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Your search keyword '"Atsushi Kinoshita"' showing total 3 results
Start Over Author "Atsushi Kinoshita" Journal bioorganic & medicinal chemistry
3 results on '"Atsushi Kinoshita"'

1. Discovery of new orally active prostaglandin D2 receptor antagonists

Author

Yoko Matsunaga, Seiji Ogawa, Hisao Nakai, Yutaka Okada, Atsushi Shimabukuro, Kohki Tsukamoto, Fumio Nambu, Atsushi Kinoshita, Rie Oumi, Yoshihiko Odagaki, Ryoji Matsumoto, Atsushi Naganawa, Jun Katagi, Maki Iwahashi, Koji Yano, Masaaki Toda, Toshihiko Nishiyama, and Kousuke Tani

Subjects
Models, Molecular, Guinea Pigs, Receptors, Prostaglandin, Clinical Biochemistry, Administration, Oral, Pharmaceutical Science, Prostaglandin, CHO Cells, Pharmacology, Biochemistry, Structure-Activity Relationship, chemistry.chemical_compound, Cricetulus, Pharmacokinetics, In vivo, Cricetinae, Drug Discovery, Animals, Humans, Receptors, Immunologic, Receptor, Molecular Biology, Phenylacetates, Prostaglandin D2 receptor, Organic Chemistry, Antagonist, Rats, chemistry, Molecular Medicine, Prostaglandin D2, Antagonism
Abstract

To identify an orally available drug candidate, a series of 3-benzoylaminophenylacetic acids were synthesized and evaluated as prostaglandin D2 (PGD2) receptor antagonists. Some of the compounds tested were found to exhibit excellent inhibitory activity against cAMP accumulation in human platelet rich plasma (hPRP), which is one of the indexes of DP antagonism. The optimization process including improvement of the physicochemical properties such as solubility, which may result in an improved pharmacokinetic (PK) profile, is presented. Optimized compounds were studied for their pharmacokinetics and in vivo potential. A structure–activity relationship study is also presented. Some of the test compounds were found to have in vivo efficacy towards the inhibition of PGD2-induced and OVA-induced vascular permeability in guinea pig conjunctiva.

Published
2011

2. 3-(2-Aminocarbonylphenyl)propanoic acid analogs as potent and selective EP3 receptor antagonists. Part 3: Synthesis, metabolic stability, and biological evaluation of optically active analogs

Author

Hisao Nakai, Toshihiko Nagase, Masaaki Toda, Yoshiyuki Yamaura, Atsushi Kinoshita, Yoshito Tobe, Kazutoyo Sato, Ken Yoshikawa, Hiroya Takizawa, Tetsuo Obitsu, Masami Narita, Tadahiro Yoshida, and Masaki Asada

Subjects
Stereochemistry, medicine.drug_class, Clinical Biochemistry, Administration, Oral, Pharmaceutical Science, Drug design, Carboxamide, CHO Cells, Binding, Competitive, Biochemistry, Chemical synthesis, Radioligand Assay, chemistry.chemical_compound, Cricetulus, Drug Stability, Pregnancy, In vivo, Cricetinae, Drug Discovery, medicine, Animals, Humans, Receptors, Prostaglandin E, Moiety, Receptor, Molecular Biology, Molecular Structure, Phenyl Ethers, Organic Chemistry, Rats, Propanoic acid, chemistry, Receptors, Prostaglandin E, EP3 Subtype, Microsomes, Liver, Microsome, Pregnancy, Animal, Molecular Medicine, Female, Propionates
Abstract

A series of 3-(2-aminocarbonylphenyl)propanoic acid analogs possessing the (1R)-1-(3,5-dimethylphenyl)-3-methylbutylamine moiety on the carboxyamide side chain were synthesized and evaluated for their binding affinity for the EP1-4 receptors and their antagonist activity for the EP3 receptor. Rational drug design based on the structure of the metabolites in human liver microsomes led us to the discovery of another series of analogs. Several compounds were further evaluated for their in vivo efficacy in rats after oral administration and also for their pharmacokinetic profiles including in vitro stability in the liver microsomes.

Published
2010

3. Design and synthesis of new potent dipeptidyl peptidase IV inhibitors with enhanced ex vivo duration

Author

Shigeyuki Takai, Yohei Tajima, Kenya Ochi, Isamu Sugimoto, Hisao Nakai, Susumu Yamamoto, Masaaki Toda, Takashi Kondo, Atsushi Kinoshita, Takahiro Nekado, and Kazuhito Kawabata

Subjects
Male, Magnetic Resonance Spectroscopy, Pyrrolidines, medicine.drug_class, Dipeptidyl Peptidase 4, Clinical Biochemistry, Pharmaceutical Science, Carboxamide, Biochemistry, Chemical synthesis, Rats, Sprague-Dawley, Dogs, Oral administration, Drug Discovery, Blood plasma, medicine, Animals, Humans, Potency, Protease Inhibitors, Molecular Biology, chemistry.chemical_classification, Dipeptidyl-Peptidase IV Inhibitors, biology, Chemistry, Organic Chemistry, Glucose Tolerance Test, Rats, Macaca fascicularis, Enzyme, Enzyme inhibitor, biology.protein, Molecular Medicine, Indicators and Reagents, Chromatography, Thin Layer, Oxidation-Reduction, Ex vivo
Abstract

A series of 5β-methylprolyl-2-cyanopyrrolidine analogs were synthesized and evaluated as DPP-IV inhibitors, and the duration of their ex vivo activity was assessed. Comparison of their potency and duration of action was done among three different species. The mode of binding was investigated, and the effect on the plasma glucose level was evaluated. Structure–activity relationships are also presented.

Published
2007

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