Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Patent
1996-11-22
1998-06-02
Shah, Mukund J.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
540560, A61K 3155, C07D49100, C07D51300, C07D51500
Patent
active
057600325
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
The present invention relates to novel thienylazole compounds and thienotriazolodiazepine compounds having cholecystokinin (hereinafter abbreviated as CCK) and gastrin antagonistic activities, which are utilized in the medical field.
BACKGROUND ART
There have been heretofore reported a 2-thienyltriazole compound (Japanese Patent Examined Publication No. 12434/1980) showing action on the central nervous system, such as anti-convulsion activity and sedative activity; a thienotriazolodiazepine compound (Japanese Patent Unexamined Publication No. 61197/1974) used as an antianxiety drug; a 2-thienyltriazole compound (Japanese Patent Unexamined Publication No. 69667/1974) used as an antianxiety drug or an intermediate for pharmaceutical products; a 2-thienyltriazole compound (Japanese Patent Unexamined Publication No. 58098/1975) which is an intermediate for a thienotriazolopyridine compound used as an antiinflammatory drug, an antipyretic analgesic and the like; a 2-thienylimidazole compound (Japanese Patent Unexamined Publication No. 89369/1975) which has central muscle relaxing activity, antianxiety activity and the like; a 2-thienyltriazole compound (Japanese Patent Examined Publication No. 45754/1982) used as a starting compound of a pharmaceutical product such as an antianxiety drug; a 2-thienyltriazole compound (Japanese Patent Unexamined Publication No. 10568 1/1980) which is used as an antianxiety drug; a 2-thienylimidazole compound (Japanese Patent Unexamined Publication No. 105682/1980) which is used as an antianxiety drug; a 2-thienylazole compound (Japanese Patent Unexamined Publication No. 294676/1989) having calmodulin antagonistic activity, coronary and cerebral vasodilating activities and PAF antagonistic activity; and the like.
In addition, Japanese Patent Unexamined Publication No. 102698/1974 discloses that a thienotriazolodiazepine compound which may be substituted by alkoxycarbonylaminoalkyl, alkylcarbonyloxyalkyl and the like at the 9-position thereof can be used as a tranquilizer or an antianxiety drug. Japanese Patent Unexamined Publication Nos. 28181/1990 and 223290/1991 disclose thienotriazolodiazepine compounds having cholecystokinin antagonistic activity, which have, at the 6-position thereof, an amide (3-(3methylphenyl)ureido!, which substituent being considered to be essential for the expression of cholecystokinin antagonistic activity.
The cholecystokinin (also referred to as CCK) is a neuropeptide consisting of 33 amino acids, and CCK-8 which consists of 8 amino acids at the C terminus also shows activity. The gastrin consists of 34 amino acids, and pentagastrin which consists of 5 amino acids at the C terminus also shows activity. The amino acid sequence of the pentagastrin is identical to that at the C terminus of CCK. There have been reported different subtypes of CCK receptors which are generally classified into CCK-A receptor distributed in peripheral tissues such as pancreas and gallbladder, and CCK-B receptor distributed in the central nervous system. It is considered that CCK-B receptor and gastrin receptor are the same. The physiological activity of CCK via CCK-A receptor reportedly includes secretion of pancreatic juice, promotion of insulin release, control of pepsinogen secretion, gastric delay of emptying, stimulation of ileum movement, contraction of gallbladder, and the like. The physiological activity of CCK via CCK-B receptor reportedly includes suppression of feeling of hunger, control of dopaminergic nerves, control of pain and pain relief with morphine, acceleration of memory, and the like, and CCK-B receptor antagonist is useful for the treatment and prophylaxis of gastric ulcer and enterelcosis, emesis, control of appetite, pain, anxiety, dementia, schizophrenia, and the like.
Mainly in experimental studies of pancreatitis in recent years, the involvement of CCK in the onset, evolution and aggravation of pancreatitis has been reported. Pancreatitis is a symptom wherein pancreatic tissues are digested by the enzyme secreted by the pancreas
REFERENCES:
patent: 4094984 (1978-06-01), Weber et al.
patent: 4199588 (1980-04-01), Weber et al.
patent: 5190939 (1993-03-01), Rault et al.
patent: 5532233 (1996-07-01), Weber et al.
T. Tahara et al. "Syntheses and Structure-Activity Relationships of Forschung Drug Research, vol. 28, 1978.
Walser, et al. J. Med. Chem. (1991), 34(3), 1209-21.
G.N. Woodruff et al., "Cholecyst Antagonists", Annu. Rev. Pharmacol. Toxicol., vol. 31, pp. 469-501, 1991.
J. Martinez et al., "Synthesis and Biological Activity of New Peptide Segments of Gastrin Exhibiting Gastrin Antagonist Property", J. Med. Chem. vol. 27, pp. 1597-1601, 1984.
B.E. Evans, "Methods for Drug Discovery: Development of Potent, Selective, Orally Effective Cholecystokinin Antagonists", J. Med. Chem., vol. 31, pp. 2235-2246, 1988.
Ehara Syuji
Kitajima Hiroshi
Moriwaki Minoru
Onishi Kenichi
Sato Hideaki
Kifle Bruck
Shah Mukund J.
Yoshitomi Pharmaceutical Industries Ltd.
LandOfFree
Thienylazole compound and thienotriazolodiazepine compound does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Thienylazole compound and thienotriazolodiazepine compound, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Thienylazole compound and thienotriazolodiazepine compound will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-1460006