Sankyo Company, Limited

Kazuyuki Wachi

Atsusuke Terada

Yoshio Iizuka

Kenji Fujibayashi

Kazuo Hasegawa

Keiichi Tabata

Hachio Miyazawa

Eiichi Misaka

Hachio Miyazwa

A process for preparing a compound of the formula (I) ##STR1## in which, R.sup.1 and R.sup.2 are the same or different and each is hydrogen or C.sub.1 -C.sub.6 alkyl, or R.sup.1 and R.sup.2 together with the nitrogen atom to which they are attached form a heterocyclic ring which is unsubstituted or substituted and is a 5-membered or 6-membered N-heterocycle which optionally has a further heteroatom which is oxygen, nitrogen or sulfur; E is methylene; ring A is a unsubstituted or unsubstituted aryl ring, or a substituted or an unsubstituted heteroaryl ring; R.sup.3 is a C.sub.1 -C.sub.6 alkyl and R.sup.4 is hydrogen, or R.sup.3 and R.sup.4 together are a group of the formula --(CR.sup.a R.sup.b).sub.m --C(.dbd.Y)-- (IV), wherein each of R.sup.a and R.sup.b is hydrogen or C.sub.1 -C.sub.3 alkyl, provided that there are not more than three alkyl groups in the formula (IV), m is 1, 2, or 3, and Y is two hydrogens or an oxygen; or a pharmaceutically acceptable salt thereof; which process comprises reacting an acid of the formula (II) ##STR2## with an amine of the following formula (III) ##STR3##

Process for preparing analgesic compounds

Described herein are of formula (I): ##STR1## and pharmaceutically acceptable salts thereof are analgesics and anti-inflammatory agents as well having anti-ulcer and 5-lipoxygenase inhibitory activities.

Use of imidazopyrazole derivatives as analgesics and anti-inflammatory

Described herein are compounds of formula (I): ##STR1## �in which: R.sup.1 and R.sup.2 are hydrogen, optionally substituted alkyl, cycloalkyl, alkenyl, aralkyl, arylalkenyl, aryl, aromatic heterocyclic, cyano or halogen; R.sup.3 is hydrogen, optionally substituted alkyl, aralkyl or acyl; R.sup.4 and R.sup.5 are hydrogen, optionally substituted alkyl, cycloalkyl, alkenyl, aralkyl, arylalkenyl, aryl or aromatic heterocyclic!; and pharmaceutically acceptable salts thereof are analgesics and anti-inflammatory agents as well having anti-ulcer and 5-lipoxygenase inhibitory activities.

Use of imidazopyrazole derivatives as analgesics anti-inflammatory agents

Optically active thiomorpholine derivatives

Described herein are compounds of formula (I): ##STR1## and pharmaceutically acceptable salts thereof are analgesics and anti-inflammatory agents as well having anti-ulcer and 5-lipoxygenase inhibitory activities.

A process for preparing a compound of the formula (I): ##STR1## in which, R.sup.1 and R.sup.2 each represents hydrogen or C.sub.1 -C.sub.6 alkyl, or R.sup.1 and R.sup.2 together with the nitrogen atom to which they are attached form a heterocycle; E represents methylene, sulfur, oxygen or imino group optionally substituted with C.sub.1 -C.sub.6 alkyl or aralkyl; ring A is aryl or heteroaryl ring, optionally substituted; R.sup.3 is hydrogen or C.sub.1 -C.sub.6 alkyl and R.sup.4 is hydrogen or R.sup.3 and R.sup.4 together represent a group of formula (IV):

Analgesic compounds of the formula (I); ##STR1## in which, R.sup.1 and R.sup.2 each represents hydrogen or C.sub.1 -C.sub.6 alkyl, or R.sup.1 and R.sup.2 together with the nitrogen atom to which they are attached form a heterocycle; E represents oxygen or an imino group optionally substituted with C.sub.1 -C.sub.6 alkyl or aralkyl; ring A is an aryl or heteroaryl ring, optionally substituted; R.sup.3 is hydrogen or C.sub.1 -C.sub.6 alkyl and R.sup.4 is hydrogen or R.sup.3 and R.sup.4 together represent a group of formula (IV):

Analgesic compounds, their preparation, and pharmaceutical compositions

Compounds of formula (I): ##STR1## [in which: R.sup.1 and R.sup.2 are hydrogen, optionally substituted alkyl, cycloalkyl, alkenyl, aralkyl, arylalkenyl, aryl, aromatic heterocyclic, cyano or halogen; R.sup.3 is hydrogen, optionally substituted alkyl, aralkyl or acyl; R.sup.4 and R.sup.5 are hydrogen, optionally substituted alkyl, cycloalkyl, alkenyl, aralkyl, arylalkenyl, aryl or aromatic heterocyclic]; and pharmaceutically acceptable salts thereof are analgesics and anti-inflammatory agents as well having anti-ulcer and 5-lipoxygenase inhibitory activities.

Analgesic compounds of the formula (I): ##STR1## in which, R.sup.1 R.sup.2 each represents hydrogen or C.sub.1 -C.sub.6 alkyl, or R.sup.1 and R.sup.2 together with the nitrogen atom to which they are attached form a 5-6-membered N-heterocyclic ring optionally having a further O, N, or S heteroatom; E represents methylene; ring A is an unsubstituted or substituted benzene or naphthalene; R.sup.3 and R.sup.4 together represent a group of formula (IV):

Compounds of formula (I): ##STR1## and pharmaceutically acceptable salts thereof are analgesics and anti-inflammatory agents as well having anti-ulcer and 5-lipoxygenase inhibitory activities.

Analgesic compounds are of the general formula (I): ##STR1## in which, R.sup.1 and R.sup.2 each represents hydrogen or C.sub.1 -C.sub.6 alkyl, or R.sup.1 and R.sup.2 together with the nitrogen atom to which they are attached form a heterocycle; E represents methylene, sulfur, oxygen or imino group optionally substituted with C.sub.1 -C.sub.6 alkyl or aralkyl; ring A is aryl or heteroaryl ring, optionally substituted; R.sup.3 is hydrogen or C.sub.1 -C.sub.6 alkyl and R.sup.4 is hydrogen or R.sup.3 and R.sup.4 together represent a group of formula (IV):

Analgesic thiomorpholins their preparation, and pharmaceutical

Cycloalkylidenemethylphenylacetic acid derivatives of formula (I): ##STR1## (wherein R.sup.1 represents hydrogen or alkyl and n is an integer from 1 to 3) are prepared by reacting a benzaldehyde acid compound of formula (II): ##STR2## with an enamine derivative of formula (III): ##STR3## (wherein R.sup.2 and R.sup.3 are various organic groups) and then hydrolizing the product. The use of the acid of formula (II) rather than its corresponding ester enables the reaction to be effected with a good yield and under moderate and economical reaction conditions.

Process for preparing anti-inflammatory

4-(2-Oxo- or hydroxyimino-cycloalkan-1-ylmethyl)phenylacetic acid derivative and nontoxic pharmaceutically acceptable salt thereof are useful as an anti-inflammatory agent. The above 2-oxo-compound may be prepared by (a) hydrolyzing and decarboxylating 4-(1-alkoxycarbonyl-2-oxocycloalkan-1-ylmethyl)phenylacetic acid ester derivative or (b) reacting p-halomethylphenylacetic acid ester derivative with an enamine of cycloalkanone and hydrolyzing the resulting product. And further, the above 2-hydroxyimino-compound may be prepared by (c) reacting 4-(2-oxocycloalkan-1-ylmethyl)phenylacetic acid derivative (the product of process (a) or (b)) with hydroxylamine or (d) reacting a dilithium salt of cycloalkanone oxime with p-halomethyl- or p-sulfonyloxymethyl-phenylacetic acid ester derivative and hydrolyzing the resulting product.

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Tokyo, Japan

Kazuyuki Wachi