Abstract: The invention relates to N-(trans-4-isopropylcyclohexylcarbonyl)-D-phenylalanine (nateglinide) in the novel crystalline form “G” and a process for the preparation thereof. A process for the preparation of chirally pure nateglinide by treating a lower alkyl ester thereof with a base to yield an alkali salt and liberating the product from said salt by proper addition of an acid, is also provided. Still another aspect of the invention is a process for the preparation of nateglinide in the crystalline form “H” from other crystalline modifications of nateglinide.

Abstract: The invention relates to N-(trans-4-isopropylcyclohexylcarbonyl)-D-phenylalanine (nateglinide) in the novel crystalline form “G” and a process for the preparation thereof. A process for the preparation of chirally pure nateglinide by treating a lower alkyl ester thereof with a base to yield an alkali salt and liberating the product from said salt by proper addition of an acid, is also provided. Still another aspect of the invention is a process for the preparation of nateglinide in the crystalline form “H” from other crystalline modifications of nateglinide.

Abstract: Process for the synthesis of high purity 2-substituted-1-(hydroxy-ethylidene)-1,1-bisphosphonic acid of formula (I), the salts and hydrates thereof—wherein the meaning of R is 3?-pyridyl or 2?-amino-ethylidene group—from compounds of formula (II)—wherein the meaning of R is as described above—or salts and hydrates thereof with phosphorous acid in the presence of methanesulfonic acid using phosphorus pentoxide as reagent and in given case the obtained acid is converted into a salt with base.

Abstract: The present invention provides a novel, industrially easily realisable and economically preferable process for production of pure 5-{2-[4-(1,2-benzisothiazol-3-yl)-1-piperazinyl]-ethyl}-6-chloro-1,3-dihydro-2H-indol-2-one i.e., ziprasidone hydrochloride shown in the reaction scheme (II), (III), (IV), (V) and (VI). According to the invention the intermediate compound 5-(2-bromoethyl)-6-chloro-1,3-dihydro-2H-indol-2-one of Formula (III) is produced from 5-(2-bromoacethyl)-6-chloro-1,3-dihydro-2H-indole-2-one of Formula (IV). The highly pure ziprasidone base of Formula (II) is obtained in the reaction of 3-piperazinyl-1,2-benzisothiazol of Formula (VI) with 5-(2-bromoethyl)-6-chloro-1,3-dihydro-2H-indol-2-one of Formula (III) in an organic solvent or organic solvent mixture.

Abstract: The present invention relates to a new process for the synthesis of high purity 3,5-diamino-6-(2,3-dichlorophenyl)-1,2,4-triazine of formula (I) using 2,3-dichlorobenzoyl cyanide and an aminoguanidine salt as starting materials. 2,3-dichlorobenzoyl cyanide is reacted with 1-2 mol equivalent of aminoguanidine salt in 3-6 mol equivalent of methanesulfonic acid, then the obtained adduct of formula (IV) is transformed without isolation into the product with magnesium oxide.

Abstract: The invention relates to N-(trans-4-isopropylcyclohexylcarbonyl)-D-phenylalanine (nateglinide) in the novel crystalline form “G” and a process for the preparation thereof. A process for the preparation of chirally pure nateglinide by treating a lower alkyl ester thereof with a base to yield an alkali salt and liberating the product from said salt by proper addition of an acid, is also provided. Still another aspect of the invention is a process for the preparation of nateglinide in the crystalline form “H” from other crystalline modifications of nateglinide.

Abstract: The present invention relates to a new process for the synthesis of high purity 3,5-diamino-6-(2,3-dichlorophenyl)-1,2,4-triazine of formula (I) using 2,3-dichlorobenzoyl cyanide and an aminoguanidine salt as starting materials. 2,3-dichlorobenzoyl cyanide is reacted with 1-2 mol equivalent of aminoguanidine salt in 3-6 mol equivalent of methanesulfonic acid, then the obtained adduct of formula (IV) is transformed without isolation into the product with magnesium oxide. In given case the obtained crude product can be recrystallized from a proper organic solvent.

Abstract: Process for the synthesis of high purity 2-substituted-1-(hydroxy-ethylidene)-1,1-bisphosphonic acid of formula (I), the salts and hydrates thereof—wherein the meaning of R is 3?-pyridyl or 2?-amino-ethylidene group—from compounds of formula (II)—wherein the meaning of R is as described above—or salts and hydrates thereof with phosphorous acid in the presence of methanesulfonic acid using phosphorus pentoxide as reagent and in given case the obtained acid is converted into a salt with base.

Abstract: The invention relates to novel 2-oxo-1-oxa-8-azaspiro[4,5]decane derivatives of the formula (I), ##STR1## wherein X means oxygen or an >NR group, whereinR stands for hydrogen; a C.sub.1-12 alkyl; C.sub.3-6 cycloalkyl; carbocyclic C.sub.6-10 aryl or carbocyclic C.sub.6-10 aryl-C.sub.1-4 alkyl group, the two latter two substituents optionally substituted on their aromatic moiety by one or more, same or different halogen, one or more C.sub.1-4 alkyl, C.sub.1-4 alkoxy or trihalomethyl group; or a tosyl group;R.sup.1 and R.sup.2 together represent a methylene group or, when X stands for an >NR group wherein R is as defined above, one of R.sup.1 and R.sup.2 m may represent a hydroxyl group and the other one is a methyl group; andR.sup.3 means hydrogen, benzyl, (C.sub.1-4 alkoxy)carbonyl, phenoxycarbonyl, benzyloxycarbonyl, formyl, piperidin-1-ylcarbonyl, morpholin-4-ylcarbonyl, 4-methylpiperazin-1-ylcarbonyl, 4-(2-hydroxethyl)piperazin-1-ylcarbonyl, 2-chloro-3-nicotinoylcarbamoyl or C.sub.

Abstract: The invention relates to novel, therapeutically active 4-methylene-2-oxo-8-azaspiro[4,5]decane derivatives of the compound, ##STR1## wherein X means oxygen or an >NR group, whereinR stands for hydrogen, C.sub.1-12 alkyl, C.sub.3-6 cycloalkyl, carbocyclic C.sub.6-10 aryl or carbocyclic C.sub.6-10 arylC.sub.1-4 alkyl group, the latter two being optionally substituted on their aromatic moiety by one or more, same or different halogen(s) or one or more C.sub.1-4 alkyl group(s) or by one or more C.sub.1-4 alkoxy group(s);R.sup.3 and R.sup.4, which are the same or different, represent hydrogen, one or more halogen(s), C.sub.1-4 alkyl, C.sub.1-4 alkoxy, trihalomethyl group or hydroxyl group optionally esterified by a C.sub.1-4 alkanoic acid; andis 1 or 2,their isomers, solvates, hydrates, acid addition and quaternary ammonium salts.

Abstract: The invention relates to, therapeutically active 2-oxo-3,8-diazaspiro[4,5]decane derivatives (I), ##STR1## wherein R means hydrogen, a C.sub.1-12 alkyl, C.sub.3-6 cycloalkyl, carbocyclic C.sub.6-10 aryl or carbocyclic C.sub.6-10 aryl-C.sub.1-4 alkyl group, the latter two optionally being substituted on their aromatic moiety by one or more, same or different halogen(s) or one or more C.sub.1-4 alkyl or C.sub.1-4 alkoxy group(s);one of R.sup.1 and R.sup.2 stands for a hydroxyl group whereas the other means a methyl gorup;R.sup.3 and R.sup.4, which are the same or different, represent hydrogen, one or more halogen(s), C.sub.1-4 alkyl, C.sub.1-4 alkoxy, trihalomethyl group or a hydroxyl group optionally esterified by a C.sub.1-4 alkanoic acid; andn is 1 or 2,their isomers, solvates, hydrates, acid addition and quaternary ammonium salts.

Abstract: The invention relates to novel compounds 1-oxa-2-oxo-8- of the formula (I), ##STR1## wherein X means oxygen or an >NR group, whereinR stands for hydrogen, a C.sub.1-12 alkyl, C.sub.3-6 cycloalkyl, carbocyclic C.sub.6-10 aryl or carbocyclic C.sub.6-10 aryl-C.sub.10-4 alkyl group, the latter two groups are optionally substituted on their aromatic moiety by one or more, same or different halogen(s), one or more C.sub.1-4 alkyl or C.sub.1-4 alkoxy group(s);R.sup.1 and R.sup.2 together represent a methylene group or, when X stands for an >NR group, wherein R is as defined above, one of R.sup.1 and R.sup.2 may represent a hydroxyl group whereas the other is a methyl group;R.sup.3 stands for hydrogen or a phenyl group optionally substituted by one or more halogen(s), one or more C.sub.1-4 alkyl or C.sub.1-4 alkoxy or hydroxyl group(s);R.sup.4 means hydrogen, one or more halogen(s), C.sub.1-4 alkyl, C.sub.

Abstract: The invention relates to novel 1,4-disubstituted piperazine derivatives of the general formula (I), pharmaceutically acceptable acid addition and quaternary ammonium salts thereof, pharmaceutical compositions containing them and a process for their preparation. In the general formula (I) ##STR1## R.sub.1, R.sub.2, R.sub.3 and R.sub.4 are the same or different and stand for hydrogen or halogen or a trihalomethyl, lower alkyl, lower alkoxy, nitro, hydroxyl, aralkyloxy or an 1-(2-propenyl-4-piperazinyl) group;R.sub.5 stands for hydrogen or a C.sub.1-4 alkyl group;R.sub.6 represents a C.sub.3-6 alkyl, alkenyl, alkynyl group or a ##STR2## group, wherein R.sub.7 means a C.sub.2-5 alkyl, alkenyl or alkinyl group; andis 2 or 3,with the provisos that:R.sub.6 is different from isopropyl, n-butyl and isobutyl group when R.sub.2, R.sub.3, R.sub.4 and R.sub.5 stand for hydrogen, R.sub.1 means 2-chloro and n is 2;R.sub.6 is different from isopropyl group when R.sub.2, R.sub.3, R.sub.4 and R.sub.5 stand for hydrogen, R.sub.

Abstract: The invention relates to novel benzhydryl-piperazine derivatives of the general formula (I) and the acid addition and quaternary ammonium salts thereof, pharmaceutical compositions containing them and a process for their preparation. In the general formula (I) ##STR1## R.sub.1, R.sub.2, R.sub.3, R.sub.4 and R.sub.5 are the same or different and stand for hydrogen or halogen, or a trihalomethyl, C.sub.1-4 alkyl or C.sub.1-4 alkoxy group;R.sub.6 means hydrogen or a C.sub.1-4 alkyl group; andn is 2 or 3.The compounds of the general formula (I) are useful for treating diseases arising from a decrease in the dopamine level, i.e. from a hypofunction of the dopaminergic system, and have low toxicity.

Abstract: The invention relates to fodder additives comprising a compound inducing the microsomal enzyme system of the liver, preferably a compound of the formula (I) ##STR1## wherein R.sub.1, R.sub.2 and R.sub.3 are identical or different and stand for hydrogen, halogen, trihalomethyl, or alkyl or alkoxy each containing from 1 to 6 carbon atoms;R.sub.4 is phenyl, dialkylaminocarbonyl or alkoxycarbonyl having from 1 to 6 carbon atoms in the alkyl and alkoxy moieties, respectively;R.sub.5 is hydrogen or methyl, or together with R.sub.4 and the adjacent nitrogen atom forms a hetero-ring having up to 8 members;n is 1, 2, 3, 4 or 5;m is 0 or 1;a is 0 or 1,with the proviso that if a=0, R.sub.1 is trihalomethyl and R.sub.2 and R.sub.3 both are hydrogen, preferably in amount of 0.5 to 99% by weight, in an admixture with conventional carriers and/or additives and optionally at least one further active ingredient conventionally used in the animal husbandry.

Abstract: The invention relates to new aminoethoxybenzylalcohol derivatives of the formula (I) ##STR1## wherein R.sub.1 is hydrogen, halogen, trihalomethyl, alkyl having from one to 4 carbon atoms or alkoxy having from one to 4 carbon atoms;R.sub.2 is halogen, trihalomethyl, or alkoxy having from one to 4 carbon atoms;R.sub.3 and R.sub.4 stand for methyl or together with the adjacent nitrogen form an up to 8-membered ring optionally containing oxygen,and acid addition or quaternary ammonium salts thereof.The compounds of formula (I) are pharmacologically active, thus show enzyme-inducing effect. The pharmaceutical compositions containing them as active ingredient are also within the scope of the invention.

Abstract: The invention relates to new dialkylaminoalkoxybenzylalcohol derivatives of the formula (I) ##STR1## wherein R.sub.1 is hydrogen, halogen, trihalomethyl, alkyl having from one to 4 carbon atoms or alkoxy having from one to 4 carbon atoms;R.sub.2 is halogen, trihalomethyl, alkyl having from one to 4 carbon atoms or alkoxy having from one to 4 carbon atoms;R.sub.3 and R.sub.4 independently stand for an alkyl group having from 3 to 5 carbon atoms; andn is 2, 3, 4 or 5,and acid addition and quanernary ammonium salts thereof.According to another aspect of the invention there are provided processes for the preparation of these compounds.The new compounds provided by the invention are pharmaceutically active, in particular, they are suitable for the treatment of acute ethanolic intoxication. Pharmaceutical compositions containing them as active ingredient are another aspect of the invention.

Abstract: The invention relates to new aminopropanol derivatives of the formula (I) ##STR1## wherein R.sub.1 is halogen, trihalomethyl, alkoxy having from one to 3 carbon atoms or alkyl having from one to 3 carbon atoms,R.sub.2 is alkyl having from one to 3 carbon atoms, andR.sub.3 is cycloalkyl having from 3 to 6 carbon atoms, orR.sub.2 and R.sub.3 together with the nitrogen they are attached to form an up to 8 membered ring optionally containing oxygen or a further nitrogen as an additional hetero atom, and optionally substituted with alkyl having from one to 4 carbon atoms or benzyl,and acid addition and quaternary ammonium salts thereof.According to another aspect of the invention there are provided processes for the preparation of these compounds.The new compounds are suitable for the treatment of acute ethanolic intoxication. Pharmaceutical compositions containing them are also within the scope of the invention.

Abstract: The invention relates to new 1,1-diphenylpropan-1-ol derivatives of the formula (I) ##STR1## wherein R.sub.1 and R.sub.2 independently represent hydrogen, halogen, trihalomethyl, alkyl having from one to 4 carbon atoms or alkoxy having from one to 4 carbon atoms,R.sub.3 is halogen, trihalomethyl, alkyl having from one to 5 carbon atoms or alkoxy having from one to 5 carbon atoms,R.sub.4 is phenyl optionally substituted by one or more identical or different substituents selected from the group of halogen, trihalomethyl, alkyl, alkoxy, cyano, nitro, amino, alkylamino, dialkylamino, hydroxyl, carboxyl or substituted carboxyl; dialkylaminocarbonyl or alkoxycarbonyl containing from one to 4 carbon atoms in the alkyl and alkoxy moieties, respectively,n is 1, 2, 3, 4, or 5.According to another aspect of the invention there are provided processes for the preparation of the compounds of formula (I).

Abstract: The invention relates to the preparation of new diethylaminoalkoxybenzhydrol derivatives of the formula (I) ##STR1## wherein R.sub.1 is hydrogen, halogen, trihalomethyl, alkyl having from one to 4 carbon atoms or alkoxy having from one to 4 carbon atoms,R.sub.2 is halogen, trihalomethyl, or alkoxy having from one to 4 carbon atoms, andn is 1, 2, 3 or 4,and acid addition and quaternary ammonium salts thereof.According to another aspect of the invention, there are provided new compounds of the formula (I), and acid addition and quaternary salts thereof. The compounds can be used for the treatment of acute ethanolic intoxication and depression syndromes. Pharmaceutical compositions containing them as active ingredient are also within the scope of the invention.