Toray Industries, Inc.

Kiyotaka Ohno

Shintaro Nishio

Hiroshi Nagase

Hisanori Wakita

Atsushi Ohtake

Toshiya Takahashi

Kazuhisa Matsumoto

Koji Kawai

Kazuhiro Hoshi

Mamoru Ishikawa

Yutaka Hosono

Hideo Yoshiwara

Takashi Endoh

Masanobu Naruto

Masato Mutoh

Masakazu Hattori

Hisao Nishiyama

Shunji Tsukamoto

Norio Naruse

Shigeki Itou

Antimetastasis agent of malignant tumors

Sulfonic acid derivative and its pharmaceutical application

The present invention provides a process for preparing 5,6,7-trinor-4,8-inter-m-phenylene PGI.sub.2 derivative using 3a,8b-cis-dihydro-3H-5,7-dibromocyclopenta[b]benzofuran as a starting material, as well as compounds which are intermediates.

Conversion of 15-beta to 15-alpha 5,6,7-trinor-4,8-inter-m-phenylene

2,5,6,7-tetranor-4,8-inter-m-phenylene PGI.sub.2, derivative,

Process of producing 5,6,7-trinor-4,8-inter-m-phenylene PGI2 derivatives

Pharmaceutically useful compounds are 2,5,6,7-tetranor-4,8-inter-m-phenylene PGI.sub.2 derivatives which are excellently stable and potent in vivo.

2,5,6,7-tetranor-4,8-inter-m-phenylene PGI.sub.2 derivatives

Disclosed herein are novel prostaglandin I.sub.2 (PGI.sub.2) derivatives exhibiting excellent physiological activities, said derivatives being represented by the general formula: ##STR1## wherein R.sub.1, R.sub.2 and R.sub.3 are as defined herein.

2,5,6,7-tetranor-18,18,19,19-tetradehydro-4,8-inter-m-phenylene

Pharmaceutically useful compounds are 5,6,7-trinor-4,8-inter-m-phenylene PGI.sub.2 derivatives such as

5,6,7,-trinor-4,8-inter-m-phenylene 2-nor PGI.sub.2 derivatives and

Disclosed herein are novel prostaglandin I.sub.2 (PGI.sub.2) derivatives exhibiting excellent in vivo duration and activities, said derivatives being represented by the general formula: ##STR1## wherein R.sub.1, X, R.sub.2 and R.sub.3 are as defined herein.

Pharmaceutically useful compounds are 5,6,7-trinor-4,8-inter-m-phenylene PGI.sub.2 derivatives such as 5,6,7-trinor-4,8-inter-m-phenylene-13,14-didehydro PGI.sub.2, 5,6,7-trinor-4,8-inter-m-phenylene-16,16-dimethyl PGI.sub.2, 5,6,7-trinor-4,8-inter-m-phenylene-17-.alpha.-methyl-20-homo PGI.sub.2, 5,6,7-trinor-4,8-inter-m-phenylene-17,18,19,20-tetranor-16-phenoxy PGI.sub.2, 5,6,7-trinor-4,8-inter-m-phenylene-20-isopropylidene PGI.sub.2, 5,6,7-trinor-4,8-inter-(5-methyl-1,3-phenylene) PGI.sub.2, and 5,6,7-trinor-4,8-inter-m-phenylene-2,3-didehydro-16,17,18,19,20-pentanor-1 5-phenyl PGI.sub.2. They are useful in treatment of ulcers, thrombii and hypertension for example.

5,6,7,-Trinor-4,8-inter-m-phenylene PGI.sub.2 derivatives and

A compound of the formula ##STR1## wherein R.sup.1 is a pharmaceutically acceptable cation, hydrogen or n-alkyl of 1 to 12 carbon atoms; R.sup.2 is hydrogen, acyl of 2 to 10 carbon atoms or aroyl of 7 to 13 carbon atoms; R.sup.3 is hydrogen, acyl of 2 to 10 carbon atoms or aroyl of 7 to 13 carbon atoms; R.sup.4 is hydrogen, methyl or ethyl; R.sup.5 is n-alkyl of 1 to 5 carbon atoms; n is an integer of 0 to 4; A is --CH.sub.2 --CH.sub.2 -- or trans --CH.dbd.CH--; and X is --CH.sub.2 --CH.sub.2 -- or trans --CH.dbd.CH--. The compounds are useful in anti-ulcer, hypotensive and platelet aggregation inhibiting compositions.

5,6,7-Trinor-4,8-inter-m-phenylene prostaglandin I.sub.2 derivatives

Pharmaceutically useful compounds are 5,6,7-trinor-4,8-inter-m-phenylene PGI.sub.2 derivatives such as 5,6,7-trinor-4,8-inter-m-phenylene-16,17,18,19,20-pentanor-15-phenyl PGI.sub.2.

5,6,7-Trinor-4,8-inter-m-phenylene PGI.sub.2 derivatives

The degradation of prostaglandins E is prevented or minimized by combining prostaglandins E with methylhesperidin.

Growing community of inventors

Fujisawa, Japan

Kiyotaka Ohno