Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1996-05-24
1998-09-15
Shah, Mukund J.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
5142352, 514249, 514294, 514307, 514314, 514339, 514381, 514394, 514411, 514414, 544144, 544355, 546 94, 546145, 546146, 546147, 546169, 5462777, 548253, 5483051, 548428, 548454, 548455, 548463, 548465, 548467, 548483, A61K 3140, A61K 31415, A61K 3144, A61K 3147, C07D20902, C07D23504, C07D21700, C07D45100
Patent
active
058078835
DESCRIPTION:
BRIEF SUMMARY
This application is a 371 of PCT/JP94/01990 filed Nov. 25, 1994.
TECHNICAL FIELD
This invention relates to a novel 2-oxoindoline derivative having an excellent antagonistic action on cholecystokinin and useful for preventing and treating pancreatic disorder and gastrointestinal diseases, etc. and a process for preparing the same.
BACKGROUND ART
Cholecystokinin (CCK) is a brain-gut peptide existing in a gastrointestinal tissue and a central nervous system, has been known as a substance which is concerned with control of pancreatic exocrine secretion and control of appetite, and has been considered to have actions of promoting motility of colon, contracting gallbladder, promoting secretion of pancreatic enzymes, controlling emptying of gastric content, etc. Further, cholecystokinin coexists with dopamine in a central nervous system so that it has been considered to have a role concerned with mechanism of a dopaminergic system.
It has been considered that a substance having an antagonistic action on this cholecystokinin is effective for preventing or treating pancreatic disorder and gastrointestinal diseases, etc. so that a number of antagonists have been studied up to the present. For example, as a cholecystokinin antagonist, there have been known amino acid derivatives such as benzotript, etc. However, such derivatives are not necessarily satisfactory in that activities thereof are relatively weak, duration of action is short, and they are unstable and poor in absorption, etc.
As a non-peptide type antagonist, there have been disclosed a benzodiazepine compound in Japanese Provisional Patent Publication No. 111774/1990 and a thienoazepine compound in Japanese Provisional Patent Publication No. 28181/1990. Further, in Japanese Provisional Patent Publication No. 68369/1989, there have been disclosed .beta.-carboline derivatives including a compound of the formula (V): ##STR3##
An object of the present invention is to provide a novel 2-oxoindoline derivative having a further excellent antagonistic action on cholecystokinin and useful as a medicine and a pharmaceutically acceptable salt thereof, and a process for preparing the same.
DISCLOSURE OF THE INVENTION
The present invention is a 2-oxoindoline derivative represented by the formula (I): ##STR4## (wherein Ring A represents a substituted or unsubstituted benzene ring, R.sup.1 represents hydrogen atom, a cycloalkyl group, a substituted or unsubstituted aryl group, a nitrogen-containing heterocyclic group, an oxygen-containing heterocyclic group, a sulfur-containing heterocyclic group, a heterocyclic group containing nitrogen atom and oxygen atom, a heterocyclic group containing nitrogen atom and sulfur atom, a lower alkoxy group, a carboxyl group which may be esterified, cyano group, a lower alkylthio group, a lower alkylsulfinyl group, a lower alkylsulfonyl group, an oxiranyl group or a 2-(lower alkylthio)-1-hydroxyethyl group, R.sup.2 represents a substituted or unsubstituted aryl group, a group represented by the formula: ##STR5## a substituted or unsubstituted nitrogen-containing heteromonocyclic group, a substituted or unsubstituted nitrogen-containing heterobicyclic group, a group represented by the formula: ##STR6## (wherein n represents 1 or 2.), an oxygen-containing heterocyclic group, a sulfur-containing heterocyclic group, a heterocyclic group containing nitrogen atom and oxygen atom or a heterocyclic group containing nitrogen atom and sulfur atom, R.sup.3 represents a substituted or unsubstituted lower alkyl group, Q represents a single bonding arm or a lower alkylene group, Y represents a single bonding arm, a lower alkylene group or a lower alkenylene group.), the same.
Best Mode for Practicing the Invention
The desired compound (I) of the present invention is a medical compound having an excellent antagonistic action on cholecystokinin and useful as a prophylactic or treating agent of pancreatic disorder and gastrointestinal diseases.
As a specific example of the desired compound of the present invention, there may be mentioned a c
REFERENCES:
patent: 4985448 (1991-01-01), Zilch et al.
Talley, N.J. Alimentary Pharmacology and Therapeutics, vol. 9, pp. 107-115 (1995).
Esaki, T. et al. Chemical Abstract, No. 122:55893, Obtained via STN Databases (1995).
Emura, T. et al. Derwent World Patent Index, No. 94-294220 (1994).
Zydowsky, T.M. et al. J. Org. Chem., vol. 53, pp. 5607-5616 (1988).
Niederau, C. et al. Hepato-Gastroenterology, vol. 40, p. 538 (1993 Dec.), Abstract Only Obtained via Medline.
Greenberger, N.J. et al. Harrison's Principles of Internal Medicine, vol. 2 (McGraw-Hill, New York), ed. by Isselbacher, K.J. et al., pp. 1520-1532 (1994).
Rothstein, R.D. et al. Internal Medicine (Mosby, St. Louis), ed. by Stein, J.H. et al., pp. 436-445 (1994).
Schulze-Delrieu, K.S. et al. Internal Medicine (Mosby, St. Louis), ed. by Stein, J.H. et al., pp. 390-395 (1994).
Hikota Masataka
Nagasaki Masaaki
Shikano Toshiro
Yamada Koichiro
Coleman Brenda
Shah Mukund J.
Tanabe Seiyaku Co. Ltd.
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