel ,Clinical Biochemistry ,T-type calcium channel ,Dihydropyridine ,Pharmacology ,N-type calcium channel ,Calcium Channel Blockers ,Cell Line ,Rats ,Electrophysiology ,Physiology (medical) ,medicine ,Animals ,Humans ,Neuralgia ,Patch clamp ,Calcium Channels ,business ,medicine.drug - Abstract
Voltage-activated calcium channels are important facilitators of nociceptive transmission in the primary afferent pathway. Consequently, molecules that block these channels are of potential use as pain therapeutics. Our group has recently reported on the identification of a novel class of dihydropyridines (DHPs) that included compounds with preferential selectivity for T-type over L-type channels. Among those compounds, M4 was found to be an equipotent inhibitor of both Cav1.2 L- and Cav3.2 T-type calcium channels. Here, we have further characterized the effects of this compound on other types of calcium channels and examined its analgesic effect when delivered either spinally (i.t.) or systemically (i.p.) to mice. Both delivery routes resulted in antinociception in a model of acute pain. Furthermore, M4 was able to reverse mechanical hyperalgesia produced by nerve injury when delivered intrathecally. M4 retained partial activity when delivered to Cav3.2 null mice, indicating that this compound acts on multiple targets. Additional whole-cell patch clamp experiments in transfected tsA-201 cells revealed that M4 also effectively blocks Cav3.3 (T-type) and Cav2.2 (N-type) currents. Altogether, our data indicate that broad-spectrum inhibition of multiple calcium channel subtypes can lead to potent analgesia in rodents.
- Published
- 2015
38. Cocrystals of diastereoisomers of 1,4-dihydropyridine derivatives
- Author
-
Rahime Şimşek, Anthony Linden, Miyase Gözde Gündüz, and Cihat Şafak
- Subjects
Models, Molecular ,Dihydropyridines ,Molecular Structure ,Stereochemistry ,Quinoline ,Cyclohexane conformation ,Diastereomer ,Substituent ,Stereoisomerism ,General Medicine ,Crystal structure ,Crystallography, X-Ray ,Ring (chemistry) ,General Biochemistry, Genetics and Molecular Biology ,chemistry.chemical_compound ,Crystallography ,chemistry ,Molecule ,Crystallization ,Unit (ring theory) - Abstract
A mixture of the RR/SS and RS/SR diastereoisomeric pairs of methyl 4-(2,4-dichlorophenyl)-2,7-dimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate, C 19 H 19 Cl 2 NO 3 , forms cocrystals in which there is one unique molecule in the asymmetric unit, but the molecule displays disorder in the region of the 7-position of the quinoline ring system as a result of the random occurrence of the diastereoisomers at the same crystallographic site. A similar arrangement exists in the monohydrate cocrystals that form from a mixture of the RRI SS and RS/SR diastereoisomeric pairs of methyl 4-(2,4-dichlorophenyl)-2-methyl-7-phenyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate monohydrate, C 24 H 21 Cl 2 NO 3 ·-H 2 O. These compounds belong to a class of 1,4-dihydropyridines whose members have calcium modulatory properties. The 1,4-dihydropyridine rings have the usual shallow boat conformation. In each structure, the 2,4-dichlorophenyl ring is oriented such that the 2-chloro substituent is in a synperiplanar orientation with respect to the 1,4-dihydropyridine ring plane. In each crystal structure, the molecules are linked into chains by N-H···O hydrogen-bonding interactions.
- Published
- 2006
39. Some arylacridine derivatives possessing potassium channel opening activity
- Author
-
Rahime Şimşek, Serdar Uma, Melike Oezkan, Cihat Şafak, and Emrah Kismetli
- Subjects
Male ,Potassium Channels ,Stereochemistry ,Pharmaceutical Science ,Vasodilation ,In Vitro Techniques ,Medicinal chemistry ,chemistry.chemical_compound ,Drug Discovery ,medicine ,Animals ,Rats, Wistar ,Mesenteric arteries ,Phenylephrine ,Dose-Response Relationship, Drug ,Acridine derivatives ,General Medicine ,Potassium channel ,Mesenteric Arteries ,Rats ,medicine.anatomical_structure ,chemistry ,Pinacidil ,Acridines ,Potassium channel opener ,medicine.drug - Abstract
In this study, six new 2,2,7,7-tetramethyl-9-aryl-2,3,4,5,6,7,9,10-octahydro-1,8-acridinedione derivatives (1-6) were synthesised and their functional effects on vascular potassium channels and mechanism of induced relaxations on phenylephrine-induced contractile responses in isolated rat mesenteric arteries were investigated. Pinacidil was used as standard potassium channel opener. Compounds 1, 2, 5, 6 and pinacidil induced concentration-dependent relaxation response of vessel rings previously contracted with phenylephrine.
- Published
- 2004
40. Exploring novel fluorine-rich fuberidazole derivatives as hypoxic cancer inhibitors: Design, synthesis, pharmacokinetics, molecular docking, and DFT evaluations.
- Author
-
Muhammad Babar Taj, Ahmad Raheel, Rabia Ayub, Afnan M Alnajeebi, Matokah Abualnaja, Alaa Hamed Habib, Walla Alelwani, Sadia Noor, Sami Ullah, Abdullah G Al-Sehemi, Rahime Simsek, Nouf Abubakr Babteen, and Heba Alshater
- Subjects
Medicine ,Science - Abstract
Sixteen fuberidazole derivatives as potential new anticancer bioreductive prodrugs were prepared and characterized. The in vitro anticancer potential was examined to explore their cytotoxic properties by employing apoptosis, DNA damage, and proliferation tests on chosen hypoxic cancer cells. Eight substances (Compound 5a, 5c, 5d, 5e, 5g, 5h, 5i, and 5m) showed promising cytotoxicity values compared to the standard control. The potential of compounds was also examined through in silico studies (against human serum albumin), including chem-informatics, to understand the structure-activity relationship (SAR), pharmacochemical strength, and the mode of interactions responsible for their action. The DFT calculations revealed that only the 5b compound showed the lowest ΔET (2.29 eV) while 5i showed relatively highest βtot (69.89 x 10-31 esu), highest αave (3.18 x 10-23 esu), and dipole moment (6.49 Debye). This study presents a novel class of fuberidazole derivatives with selectivity toward hypoxic cancer cells.
- Published
- 2023
- Full Text
- View/download PDF
41. 1,4-Dihydropyridine derivatives with T-type calcium channel blocking activity attenuate inflammatory and neuropathic pain
- Author
-
Miyase Gözde Gündüz, Cihat Şafak, Chris Bladen, N. Daniel Berger, Gerald W. Zamponi, Rahime Şimşek, and Vinicius M. Gadotti
- Subjects
Dihydropyridines ,Calcium Channels, L-Type ,Physiology ,Clinical Biochemistry ,Gating ,Pharmacology ,Cell Line ,Small Molecule Libraries ,Calcium Channels, T-Type ,Mice ,Physiology (medical) ,medicine ,Animals ,Humans ,Patch clamp ,Receptor ,Inflammation ,Voltage-dependent calcium channel ,Chemistry ,Dihydropyridine ,T-type calcium channel ,Transfection ,Calcium Channel Blockers ,Mice, Inbred C57BL ,Neuropathic pain ,Neuralgia ,Ion Channel Gating ,medicine.drug - Abstract
We have recently identified a class of dihydropyridine (DHP) analogues with 30-fold selectivity for T-type over L-type calcium channels that could be attributed to a modification of a key ester moiety. Based on these results, we examined a second series of compounds with similar attributes to determine if they had enhanced affinity for T-type channels. Whole-cell patch clamp experiments in transfected tsA-201 cells were used to screen these DHP derivatives for high affinity and selectivity for Cav3.2 over Cav1.2 L-type channels. The effects of the two lead compounds, termed N10 and N12, on Cav3.2 channel activity and gating were characterized in detail. When delivered intrathecally or intraperitoneally, these compounds mediated analgesia in a mouse model of acute inflammatory pain. The best compound from the initial screening, N12, was also able to reverse mechanical hyperalgesia produced by nerve injury. The compounds were ineffective in Cav3.2 null mice. Altogether, our data reveal a novel class of T-type channel blocking DHPs for potential pain therapies.
- Published
- 2014
42. Racemic Ethyl 4-(2-Fluorophenyl)-2,6,6-trimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate
- Author
-
Cihat Şafak, Rahime Şimşek, and Anthony Linden
- Subjects
Steric effects ,chemistry.chemical_compound ,chemistry ,Hydrogen bond ,Stereochemistry ,Quinoline ,Cyclohexane conformation ,Substituent ,General Medicine ,Carboxylate ,Ring (chemistry) ,Enone ,General Biochemistry, Genetics and Molecular Biology - Abstract
The title compound, C21H24FNO3, has potential calcium modulatory properties. The 1,4-dihydropyridine ring has a shallow boat conformation with the 2-fluorophenyl substituent in an axial synperiplanar orientation. The quinoline ring has a half-chair conformation. Steric interactions between the adjacent methyl and ethoxycarbonyl substituents cause local bond-angle distortions. The molecules are linked into chains by intermolecular N—H⋯O hydrogen bonds.
- Published
- 1998
43. 2,2,7,7-Tetramethyl-1,2,3,4,5,6,7,8-octahydroacridine-1,8-dione
- Author
-
Rahime Şimşek, Ahmed El-Khouly, Sema Öztürk Yıldırım, Cihat Şafak, Ray J. Butcher, and Farmasötik Kimya
- Subjects
Cyclohexene ,Stacking ,General Chemistry ,Crystal structure ,Condensed Matter Physics ,Ring (chemistry) ,Bioinformatics ,Organic Papers ,Crystal ,lcsh:Chemistry ,chemistry.chemical_compound ,Crystallography ,chemistry ,lcsh:QD1-999 ,Pyridine ,Acridine ,Molecule ,General Materials Science - Abstract
The whole molecule of the title compound, C17H21NO2, is generated by twofold rotational symmetry. The N atom and the C and H atoms in position 4 of the pyridine ring lie on the twofold axis. The cyclohexene ring has a sofa conformation with the CH2 C atom adjacent to the dimethyl-substituted C atom displaced by 0.5949 (16) Å from the mean plane of the other five C atoms. In the crystal, weak C—H...O interactions link the molecules into chains parallel to the a axis. In addition, π–π stacking interactions [centroid–centroid distance = 3.8444 (7) Å] contribute to the stabilization of the crystal structure.
- Published
- 2013
44. 3,3,6,6-Tetramethyl-9-(1-methyl-1H-indol-2-yl)-1,2,3,4,5,6,7,8,9,10-decahydroacridine-1,8-dione
- Author
-
Rahime Şimşek, Sema Öztürk Yıldırım, Cihat Şafak, Ahmed El-Khouly, Ray J. Butcher, and Farmasötik Kimya
- Subjects
Indole test ,Crystallography ,biology ,Hydrogen bond ,Chemistry ,Maximum deviation ,General Chemistry ,Condensed Matter Physics ,biology.organism_classification ,Bioinformatics ,Ring (chemistry) ,Medicinal chemistry ,Organic Papers ,Crystal ,chemistry.chemical_compound ,QD901-999 ,Acridine ,Tetra ,General Materials Science ,Deca - Abstract
In the acridine system of the title molecule, C26H30N2O2, both cyclohex-2-enone rings adopt sofa conformations. The indole ring system is essentially planar, with a maximum deviation of 0.017 (2) Å for a bridgehead C atom. An intramolecular C—H...O hydrogen bond occurs. The molecules assemble into C(6) chains in the crystal by way of N—H...O hydrogen bonds.
- Published
- 2012
45. Ethyl 2,7,7-trimethyl-4-(1-methyl-1H-indol-3-yl)-5-oxo-1,4,5,6,7,8-hexa-hydro-quinoline-3-carboxyl-ate
- Author
-
Sema Öztürk Yıldırım, Cihat Şafak, Miyase Gözde Gündüz, Ahmed El-Khouly, Ray J. Butcher, and Rahime Şimşek
- Subjects
Indole test ,Quantitative Biology::Biomolecules ,Hydrogen bond ,Quinoline ,Cyclohexane conformation ,General Chemistry ,Dihedral angle ,Condensed Matter Physics ,Ring (chemistry) ,HEXA ,Bioinformatics ,Medicinal chemistry ,Organic Papers ,lcsh:Chemistry ,chemistry.chemical_compound ,chemistry ,lcsh:QD1-999 ,General Materials Science ,Pyrrole - Abstract
In the title molecule, C24H28N2O3, the cyclohexene ring is in a sofa conformation and the 1,4-dihydropyridine ring is in a slight boat conformation. In the indole ring system, the pyrrole and benzene rings form a dihedral angle of 2.63 (7)°. In the crystal, N—H...O hydrogen bonds connect the molecules into C(6) chains parallel to the b axis and pairs of weak C—H...O hydrogen bonds link inversion-related chains into a ladder motif through R22(18) rings. A weak intramolecular C—H...O hydrogen bond is also observed.
- Published
- 2012
46. 9-(5-Bromo-1H-indol-3-yl)-1,2,3,4,5,6,7,8,9,10-deca-hydro-acridine-1,8-dione dimethyl sulfoxide monosolvate
- Author
-
Sema Öztürk Yildirim, Ray J. Butcher, Ahmed El-Khouly, Cihat Şafak, Rahime Şimşek, and Farmasötik Kimya
- Subjects
Indole test ,Hydrogen bond ,Dimethyl sulfoxide ,Atom (order theory) ,General Chemistry ,Condensed Matter Physics ,Ring (chemistry) ,Bioinformatics ,Medicinal chemistry ,Organic Papers ,lcsh:Chemistry ,Crystal ,Solvent ,chemistry.chemical_compound ,lcsh:QD1-999 ,chemistry ,Acridine ,General Materials Science - Abstract
In the title compound, C21H19BrN2O2·C2H6OS, the indole ring system is essentially planar, with a maximum deviation of 0.050 (3) Å for the non-bridgehead C atom adjacent to the N atom. The two cyclohex-2-enone rings adopt half-chair conformations. An intramolecular C—H...O hydrogen bond occurs. The solvent molecule exhibits minor disorder of the S atom [site occupancies = 0.8153 (16) and 0.1847 (18)]. In the crystal, molecules are linked by N—H...O hydrogen bonds, forming layers parallel to the bc plane.
- Published
- 2012
47. Synthesis of cyclopentapyridine and thienopyridine derivatives as potential calcium channel modulators
- Author
-
B Koşar, Kevser Erol, B Kaygısız, Cihat Şafak, Miyase Gözde Gündüz, Anthony Linden, Rahime Şimşek, and University of Zurich
- Subjects
10120 Department of Chemistry ,Male ,Models, Molecular ,alcium channel modulator ,Thienopyridine Derivatives ,Magnetic Resonance Spectroscopy ,Thienopyridine ,Spectrophotometry, Infrared ,Thienopyridines ,Stereochemistry ,Pyridines ,Muscle Relaxation ,chemistry.chemical_element ,Aorta, Thoracic ,Cyclopentanes ,Calcium ,In Vitro Techniques ,Ring (chemistry) ,Cyclopentanone ,cyclopentapyridine ,chemistry.chemical_compound ,Nicardipine ,Structure-Activity Relationship ,Dihydropyridine ,Ileum ,Tandem Mass Spectrometry ,Drug Discovery ,540 Chemistry ,Animals ,thienopyridine ,Calcium channel ,3002 Drug Discovery ,Muscle, Smooth ,Calcium Channel Blockers ,Rats ,chemistry ,Female ,Indicators and Reagents ,Calcium Channels - Abstract
In this study, novel condensed 1,4-dihydropyridines bearing cyclopentanone (1-21) or tetrahydrothiophene-1,1-dioxide ring (22-42) with various ester substituents were synthesized via a modified Hantzsch reaction and their calcium channel modulator activities were investigated on isolated rat ileum and rat thoracic aorta. The introduction of a cyclopentanone ring fused to the 1,4-dihydropyridine nucleus and methyl, ethyl and allyl moieties to the ester group led to more active calcium modulators.
- Published
- 2012
48. Two 1,4-dihydropyridine derivatives with potential calcium-channel antagonist activity
- Author
-
Cihat Şafak, Anthony Linden, Rahime Şimşek, Miyase Gözde Gündüz, University of Zurich, and Linden, Anthony
- Subjects
10120 Department of Chemistry ,Dihydropyridines ,Molecular Structure ,Hydrogen bond ,Pyridines ,Molecular Conformation ,Atom (order theory) ,Hydrogen Bonding ,Stereoisomerism ,General Medicine ,Crystal structure ,Cyclopentanes ,Ring (chemistry) ,Calcium Channel Blockers ,Crystallography, X-Ray ,General Biochemistry, Genetics and Molecular Biology ,chemistry.chemical_compound ,Crystallography ,chemistry ,1300 General Biochemistry, Genetics and Molecular Biology ,Pyridine ,Halogen ,540 Chemistry ,Amine gas treating ,Benzene - Abstract
The title compounds, benzyl 4-(3-chloro-2-fluorophenyl)-2-methyl-5-oxo-4,5,6,7-tetrahydro-1H-cyclopenta[b]pyridine-3-carboxylate, C23H19ClFNO3, (I), and 3-pyridylmethyl 4-[2-fluoro-3-(trifluoromethyl)phenyl]-2,6,6-trimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate, C26H24F4N2O3, (II), belong to a class of 1,4-dihydropyridines whose members sometimes display calcium modulatory properties. The 1,4-dihydropyridine ring in each structure has a shallower than usual shallow-boat conformation and is nearly planar in (I). In each structure, the halogen-substituted benzene ring is oriented such that the halogen substituents are in a synperiplanar orientation with respect to the 1,4-dihydropyridine ring plane. The oxocyclopentene ring in (I) is planar, while the oxocyclohexene ring in (II) has a half-chair conformation, which is less commonly observed than the envelope conformation usually found in related compounds. In (I), the frequently observed intermolecular N—H⋯O hydrogen bond between the amine group and the carbonyl O atom of the oxocyclopentene ring of a neighbouring molecule links the molecules into extended chains; there are no other significant intermolecular interactions. By contrast, the amine group in (II) forms an N—H⋯N hydrogen bond with the pyridine ring N atom of a neighbouring molecule. Additional C—H⋯O interactions complete a two-dimensional hydrogen-bonded network. The halogen-substituted benzene ring has a weak intramolecular π–π interaction with the pyridine ring. A stronger π–π interaction occurs between the 1,4-dihydropyridine rings of centrosymmetrically related molecules.
- Published
- 2011
49. ChemInform Abstract: Synthesis and Antimicrobial Activity of Some 2-(2-Oxobenzothiazol-3-yl) -1-arylethanone Derivatives
- Author
-
Rahime Şimşek, Cihat Şafak, Yesim Altas, U. Abbasoglu, and B. Oezcelik
- Subjects
Chemistry ,General Medicine ,Antimicrobial ,Combinatorial chemistry - Published
- 2010
50. ChemInform Abstract: Some Azolylthioacetamides and Their Analgesic and Antiinflammatory Activities
- Author
-
Pelin Kelicen, Rahime Şimşek, Rümeysa Demirdamar, Cihat Şafak, and H. Akguen
- Subjects
Chemistry ,Analgesic ,Organic chemistry ,General Medicine ,Pharmacology - Published
- 2010
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.