Seiichiro Tabuchi

A novel pyridazinone derivative as a nonprostanoid PGI2 agonist.

A novel optically pure pyridazinone derivative was synthesized and identified as a nonprostanoid PGI2 agonist. It inhibited ADP-induced aggregation of human platelets with an IC50 value of 0.081 microM and has high oral bioavailability (56%) with a long half-life (4.3 h) in rats.

Novel potent antagonists of human neuropeptide Y Y5 receptor. Part 1: 2-Oxobenzothiazolin-3-acetic acid derivatives

Novel NPY-Y5 antagonist FR73966 was discovered by screening of our in-house chemical library. The analogues were prepared by application of parallel synthesis techniques. Some of the resulting 2-oxobenzothiazolin-3-acetic acid derivatives exhibited nanomolar binding affinity for human NPY-Y5 receptors.

Dual CCK-A and -B receptor antagonists (I) C9-methyl-1,4-benzodiazepines

Abstract A novel series of potent CCK-A and CCK-B dual antagonists has been prepared which incorporate a methyl substituent at the 9 position of a 1,4-benzodiazepine ring system. FR193108 ((+)- 11 ) was selected for further biological evaluation, and is expected to be more efficacious than CCK-A selective antagonists for the treatment of pancreatitis, since it has high and well-balanced affinities for both CCK-A and -B receptors.

Relationship between dihedral angles of N1 and C9 substituents in 1,4-benzodiazepines and dual cholecystokinin-A and -B antagonistic activities

Introduction of a methyl moiety to the C9 position of a 1,4-benzodiazepine ring system afforded dual CCK-A and -B antagonistic activity. Novel derivatives having ethyl, isopropyl and chloro substituents at C9 were prepared in order to obtain more potent antagonistic activities. AM1(MOPAC93) calculations of the dihedral angles between the N1 and C9 substituents indicated that dihedral angles for dual antagonistic activities were between 50 degrees and 60 degrees. A methyl moiety was selected as the most suitable C9 substituent in this series for potent dual CCK-A and -B receptor antagonistic properties.