Ono Pharmaceutical Co., Ltd.

Nobuyuki Hamanaka

Kanji Takahashi

Hidekado Tokumoto

Mitoshi Konno

Yuuki Nagao

Takahiko Nakae

Kazuhiko Torisu

Yoshinobu Arai

Takayuki Maruyama

Tsumoru Miyamoto

Akio Hayashi

Makoto Hiramatsu

Hisao Nakai

Tohru Miyazaki

Masayasu Kurono

Shigeru Sakuyama

Takeshi Chiba

Hideo Takada

Takahiko Nakao

Naphthyloxy acetic acid derivatives and a pharmaceutical composition comprising them as an active ingredient

The naphthyloxyacetic acid derivatives of the formula (I)

Naphthyloxyacetic acid derivatives and a pharmaceutical composition comprising them as an active ingredient

(1) Prostaglandin (PG) E.sub.2 antagonist or agonist containing carbocyclic sulfonamides represented by the compound of the formula (I): ##STR1## cyclodextrin clathrates thereof, non-toxic salts thereof as active ingredient, (2) carbocyclic sulfonamides represented by the compound of the formula (II): ##STR2## cyclodextrin clathrates thereof, non-toxic salts thereof, (3) process for the preparation of the compound represented by the compound of the formula (II) described hereinbefore, (4) PGE.sub.2 antagonist or agonist containing the compound represented by the compound of the formula (II) as active ingredient. The compounds represented by the compounds of the formula (I) and (II) can be adapted to medicines which possess an inhibitory effect of uterine contraction, an analgetic action, an inhibitory effect of digestive peristalsis, a sleep-inducing effect as PGE.sub.2 antagonists, and an uterine contractile activity, a promoting effect of digestive peristalsis, a suppressive effect of gastric acid secretion, a hypotensive activity as PGE.sub.2 agonists, because they bind onto PGE.sub.2 receptor and have an activity of antagonist or agonist against the action thereof.

Carbocyclic sulfonamides

Naphthyloxyacetic acid derivatives and drugs comprising the same as

The phenylalkan(en)oic acids of the formula: ##STR1## as defined herein, posses an antagonistic activity on leukotriene B.sub.4.

Phenylalkan(en)oic acid

Fused benzeneoxyacetic acid derivatives of the formula (I): ##STR1## or salts thereof possess an agonistic effect on the PGI.sub.2 receptor and thus are useful for preventing and/or treating thrombosis, arteriosclerosis, ischemic heart diseases, gastric ulcer and hypertension. A, B, D, and R.sup.1 are as defined in the specification.

Fused benzeneoxyacetic acid derivatives

We proposed a novel compound having an activity of PGI.sub.2 receptor agonist. A phenoxyacetic acid derivative of the formula ##STR1## A is --C(R.sup.1).dbd.N.about.OR.sup.2, --CH(R)NH--OR.sup.2, --COE, --SO.sub.2 E, --CH.sub.2 --NR.sup.3 --Y, --Z--NR.sup.3 --CONR.sup.4 R.sup.5, --CH.sub.2 --OR.sup.6, --CO.sub.2 R.sup.6, --CH.sub.2 --O.about.N.dbd.CR.sup.7 R.sup.8, --CH.sub.2 --O--NHCHR.sup.7 R.sup.8, substituted by imidazolyl(methyl), pyrazolylmethyl, oxazolyl(methyl), thioxazolyl, isoxazolyl, isothiazolyl, oxadiazolyl, triazolylmethyl;

Phenoxyacetic acid derivatives

A fused benzeneoxyacetic acid derivative of the formula (I): ##STR1## wherein D is a 3-5-membered ring; B is a C.sub.1-4 group; R.sup.1 is OH alkoxy, (alkyl) amino, residue of an amino acid; A is phenyl, alkyl substituted by phenyl, residue of an imidazole, imidazole-2-yloxy(thio), 2-oxoimidazole, pyrazole, oxadiazole, oxazole, trizole, isoxazole or isothiazole, in the group of benzene may be substituted by one to three of alkyl, alkoxy, halogen, nitro or trihalomethyl; and salts thereof possess an agonistic effect on the PGI.sub.2 receptor, so is useful for prevention and/or treatment of thrombosis, arteriosclerosis, ischemic heart diseases, gastric ulcer and hypertension.

Fused benzeneoxyacetic acid derivatives which have PGI.sub.2 receptor

The phenylalkan(en)oic acids of the formula: ##STR1## wherein the substituents are defined in the specification.

(1) Naphthyloxyaetic acid represented by the compound of the formula (I): ##STR1## and non-toxic salts thereof, (2) process for the preparation of the compounds represented by the compound of the formula (I) described hereinbefore, (3) PGE.sub.2 antagonist or agonist containing the compound represented by the compound of the formula (I) as the active ingredient. The compounds represented by the compounds of the formula (I) can be adapted to medicines which possess an inhibitory effect of uterine contraction, an analgesic action, an inhibitory effect of digestive peristalsis, a sleep-inducing effect as PGE.sub.2 antagonists, and an uterine contractile activity, a promoting effect of digestive peristalsis, a suppressive effect of gastric acid secretion, hypotensive activity as PGE.sub.2 agonists. The compounds bind to PGE.sub.2 receptor and have an activity of antagonist or agonist against the action thereof.

Naphthyloxyacetic acid

A fused benzeneoxyacetic acid derivative of the formula (I): ##STR1## A is --COW, --NR.sup.4 --Y or --Z--NR.sup.4 --CONR.sup.2 R.sup.3 ; and salts thereof possess an agonistic on PGI.sub.2 receptor, so it is useful for prevention and/or treatment of thrombosis, arteriosclerosis, ischemic heart diseases, gastric ulcer and hypertention.

Polyclonal and monoclonal antibodies are obtained specific to mevalonic acid, having low cross-reactivity with mevalonic acid analogues, such as glutaric acid, 3-methylglutaric acid and 3-hydroxy-3-methylglutaric acid. The antibodies may be used for determination of mevalonic acid providing an immunoassay excellent in sensitivity, specificity and reproducibility.

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Osaka, Japan

Nobuyuki Hamanaka