Yamanouchi Pharmaceutical Company Ltd.

Toshinari Tamura

Hidenori Iwamoto

Isao Yanagisawa

Shin-ichi Tsukamoto

Makoto Yoshida

Masuo Murakami

Kenichi Tomioka

Shinji Usuda

Yoshio Ishii

Hitoshi Nagaoka

Minoru Yamamoto

Masatomi Harada

Noriyoshi Inukai

Yasufumi Hirata

Masaaki Takeda

Tetsuya Shiozaki, Deceased

Hideya Matsuda

Osamu Hasegawa

Soichi Kagami

Tetsuya Shizaoki

Tokuichi Takagi

Tetsuya Shiozaki

Hydrochloride salts of heterocyclic spiro compounds are provided and can be represented by the following general formula: ##STR1## wherein A represents piperidine or N alkyl piperidine or N alkylene attached to a non adjacent piperidine ring carbon, X is S or O, Y is carbonyl, thiocarbonyl, methylene, R.sup.5 methylene, ##STR2## alk in which R.sup.1 to R.sub.3,R.sub.6,R.sub.7 are H or alkyl, R.sub.4 is H, alkyl, COOH, or ester, or --C alkyl, R.sub.5 is halo, OH,SH, O alkyl, S alkyl, O acyl or S acyl, and Z, and Z.sub.2 are O or S. The above compounds act upon muscarinic acetylcholine receptors, thereby activating the acetylcholine nervous functions in the central nervous system.

Hydrochloride salts of heterocyclic spiro compounds

Heterocyclic spiro compounds represented by the following general formula and salts thereof: ##STR1## wherein A represents piperidine or N alkyl piperidine or N alkylene attached to a non adjacent piperidine ring carbon, X is S or O, Y is carbonyl, thiocarbonyl, methylene, R.sup.5 methylene, ##STR2## in which R.sup.1 to R.sub.3, R.sub.6, R.sub.7 are H or alkyl, R.sub.4 is H, alkyl, --COOH, or ester, or ##STR3## R.sub.5 is halo, OH, SH, O alkyl, S alkyl, O acyl or S acyl, and Z.sub.1 and Z.sub.2 are O or S. The above compounds act upon muscarinic acetylcholine receptors, thereby activating the acetylcholine nervous functions in the central nervous system.

Heterocyclic spiro compounds and methods for preparing the same

Heterocyclic spiro compounds represented by the following general formula and salts thereof ##STR1## The above compounds act upon muscarinic acetylcholine receptors, thereby activating the acetylcholine nervous functions in the central nervous system.

Heterocyclic spiro compounds represented by the following general formula and salts thereof: ##STR1## The above compounds act upon muscarinic acetylcholine receptors, thereby activating the acetylcholine nervous functions in the central nervous system.

A novel crystal form of N.sup..alpha. -[[(S)-4-oxo-2-azetidinyl]-carbonyl]-L-histidyl-L-prolinamide is provided and a process for preparing such crystals. The crystals provided by the present invention are the dihydrate form of the compound which exhibits a specific X-ray powder diffraction pattern, infared absorption spectrum and thermogravimetry-differential scanning calorimetry. The compound in its novel crystal form is useful in the treatment of consciousness disturbances and memory disorders.

Crystalline form III of N.sup..alpha. -[[(S)-4-oxo-2-azetidinyl]-carbonyl]-

Substituted azetidinone compounds are provided which have the formula: ##STR1## wherein one of R.sup.1 and R.sup.2 represents a substituted lower alkyl group, an azido group, an amino group, a lower acylamino group, a mercapto group or a lower alkylthio group and the other represents a hydrogen group, or, both represent hydrogen atoms or lower alkyl groups; R.sup.3 represents a hydrogen atom or a group shown by formula: ##STR2## (wherein X represents ##STR3## (wherein R.sup.5 represents a hydrogen atom or a lower alkyl group) and Y represents a hydroxy group, a lower alkoxy group, an amino group, a mono- or di-lower alkylamino group); R.sup.4 represents a hydrogen atom, a substituted or unsubstituted lower alkyl group or a group shown by formula: --CH.sub.2 CO--A (wherein A represents an amino group or a group shown by formula: ##STR4## (wherein X and Y are as defined above), provided that when R.sup.1 and R.sup.2 are both hydrogen atoms, at least R.sup.4 represents a group other than a hydrogen atom and provided that either R.sup.3 or R.sup.4 represents a group other than a hydrogen atom. The compounds have strong CNS action.

CNS active substituted azetidinone compounds

A novel-4-substituted-2-azetidinone compound shown by the general formula ##STR1## and salts thereof. The compounds of this invention have a strong CNS activity and are useful for improving a disturbance of consciousness in schizophrenia, a head injury, etc., or improving hypobulia, memory loss, etc.

4-substituted-2-azetidinone compound

A novel 4-substituted-2-azetidinone compound shown by the general formula ##STR1## and salts thereof. The compounds of this invention have a strong CNS activity and are useful for improving a disturbance of consciousness in shizophrenia, a head injury, etc., or improving hypobulia, memory loss, etc.

4-substituted-2-azetidinone compound, process of producing the

A novel 4-substituted-2-azetidinone compound shown by the general formula ##STR1## and salts thereof. The compounds of this invention have a strong CNS activity and are useful for improving a disturbance of consciousness in schizophrenia, a head injury, etc., or improving hypobulia, memory loss, etc.

4-Substituted-2-azetidinone compound, process of producing the

Novel heterocyclic compounds shown by the formula ##STR1## wherein Het represents a 5-membered or 6-membered heterocyclic group which may have substituent(s); Z represents a sulfur atom or oxygen atom; X represents an oxygen atom or the unsubstituted or substituted imino group shown by N--R.sub.1 (wherein R.sub.1 is a hydrogen atom, a lower alkyl group, a cyano group, an unsubstituted or alkyl substituted carbamoyl group, an unsubstituted or lower alkyl substituted thiocarbamoyl group, or a lower alkanoylamino group); Y represents a hydrogen atom, a lower alkyl group which may have substituent(s), a cycloalkyl group of 3-6 carbon atoms, a lower alkenyl group, a lower alkynyl group, an aryl group which may have substituent(s), an aralkyl group which may have substituent(s), a hydroxyl group, a cyano group, a carbamoyl group, an amidino group, an alkanoyl group which may have been substituted by halogen atom(s), an alkanoylamino group, an arylcarbonylamino group, an alkylamino group, an arylamino group, an arylsulfamoyl group, a lower alkoxycarbamoyl group, or an oxamoylamino group; and m and n represent an integer of 1-3; when X is N--R.sub.1, said X and Y may combine with each other to form a 5-membered or 6-membered heterocyclic ring containing 2-3 nitrogen atoms which may have substituent(s), and the pharmacologically acceptable acid addition salts thereof. The compounds of this invention are useful as gastric acid secretion inhibitors.

Antisecretory imidazole amidine compounds, composition and method of use

Novel heterocyclic compounds shown by the formula ##STR1## wherein Het represents a 5-membered or 6-membered heterocyclic group which may have substituent(s); Z represents a sulfur atom or oxygen atom; X represents an oxygen atom or the unsubstituted or substituted imino group shown by N--R.sub.1 (wherein R.sub.1 is a hydrogen atom, a lower alkyl group, a cyano group, an unsubstituted or alkyl substituted carbamoyl group, an unsubstituted or lower alkyl substituted thiocarbamoyl group, or a lower alkanoylamino group); Y represents a hydrogen atom, a lower alkyl group which may have substituent(s), a cycloalkyl group of 3-6 carbon atoms, a lower alkenyl group, a lower alkynyl group, an aryl group which may have substituent(s), an aralkyl group which may have substituent(s), a hydroxyl group, a cyano group, a carbamoyl group, an amidino group, an alkanoyl group which may have been substituted by halogen atom(s),

Antisecretory heterocyclic amidine compounds

There are disclosed 20-alkoxy-16-alkyl-prostadienoic acid derivatives of the formula: ##STR1## wherein A represents ##STR2## R and R.sup.5, which may be the same or different, each represents a hydrogen atom or a lower alkyl group; and R.sup.1 and R.sup.4, which may be the same or different, each represents a lower alkyl group, and the pharmaceutically acceptable non-toxic salts thereof. These compounds have excellent pharmacological effects as prostaglandin E.sub.2 and prostaglandin F.sub.2.alpha..

20-Alkoxy-16-alkyl-prostadienoic acid derivatives

3,15-Dilower alkyl prostaglandin E.sub.2 derivatives and 3,15-dilower alkyl prostaglandin D.sub.2 derivatives are disclosed. These compounds have antigastric ulcer activity without undesirable side effects to intestinal organs.

Novel 3,15-dilower alkyl PGE.sub.2 derivatives

A 20-alkoxy-16-alkyl-prostadienoic acid derivative shown by the formula ##STR1## wherein A represents ##STR2## R and R.sup.5, which may be the same or different, each represents a hydrogen atom or a lower alkyl group; and R.sup.1 and R.sup.4, which may be the same or different, each represents a lower alkyl group, And the pharmacologically acceptable nontoxic salts thereof. The compounds have excellent effects as prostaglandin E.sub.2 and prostaglandin F.sub.2.alpha..

20-Alkoxy-16-alkyl prostadienoic acid derivatives

Novel prostaglandin derivatives are provided having the formula: ##STR1## wherein A represents ##STR2## one of R.sub.3 and R.sub.4 represents a hydrogen atom and the other of them represents a lower alkyl group; one of R.sub.5 and R.sub.6 represents a hydrogen atom and the other of them represents a hydroxyl group; and one of R.sub.7 and R.sub.8 represents a hydrogen atom and the other of them represents a lower alkyl group. The compounds of this invention have excellent effects as prostaglandin E.sub.2 and prostaglandin F.sub.2.sub..alpha..

Growing community of inventors

Saitama, Japan

Toshinari Tamura