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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.

Background: Spinal anesthesia is a very common technique used in lower limb surgeries. Dexmedetomidine is a highly selective α2-adrenergic agonist which has been used as pre-medication and as an adjuvant to general anesthesia. It is found that injection of dexmedetomidine intrathecally prolongs both sensory and motor block and has antinociceptive action for both visceral and somatic pain by depressing the release of nociceptive C fibers transmission and hyperpolarization of post synaptic dorsal horn cells. Objective: To compare the effect of addition of different doses of dexmedetomidine to bupivacaine on the duration of spinal anesthesia, quality of block, intraoperative and postoperative complications and postoperative analgesia in patients undergoing lower limb amputation surgeries. Methods: This prospective double blind randomized controlled clinical trial was done on sixty six adult patients of both sexes, aging from 21 to 60 years old, ASA I and II presented to Ain Shams University Hospitals for lower limb amputation surgeries were involved in this study during the period from July 2021 till May 2022. Results: The addition of dexmedetomidine to bupivacaine in spinal anesthesia significantly prolonged both sensory and motor blockades duration compared with bupivacaine alone. It was significantly faster in group B (2.1 ± 0.124) compared with A and C groups (2.64 ± 0.34) and (4.72 ± 0.31) respectively and in group A compared with group C. They also prolonged the time of postoperative analgesia as evidenced by significantly longer time to first rescue analgesia Time to first call for rescue analgesia was significantly longer in group B (350 ± 45 mins) compared with A(287.41 ± 40.83 mins) and C(192 ± 42 mins) groups and in group B compared with group A. Also, there was significant difference in number of analgesic doses in group B compared to A and C groups and in group B compared to group A. Lower VAS scores with minimal adverse effects and hemodynamic stability. Comparing two different doses of dexmedetomidine showed that 15 µg dexmedetomidine caused more prolongation of the spinal block duration and the time of postoperative analgesia than dexamethasone. It also decreased shivering during spinal anesthesia with only 4 patients compared to group A with 8 patients and group C with 9 patients. Conclusion: 5 µg dexmedetomidine seems to be an attractive as an adjuvant to spinal bupivacaine in surgical procedures. It provided good quality of intraoperative analgesia, hemodynamically stable conditions, minimal side effects, and excellent quality of postoperative analgesia. Unfortunately, it had not any effect on incidence or severity of phantom pain and sensation in lower limb amputation surgery, but 15 µg had better time of analgesia and longer time till the patient needed rescue analgesia with lower VAS score with no remarkable difference in the side effect as revealed. [ABSTRACT FROM AUTHOR]

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AbstractQuinolines have long been recognized as a versatile scaffold for the development of various bioactive compounds. In this context, a series of quinoline-based compounds were designed and synthesized using two key building block synthons: chalcone and thiocarbohydrazone derivatives. These compounds were synthesized following a design strategy inspired by the bis-indolyl maleimide-based PDK1 ATP-competitive inhibitor BIM-1. The final compounds were evaluated for their in vitro antiproliferative activity against MCF7 and HCT116 human cancer cell lines. Antiproliferative activity revealed that compound 11 displayed the best activity with IC50 of 7.09 and 6.18 µM against HCT116 and MCF7 cell lines respectively. Furthermore, an in silico molecular docking study was performed on the PDK1 enzyme to investigate the binding affinity of compounds at the ATP-binding site. The docking analysis provided insight into the molecular interactions and binding modes of these compounds. Compound 4 showed the highest affinity with a binding score of −11 kcal/mol and an estimated Ki of 8.65 nM. Additionally, ADME (Absorption, Distribution, Metabolism, and Excretion) predictions indicated favorable drug-likeness and oral bioavailability profiles. This study aims to contribute to the development of promising anticancer agents. [ABSTRACT FROM AUTHOR]

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 inter-actions link the mol-ecules into chains parallel to the a axis. In addition, π-π stacking inter-actions [centroid-centroid distance = 3.8444 (7) Å] contribute to the stabilization of the crystal structure.

In the title mol-ecule, C24H28N2O3, the cyclo-hexene ring is in a sofa conformation and the 1,4-dihydro-pyridine 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 mol-ecules 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 R2(2)(18) rings. A weak intra-molecular C-H⋯O hydrogen bond is also observed.

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 cyclo-hex-2-enone rings adopt half-chair conformations. An intra-molecular C-H⋯O hydrogen bond occurs. The solvent mol-ecule exhibits minor disorder of the S atom [site occupancies = 0.8153 (16) and 0.1847 (18)]. In the crystal, mol-ecules are linked by N-H⋯O hydrogen bonds, forming layers parallel to the bc plane.

The title compound, C23H25BrN2O3, crystallizes with two independent mol-ecules 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-hexa-hydro-quinoline 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 cyclo-hexene ring has adopts a sofa conformation. In the crystal, mol-ecules are linked by pairs of N-H⋯O hydrogen bonds, forming dimers with R1(2)(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 mol-ecules.

In the acridine system of the title mol-ecule, C26H30N2O2, both cyclo-hex-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 intra-molecular C-H⋯O hydrogen bond occurs. The mol-ecules assemble into C(6) chains in the crystal by way of N-H⋯O hydrogen bonds.