E.i. Dupont De Nemours and Company

Bristol-myers Squibb Pharma Company

Bristol-myers Squibb Compnay

The Dupont Merck Pharmaceutical Company

Bristol Meyers Squibb Company

George L Trainor

Robert F Kaltenbach

Frank W Hobbs

Simon P Robinson

Charles W Robertson, Jr

James M Prober

Rudy J Dam

Nicholas A Meanwell

Ashvinikumar V Gavai

David R Langley

Dolatrai M Vyas

Annapurna Pendri

Subramaniam Sabesan

Harold A Mastalerz

Samuel Gerritz

Guo Li

Edward M Huie

The disclosure generally relates to compounds of formula I, including compositions and methods for treating human immunodeficiency virus (HIV) infection. The disclosure provides novel inhibitors of HIV, pharmaceutical compositions containing such compounds, and methods for using these compounds in the treatment of HIV infection. 

Inhibitors of human immunodeficiency virus replication

The invention relates to at least one pyrrolotriazine derivative, at least one pharmaceutical composition comprising at least one pyrrolotriazine derivative, and at least one method of using at least one pyrrolotriazine derivative to treat at least one kinase associated condition.

Pyrrolotriazine compounds useful as kinase inhibitors and methods of treating kinase-associated conditions therewith

The present invention provides, inter alia, triphenylethylene derivatives, such as, 3-{4-[6-(3-Methoxy-phenyl)-8,9-dihydro-7H-benzocyclohepten-5-yl]-phenyl}-acrylic acid, as selective estrogen receptor modulators. Also provided are methods for treating estrogen stimulated diseases in mammals including, but not limited to, for example, breast, uterine, ovarian, prostate and colon cancer; osteoporosis; endometriosis; uterine fibroid; Alzheimer's disease; macular degeneration; urinary incontinence; and type II diabetes, as well as, pharmaceutical compositions comprising at least one compound of the present invention.

Selective estrogen receptor modulators

The present invention provides, inter alia, triphenylethylene derivatives, such as, 5-{2-[4-(1,2-Diphenyl-but-1-enyl)-phenyl]-vinyl}-1H-tetrazole, as selective estrogen receptor modulators. Also provided are methods for treating estrogen stimulated diseases in mammals including, but not limited to, for example, breast, uterine, ovarian, prostate and colon cancer; osteoporosis; endometriosis; uterine fibroid; Alzheimer's disease; macular degeneration; urinary incontinence; and type II diabetes, as well as, pharmaceutical compositions comprising at least one compound of the present invention.

The present invention provides, inter alia, triphenylethylene derivatives, such as, 3-{4-[6-(3-Methoxy-phenyl)-8,9-dihydro-7H-benzocyclohepten-5-yl]-phenyl}-acrylic acid, as selective estrogen receptor modulators. Also provided are methods for the treatment and/or prevention of estrogen stimulated diseases in mammals including breast, uterine, ovarian, prostrate and colon cancer, osteoporosis, cardiovascular disease, and benign proliferative disorders, as well as pharmaceutical compositions of the compounds of the present invention.

Phosphate esters of bis-amino acid sulfonamides containing substituted benzyl amines

The present invention describes novel halogenated triphenylethylene derivatives, or pharmaceutically acceptable prodrug or salt forms thereof, as selective estrogen receptor modulators for the treatment of and/or prevention of breast, uterine, ovarian, prostrate and colon cancer, osteoporosis, cardiovascular disease, and benign proliferative disorders, as well as methods for making the compounds and pharmaceutical compositions of this invention.

Halogenated triphenylethylene derivatives as selective estrogen receptor modulators

Bis-amino acid sulfonamides containing substituted benzyl amines HIV protease inhibitors

Intermediates for fluorescent dyes based on 9-carboxyethyl-6-hydroxy-3-oxo-3H-xanthene which are useful as reporters for reporter-labeled DNA fragments are described. The intermediates are protected fluorescent dyes bearing acyloxy groups at the 3 and 9 positions and an alkoxy group at the 9 position. Deprotection of the protected fluorescent dye by treatment with aqueous ammonia regenerates free dye.

Fluorescent dye intermediates

A DNA sequencing system and method are described to detect the presence of radiant energy emitted from different excited reporter dye-labeled species (DNA fragments) following separation in time and/or space, and the identity of the species which emit radiant energy closely spaced in wavelength. Functions of the emitted energy are obtained which vary over the wavelengths of the closely spaced spectra in different senses and the functions ratioed, whereby the ratio is indicative of the identity of the DNA fragments. The emitting portion of the reporter-labeled DNA fragment is preferably one of a family of fluorescent dyes based on 9-carboxyethyl-6-hydroxy-3 -oxo-3H-xanthene. These xanthene dyes are covalently attached to the DNA fragments through the carboxylic acid functionality, preferably via an amide linkage. The dyes may be protected by including an alkoxy group at the 9-position. A spacer may be inserted between the dye and the amine. The fluorescent dye preferably is attached to the DNA chain terminators and provides many advantages. Thus only DNA sequencing fragments resulting from bona fide termination events will carry a reporter. The DNA sequencing may also be labeled using the xanthene dyes which have general utility as fluorescent labels. Also acyclonucleoside triphosphates are described as being useful as chain terminators in DNA sequencing using a modification of the Sanger method.

Method, system and reagents for DNA sequencing

Acyclonucleoside triphosphates are described as being useful as chain terminators in DNA sequencing using a modification of the Sanger method.

DNA sequencing method using acyclonucleoside triphosphates

Oligonucleotides possessing at least one sulfamate or sulfamide internucleotides linkages. These compounds can be used as specific hybridization probes to detect complementary nucleic acid sequences.

Oligonucleotide analogs with sulfamate linkages

A DNA sequencing system and method are described to detect the presence of radiant energy emitted from different excited reporter dye-labeled species (DNA fragments) following separation in time and/or space, and the identity of the species which emit radiant energy closely spaced in wavelength. Functions of the emitted energy are obtained which vary over the wavelengths of the closely spaced spectra in different senses and the functions ratioed, whereby the ratio is indicative of the identity of the DNA fragments. The emitting portion of the reporter-labeled DNA fragment is preferably one of a family of fluorescent dyes based on 9-carboxyethyl-6-hydroxy-3-oxo-3H-xanthene. These xanthene dyes are covalently attached to the DNA fragments through the carboxylic acid functionality, preferably via an amide linkage. The dyes may be protected by including an alkoxy group at the 9-position. A spacer may be inserted between the dye and the amine. The fluorescent dye preferably is attached to the DNA chain terminators and provides many advantages. Thus only DNA sequencing fragments resulting from bona fide termination events will carry a reporter. The DNA sequencing may also be labeled using the xanthene dyes which have general utility as fluorescent labels. Also acyclonucleoside triphosphates are described as being useful as chain terminators in DNA sequencing using a modification of the Sanger method.

Method systems and reagents for DNA sequencing

Disclosed are deoxyfructonucleotides and dideoxyfructonucleotides which may be used as propagators and terminators in DNA extension reactions.

Growing community of inventors

Wilmington, DE, United States of America

George L Trainor