Ono Pharmaceutical Co., Ltd.

Ono Pharmaceuticals Co., Ltd.

Shinsuke Hashimoto

Kaoru Kobayashi

Takayuki Maruyama

Atsushi Naganawa

Hirohisa Wakatsuka

Tetsuji Saito

Yoshihiko Nakai

Masaki Hayashi

Shuichi Ohuchida

Yoshinobu Arai

Katsuhiro Imaki

Yoshitaka Konishi

Katsuichi Shimoji

Takashi Yamato

Tetsuji Saitoh

An N-phenylarylsulfonylamide compound of formula (I) (Ris COOH etc.; Ris hydrogen, methyl, etc.; Rand Rare a combination of methyl and methyl, etc.; Ris isopropyl etc.; Ar is thiazolyl, pyridyl, 5-methyl-2-furyl each optionally substituted with methyl; n is zero or 1), a synthetic intermediate for the compound and a process for its preparation. The compound of formula (I) binds to a prostaglandin Ereceptor, especially an EPsubtype receptor, and antagonizes it. It is less affected by protein binding, so it has a satisfactory in vivo activity. Therefore, it is considered to be useful as an analgesic, an antipyretic agent, an agent for the treatment of pollakiuria (frequent urination) and/or lower urinary tract disease syndrome or an antineoplastic agent.

N-phenylarylsulfonamide compound, pharmaceutical composition comprising the compound as active ingredient, synthetic intermediate for the compound and process for its preparation

A method for improving the solubility of a salt of a glucopyranose derivative of formula (I) ##STR1## wherein R.sup.2, R.sup.3 and Y.sup.+ are as defined herein. The compound of formula (I) possesses enhanced activity for cellular immunity, and therefore is useful as an enhancing agent for immunity. It also possesses inducing activity for TNF, IL-1, and IFN, and therefore is useful as an anti-tumor agent.

Salts of glucopyranose derivative and solutions of the same

A salt of glucopyranose derivative of the formula (I) ##STR1## wherein R.sup.2 is ##STR2## R.sup.3 is ##STR3## Y.sup.+ is sodium ion or tris(hydroxymethyl)methylammonium ion; and a glucopyranose derivative of the formula (II) ##STR4## wherein all the symbols are the same meaning as hereinbefore defined, is an important intermediate for the preparation of compound of the formula (I).

Salts of glucopyranose derivatives and its intermediate

Trans-.DELTA..sup.2 -prostaglandin D derivatives of the formula: ##STR1## wherein [A] is a group of the formula: ##STR2## X is ethylene or cis-vinylene, C.sub.13 -C.sub.14 -C.sub.15 is: (i) a group of the formula: ##STR3## when [A] is a group of the formula (II) or (III), or (ii) a group of the formula: ##STR4## when [A] is a group of the formula (IV), R is hydrogen or alkyl, R.sup.1 is a single bond or alkylene, R.sup.2 is alkyl, cycloalkyl, phenyl or phenoxy, the double bonds between C.sub.2 -C.sub.3 and between C.sub.13 -C.sub.14 are both E, the double bond between C.sub.9 -C.sub.10 is Z and the double bonds between C.sub.12 -C.sub.13 and between C.sub.14 -C.sub.15 are E, Z or a mixture thereof, provided that when R.sup.1 is a single bond, R.sup.2 does not represent a substituted or unsubstituted phenoxy group, and cyclodextrin clathrates and non-toxic salts thereof, possess anti-tumor activity.

Trans-.DELTA..sup.2 -prostaglandin D derivatives, process for their

Prostaglandin I.sub.2 analogues of the formula: ##STR1## [wherein Y represents ethylene or trans-vinylene, R.sup.1 represents hydrogen, alkyl of 1 to 12 carbon atoms, aralkyl of 7 to 12 carbon atoms, cycloalkyl of 4 to 7 carbon atoms optionally substituted by at least one alkyl group containing from 1 to 4 carbon atoms, phenyl unsubstituted or substituted by at least one chlorine atom, trifluoromethyl group, alkyl group containing from 1 to 4 carbon atoms or phenyl group, a --C.sub.m H.sub.2m COOR.sup.4 group (wherein m is an integer from 1 to 12 and R.sup.4 represents alkyl of 1 to 4 carbon atoms), a C.sub.n H.sub.2n OR.sup.5 group (wherein n is an integer from 2 to 12 and R.sup.5 represents hydrogen or alkyl of 1 to 4 carbon atoms), or a ##STR2## (wherein n is as hereinbefore defined and R.sup.6 and R.sup.7 each represent alkyl of 1 to 4 carbon atoms), R.sup.2 represents hydrogen, methyl or ethyl, X represents a --C.sub.p H.sub.2p --group (wherein p is an integer from 2 to 8) or a ##STR3## (wherein R.sup.8 represents a single bond, or alkylene of 1 to 4 carbon atoms, R.sup.9 represents a single bond or alkylene of 1 to 8 carbon atoms, and q is an integer from 3 to 6), R.sup.3 represents chlorine or fluorine, the wavy line attached to the carbon atoms in positions 11 and 15 represents .alpha.- or .beta.-configuration or mixtures thereof, and the double bond between C.sub.5 -C.sub.6 is Z] and cyclodextrin clathrates thereof and, when appropriate non-toxic salts, including acid addition salts, thereof, are new compounds possessing prostaglandin-like activity.

.omega.-Halo-PGI.sub.2 analogues

Prostaglandin analogues of the general formula: ##STR1## [wherein Y represents ethylene or trans-vinylene, R.sup.1 represents a group --C.sub.m H.sub.2m COOR.sup.5, --C.sub.n H.sub.2n OR.sup.6 or ##STR2## (wherein R.sup.5 represents an alkyl group containing from 1 to 4 carbon atoms, R.sup.6 represents a hydrogen atom or an alkyl group containing from 1 to 4 carbon atoms, R.sup.7 and R.sup.8, which may be the same or different, each represents an alkyl group containing from 1 to 4 carbon atoms, m represents an integer of from 1 to 12 and n represents an integer of from 2 to 12), R.sup.2 represents a hydrogen atom or a methyl or ethyl group, R.sup.3 represents a single bond, or an alkylene group containing from 1 to 4 carbon atoms, R.sup.4 represents a hydrogen atom, an alkyl group containing from 1 to 8 carbon atoms, a cycloalkyl group containing from 4 to 7 carbon atoms in the ring, which may be unsubstituted or substituted by at least one alkyl group containing from 1 to 8 carbon atoms, or represents a phenyl or phenoxy group which may be unsubstituted or substituted by at least one chlorine atom, trifluoromethyl group or alkyl group containing from 1 to 3 carbon atoms, the wavy line  attached to the carbon atoms in positions 11 and 15 represents .alpha.- or .beta.-configuration, or mixtures thereof, and the double bond between C.sub.5 -C.sub.6 is Z] and cyclodextrin clathrates thereof, and, when R.sup.1 represents a group ##STR3## in which n, R.sup.7 and R.sup.8 are as hereinbefore defined, non-toxic acid addition salts thereof, are new compounds and possess characteristic prostaglandin-like properties.

Growing community of inventors

Sakai-gun, Japan

Shinsuke Hashimoto