Roussel Uclaf

Hoechst Marion Roussel

Other

Ipsen Pharma S.a.s.

Societe De Conseils De Recherches Et D'applications Scientifiques

Christian Diolez

Francis Brion

Jean Buendia

Michel Vivat

Alain Mazurie

Edmond Toromanoff

Didier Pronine

Christian Marie

Bernadette Chappert

Michel Middendorp

Alain Rolland

Barry Victor Lloyd Potter

Lok Wai Lawrence Woo

Gérard Coquerel

Eric Manginot

Rene Peters

Marc Veyrat

Francis Diancourt

Damien Martins

Delphine Delahaye

The present invention relates to a solid pharmaceutical composition including the active principle 6-oxo-6,7,8,9,10,11-hexahydrocyclohepta[c]chromen-3-yl sulfamate. The present invention also relates to polymorphs of the 6-oxo-6,7,8,9,10,11-hexahydrocyclohepta[c]chromen-3-yl sulfamate compound.

Solid pharmaceutical composition containing 6-oxo-6,7,8,9,10,11-hexahydrocyclohepta (C)chromen-3-yl  sulfamate and polymorphs thereof

The present application relates to a new process for the asymmetric production of 3-(pyridin-4-yl)-3-hydroxy-pentanoic acid derivatives, which are useful intermediates in the manufacture of compounds that are known to show antiproliferative activity.

Processes for the production of useful intermediates

Novel tricyclic compounds of formula I as defined in the specification, a process for their preparation and their use for the preparation of optically active or racemic colchicine and thiocolchicine derivatives.

Tricyclic compounds

A process for the production of a compound of the formula ##STR1## wherein R.sub.1 is acyl of 1 to 8 carbon atoms,. The compound is formed by the reduction of an intermediary to form an alcohol, epoxidation and hydrolyzation of the alcohol to form a compound of formula ##STR2## followed by the acylation of the hydroxy functions and the elimination of the 17.alpha.-substituent.

Process for the production of 21-acyloxy-4,9

The novel intermediates of the formula ##STR1## wherein L, K and M are as defined in the specification which are useful intermediates for the preparation of .DELTA..sup.4,9(11),16 -pregnatriene-3-ones.

Intermediates for the preparation of .DELTA..sup.4,9(11),17(20)

A compound having a formula ##STR1## in which K is defined as above, C--P being CH.sub.2 or --C.dbd.CH.sub.2 or ##STR2## and J is --SO.sub.2 R.sub.2, or C--P is C.dbd.O and J is --CH.sub.2 Hal.sub.2, or C--P is --CH SO.sub.2 R.sub.2 and J is CO.sub.2 R or Hal.sub.1, R.sub.2 is methyl, phenyl, tolyl or xylyl, R is alkyl of 1 to 6 carbon atoms, aralkyl of 7 to 15 is carbon atoms or a silylated remainder selected from the group consisting of trimethylsilyl, tert.-butyldimethylsilyl, triphenylsilyl and diphenyltert.-butylsilyl, Hal.sub.1 is halogen, Hal.sub.2 is chlorine, bromine or iodine and the wavy lines symbolize any one of the isomer forms or their mixtures which are intermediates.

A process for the preparation of a compound of the formula ##STR1## wherein R and R' and the A and B are as defined in the specification. ##STR2## K is selected from the group consisting of ##STR3## n is 2 or 3 and the dotted lined is an optional bond.

Preparation of 11-keto steroids

A compound of the formula ##STR1## wherein K is a protective group of the oxo of the formula ##STR2## wherein n is 2 or 3 and L is a 11.beta.-hydroxy, the dotted line in the 11-position is not a bond and X is chlorine, bromine or iodine which avoids an 11-hydroxylation step in the preparation of hydrocortisone.

Process for the preparation of hydrocortisone

A process for the preparation of a compound of the formula ##STR1## wherein R.sub.1 is acyl of an organic carboxylic acid of 1 to 8 carbon atoms useful as intermediates for synthesis of therapeutically active steroids.

Process for preparation of .DELTA..sup.4,9(11),16

A compound of the formula ##STR1## wherein K represents a protective group of the oxo of the formula ##STR2## wherein n is 2 or 3, and M is chlorine, bromine, or ##STR3## wherein R.sub.a and R.sub.b are individually selected from the group consisting of hydrogen, --OH, and alkyl and alkoxy of 1 to 4 carbon atoms and R is selected from the group consisting of alkyl of 1 to 6 carbon atoms, aralkyl of 7 to 15 carbon atoms, trialkyl silyl triphenyl silyl and diphenyl alkyl silyl.

Novel compounds of the formula ##STR1## wherein either K' is oxygen or a K, a protective group of the oxo of the formula ##STR2## wherein n is 2 or 3, the 17-position dotted line is a bond, R.sub.a and R.sub.b are individually selected from the group consisting of hydrogen, hydroxy, alkyl and alkoxy of 1 to 4 carbon atoms or K' is an oxygen, the 17-position dotted line is an epoxy and R.sub.a and R.sub.b have the meaning indicated above which are useful intermediates for the preparation of hydrocortisone.

Intermediate steroid compounds

A process for the preparation of a compound of the formula ##STR1## wherein R.sub.1 is acyl of 1 to 8 carbon atoms, by reducing an intermediary to form an alcohol, oxidizing the alcohol to form an aidehyde, which is subjected to the action of an acyloxylation agent.

Process for preparing 21 acyloxy-.DELTA.4,9(11),16 pregnatrienes

A process for the production of a compound of the formula ##STR1## wherein R is an acyl group of 1 to 8 carbon atoms. The compound is formed through an intermediate compound of the formula ##STR2## wherein R.sub.1 is selected from the group consisting of methyl, phenyl, tolyl, and xylyl and wherein K is a protective group selected from the group consisting of ##STR3## in which n is 2 or 3 and the wavy line means that the group SO.sub.2 --R.sub.1 may have either isomeric form or are mixtures thereof.

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Palaiseau, France

Christian Diolez