29 results on '"Daisuke Wakasugi"'
Search Results
2. Lead identification of novel tetrahydroimidazo[1,2-a]pyridine-5-carboxylic acid derivative as a potent heparanase-1 inhibitor
- Author
-
Yudai, Imai, Daisuke, Wakasugi, Ryo, Suzuki, Sota, Kato, Mami, Sugisaki, Masashi, Mima, Hiroh, Miyagawa, Mayumi, Endo, Natsuko, Fujimoto, Takuya, Fukunaga, Sayaka, Kato, Shoichi, Kuroda, Teisuke, Takahashi, and Hiroyuki, Kakinuma
- Subjects
Pyridines ,Organic Chemistry ,Clinical Biochemistry ,Drug Discovery ,Carboxylic Acids ,Pharmaceutical Science ,Molecular Medicine ,Heparitin Sulfate ,Sugars ,Molecular Biology ,Biochemistry ,Glucuronidase - Abstract
Heparanase-1 (HPSE1) is an endo-β-d-glucuronidase that cleaves heparan sulfate proteoglycans into short-chain heparan sulfates (HS). The inhibition of HPSE1 has therapeutic potential for proteinuric diseases such as nephrotic syndrome because increased HPSE1 expression is associated with the loss of HS in the glomerular basement membrane, leading to the development of proteinuria. The present study examined the generation of a lead compound focusing on chemical structures with a sugar moiety, such as glycosides and sugar analogs, taking their physical properties into consideration. Compound 10, an exo-β-d-glucuronidase (GUSβ) inhibitor, was found to have a weak inhibitory activity against endo-β-d-glucuronidase HPSE1. A structure-activity relationship study using the X-ray co-crystal structure of 10 and HPSE1 resulted in 12a, which showed a more than 14-fold increase in HPSE1 inhibitory activity compared with that of 10. Compound 12a could be a novel lead compound for the development of a potent HPSE1 inhibitor.
- Published
- 2023
3. A case of acute diffuse large B cell lymphoma in an anti-human T-cell leukaemia virus type 1-positive rheumatoid arthritis patient treated with methotrexate, who died
- Author
-
Satoshi Yamasaki, Yutaro Mihara, Gen Sugiyama, Munetoshi Nakashima, Naomi Yoshida, Suzuna Sugi, Daisuke Wakasugi, Kotaro Matsuda, Koichi Ohshima, Koki Satake, Hiroaki Ida, and Rin Yamaguchi
- Subjects
musculoskeletal diseases ,medicine.medical_specialty ,Gastroenterology ,Arthritis, Rheumatoid ,Fatal Outcome ,Internal medicine ,medicine ,Humans ,skin and connective tissue diseases ,B-cell lymphoma ,Aged ,Human T-lymphotropic virus 1 ,business.industry ,Jaundice ,medicine.disease ,HTLV-I Infections ,Methotrexate ,Virus type ,Rheumatoid arthritis ,Female ,Autopsy ,Disease Susceptibility ,Lymphoma, Large B-Cell, Diffuse ,medicine.symptom ,business ,Diffuse large B-cell lymphoma ,Biomarkers ,Immunosuppressive Agents ,T cell leukaemia ,Acute diffuse ,medicine.drug - Abstract
A 70-year-old woman was hospitalised due to jaundice and fever. She was diagnosed with rheumatoid arthritis (RA) at 54 years of age. Treatment with methotrexate (MTX) was successful, and her RA was in remission. Five weeks before the hospitalisation, she was diagnosed with optic neuritis due to a decline in the visual acuity of the right eye. She was treated with methylprednisolone pulse therapy, followed by prednisolone (PSL), before the hospitalisation, which were not effective. Blood tests showed increased C-reactive protein (CRP) levels, liver injury, and thrombocytopenia. Abdominal echo revealed numerous enlarged lymph nodes in the hepatic portal region. Malignant lymphoma was suspected due to high serum levels of soluble interleukin-2 receptor. None of the treatments were effective, and she died on the fifth hospital day. Diffuse large B cell lymphoma was diagnosed during the autopsy, which showed infiltration of CD20-positive atypical lymphocytes in almost all organs. Since she was taking MTX, she was diagnosed with immunosuppressive drug-associated lymphoproliferative disease (LPD). Anti-human T-cell leukaemia virus type 1 (HTLV-1) antibody was detected in her serum after her death; however, adult T cell leukaemia/lymphoma was not observed. LPD develops during the treatment of RA with disease modifying anti-rheumatic drugs; however, a rapid clinical course leading to death is rarely observed. Previous reports suggest that T cell dysregulation observed in HTLV-1 may contribute towards the development of B cell lymphoma. We have discussed the possible roles of HTLV-1 in LPD development in this case.
- Published
- 2019
4. Effectiveness of cryofiltration and mizoribine combination with oral steroid therapy in a patient with membranoproliferative glomerulonephritis due to essential cryoglobulinemia
- Author
-
Takuma Hazama, Kiyomi Koike, Ryo Shibata, Sakuya Ito, Yusuke Kaida, Nao Nakamura, Tomofumi Moriyama, Hirotane Chiba, Daisuke Wakasugi, Kei Fukami, Seiya Okuda, Yuka Kurokawa, Tetsurou Imai, and Kengo Urae
- Subjects
Nephrology ,medicine.medical_specialty ,Mizoribine ,medicine.drug_class ,business.industry ,030232 urology & nephrology ,Case Report ,General Medicine ,030204 cardiovascular system & hematology ,medicine.disease ,Gastroenterology ,Cryoglobulinemia ,03 medical and health sciences ,0302 clinical medicine ,Cryoglobulin ,Internal medicine ,Membranoproliferative glomerulonephritis ,medicine ,Prednisolone ,Corticosteroid ,business ,Nephrotic syndrome ,medicine.drug - Abstract
A 65-year-old male patient with nephrotic syndrome was admitted to our hospital due to worsening systemic edema and purpura on the limbs. He had an impaired renal function, low serum complement level, and elevated rheumatoid factor level. He was positive for cryoglobulin (monoclonal IgM-κ and polyclonal mixed-type IgG), and the results of his kidney biopsy showed a tissue profile of membranoproliferative glomerulonephritis (MPGN). Due to the fact that the secondary cause was unclear, he was diagnosed with MPGN due to essential mixed cryoglobulinemia. On hospital day 20, he was initiated on 50 mg/day prednisolone (PSL). On hospital day 43, oral mizoribine (MZR) at a dose of 150 mg/day was prescribed. On hospital day 49, cryofiltration was performed because the disease was steroid resistant. The treatment promptly decreased urine protein levels. Serum albumin and serum complement levels increased, and complete remission was achieved approximately three months after the initiation of treatment. The PSL and MZR doses were gradually reduced to 2 mg/day and 100 mg/day, respectively, without any reemergence of the symptoms of cryoglobulinemia or relapse of the nephrotic syndrome for three years. Here, we report this case with essential mixed cryoglobulinemia in whom we could achieve complete remission of the disease by adding cryofiltration to the oral corticosteroid and immunosuppressant therapy with mizoribine and could maintain for a long time.
- Published
- 2019
5. The Successful Treatment of Myeloperoxidase Antineutrophil Cytoplasmic Antibody-positive Hypertrophic Pachymeningitis in Patients with the Limited Form of Granulomatosis with Polyangiitis Using Methotrexate: Two Case Reports
- Author
-
Shuri Ushijima, Shiroh Miura, Naomi Yoshida, Midori Minezaki, Yusuke Uchiyama, Hiroaki Ida, Tomoaki Hoshino, Daisuke Wakasugi, and Shinjiro Kaieda
- Subjects
medicine.medical_specialty ,Cyclophosphamide ,Case Report ,macromolecular substances ,Gastroenterology ,Antibodies, Antineutrophil Cytoplasmic ,03 medical and health sciences ,0302 clinical medicine ,stomatognathic system ,Internal medicine ,Internal Medicine ,medicine ,Humans ,Meningitis ,hypertrophic pachymeningitis ,In patient ,cardiovascular diseases ,Aged ,Peroxidase ,Anti-neutrophil cytoplasmic antibody ,030203 arthritis & rheumatology ,granulomatosis with polyangiitis ,biology ,methotrexate (MTX) ,business.industry ,Antineutrophil cytoplasmic antibody positive ,Hypertrophy ,General Medicine ,Middle Aged ,medicine.disease ,Alternative treatment ,MPO-ANCA ,Methotrexate ,Myeloperoxidase ,biology.protein ,Female ,Granulomatosis with polyangiitis ,business ,Immunosuppressive Agents ,030217 neurology & neurosurgery ,medicine.drug - Abstract
Recent findings have indicated a close relationship between myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA)-positive hypertrophic pachymeningitis and the limited form of granulomatosis with polyangiitis (GPA). In Japan, MPO-ANCA-positive hypertrophic pachymeningitis predominantly occurs in elderly individuals. We herein describe the cases of two patients with MPO-ANCA-positive hypertrophic pachymeningitis associated with the limited form of GPA who were successfully treated with a combination of corticosteroids and methotrexate. Although methotrexate has been shown to be less effective than cyclophosphamide for inducing the remission of GPA in patients with organ-threatening diseases, its safety and efficacy may make it a useful alternative treatment modality for patients with the limited form of GPA who show meningeal involvement.
- Published
- 2017
6. Association of anti-aminoacyl-transfer RNA synthetase antibody and anti-melanoma differentiation-associated gene 5 antibody with the therapeutic response of polymyositis/dermatomyositis-associated interstitial lung disease
- Author
-
Naomi Yoshida, Tomohiro Ebata, Masataka Kuwana, Tomoaki Hoshino, Morihiro Tajiri, Daisuke Wakasugi, Hiroaki Ida, Masayuki Nakamura, Masaki Tominaga, Kiminori Fujimoto, Shinjiro Kaieda, Masaki Okamoto, Tsuneyo Mimori, and Tomotaka Kawayama
- Subjects
Male ,Pulmonary and Respiratory Medicine ,Interferon-Induced Helicase, IFIH1 ,Antisynthetase syndrome ,Polymyositis ,Dermatomyositis ,Amino Acyl-tRNA Synthetases ,03 medical and health sciences ,0302 clinical medicine ,Cyclosporin a ,Diffusing capacity ,medicine ,Humans ,Autoantibodies ,Retrospective Studies ,030203 arthritis & rheumatology ,Lung ,biology ,business.industry ,Interstitial lung disease ,Middle Aged ,medicine.disease ,Polymyositis-Dermatomyositis ,Treatment Outcome ,medicine.anatomical_structure ,030228 respiratory system ,Immunology ,biology.protein ,Female ,Antibody ,Lung Diseases, Interstitial ,Tomography, X-Ray Computed ,business - Abstract
Background We attempted to clarify whether the presence of anti-aminoacyl-transfer RNA synthetase antibody (anti-ARS Ab) or anti-melanoma differentiation-associated gene 5 antibody (anti-MDA5 Ab) is associated with the therapeutic response of polymyositis/dermatomyositis-associated interstitial lung disease (PM/DM-ILD). Methods We retrospectively investigated 22 patients with PM/DM-ILD (10 positive for anti-ARS Ab and nine positive for anti-MDA5 Ab) for whom antibody analysis of conserved serum was possible. We assessed mortality in the first three months as the therapeutic response in the acute phase and compared changes in clinical data for up to one year considered as the chronic phase. We classified the clinical changes over the year into three groups: Improvement (increased % vital capacity [%VC] or diffusing capacity of the lung for carbon monoxide [%D LCO ]≥10 or 15%), deterioration (decreased %VC or %D LCO ≥10 or 15%), and no change (remainder of the changes). The extent of abnormality demonstrated by high-resolution computed tomography (HRCT) was scored. Results Positivity for anti-MDA5 Ab, but not for anti-ARS Ab, was associated with mortality in the first 3 months. Evaluation of the therapeutic response in the first year showed that positivity for the anti-ARS Ab, but not for the anti-MDA5 Ab, was associated with an improvement in %D LCO and a decline in the serum KL-6 levels. Positivity for the anti-ARS Ab or negativity for anti-MDA5 Ab was associated with a greater decrease in bronchial dilatation as seen by HRCT. Conclusions Anti-ARS and anti-MDA5 Abs are associated with the therapeutic response of PM/DM-ILD.
- Published
- 2017
7. An Autopsy Case of Anti-melanoma Differentiation-associated Gene-5 Antibody-positive Clinical Amyopathic Dermatomyositis Complicated by Rapidly Progressive Interstitial Lung Disease
- Author
-
Kumi Tomozoe, Morihiro Tajiri, Naomi Yoshida, Masaki Tominaga, Daisuke Wakasugi, Hiroaki Ida, Tomoaki Hoshino, Shinjiro Kaieda, and Masaki Okamoto
- Subjects
Male ,Pathology ,medicine.medical_specialty ,Autopsy ,Dermatomyositis ,Serology ,03 medical and health sciences ,0302 clinical medicine ,Japan ,Internal Medicine ,Humans ,Medicine ,030212 general & internal medicine ,Diffuse alveolar damage ,Melanoma ,030203 arthritis & rheumatology ,Lung ,biology ,business.industry ,Interstitial lung disease ,Heliotrope rash ,General Medicine ,Middle Aged ,medicine.disease ,Antibodies, Anti-Idiotypic ,medicine.anatomical_structure ,Respiratory failure ,biology.protein ,Antibody ,Lung Diseases, Interstitial ,business - Abstract
A 62-year-old man presented with heliotrope rash, Gottron's sign, and mild muscle weakness. Both of his lung fields showed interstitial changes that worsened rapidly. He was diagnosed with clinical amyopathic dermatomyositis with rapidly progressive interstitial lung disease. The patient died of respiratory failure, despite the administration of immunosuppressive therapy. Autopsy revealed diffuse alveolar damage. An antibody analysis, which was performed postmortem, detected the presence of anti-melanoma differentiation-associated gene (MDA)-5 antibodies. Clinicians should note the clinical, radiologic, and serologic findings to predict anti-MDA-5 antibody-associated rapidly progressive interstitial lung disease.
- Published
- 2016
8. Isoquinoline derivatives as potent CRTH2 antagonists: Design, synthesis and SAR
- Author
-
Shunichi Wakahara, Tetsuo Takayama, Kayo Kimura, Daisuke Wakasugi, Takeshi Koami, Susumu Yamanobe, Kazuhito Watanabe, Yoshinori Sekiguchi, Madoka Kawamura, and Rie Nishikawa-Shimono
- Subjects
Models, Molecular ,Stereochemistry ,Receptors, Prostaglandin ,Clinical Biochemistry ,Pharmaceutical Science ,Biochemistry ,Structure-Activity Relationship ,chemistry.chemical_compound ,Th2 Cells ,Drug Discovery ,Humans ,Potency ,Receptors, Immunologic ,Isoquinoline ,Receptor ,Molecular Biology ,IC50 ,chemistry.chemical_classification ,Dose-Response Relationship, Drug ,Molecular Structure ,Chemistry ,Organic Chemistry ,Antagonist ,Chemotaxis ,Isoquinolines ,Combinatorial chemistry ,Enzyme ,Drug Design ,Molecular Medicine ,Chemotaxis assay - Abstract
In this study, we describe the synthesis and structure-activity relationship (SAR) of a series of isoquinoline chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2) antagonists. TASP0376377 (15-20), one of the most potent compounds, showed a potent binding affinity (IC50=19 nM) in addition to the excellent functional antagonist activity (IC50=13 nM). Moreover, the efficacy of this compound in a chemotaxis assay (IC50=23 nM) was in good agreement with its potency as a CRTH2 antagonist. In addition, 15-20 exhibited greater selectivity in binding to CRTH2 than to the DP1 prostanoid receptor (IC50 >1 μM) or the enzymes COX-1 and COX-2 (IC50 >10 μM).
- Published
- 2013
9. Extreme efficacy of intravenous immunoglobulin therapy for severe burning pain in a patient with small fiber neuropathy associated with primary Sjögren’s syndrome
- Author
-
Masako Hara, Daisuke Wakasugi, Hisashi Yamanaka, Eiichi Ito, Takashi Kato, Takahisa Gono, Yasushi Kawaguchi, and Hiroyuki Nodera
- Subjects
Adult ,medicine.medical_specialty ,Diabetic neuropathy ,Central nervous system ,Pain ,Gastroenterology ,Pathogenesis ,Intravenous Immunoglobulin Therapy ,Rheumatology ,Internal medicine ,medicine ,Humans ,Immunologic Factors ,Paresthesia ,Pain Measurement ,biology ,business.industry ,Immunoglobulins, Intravenous ,Peripheral Nervous System Diseases ,medicine.disease ,Sjogren's Syndrome ,Treatment Outcome ,medicine.anatomical_structure ,Peripheral nervous system ,Immunology ,biology.protein ,Female ,Antibody ,business ,Polyneuropathy - Abstract
Neurological involvement occurs in approximately 20% of patients with primary Sjögren's syndrome. Although neurological symptoms can affect the peripheral nervous system and the central nervous system, the most frequent symptom is polyneuropathy. Small fiber neuropathy (SFN) is a form of painful peripheral polyneuropathy that is common in patients with diabetic neuropathy, but may also occur in toxic, infectious, or immune-mediated neuropathy. We show here a patient with Sjögren's syndrome who developed SFN and was treated with intravenous immunoglobulin (IVIG) therapy, which was immediately and extremely effective. Because of the efficacy of IVIG therapy, we propose that direct immune-mediated mechanisms may be involved in the pathogenesis of SFN complicated by Sjögren's syndrome.
- Published
- 2009
10. Selective expression of MHC class I in the affected muscle of a patient with idiopathic inflammatory myopathy
- Author
-
Daisuke Wakasugi, Yasushi Kawaguchi, Makoto Soejima, Masako Hara, M. Miyawaki, So Tsukahara, Takahisa Gono, Hisashi Yamanaka, and Yasuhiro Katsumata
- Subjects
Pathology ,medicine.medical_specialty ,Weakness ,Muscle Fibers, Skeletal ,Inflammation ,Major histocompatibility complex ,Polymyositis ,Immunoenzyme Techniques ,Rheumatology ,Neck Muscles ,MHC class I ,medicine ,Humans ,Myositis ,Aged ,Muscle Weakness ,Muscle biopsy ,medicine.diagnostic_test ,biology ,Electromyography ,business.industry ,Histocompatibility Antigens Class I ,General Medicine ,Dermatomyositis ,medicine.disease ,Up-Regulation ,Muscular Atrophy ,Immunology ,biology.protein ,Female ,medicine.symptom ,business ,Biomarkers - Abstract
The dominant clinical feature of polymyositis/dermatomyositis is weakness in proximal, rather than distal, musculature. Although rare, cases of focal/localized myositis in which polymyositis-like muscle inflammation is present in only one muscle or extremity have also been reported. The underlying mechanisms dictating involvement of specific muscle groups in polymyositis/dermatomyositis and focal/localized myositis have not been identified. Here, we describe a rare case of dropped-head syndrome due to localized idiopathic inflammatory myopathy (IIM) in the splenius capitis (neck extensor) muscle where major histocompatibility complex (MHC) class I expression was up-regulated in involved muscle fibers. Interestingly, the adjacent trapezius muscle was not affected, corresponding to muscle biopsy findings that did not show any sign of inflammation or MHC class I expression. Our case report therefore suggests that selection of affected muscle in IIM might be influenced by the MHC class I expression of the muscle.
- Published
- 2009
11. A synthesis of bicyclo[n.1.0]alkanes having tert-butyl carboxylate or acetamide moiety via the intramolecular 1,3-CH insertion of magnesium carbenoids
- Author
-
Shingo Ogata, Tsuyoshi Satoh, Hideki Saitoh, and Daisuke Wakasugi
- Subjects
chemistry.chemical_classification ,Carboxylic acid ,Organic Chemistry ,Ether ,Sulfoxide ,Biochemistry ,Medicinal chemistry ,chemistry.chemical_compound ,chemistry ,Insertion reaction ,Drug Discovery ,Moiety ,Organic chemistry ,Carboxylate ,Carbenoid ,Acetamide - Abstract
Treatment of 1-chlorovinyl p-tolyl sulfoxides, derived from various cyclic ketones and chloromethyl p-tolyl sulfoxide, with lithium enolate of carboxylic acid tert-butyl esters or N,N-dimethylacetamide gave adducts in high yields. The adducts were treated with ether solution of isopropylmagnesium chloride in dry toluene to give bicyclo[n.1.0]alkane derivatives having tert-butyl carboxylate or acetamide moiety on the bridgehead carbon in high to quantitative yields via magnesium carbenoid 1,3-CH insertion reaction. The 1,3-CH insertion reaction proved to be regioselective and stereospecific. The reaction mechanism and origin of the selectivity and specificity are discussed.
- Published
- 2008
12. A method for synthesis of bicyclo[3.3.0]oct-1-en-3-ones from cyclobutanones with one-carbon ring expansion and its application to a formal synthesis of racemic 1-desoxyhypnophilin
- Author
-
Tsuyoshi Satoh, Tadashi Kawashima, Hiroaki Kashima, and Daisuke Wakasugi
- Subjects
chemistry.chemical_classification ,Bicyclic molecule ,Stereochemistry ,Organic Chemistry ,Cyclobutanone ,Sulfoxide ,General Medicine ,Ring (chemistry) ,Biochemistry ,Cyclobutane ,Alicyclic compound ,chemistry.chemical_compound ,Formal synthesis ,chemistry ,1-desoxyhypnophilin ,Drug Discovery - Abstract
A method for synthesis of 2-cyanobicyclo[3.3.0]oct-1-en-3-ones and 2-substituted bicyclo[3.3.0]oct-1-en-3-ones was developed by assembly of three components, cyclobutanones, chloromethyl p-tolyl sulfoxide, and nitriles, with one-carbon ring expansion of the cyclobutane ring. As an application of this method, a formal synthesis of 1-desoxyhypnophilin in racemic form was performed starting from 3,3-di(phenylthiomethyl)cyclobutanone.
- Published
- 2007
13. A case of cholesterol embolism (CE) with end-stage renal disease who was able to continue stable outpatient hemodialysis for about five years
- Author
-
Koji Sugawara, Shuhei Miura, Kazuhito Takeda, Kyoko Tobino, Takuya Fukuda, and Daisuke Wakasugi
- Subjects
medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,medicine ,Hemodialysis ,Intensive care medicine ,business ,Cholesterol embolism ,medicine.disease ,End stage renal disease - Published
- 2007
14. Clinical and genetic analyses in a patient with PAPA syndrome complicated with inflammatory bowel disease
- Author
-
Daisuke Wakasugi, Kumi Fujita, Ryuta Nishikomori, Y Kunitake, K Iwamoto, Shinjiro Kaieda, Naomi Yoshida, Hiroaki Ida, and Keiichi Mitsuyama
- Subjects
medicine.medical_specialty ,Pathology ,business.industry ,Inflammasome ,PAPA syndrome ,medicine.disease ,Inflammatory bowel disease ,Rheumatology ,Internal medicine ,Pediatrics, Perinatology and Child Health ,Immunology ,Poster Presentation ,Immunology and Allergy ,Medicine ,Pediatrics, Perinatology, and Child Health ,Autoinflammatory disease ,ComputingMethodologies_GENERAL ,Pyogenic arthritis ,business ,Pyoderma gangrenosum ,Acne ,medicine.drug - Abstract
PAPA (pyogenic arthritis, pyoderma gangrenosum and acne) syndrome is an autoinflammatory disease linked to mutations in the PSTPIP1 gene. These mutations produce a hyper-phosphorylated PSTPIP1 protein and alter its participation in the activation of the “inflammasome”.
- Published
- 2015
15. Social Skills Education for a Child With Hyperactive Behavior
- Author
-
Daisuke Wakasugi and Reizo Koizumi
- Subjects
Medical education ,Social skills ,Developmental and Educational Psychology ,Field research ,Psychology ,Training (civil) ,Education ,Developmental psychology - Published
- 2006
16. A novel synthesis, including asymmetric synthesis, of 2,4,4-trisubstituted 2-cyclopentenones based on the reaction of 1-chlorovinyl p-tolyl sulfoxides with acetonitrile and its homologues
- Author
-
Daisuke Wakasugi and Tsuyoshi Satoh
- Subjects
Organic Chemistry ,Enantioselective synthesis ,chemistry.chemical_element ,Sulfoxide ,General Medicine ,Optically active ,Biochemistry ,Medicinal chemistry ,Adduct ,chemistry.chemical_compound ,Hydrolysis ,chemistry ,Drug Discovery ,Organic chemistry ,Lithium ,Acetonitrile - Abstract
Reaction of 1-chlorovinyl p-tolyl sulfoxides, which were synthesized from chloromethyl p-tolyl sulfoxide and ketones in high overall yields, with cyanomethyllithium (lithium α-carbanion of acetonitrile) gave adducts in high to quantitative yields. The adducts were treated with LDA followed by lithium α-carbanion of the homologues of acetonitrile to give 3,5,5-trisubstituted enaminonitriles in good to high yields. Hydrolysis of the enaminonitriles under acidic conditions gave 2,4,4-trisubstituted 2-cyclopentenones in good yields. By using the optically active chloromethyl p-tolyl sulfoxide and unsymmetrical ketones, this procedure gave the optically pure 2,4,4-trisubstituted 2-cyclopentenones. The scope and limitations of this method and the mechanism of the reactions are also discussed. These procedures offer a new and effective method for the synthesis of 2,4,4-trisubstituted 2-cyclopentenones from four components, ketones, chloromethyl p-tolyl sulfoxide, acetonitrile, and its homologues.
- Published
- 2005
17. A novel synthesis of 2,4,4-trisubstituted 2-cyclopentenones by consecutive reaction of 1-chlorovinyl p-tolyl sulfoxides with acetonitrile and its homologues
- Author
-
Daisuke Wakasugi and Tsuyoshi Satoh
- Subjects
Organic Chemistry ,chemistry.chemical_element ,Sulfoxide ,General Medicine ,Medicinal chemistry ,Biochemistry ,Adduct ,Hydrolysis ,chemistry.chemical_compound ,Consecutive reaction ,chemistry ,Cyclopentadienyl complex ,Drug Discovery ,Organic chemistry ,Lithium ,Acetonitrile - Abstract
1-Chlorovinyl p-tolyl sulfoxides were synthesized from several kinds of ketones and chloromethyl p-tolyl sulfoxide in three steps in high overall yields. Treatment of the 1-chlorovinyl p-tolyl sulfoxides with cyanomethyllithium (lithium α-carbanion of acetonitrile) at low temperature gave the adducts in almost quantitative yields. The adducts were then treated with LDA followed by excess lithium α-carbanion of the homologues of acetonitrile to afford 3,5,5-trisubstituted cyclopentadienyl enaminonitriles, which were hydrolyzed and heated under acidic conditions to give 2,4,4-trisubstituted 2-cyclopentenones in good overall yields.
- Published
- 2003
18. [A case of atypical hemolytic uremic syndrome successfully weaned from plasma exchange by treatment with eculizumab]
- Author
-
Akiko, Nagata, Atsuko, Ohara, Daisuke, Wakasugi, Chikei, Natori, Sakuya, Ito, Kensei, Taguchi, Kei, Fukami, and Seiya, Okuda
- Subjects
Male ,Treatment Outcome ,Plasma Exchange ,Complement Factor H ,Hemolytic-Uremic Syndrome ,Secondary Prevention ,Humans ,Middle Aged ,Antibodies, Monoclonal, Humanized ,Atypical Hemolytic Uremic Syndrome - Abstract
The patient was a 48-year-old man hospitalized for jaundice and anemia after a 6-day history of diarrhea. Examination demonstrated hemolytic anemia, renal dysfunction, and thrombocytopenia. Typical hemolytic uremic syndrome (HUS) was suspected based on the preceding colitis; however, plasma exchange (PE) was performed because the possibility of atypical HUS (aHUS) could not be ignored, given that the patient was an adult male. After 4 days of PE, his laboratory results improved. Stool culture on admission yielded negative results for Escherichia coli serotype O157 and ADAMTS13 activity. Antinuclear antibodies were normal, and no other drugs or infections indicating HUS were detected. Four months after onset, he suffered recurrence of aHUS after colitis. As a result, aHUS was suspected and therefore, PE was performed on the day of hospitalization. We diagnosed aHUS due to a result indicating complement dysregulation on hemolytic assay testing, which detected a complement factor H abnormality. After undergoing PE and maintaining a stable condition, the interval between PEs was extended; however, on day 17 after the last PE, he suffered a recurrent aHUS attack again. He could not be weaned from PE and started showing an allergic reaction to PE treatment, thereby leading to a switch from PE to eculizumab. Since switching to eculizumab treatment, the patient has not experienced another aHUS attack and his condition remains stable.
- Published
- 2014
19. Isoquinoline derivatives as potent, selective, and orally active CRTH2 antagonists
- Author
-
Daisuke Wakasugi, Rie Nishikawa-Shimono, Kazuhito Watanabe, Yoshinori Sekiguchi, Madoka Kawamura, Masahumi Kawanishi, Yumiko Asakura, Tetsuo Takayama, and Akiko Takaoka
- Subjects
Male ,Guinea Pigs ,Receptors, Prostaglandin ,Mice, Inbred Strains ,Pharmacology ,Cell Line ,chemistry.chemical_compound ,Mice ,Structure-Activity Relationship ,Th2 Cells ,Oral administration ,In vivo ,Drug Discovery ,Animals ,Humans ,Methylene ,Isoquinoline ,Receptors, Immunologic ,Benzamide ,IC50 ,Dose-Response Relationship, Drug ,Molecular Structure ,General Chemistry ,General Medicine ,Isoquinolines ,chemistry ,Prostaglandin D2 ,Linker - Abstract
Synthesis and structure-activity relationship of a novel series of isoquinoline CRTH2 antagonists bearing a methylene linker between the isoquinoline and benzamide moieties were described. Optimization focusing on the substituents of the benzamide portion in the right hand part of the molecule led to the identification of TASP0412098 (9l), which is a potent, selective CRTH2 antagonist (binding affinity: IC50=2.1 nM, functional activity: IC50=12 nM). Compound 9l, which was orally bioavailable in mice and guinea pigs, showed in vivo efficacy after oral administration in a bronchial asthma model of guinea pigs.
- Published
- 2014
20. ChemInform Abstract: Isoquinoline Derivatives as Potent CRTH2 Receptor Antagonists: Synthesis and SAR
- Author
-
Kazuhito Watanabe, Daisuke Wakasugi, Kayo Matsumoto, Shunichi Wakahara, Tetsuo Takayama, Yoshinori Sekiguchi, Madoka Kawamura, Takeshi Koami, and Rie Nishikawa-Shimono
- Subjects
chemistry.chemical_classification ,chemistry.chemical_compound ,Enzyme ,chemistry ,Stereochemistry ,Prostanoid ,Potency ,Structure–activity relationship ,General Medicine ,Isoquinoline ,Selectivity ,Crth2 antagonist ,Receptor - Abstract
The most potent compound, TASP0376377 (I) shows good CRTH2 antagonist potency, as well as sufficient selectivity for binding to CRTH2 over the DP1 prostanoid receptor and COX-1 and COX-2 enzymes.
- Published
- 2012
21. Frequency of class III and IV nephritis in systemic lupus erythematosus without clinical renal involvement: an analysis of predictive measures
- Author
-
Yasuhiro Katsumata, Takahisa Gono, Masako Hara, Yumi Koseki, Yasushi Kawaguchi, Hisashi Yamanaka, Masanori Hanaoka, and Daisuke Wakasugi
- Subjects
Nephrology ,Adult ,Male ,medicine.medical_specialty ,Adolescent ,Urinary system ,Biopsy ,Immunology ,Lupus nephritis ,Renal function ,Kidney ,Kidney Function Tests ,Gastroenterology ,Young Adult ,Rheumatology ,immune system diseases ,Predictive Value of Tests ,Internal medicine ,medicine ,Immunology and Allergy ,Humans ,Lupus Erythematosus, Systemic ,skin and connective tissue diseases ,Child ,Aged ,Retrospective Studies ,Lupus erythematosus ,business.industry ,Middle Aged ,medicine.disease ,Lupus Nephritis ,Renal pathology ,Predictive value of tests ,Female ,business ,Nephritis - Abstract
Objective.To determine the frequency of International Society of Nephrology/Renal Pathology Society (ISN/RPS) class III or IV lupus nephritis in patients with systemic lupus erythematosus (SLE) without clinical renal involvement.Methods.We investigated the renal pathology of 195 patients with SLE, including 86 patients without clinical renal involvement.Results.Lupus nephritis other than class I was found in 58% of the patients without clinical renal involvement, and class III and IV nephritis was found in 15% of these patients. To reveal the predictive measures involved in class III or IV lupus nephritis, we explored the clinical measures in patients with SLE who did not have clinical renal involvement. Anti-dsDNA antibody titers were significantly higher (p = 0.0266) and C3 values were significantly lower (p = 0.0073) in patients with class III or IV lupus nephritis than in patients without class III or IV lupus nephritis. The sensitivity and specificity values were 77% and 73%, respectively, for cutoff levels of both 40 IU/ml for anti-dsDNA antibodies and 55 mg/dl for C3 (OR 8.8, p = 0.0011).Conclusion.The frequency of nephritis, including ISN/RPS class III and IV, was unexpectedly high in SLE patients without clinical renal involvement. ISN/RPS class III or IV lupus nephritis could be hidden in patients with SLE who present both a high titer of anti-dsDNA antibody and a low concentration of C3, even when they have clinically normal urinary findings and renal function.
- Published
- 2011
22. Discovery of novel (4-piperidinyl)-piperazines as potent and orally active acetyl-CoA carboxylase 1/2 non-selective inhibitors: F-Boc and triF-Boc groups are acid-stable bioisosteres for the Boc group
- Author
-
Daisuke Yamamoto, Akira Hiratate, Tomomichi Chonan, Miyoko Yashiro, Daisuke Wakasugi, Fusayo Io, Hiroko Koretsune, Hiroaki Tanaka, Ayumi Ohoka-Sugita, and Takahiro Oi
- Subjects
Stereochemistry ,Formic Acid Esters ,Clinical Biochemistry ,Pharmaceutical Science ,Administration, Oral ,Biochemistry ,Piperazines ,chemistry.chemical_compound ,Structure-Activity Relationship ,Piperidines ,Oral administration ,Drug Discovery ,Acid stable ,Animals ,Molecular Biology ,Piperazine ,Fatty acid synthesis ,Molecular Structure ,Organic Chemistry ,Stereoisomerism ,Fluorine ,Acetyl-CoA Carboxylase 1 ,Rats ,Orally active ,chemistry ,TRIF ,Molecular Medicine ,Piperidine ,Acetyl-CoA Carboxylase - Abstract
Novel (4-piperidinyl)-piperazine derivatives were synthesized and evaluated as ACC1/2 non-selective inhibitors. Optimization of the substituents on the nitrogen of the piperidine ring led to the identification of the fluorine substituted tert-butoxycarbonyl group. Advanced analog, 1,1,1-trifluoro-2-methylpropan-2-yl 4-{4-[(2-amino-6-methyl-1-benzothiophen-3-yl)carbonyl]piperazin-1-yl}piperidine-1-carboxylate (12c) showed potent inhibitory activities in enzyme-assay and cell-based assays. Compound 12c also exhibited reduction of hepatic de novo fatty acid synthesis in rats after oral administration.
- Published
- 2010
23. Design and synthesis of disubstituted (4-piperidinyl)-piperazine derivatives as potent acetyl-CoA carboxylase inhibitors
- Author
-
Daisuke Yamamoto, Akira Hiratate, Hiroaki Tanaka, Tomomichi Chonan, Miyoko Yashiro, Hiroko Koretsune, Daisuke Wakasugi, Ayumi Ohoka-Sugita, Fusayo Io, and Takahiro Oi
- Subjects
Models, Molecular ,medicine.drug_class ,Clinical Biochemistry ,Pharmaceutical Science ,Carboxamide ,Crystallography, X-Ray ,behavioral disciplines and activities ,Biochemistry ,Chemical synthesis ,Piperazines ,chemistry.chemical_compound ,Structure-Activity Relationship ,Piperidines ,Drug Discovery ,medicine ,Enzyme Inhibitors ,Molecular Biology ,chemistry.chemical_classification ,Indole test ,biology ,Dose-Response Relationship, Drug ,Molecular Structure ,Chemistry ,Organic Chemistry ,Acetyl-CoA carboxylase ,Lipid metabolism ,Stereoisomerism ,Piperazine ,Enzyme ,Enzyme inhibitor ,Drug Design ,biology.protein ,Molecular Medicine ,Acetyl-CoA Carboxylase - Abstract
Acetyl-CoA carboxylases (ACCs), the rate limiting enzymes in de novo lipid synthesis, play important roles in modulating energy metabolism. The inhibition of ACC has demonstrated promising therapeutic potential for treating obesity and type 2 diabetes mellitus in transgenic mice and preclinical animal models. We describe herein the structure-based design and synthesis of a novel series of disubstituted (4-piperidinyl)-piperazine derivatives as ACC inhibitors. Our structure-based approach led to the discovery of the indole derivatives 13i and 13j, which exhibited potent in vitro ACC inhibitory activity.
- Published
- 2010
24. (4-Piperidinyl)-piperazine: a new platform for acetyl-CoA carboxylase inhibitors
- Author
-
Daisuke Wakasugi, Takahiro Oi, Miyoko Yashiro, Hiroaki Tanaka, Ayumi Ohoka-Sugita, Tomomichi Chonan, Akira Hiratate, Fusayo Io, Hiroko Koretsune, and Daisuke Yamamoto
- Subjects
Genetically modified mouse ,Models, Molecular ,medicine.drug_class ,Clinical Biochemistry ,Pharmaceutical Science ,Carboxamide ,Crystallography, X-Ray ,Biochemistry ,Chemical synthesis ,Piperazines ,chemistry.chemical_compound ,Structure-Activity Relationship ,Piperidines ,Drug Discovery ,medicine ,Structure–activity relationship ,Enzyme Inhibitors ,Molecular Biology ,chemistry.chemical_classification ,Molecular Structure ,Organic Chemistry ,Acetyl-CoA carboxylase ,Lipid metabolism ,Stereoisomerism ,Piperazine ,Enzyme ,chemistry ,Drug Design ,Molecular Medicine ,Acetyl-CoA Carboxylase - Abstract
Acetyl-CoA carboxylases (ACCs), the rate limiting enzymes in de novo lipid synthesis, play important roles in modulating energy metabolism. The inhibition of ACC has demonstrated promising therapeutic potential for treating obesity and type 2 diabetes mellitus in transgenic mice and preclinical animal models. We describe herein the synthesis and structure-activity relationships of a series of disubstituted (4-piperidinyl)-piperazine derivatives as a new platform for ACC1/2 non-selective inhibitors.
- Published
- 2009
25. Successful treatment for sympathetic storms in a patient with neuro-Behçet's disease
- Author
-
Megumi Murata, Masako Hara, Makoto Soejima, Hisashi Yamanaka, Yasushi Kawaguchi, Daisuke Wakasugi, and Takahisa Gono
- Subjects
Tachycardia ,Adult ,Male ,endocrine system ,medicine.medical_specialty ,Central nervous system ,Administration, Oral ,Methylprednisolone ,Norepinephrine ,Cerebrospinal fluid ,Pharmacotherapy ,Rheumatology ,medicine ,Humans ,Cyclophosphamide ,Glucocorticoids ,Hyperhidrosis ,business.industry ,Behcet Syndrome ,Interleukin-8 ,Remission Induction ,General Medicine ,medicine.disease ,Surgery ,Hydrocephalus ,medicine.anatomical_structure ,Autonomic Nervous System Diseases ,Anesthesia ,Injections, Intravenous ,Drug Therapy, Combination ,medicine.symptom ,Neuro-Behçet's disease ,business ,Immunosuppressive Agents ,medicine.drug - Abstract
Sympathetic storms (SyS) are characterized by hyperactivity of autonomic functions, resulting in episodes of hyperthermia, hypertension, tachycardia, and hyperhidrosis. We show here a patient with neuro-Behcet’s disease (NBD) complicated by SyS. Although SyS is well known to occur with brain tumors, trauma, and hydrocephalus, this is the first report to show that SyS is a manifestation of central nervous system involvement in a patient with NBD. High concentrations of norepinephrine (NE) and IL-8 in cerebrospinal fluid reflected the activity of SyS. The patient’s symptoms showed almost complete improvement after treatment with corticosteroids and intravenous cyclophosphamide. Also, the concentrations of NE and IL-8 were decreased to normal levels. An awareness of the potential for SyS and adequate immunosuppressant therapy are of importance when dealing with patients with NBD.
- Published
- 2008
26. A Versatile Synthesis, Including Asymmetric Synthesis, of Bicyclo[n.1.0]alkanes from Cyclic Ketones via the Magnesium Carbenoid 1,3-CH Insertion as a Key Reaction
- Author
-
Daisuke Wakasugi, Tsuyoshi Satoh, and Shingo Ogata
- Subjects
Alkane ,chemistry.chemical_classification ,Bicyclic molecule ,Chemistry ,Magnesium ,Organic Chemistry ,Enantioselective synthesis ,chemistry.chemical_element ,Ether ,Sulfoxide ,General Medicine ,Biochemistry ,Medicinal chemistry ,Cyclopropane ,Solvent ,chemistry.chemical_compound ,Drug Discovery ,Organic chemistry ,Carbenoid - Abstract
Treatment of 1-chlorovinyl p-tolyl sulfoxides, which were synthesized from various cyclic ketones and chloromethyl p-tolyl sulfoxide in three steps, in high yields, with lithium enolate of tert-butyl acetate or its homologues gave the adducts in quantitative yields. The adducts were treated with isopropylmagnesium chloride in ether in dry toluene as the reaction solvent to afford bicyclo[n.1.0]alkanes in high to quantitative yields via magnesium carbenoid 1,3-CH insertion. When this method was carried out starting from unsymmetrical cyclic ketones and (R)-chloromethyl p-tolyl sulfoxide, an asymmetric synthesis of bicyclo[n.1.0]alkane was realized.
- Published
- 2007
27. A Novel Synthesis of Bicyclo[3.3.0]oct-1-en-3-ones from Cyclobutanones Through [Chloro(p-tolylsulfinyl)methylidene]cyclobutanes with Ring Expansion
- Author
-
Tadashi Kawashima, Daisuke Wakasugi, Tsuyoshi Satoh, and Hiroaki Kashima
- Subjects
Cyclobutanes ,Bicyclic molecule ,Chemistry ,Organic Chemistry ,Substituent ,Sulfoxide ,General Medicine ,Biochemistry ,Medicinal chemistry ,chemistry.chemical_compound ,Acetic acid ,Yield (chemistry) ,Drug Discovery ,Organic chemistry ,Acetonitrile ,Carbanion - Abstract
Treatment of [chloro(p-tolylsulfinyl)methylidene]cyclobutanes, which were synthesized from cyclobutanones and chloromethyl p-tolyl sulfoxide in three steps in high overall yields, with excess cyanomethyllithium gave enaminonitriles in high yields. Heating of these enaminonitriles with H3PO4 in acetic acid gave 2-cyanobicyclo[3.3.0]oct-1-en-3-ones in good yield. On the other hand, treatment of the [chloro(p-tolylsulfinyl)methylidene]cyclobutanes with cyanomethyllithium followed by lithium carbanion of the homologues of acetonitrile afforded enaminonitriles having a substituent at the 3-position. Heating of the enaminonitriles with H3PO4 in acetic acid gave 2-substituted bicyclo[3.3.0]oct-1-en-3-ones in good to high yields. This method offers a novel and versatile procedure for synthesis of 2-substituted bicyclo[3.3.0]oct-1-en-3-ones from cyclobutanones in good overall yields.
- Published
- 2005
28. [Steroid pulse therapy combined with tonsillectomy in a patient with IgA nephropathy complicated with tuberculous pleurisy]
- Author
-
Kiyomi, Koike, Kiyoshi, Tamaki, Kazuhito, Takeda, Kouji, Sugawara, Daisuke, Wakasugi, and Seiya, Okuda
- Subjects
Adult ,Treatment Outcome ,Pulse Therapy, Drug ,Prednisolone ,Humans ,Female ,Glomerulonephritis, IGA ,Tuberculosis, Pleural ,Methylprednisolone ,Tonsillectomy - Abstract
We report a case of IgA nephropathy with tuberculous pleurisy that was treated with steroid pulse therapy combined with tonsillectomy. A 27-year-old female was referred to our hospital because of hematuria and proteinuria. Her urinalysis showed mild proteinuria (0.7 to 0.9 g/day) with dysmorphic red blood cells and cellular casts. Her serum creatinine level was within the normal range. Renal biopsy specimens revealed mild mesangial proliferation with cellular crescent and adhesion of glomeruli to the Bowman's capsule. Tubulointerstitial changes including mononuclear cell infiltration and tubular atrophy were also observed. Immunohistochemical staining of IgA and C3 was detected in the mesangial area, leading to the diagnosis of IgA nephropathy. She had a past history of tuberculous pleurisy at 13 years of age and had taken antituberculosis drug for one and a half year. Although treatment with angiotensin receptor antagonist was started, the amount of proteinuria was not changed. Steroid pulse therapy with tonsillectomy followed by oral prednisolone 20 mg/day was conducted. Proteinuria and hematuria gradually decreased. Her respiratory status and chest X-ray had been closely followed up by her respiratory physician. After one and a half years of treatment with low-dose prednisolone, her urinalysis became almost normal. Recurrence of tuberculosis was not observed during the follow-up period. The successful outcome of this case encouraged us to treat IgA nephropathy with a past history of tuberculosis using interventions including steroid pulse therapy.
- Published
- 2005
29. Pharmacological Characterization of TASP0412098, A Selective CRTH2 (Chemoattractant Receptor-Homologous Molecule Expressed on Th2 Cells) Antagonist
- Author
-
Rie Nishikawa, M. Kawanishi, Daisuke Wakasugi, A. Oka, Madoka Kawamura, S. Tokita, Yumiko Asakura, Takumi Naruse, Kazuhito Watanabe, Tetsuo Takayama, Takeshi Koami, and Akiko Takaoka
- Subjects
Chemoattractant Receptor ,Chemistry ,Immunology ,Homologous chromosome ,Antagonist ,Immunology and Allergy ,Molecule ,Cell biology - Published
- 2012
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.