Rhone-poulenc Sante

Rhone-poulenc Industries

Rhone-poulenc Rorer S.a.

Claude James

Daniel Farge

Jean-Louis Fabre

Jean Bouchaudon

Daniel Lave

Jean-Claude Aloup

Francoise Soler

Michel Evers

Gilles Dutruc-Rosset

Daniel Reisdorf

Rodolphe Margraff

Yves Ribeill

Francois Audiau

Norbert Dereu

Francois Debarre

Jean-Christophe Gueguen

Jean C Aloup

Christele Poujade

Romaine Bouboutou

The present invention relates to new lupane dervivatives of the general formula: ##STR1## to their salts, to their preparation and to the pharmaceutical compositions which contain them.

Lupane derivatives, their preparation and the pharmaceutical

Pharmaceutical compositions are disclosed. They are useful for the treatment of medical conditions associated with the effects of glutamate, comprise as active principle, at least one compound of formula: ##STR1## or a salt thereof, in which either R.sub.1 represents polyfluoroalkoxy, 2,2,2-trifluoroethyl, pentafluoroethyl, tert-butyl, trimethylsilyl or trifluoromethylthio and R.sub.2 and R.sub.3 represent hydrogen,

Pharmaceutical compositions, 2-benzothiazolamine derivatives, and their

Process for preparing (1R,2R)-2-(3-pyridyl)tetrahydrothiopyran-2-carbothioamide 1-oxides of general formula: ##STR1## (R.sub.1 =alkyl containing 1 to 4 carbon atoms), by the action of an alkyl isothiocyanate on the 1R,2R and 1R,2S sulphoxides of formulae: ##STR2## employed alone or mixed, the (1R,2R)-2-(3-pyridyl)tetrahydrothiopyran-2-carbothioamide 1-oxides thereby obtained and pharmaceutical compositions containing them. (1R,2R)-2-(3-Pyridyl)tetrahydrothiopyran-2-carbothioamide 1-oxides are especially useful as antihypertensives.

Process for preparing

New derivatives of formula (I) in which R.sub.1 =H, halogen, alkyl, alkyloxy, CF.sub.3, NH.sub.2, alkylamino, dialkylamino, OH, CH, phenyl or phenoxy, Ar=phenyl, naphthyl, pyridyl, quinolyl, isoquinolyl, thienyl, thieno[2,3-b]thienyl or thieno[3,2-b]thienyl (these groups optionally substituted with halogen, alkyl, alkyloxy, CF.sub.3, NH.sub.2, alkylamino, dialkylamino, OH or CN), p=0, 1 or 2, and

1H, 3H-pyrrolo[1,2-c]thiazole-7-carboxamide derivatives and

Tripeptides of the general formula: ##STR1## wherein the symbols R, which may be the same or different represent hydrogen or a fatty acid residue (at least one of them representing a fatty acid residue), R.sub.1 represents hydroxy, amino or alkoxy and R.sub.2 and R.sub.3, which may be the same or different, represent hydrogen, carboxy, carbamoyl or alkoxycarbonyl radical (with the proviso that R.sub.2 and R.sub.3 cannot simultaneously represent a hydrogen atom), the alanine moiety being in the L form, the glutamic acid moiety being in the D form, the lysine moiety (when R.sub.2 or R.sub.3 =a hydrogen atom) being in the L form and the 2,6-diaminopimelic acid moiety or its derivatives (when R.sub.2 and/or R.sub.3 =carboxy, carbamoyl or alkoxycarbonyl) being in the D,D, L,L, D,D/L,L (racemic) or D,L (meso) form, and salts thereof, possess immunological adjuvant and immunostimulant activity.

Peptides, their preparation and compositions containing them

N.sup.6 -Benzyloxycarbonyl-2,6-diaminopimelamic acid in L,L or D,D or racemic form is prepared by amidation of O.sup.1 -p-nitrobenzyl-N.sup.2 -benzyloxycarbonyl-2,6-diaminopimelic acid in L,L or D,D or racemic form.

Process for the preparation of N.sup.6

A compound of the general formula I: ##STR1## in which Ar is a pyridyl, quinolinyl, isoquinolinyl, naphthyridinyl, pyrimidyl, quinazolinyl, thiazolyl, benzothiazolyl, imidazolyl, benzimidazolyl, oxazolyl, benzoxazolyl, thienyl, benzothienyl or naphthyl group; optionally substituted with one or more halogen or alkyl, alkyloxy, alkylthio, trifluoromethyl, amino, alkylamino, dialkylamino, hydroxy, cyano, alkylsulphinyl, alkylsulphonyl, sulphamido, alkylsulphamido, dialkylsulphamido, alkylcarbonyl, benzoyl, alkyloxycarbonyl, carboxy, phenoxycarbonyl, alkylcabonyloxy, benzoyloxy, alkylcarbonylamino, benzamido, phenyl, benzyl, phenoxy or phenylthio group, provided that (i) when Ar is a pyridyl group, the pyridyl group must be substituted, (ii) an alkyl moiety contains 1 to 4 straight- or branched chain carbon atoms; (iii) a phenyl moiety may be unsubstituted or substituted with one or more halogen or alkyl, alkyloxy, alkylthio, trifluoromethyl, amino, alkylamino, dialkylamino, hydroxy, cyano, phenyl or benzyl group in separate enantiomeric form or mixtures thereof, or a pharmaceutically acceptable salt thereof is useful in the treatment of all pathological conditions in which PAF-acether may be implicated directly or indirectly.

1H, 3H-pyrrolo (1,2-C) thiazole derivatives and pharmaceutical

A compound of the general formula I; ##STR1## in which R is hydrogen or a halogen or an alkyl, alkyloxy, alkylthio, trifluoromethyl, amino, alkylamino, dialkylamino, hydroxy, cyano, carboxy, alkylsulphinyl, alkylsulphonyl, sulphamido, alkylsulphamido, dialkylsulphamido, carbamoyl, alkylcarbamoyl, dialkylcarbamoyl, phenylcarbamoyl, diphenylcarbamoyl, pyridylcarbamoyl, dipyridylcarbamoyl, benzyl, alkylcarbonyl, benzoyl, alkyloxycarbonyl, phenoxycarbonyl, alkylcarbonyloxy, benzoyloxy, alkylcarbonylamino, benzamido, phenyl, phenoxy or phenylthio group, X is oxygen or sulphur or an imino, alkylimino, phenylimino, benzylimino, sulphinyl, sulphonyl, carbonyl, carbonylmethylene, methylenecarbonyl, carbonylvinylene or vinylenecarbonyl group, or X represents a valency bond or a straight-chain alkylene group containing 1 to 4 carbon atoms and Ar is a phenyl, naphthyl, pyridyl, quinolinyl, isoquinolinyl, thienyl, benzothienyl, thieno[3,2-b]thien-2-yl or thieno[2,3-b]thien-2-yl group, it being possible for the group Ar to be unsubstituted or substituted with one or more halogen or alkyl, alkyloxy, alkylthio, trifluoromethyl, amino, alkylamino, dialkylamino, hydroxy, cyano, carboxy, alkylsulphinyl, alkylsulphonyl, sulphamido, alkylsulphamido, dialkylsulphamido, carbamoyl, alkylcarbamoyl, dialkylcarbamoyl, phenylcarbamoyl, diphenylcarbamoyl, pyridylcarbamoyl, dipyridylcarbamoyl, benzyl, alkylcarbonyl, benzoyl, alkyloxycarbonyl, phenoxycarbonyl, alkylcarbonyloxy, benzoyloxy, alkylcarbonylamino or benzamido group; each alkyl moiety containing 1 to 4 straight- or branched-chain carbon atoms; the compound being in separate enantiomeric form or mixtures thereof or a pharmaceutically acceptable salt thereof is useful in the treatment of all the pathological conditions in which PAF-acether may be directly or indirectly implicated.

1H,3H-pyrrol[1,2-c]thiazole derivatives and pharmaceutical compositions

Thioformamide derivatives of the formula: ##STR1## wherein R is hydrogen or alkyl (1 to 4 C), Het is pyridin-3-yl[optionally substituted by alkyl (1 to 4 C) or a halogen], quinolin-3-yl, pyridazin-4-yl, pyrimidin-5-yl, thiazol-5-yl, thieno[2,3-b]pyridin-5-yl or thieno[3,2-b]pyridin-6-yl, and Y is a valency bond or a methylene radical, are new compounds, which are particularly useful as antihypertensive agents.

Certain N-alkyl-2-[(quinolin-3-yl)-tetrahydro-pyran or

Tetrapeptides and pentapeptides of the formula: ##STR1## wherein R represents hydrogen or a fatty acid residue, R.sub.1 represents hydroxy, amino, alkoxy of 1 to 4 carbon atoms, optionally substituted by phenyl or nitrophenyl, one of R.sub.2 and R.sub.4 represents hydrogen, carboxy, carbamoyl, alkoxycarbonyl of 2 to 5 carbon atoms, optionally substituted by phenyl or nitrophenyl, or a N-carbonylglycine or N-carbonyl-D-alanine radical optionally esterified by alkyl of 1 to 4 carbon atoms (which is optionally substituted by phenyl or nitrophenyl) and the other symbol represents hydrogen, carboxy, carbamoyl, or alkoxycarbonyl fof 2 to 5 carbon atoms, optionally substituted by phenyl or nitrophenyl, and R.sub.3 represents hydrogen, a fatty acid residue or a glycyl or D-alanyl moiety in which the amine group is optionally substituted by a fatty acid residue, it being understood that R.sub.2 and R.sub.4 cannot simutaneously represent hydrogen, that at least one of R.sub.2, R.sub.3 and R.sub.4 represents a glycyl or D-alanyl moiety, that at least one of R and R.sub.3 represents or contains a fatty acid residue, and that the alanine moiety is in the L form, the glutamic acid moiety or its derivatives are in the D form, the lysine moiety or its derivatives, when one of the symbols R.sub.2 and R.sub.4 represents a hydrogen atom, are in the L form, and the 2,6-diaminopimelic acid moiety or fits derivatives, when R.sub.2 and R.sub.4 represent a carboxy, carbamoyl or alkoxycarbonyl radical, are in the D,D L,L,D,D/L,L (racemic) or D,L (meso) form, and salts thereof possess immunostimulant activity.

Tetrapeptides and pentapeptides, their preparation and compositions

The invention provides novel pyrrole derivatives of formula: ##STR1## in which R'=H, alkyl or phenyl optionally substituted by halogen, alkyl, alkyloxy or alkylthio, Z=0 or S, p=0 or 1, and

Anti-thrombotic ortho-condensed pyrrole derivatives, compositions, and

Thioformamide derivatives of formula: ##STR1## in which R is hydrogen or alkyl (1 to 4 C), R.sub.1 is alkyl (1 to 4 C), and X denotes sulphur or oxygen and Y is sulphur, oxygen, methylene radical, or, when X is oxygen, a valency bond, are inhibitors of gastric secretion and therefore useful in the treatment of gastric ulcers. They may be made by reaction of an amine R--NH.sub.2 with a corresponding thioester or, when R is alkyl, by reaction of an alkyl isothiocyanate with the product of reacting a base with a compound of formula: ##STR2##

Thioformamide derivatives and use in inhibiting gastric secretion

Antithrombotics of the formula ##STR1## in which A=S, SO or SO.sub.2, R.sub.3 =H, alkyl or substituted or unsubstituted phenyl, X=O, S, NH or variously substituted nitrogen, p is 0 or 1 and y=H, NH.sub.2, or various substituted amines.

Pyrrolo[1,2-c]-1,3-thiazines

Thioformamide derivatives of the formula: ##STR1## wherein R is hydrogen or alkyl (1 to 4 C), Het is pyridin-3-yl [optionally substituted by alkyl (1 to 4 C) or a halogen], quinolin-3-yl, pyridazin-4-yl, pyrimidin-5-yl, thiazol-5-yl, thieno[2,3-b]pyridin-5-yl or thieno[3,2-b]pyridin-6-yl, and Y is a valency bond or a methylene radical, are new compounds, which are particularly useful as antihypertensive agents.

Certain N-lower-alkyl-2-(pyridin-3yl)-tetrahydrothiophene or

Pyrrolidine derivatives of the formula: ##STR1## wherein X represents an oxygen or sulphur atom, R represents a hydrogen atom or an alkyl radical, R.sub.o represents a hydrogen atom, an alkyl radical or a phenyl radical optionally substituted by a halogen atom or by an alkyl, alkoxy, alkylthio or nitro radical, A represents a nitrogen atom or a radical .dbd.CH--, the symbol Y represents a hydrogen or halogen atom or an alkyl, alkoxy, alkylthio, alkylcarbonyl, nitro, amino, alkylcarbonylamino, alkylamino, dialkylamino, alkylsulphinyl, alkylsulphonyl, alkoxycarbonyl, cyano, trifluoromethyl, hydroxy, mercapto, alkylcarbonyloxy or alkylcarbonylthio radical, n represents zero or 1, and p represents 1, 2 or 3, it being understood that the alkyl and alkoxy radicals, and alkyl and alkoxy moieties of any of the aforementioned groups, contain from 1 to 4 carbon atoms are new therapeutically useful compounds, more particularly useful as antidepressants.

Growing community of inventors

Paris, France

Claude James