Dana-farber-cancer Institute Inc.

Other

Ash Stevens, Inc.

Andre Rosowsky

Karl Y Hostetler

James R Beadle

Peter Blumbergs

Ganesh D Kini

Ruth M Ruprecht

Han Chen

Douglas Richman

Ronald A Forsch

Henry Bader

Ming-The Lin

The present invention relates to dihydrofolate reductase inhibitors having an aromatic group and a heteroaromatic group linked by a methylene group; methods of preparation of dihydrofolate reductase inhibitors that include metal mediated cross coupling of an aromatic halide or heteroaromatic halide with an organozinc reagent; and methods of treatment and pharmaceutical compositions that utilize or comprise one or more of such dihydrofolate reductase inhibitors.

Methods for synthesis of diarylmethanes

The present invention relates to dihydrofolate reductase inhibitors having an aromatic group and a heteroaromatic group linked by a methylene group; and methods of treatment and pharmaceutical compositions that utilize or comprise one or more of such dihydrofolate reductase inhibitors.

Pharmaceutically active compounds and methods of use thereof

The invention relates to pharmaceutically active compounds, and methods of treatment and pharmaceutical compositions that utilize or comprise one or more such compounds. Compounds of the invention and particularly useful for the treatment or prophylaxis of diseases associated with parasitic infection such as pneumocystis pneumonia, toxoplasmosis, cryptosporidiosis, leischmaniasis and malaria.

Dibenz[B,F]azepine compounds, pharmaceutical compositions comprising same and methods of use thereof

In one embodiment, the present invention relates to a new class of ammonium salts of N-acyl derivatives of N-(4-amino-4-deoxypteroyl)-L-ornithine compounds having a structure according to formula II-IV. Formula II has the structure of: The ammonium salts provided by the invention exhibit high inhibitory activity against the growth o methotrexate-resistant cells, and also exhibit superior chemical stability than corresponding acidic N-acyl derivatives of N-acyl derivatives of N(4-amino-4-deoxypteroyl)-L-ornithine compounds.

Pharmaceutically active ornithine derivatives, ammonium salts thereof and methods of making same

The invention provides lipophilic phosphonoacid/nucleoside conjugates that exhibit exceptional antiviral activity, including activity against drug-resistant HIV strains. Compounds of the invention include phosphonoacid/nucleoside conjugates where the carboxyl group and phosphonyl groups of the phosphonacid are esterified whereby the compound contains at least one lipophilic group and at least one nucleoside group.

Antiviral compounds and methods of administration

2-Aza-2-desamino analogues of 5,8-dideazafolic acid, which analogues have the formula ##STR1## wherein X is an aryl or heteroaryl moiety;

2-aza-2-desamino analogues of 5,8-dideazafolic acid

Compounds having the structure ##STR1## in which R is alkyl, aryl, or aralkyl, A is hydrogen or a water-soluble cation, B is hydrogen, fluorine, or azido, the bond  is saturated when B is fluorine or azido and is saturated or unsaturated when B is hydrogen, and D is a purine or pyrimidine base are effective inhibitors of retrovirus replication.

Dideoxynucleoside-5'-phosphonoformic acid compounds

A compound having the structure ##STR1## in which R.sub.1 is hydrogen or a lower alkyl group and R.sub.2 is hydrogen or methyl.

Desamino-aminopterin and -methotrexate

Compounds having the structure ##STR1## in which R is --CO--Ar--COOR.sub.1 where R.sub.1 is hydrogen or lower alkyl, and pharmaceutical compositions containing the same exhibiting high growth inhibitory activity against methotrexate resistant cells.

Ornithine derivatives and their use as methotrexate-resistant cell

Cysteic acid and homocysteic acid analogues of methotrexate and aminopterin having antitumor activity and low toxicity are soluble in water at a physiological pH ranging from 7.2-7.5.

Growing community of inventors

Needham, MA, United States of America

Andre Rosowsky