Banyu Pharmaceutical Co. Ltd

Kiyofumi Ishikawa

Mitsuo Yano

Takashi Hayama

Takehiro Fukami

Toshio Nagase

Masaki Ihara

Toshiaki Mase

Kenji Niiyama

Masaru Nishikibe

Kagari Fujita

Fumihiko Ikemoto

Ryosuke Ushijima

Kenji Matsuyama

Ikuo Matsumoto

Kazuhito Noguchi

Junji Yoshizawa

Akira Okuyama

Nobuo Tanaka

Nobuo Harada

Kyoko Nakamichi

Kyozo Naito

Shigemitsu Okada

Hidetoshi Ogino

Takeshi Hayama

Hiroshi Naganuma

Process for producing halogenated heteroaryl compounds

Endothelin antagonistic heteroaromatic ring-fused cyclopentene

The invention relates to compounds which are antagonists of endothelin, to processes for their preparation, and to their use as pharmaceuticals. The compounds of the invention are Useful in the treatment of hypertension, pulmonary hypertension, Reynaud's disease, myocardial infarction, angina pectoris, acute renal failure, cerebral infarction, cerebral vasospasm, arteriosclerosis, asthma, endotoxin shock, endotoxin-induced multiple organ failure or disseminated intravascular coagulation, and/or cyclosporin-induced renal failure or hypertension.

Endothelin antagonistic peptide derivatives

Peptides having the formula: ##STR1## inhibit the binding of endothelin to its ET.sub.B receptor and are useful in treating diseases associated with excess production or secretion of endothelin.

Endothelin antagonistic substance

This invention relates to novel 6,7-dialkoxy-3,4-dihydroisoquinolin-8-ols, a process for preparing the 6,7-dialkoxy-3,4-dihydroisoquinolin-8-ols reioselectively and in a high yield utilizing the Bischler-Napieralski reaction, a process for synthesizing 6,7-dialkoxy-1,2,3,4-tetrahydroisoquinolin-8-ols via the compounds, and use of the 6,7-dialkoxy-3,4-dihydroisoquinolin-8-ols for preparation of the 6,7-dialkoxy-1, 2,3,4-tetrahydroisoquinolin-8-ols. It is possible according to this invention, to obtain the 6,7 -dialkoxy-1,2,3,4-tetrahydroisoquinolin-8-ols, which have hitherto been difficult to synthesize, via the 6,7-dialkoxy-3,4-dihydroisoquinolin-8-ols in a high yield.

6,7-dialkoxy-3,4-diydroisoquinolin-8-yl compounds

Peptides having the formula: ##STR1## inhibit the binding of endothelin and are useful in treating diseases associated with excess production or secretion of endothelin.

A peptide derivative of the formula: ##STR1## is a novel compound having antagonism against three endothelin isopeptides. A 2-cyanotryptophan or a protected compound thereof, is an intermediate for the preparation of the endothelin antagonist.

Endothelin antagonistic peptide

Peptides having the formula: ##STR1## inhibit the binding of endothelin to its receptor and are useful in treating diseases associated with excess production or secretion of endothelin.

This invention relates to novel 6,7-dialkoxy-3,4-dihydroisoquinolin-8-ols, a process for preparing the 6,7-dialkoxy-3,4-dihydroisoquinolin-8-ols reioselectively and in a high yield utilizing the Bischler-Napieralski reaction, a process for synthesizing 6,7-dialkoxy-1,2,3,4-tetrahydroisoquinolin-8-ols via the compounds, and use of the 6,7-dialkoxy-3,4-dihydroisoquinolin-8-ols for preparation of the 6,7-dialkoxy-1,2,3,4-tetrahydroisoquinolin-8-ols. It is possible, according to this invention, to obtain the 6,7-dialkoxy-1,2,3,4-tetrahydroisoquinolin-8-ols, which have hitherto been difficult to synthesize, via the 6,7-dialkoxy-3,4-dihydroisoquinolin-8-ols in a high yield.

Process for preparing 6,7-dialkoxy-3,4-dihydroisoquinolin-8-ol

Peptides having the formula ##STR1## inhibit the binding of endothelin to its receptor and are useful in treating diseases associated with excess production or secretion of endothelin.

A heteroaromatic ring-fused cyclopentene derivative of the formula: ##STR1## wherein the variables are as defined in the specification; or a pharmaceutically acceptable salt thereof.

There are provided novel aminophosphonic acid derivatives of the general formula [I]: ##STR1## wherein n is an integer of 2 or 3; R.sup.1 is a phenyl, naphthyl, indolyl, benzothienyl, benzofuryl or benzoxazolyl group which may have 1 to 3 substituents selected from the group consisting of hydroxyl and lower alkyloxy groups, or a hydrogen atom; R.sup.2 is a lower alkyl group, a benzyl group, a 4-hydroxybenzyl group, a 3-indolylmethyl group or a .beta.-phenethyl group; and A is an optional residue of an amino acid selected from the group consisting of tryptophane, tyrosine, phenylalanine, homophenylalanine, naphthylalanine or N.sup..omega. -nitroarginine, and their pharmaceutically acceptable salts. The compounds according to the present invention and their pharmaceutically acceptable salts exhibit an inhibitory activity against endothelin-converting enzyme, and are expected to be useful as a drug treating various diseases with which endothelin is concerned.

Aminophosponic acid derivative

Novel isoquinoline derivatives represented by formula (I): ##STR1## wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, X.sup.1 and X.sup.2 are as defined in the specification, have an anti-arrhythmic activity and bradycardiac activity and are effective for the treatment of arrhythmia, myocardiac infarction or angina pectoris.

Isoquinoline derivatives

A guanidinobenzene derivative represented by the formula (I): ##STR1## wherein R.sup.1 represents a substituent selected from the group consisting of a phenyl group substituted by an amidino group and a naphthyl group substituted by an amidino group, and salt thereof; a process for the production thereof; and an antiviral pharmaceutical composition comprising the compound.

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Tokyo, Japan

Kiyofumi Ishikawa