Ono Pharmaceutical Co., Ltd.

Hidekado Tokumoto

Nobuyuki Hamanaka

Kanji Takahashi

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

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.

A fused benzeneoxyacetic acid derivative of the formula (I): ##STR1## where the substituents are defined in the specification and salts thereof possess an agonistic on PGI.sub.2 receptor, so it is useful for prevention and/or treatment of thrombosis, arteriosclerosis, inchemic heart diseases, gastric alcer and hypertension.

Triazolyl-phenoxyacetic acid compounds which have useful pharmaceutical

An oxime derivative (I): ##STR1## that D ring and B bonding to D ring are (i)-(iv), wherein R.sup.1 is hydrogen, lower alkyl; R.sup.2 is hydrogen, alkyl, phenyl, cycloalkyl, monocyclic ring containing nitrogen, lower alkyl substituted by benzene ring or cycloalkyl, lower alkyl substituted by monocyclic ring containing nitrogen; R.sup.3 is alkyl, phenyl, cycloalkyl, monocyclic ring containing nitrogen, lower alkyl substituted by benzene ring or cycloalkyl, lower alkyl substituted by monocyclic ring containing nitrogen; e is 3-5, f is 1-3, p is 1-4, q is 1-2, r is 1-3; the position of the bond to D ring in (iii) and (iv) is a or b, and the ring in R.sup.2 and R.sup.3 may be substituted by lower alkyl, alkoxy, halogen, nitro, trihalomethyl; and salts thereof, possess an agonistic activity on PGl2 receptor, and therefore are useful for prevention and/or treatment of thrombosis, arteriosclerosis, ischemic heart diseases, gastric ulcer and hypertension.

Oxime derivative

A fused benzeneoxyacetic acid derivative of the formula: ##STR1## wherein ##STR2## is (i) ##STR3## (ii) ##STR4## (iii) ##STR5## or (iv) ##STR6## A is (i) ##STR7## or (ii) ##STR8## R.sup.1 is hydrogen or C.sub.1-4 alkyl; R.sup.2 is hydrogen, C.sub.1-6 alkyl or phenyl;

A fused benzeneoxyacetic acid derivative of the formula (I): ##STR1## 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, triazole, isoxazole or isothiazole, in the group of benzene may be substituted by one to three of alkyl, alkoxy, halogen, nitro or trihalomethyl;

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; T is alkylene, alkenylene, etc.; D is --CO.sub.2 R.sup.10, --CONR.sup.11 R.sup.12 ; E is (substitution) amino, hydradino; Y is substituted (thio) carbonyl, substituted sulfonyl; Z is --CH.dbd.N--, --CH.sub.2 NR.sup.3 --; R.sup.1, R.sup.3, R.sup.10 -R.sup.13 is each H or alkyl, etc.; R.sup.2, R.sup.4 -R.sup.9 is each H, alkyl or alkyl substituted by phenyl or hetero ring, etc. and non-toxic salts thereof, non-toxic acid addition salts thereof, possess an agonistic on PGI.sub.2 receptor, so it is useful for prevention and/or treatment of thrombosis, arteriosclosis, ischemic heart diseases, gastric ulcer and hypertention.

Pyrazol-1-yl phenoxyacetic acid compounds which have useful

A fused benzenoxyacetic acid derivative of the formula (I): ##STR1## 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.

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Osaka, Japan

Hidekado Tokumoto