Merrell Dow Pharmaceuticals

The United States of America, As Represented by the Secretary, Department of Health and Human Services

Spirogen Limited

Midwest Research Institute

Starks Associates Inc.

Merrell Pharmaceuticals, Inc.

Alchem Laboratories Corporation

Aventis Pharma Limited

Creemer, Laura J.

Liu, Paul S.

Anzeveno, Peter B.

Daniel, John K.

Paul S Liu

Sai P Sunkara

Barry L Rhinehart

Philip Wilson Howard

David Edwin Thurston

B Rao Vishnuvajjala

Kenneth M Snader

John K Daniel

Mohinder S Kang

Gregory Turner

Luke Y Hsiao

Peter Biagio Anzeveno

Stephen John Gregson

Terry L Bowlin

A Stanley Tyms

Laura J Creemer

Sergiy M Denysenko

Debra L Taylor

Guangfei Huang

Roland S Rogers

Peter B Anzeveno

B Rao Vishnuvaijala

Disclosed is a process for preparing (Z)-endoxifen, comprising (i) recrystallizing an input crystalline solid comprising a mixture of (Z)-endoxifen (1) and (E)-endoxifen (2) from a first solvent to provide a first crystalline solid and a first mother liquor, wherein the first mother liquor has a ratio of (1) to (2) at least 1.3 times greater than the ratio in the input crystalline solid (1) and (2); (ii) recrystallizing a solid produced by concentrating the first mother liquor, or by removal of the first solvent from the first mother liquor, from a second solvent to give a second crystalline solid and a second mother liquor; (iii) optionally recrystallizing the second crystalline solid from the second solvent one to five additional times to give a third crystalline solid; wherein the third crystalline solid has a ratio of (Z)-endoxifen (1) to (E)-endoxifen (2) greater than 20:1. 

Process for preparing Z-endoxifen of high purity

Disclosed are compounds of Formula I wherein X, Y, R-R, T, T, Z, and p are as described herein; a pharmaceutical composition comprising a compound of Formula I and a carrier; a method of inhibiting growth of a cell, which method comprises administering in an amount effective to inhibit growth a compound of Formula I; a method of treating cancer in a mammal, which method comprises administering in an amount effective to treat cancer a compound of Formula I; a method of treating a viral, parasitic, or bacterial infection of a cell, which method comprises administering in an amount effective to treat a viral, parasitic, or bacterial infection a compound of Formula I; and a method of preparing a compound of Formula I as described herein.

Pyrrolobenzodiazepine derivatives, compositions comprising the same and methods related thereto

Disclosed are compounds of Formula (I) wherein X, Y, Ri-R, T, T, Z, and p are as described herein; a pharmaceutical composition comprising a compound of Formula (I) and a carrier; a method of inhibiting growth of a cell, which method comprises administering in an amount effective to inhibit growth a compound of Formula (I); a method of treating cancer in a mammal, which method comprises administering in an amount effective to treat cancer a compound of Formula (I); a method of treating a viral, parasitic, or bacterial infection of a cell, which method comprises administering in an amount effective to treat a viral, parasitic, or bacterial infection a compound of Formula (I); and a method of preparing a compound of Formula (I) as described herein. 

A compound of formula I: or solvate thereof, wherein n is 1 to 10, and M and M' are independently selected from monovalent pharmaceutically acceptable cations, or together represent a divalent pharmaceutically acceptable cation.

Pyrrolobenzodiazepines

A method for inhibiting the formation of glucose by the administration of castanospermine is described herein. In addition, a new process for the isolation of castanospermine from Castanospermum australe is also described.

Isolation of castanospermine and its use as an antidiabetic agent

Certain Castanospermine ester derivatives of the formula: ##STR1## wherein R, R.sub.1 and R.sub.2 are each independently hydrogen, C.sub.1-14 alkanoyl, C.sub.1-14 alkenoyl, cyclohexanecarbonyl, C.sub.1-8 alkoxyacetyl, ##STR2## naphthalenecarbonyl optionally substituted by methyl or halogen; phenyl (C.sub.2-6 alkanoyl) wherein the phenyl is optionally substituted by methyl or halogen; cinnamoyl; pyridinecarbonyl optionally substituted by methyl or halogen; dihydropyridine carbonyl optionally substituted by C.sub.1 -C.sub.10 alkyl; thiophenecarbonyl optionally substituted by methyl or halogen; or furancarbonyl optionally substituted by methyl or halogen; Y is hydrogen, C.sub.1-4 alkyl, C.sub.1-4 alkoxy, halogen, trifluoromethyl, C.sub.1-4 alkylsulfonyl, C.sub.1-4 alkylmercapto, cyano or dimethylamino; Y' is hydrogen, C.sub.1-4 alkyl, C.sub.1-4 alkoxy, halogen or it is combined with Y to give 3,4-methylenedioxy; Y' is hydrogen, C.sub.1-4 alkyl, C.sub.1-4 alkoxy or halogen; with R, R.sub.1 and R.sub.2 being selected in such a way that at least one of them, but not more than two of them, is hydrogen; are disclosed to be effective in treating diseases caused by Herpes Simplex Virus (HSV) Types 1 and 2.

Anti-herpes castanospermine esters

Amide and ester derivatives of 6-amino-octahydro-1,7,8-indolizinetriol are described herein. The compounds are prepared from castanospermine by replacing the appropriate hydroxy function with an amino function while protecting the other hydroxy groups in the meantime. The compounds are useful as hexosaminidase inhibitors.

Derivatives of 6-aminooctahydroindolizinetriol

The present invention describes a group of polyhydroxylated indolizidines and quinolizidines and their esters. These compounds are prepared starting from 2,6-dideoxy-2,6-dideoxy-2,6-imino-1,3,4,5-tetrakis-O- (phenylmethyl)-D-glycero-L-gulo-heptitol or a corresponding N-substituted compound. The compounds are useful in the treatment of diabetes and as .alpha.-glucosidase I inhibitors.

Hydroxymethyl-indolizidines and quinolizidines and their use as

Castanospermine mono- and di-esters and glycosides active as inhibitors of carbohydrate digestive enzymes and useful in treating diabetes are described herein. The compounds are prepared by the reaction of castanospermine with an appropriate acid halide or anhydride or with an appropriate glycosyl halide or glycosyl acetimidate under conditions which would favor the isolation of the mono- and di-esterified and glycosylated products. Various blocking groups, which can be selectively removed under mild conditions, can also be used to favor the formation of certain isomers.

Castanospermine esters and glycosides

Certain Castanospermine ester derivatives are disclosed to be effective in treating retroviral infections including HIV infections and are thus useful in the treatment of AIDS and ARC.

Anti-retroviral castanospermine esters

A method for the inhibition of tumor metastases is described herein. The method makes use of the administration of certain castanospermine esters or their pharmaceutically acceptable salts.

Castanospermine esters in the inhibition of tumor metastasis

A procedure for the mild conversion of a carbonitrile to the corresponding carboxylic acid by first using trifluoroacetic acid in the presence of a catalytic amount of mercuric ion followed by oxidative hydrolysis with dinitrogen tetroxide is described herein. The use of this procedure in the preparation of 1,3,4,5-tetra-O-benzoyl-2,6-dideoxy-2,6-imino-D-glycero-L-gulo-heptitol hydrochloride is also described here.

Process for hydrolyzing 2,6-dideoxy-2,6-iminoheptononitrile derivatives

A method for the inhibition of tumor metastases is described herein. The method makes use of the administration of castanospermine.

Castanospermine for inhibiting tumor metastasis

Homonojirimycin glycosides active as inhibitors of carbohydrate digestive enzymes are described herein. The compounds are prepared by the reaction of an appropriately protected homonojirimycin with a protected glycosyl halide followed by removal of the protecting groups.

Growing community of inventors

Chevy Chase, MD, United States of America

Paul S Liu