Ono Pharmaceutical Co., Ltd.

Other

Warner-Lambert Company

Seiji Kori

Masaki Hayashi

Hajimu Miyake

Takanori Okada

Yoshitaka Konishi

Hirohisa Wakatsuka

Isao Ohyama

Yoshinobu Arai

Sadahiko Iguchi

Hirofumi Endo

Tadao Tanouchi

Katsuichi Shimoji

Kimiichiro Matsumoto

Takashi Yamato

Hisashi Suga

This invention relates to prostaglandin analogues of the formula: ##STR1## (wherein R represents a hydrogen atom or a methyl group, and the double bonds between C.sub.2 -C.sub.3 and C.sub.13 -C.sub.14 are trans) and cyclodextrin clathrates of such compounds and, when R represents a hydrogen atom, non-toxic salts thereof, which possess characteristic prostaglandin-like activity.

Trans-.DELTA..sup.2 -prostaglandin analogues

The present invention relates to 15-cycloalkyl-prostaglandins of the formula: ##STR1## wherein A represents a grouping of the formula: ##STR2## W represents ethylene or trans-vinylene, X represents ethylene or cis-vinylene, Y represents ethylene or trans-vinylene, R represents a hydrogen atom or a straight- or branched-chain alkyl group containing from 1 to 12 carbon atoms, R.sup.1 represents a hydrogen atom or a methyl or ethyl group, R.sup.2 represents a straight- or branched-chain alkyl group containing from 2 to 8 carbon atoms or a phenyl group unsubstituted or substituted by an alkyl group containing from 1 to 3 carbon atoms, R.sup.3 represents a hydrogen atom or a straight- or branched-chain alkyl group containing from 1 to 3 carbon atoms, and n represents 4 or 5 and cyclodextrin clathrates of such acids and esters and, when R represents a hydrogen atom, non-toxic salts thereof. These new compounds exhibit characteristic prostaglandin-like activities.

15-Cycloalkyl-prostaglandin derivatives

The present invention relates to prostaglandin analogues of the general formula: ##STR1## [wherein X represents cis or trans-vinylene or ethylene, R represents ##STR2## R.sup.1 represents a hydrogen atom or a straight- or branched-chain alkyl group containing from 1 to 12 carbon atoms, R.sup.2 represents a hydrogen atom or a methyl group, R.sup.3 represents a straight- or branched-chain alkylene group containing from 1 to 7 carbon atoms and R.sup.4 represents a cycloalkyl group containing from 5 to 7 carbon atoms, a grouping of the formula: ##STR3## (wherein R.sup.5 and R.sup.6, which may be the same or different, each represent a hydrogen atom or halogen atom, a trifluoromethyl group or a straight- or branched-chain alkyl group containing from 1 to 4 carbon atoms), or a grouping of the formula: ##STR4## (wherein R.sup.5 and R.sup.6 are as hereinbefore defined), or R.sup.3 and R.sup.4 together represent a straight- or branched-chain alkyl group containing from 1 to 10 carbon atoms, and (1) the double bond between C.sub.3 -C.sub.4 is trans or cis, or trans and cis, when X is cis-vinylene or ethylene, and (2) the double bond between C.sub.3 -C.sub.4 is trans, when X is trans-vinylene, and the double bond between C.sub.13 -C.sub.14 is trans] and cyclodextrin clathrates of such acids and esters, and when R.sup.1 represents a hydrogen atom, non-toxic salts thereof, which exhibit characteristic prostaglandin-like activities.

.DELTA..sup.3 -Prostaglandin analogs

The present invention relates to prostaglandin analogues of the general formula: ##STR1## �wherein X represents cis or trans-vinylene or ethylene, Z represents ##STR2## R.sup.1 represents a hydrogen atom or a straight- or branched-chain alkyl group containing from 1 to 12 carbon atoms, R.sup.2 represents a hydrogen atom or a methyl group, R.sup.3 represents a straight- or branched-chain alkylene group containing from 1 to 7 carbon atoms and R.sup.4 represents a cycloalkyl group containing from 5 to 7 carbon atoms, a grouping of the formula: ##STR3## (wherein R.sup.5 and R.sup.6, which may be the same or different, each represent a hydrogen atom or halogen atom, a trifluoromethyl group or a straight- or branched-chain alkyl group containing from 1 to 4 carbon atoms), or a grouping of the formula: ##STR4## (wherein R.sup.5 and R.sup.6 are as hereinbefore defined), or R.sup.3 and R.sup.4 together represent a straight- or branched-chain alkyl group containing from 1 to 10 carbon atoms, and (1) the double bond between C.sub.3 -C.sub.4 is trans or cis, or trans and cis, when X is cis-vinylene or ethylene, and (2) the double bond between C.sub.3 -C.sub.4 is trans, when X is trans-vinylene, and the double bond between C.sub.13 -C.sub.14 is trans! and cyclodextrin clathrates of such acids and esters, and when R.sup.1 represents a hydrogen atom, non-toxic salts thereof, which exhibit characteristic prostaglandin-like activities.

The present invention relates to 20-hydroxy prostaglandins of the formula: ##STR1## wherein A represents a grouping of the formula: ##STR2## and X represents ethylene or cis-vinylene and Y represents trans-vinylene, or X and Y each represent ethylene, R represents a hydrogen atom or a straight- or branched-chain alkyl group containing from 1 to 12 carbon atoms, R.sup.1 , R.sup.2, R.sup.3, R.sup.4 and R.sup.5, which may be the same or different, each represent a hydrogen atom or a methyl or ethyl group, and n represents zero or an integer from 1 to 3 inclusive, and cyclodextrin clathrates of such acids and esters and, when R represents a hydrogen atom, the non-toxic salts thereof. These compounds exhibit characteristic prostaglandin activity.

20-Hydroxy-prostaglandins

Prostaglandins of the formula: ##STR1## wherein A represents a grouping of the formula: ##STR2## X represents ethylene or cis-vinylene, Y represents ethylene or trans-vinylene, R represents a hydrogen atom or a straight- or branched-chain alkyl group containing from 1 to 12 carbon atoms, R.sup.1 represents a hydrogen atom or a straight- or branched-chain alkyl group containing from 1 to 10 carbon atoms, R.sup.2 represents a straight- or branched-chain alkyl group containing from 1 to 4 carbon atoms, R.sup.3 represents a straight- or branched-chain alkyl group containing from 1 to 4 carbon atoms, a cycloalkyl group containing from 4 to 7 carbon atoms, or a grouping of the formula: ##STR3## wherein R.sup.4 and R.sup.5 each represents a hydrogen or halogen atom, a trifluoromethyl group or an alkyl group containing from 1 to 3 carbon atoms, or R.sup.2 and R.sup.3 together represent an ethylene or trimethylene group and cyclodextrin clathrates of such acids and esters and, when R represents a hydrogen atom, non-toxic salts of such acids, are disclosed. These compounds exhibit characteristic prostaglandin activity, in particular, inhibitory activity on gastric secretion, luteolytic activity and so on.

Prostaglandin analogues

Prostaglandin analogues of the formula: ##STR1## wherein A represents a grouping of the formula: ##STR2## X represents ethylene or cis-vinylene, Y represents ethylene or trans-vinylene, R.sup.1 represents a straight- or branched-chain alkyl group containing from 4 to 10 carbon atoms, and R.sup.2 represents a hydrogen atom or a straight- or branched-chain alkyl group containing from 1 to 12 carbon atoms and cyclodextrin clathrates of such acids and esters and, when R.sup.2 represents a hydrogen atom, non-toxic salts thereof, the bonds attaching the epidithio radical to the carbon atoms in the 9- and 11-positions in the grouping of formula VA being either botn in .alpha.-configuration or both in .beta.-configuration are disclosed. These compounds exhibit characteristic prostaglandin properties.

Dithio prostaglandin derivatives

The present invention relates to 15-cycloalkyl-prostaglandins of the formula: ##STR1## WHEREIN A represents a grouping of the formula: ##STR2## W represents ethylene or trans-vinylene, X represents ethylene or cis-vinylene, Y represents ethylene or trans-vinylene, R represents a hydrogen atom or a straight- or branched-chain alkyl group containing from 1 to 12 carbon atoms, R.sup.1 represents a hydrogen atom or a methyl or ethyl group, R.sup.2 represents a straight- or branched-chain alkyl group containing from 2 to 8 carbon atoms or a phenyl group unsubstituted or substituted by an alkyl group containing from 1 to 3 carbon atoms, R.sup.3 represents a hydrogen atom or a straight- or branched-chain alkyl group containing from 1 to 3 carbon atoms, and n represents 4 or 5) and cyclodextrin clathrates of such acids and esters and, when R represents a hydrogen atom, non-toxic salts thereof. These new compounds exhibit characteristic prostaglandin-like activities.

The present invention relates to 17-oxo-17-phenyl-prostaglandins having the following structural formula: ##STR1## wherein A represents a grouping of the formula: ##STR2## X represents ethylene or cis-vinylene, Y represents ethylene or trans-vinylene, R.sup.1 represents a hydrogen atom or a methyl or ethyl group, R.sup.2 and R.sup.3, which may be the same or different, each represent a hydrogen or halogen atom, a trifluoromethyl group or a straight- or branched-chain alkyl group containing from 1 to 3 carbon atoms, and R.sup.4 represents a hydrogen atom or a straight- or branched-chain alkyl group containing from 1 to 12 carbon atoms and cyclodextrin clathrates of such acids and esters, and when R.sup.4 represents a hydrogen atom, non-toxic salts thereof. These compounds exhibit characteristic prostaglandin activity, e.g., abortifacient activity, stimulation activity on uterine contraction, and so on.

17-Oxo-17-phenyl-prostaglandins

The present invention relates to compounds of the formula: ##STR1## wherein A represents a grouping of the formula: ##STR2## B represents a single bond or a straight- or branched-chain alkylene group containing from 1 to 9 carbon atoms, W represents ethylene or trans-vinylene, X represents ethylene or cis-vinylene, Y represents ethylene or trans-vinylene, R represents a hydroxymethyl group or a grouping of the formula --COOR.sup.4, in which R.sup.4 represents a hydrogen atom or a straight- or branched-chain alkyl group containing from 1 to 12 carbon atoms, R.sup.1 represents a hydrogen atom or a methyl or ethyl group, R.sup.2 represents a hydrogen atom or a methyl or ethyl group and R.sup.3 represents a hydrogen or chlorine atom or a hydroxy group and cyclodextrin clathrates of such alcohols, acids and esters and, when R.sup.4 in the formula --COOR.sup.4 represents a hydrogen atom, non-toxic salts thereof, and intermediates therefor. These compounds exhibit characteristic prostaglandin-like activity.

16-Chloro-substituted prostaglandins and derivatives thereof

Prostaglandin analogues of the formula: ##STR1## wherein X represents oxygen or sulphur, R.sup.1 and R.sup.2 each represent hydrogen or alkyl of from 1 to 3 carbon atoms, alkenyl of from 2 to 4 carbon atoms or trifluoromethyl, and the double bonds depicted in positions C.sub.5 -C.sub.6 and C.sub.13 -C.sub.14 are cis and trans respectively. These compounds are indicated in the treatment of impaired fertility, induction of labor or termination of pregnancy in females.

The present invention relates to compounds of the formula: ##STR1## wherein A represents a grouping of the formula: ##STR2## B represents an oxygen or sulphur atom, R.sup.1 and R.sup.2, which may be the same or different, each represent a hydrogen or halogen atom, a trifluoromethyl group, or a straight- or branched-chain alkyl or alkoxy group containing from 1 to 4 carbon atoms, R represents a group of the formula --COOR.sup.3, in which R.sup.3 represents a hydrogen atom or a straight- or branched-chain alkyl group containing from 1 to 12 carbon atoms, or a group of the formula --CH.sub.2 OR.sup.4, in which R.sup.4 represents a hydrogen atom or an alkylcarbonyl group containing from 2 to 5 carbon atoms and the double bonds depicted in positions C.sub.2 -C.sub.3, C.sub.5 -C.sub.6 and C.sub.13 -C.sub.14 are trans, cis and trans respectively, the cyclodextrin clathrates thereof and, when R.sup.3 in the group --COOR.sup.3 represents a hydrogen atom, non-toxic salts thereof. These compounds exhibit characteristics of prostaglandin-like activity.

16-Phenoxy and phenylthio prostaglandin derivatives

New trans-.DELTA..sup.2 -prostaglandins of the formula ##STR1## (wherein R.sup.1 represents a hydrogen atom or a straight- or branched-chain alkyl group containing from 1 to 10 carbon atoms, R.sup.2 represents a 1,1-dimethyl-pentyl group or a 2-ethylheptyl group, the wavy line  indicates attachment of the depicted group in .alpha.-configuration or racemic form consisting of equimolecular mixtures of .alpha.-configuration and .beta.-configuration and the C.sub.2 -C.sub.3 and C.sub.13 -C.sub.14 double bonds are trans), which are useful for the treatment of hypertension, contraception menstrual regulation.

15-Cycloalkyl-prostaglandins of the formula:- ##STR1## wherein A represents a grouping of the formula:- ##STR2## X represents ethylene of cis-vinylene, Y represents ethylene or trans-vinylene, B represents ethylene or trans-vinylene, R represents hydrogen or alkyl of 1 through 4 carbon atoms, R.sup.1 represents cycloalkyl of 4 through 7 carbon atoms, and R.sup.2 represents hydrogen or alkyl of 1 through 12 carbon atoms, are new compounds possessing the useful pharmacological properties typical of prostaglandins; they are of especial interest in the inhibition of blood platelet aggregation.

15-Cycloalkyl-prostaglandins

Trans-.DELTA..sup.2 -prostaglandin compounds are disclosed of the formula: ##STR1## wherein A represents a grouping of the formula: ##STR2## R.sup.1 represents an alkyl group containing from 1 to 10 carbon atoms, or an alkyl group containing from 1 to 6 carbon atoms carrying a phenyl substituent or a cycloalkyl substituent of 5 to 7 carbon atoms, R.sup.2 represents a hydrogen atom or an alkyl group containing from 1 to 4 carbon atoms, and R.sup.3.sup.' represents a hydrogen atom or an alkyl group containing from 1 to 12 carbon atoms, the double bonds in the 2- and 5-positions being in the trans- and cis-configurations respectively. These compounds are indicated in the management of conditions such as autoimmune conditions, e.g. rheumatoid arthritis.

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Takatsuki, Japan

Seiji Kori