Other

Southern Research Institute

Sri International

The United States of America As Represented by the Department of Health

Sloan-kettering Institute for Cancer Research

U.S. Bioscience, Inc.

Sloan-kettering Institute

Piper Hydro, Inc.

James R Piper

Francis M Sirotnak

Joseph I DeGraw

John A Montgomery

William T Colwell

R Lane Smith

John A Secrist, Iii

Philip S Schein

Robert F Struck

Herbert M Blatter

Carroll Temple

Donald R Kahn

Method for prevention or treatment of acute allograft rejection and a pharmaceutical composition therefor

Preliminary clinical studies in humans have now been done which show both the efficacy of 10-propargyl-10dAM and a preferred dosage schedule for such treatments. In addition, it has now been determined that combinations of 10-propargyl-10-deazaaminopterin (preferably highly purified forms, substantially free of 10-deazaaminopterin) with taxols exhibit synergistic effectiveness in the treatment of tumors. 10-propargyl-10-deazaaminopterin and a taxol in therapeutically effective amounts can be administered concurrently, one right after the other, or with a period of time in between.

Combinations of 10-propargyl-10-deazaaminopterin and taxols and methods of using same in the treatment of tumors

Purified compositions of 10-propargyl-10-deazaaminopterin and methods of

Antiinflammatory and antineoplastic 5-deazaaminopterins and 5,10-dideazaaminopterins and their 5 and 10 alkyl analogs. A method for the treatment and prevention of inflammatory disease, such as rheumatoid arthritis, and for suppression and prevention of neoplastic growth in tumors and in blood forming tissues. A process for preparation of 10-deazaaminopterins.

Antiinflammatory and antineoplastic 5-deazaaminopterins and

A process is provided for the preparation of 10-deazaaminopterins and 5,10- and 8,10-dideazaaminopterins starting from the corresponding homoterephthalic acid diester coupling the corresponding dicarboxylic acid diester having the formula: ##STR1## with the corresponding diaminopterin 6-methylene halide having the formula: ##STR2## thereby forming a pteroic acid diester having the formula: ##STR3## hydrolysing the two ester groups to form the corresponding carboxylic acid groups, and then monodecarboxylating the diacid, thereby removing the carboxylic acid group attached to the carbon alpha to the A group and forming a pteroic acid.

Process for preparing 10-deazaaminopterins and 5,10-and

There is disclosed certain heteroaroyl 10-deazaaminopterin and 5, 10 and 8, 10 di deazaminopterin compounds and their use for treatment of rheumatoid arthritis and related diseases and preparative process. Also disclosed are 10 alkenyl-(and alkynyl) 10-deazaminopterins also disclosed for treatment of rheumatoid arthritis and for leukemia and ascites tumors and preparative process.

Heteroaroyl 10-deazaamino-pterine compounds and use for rheumatoid

A method of decreasing the toxicity of chemical therapeutic agents administered in cancer chemotherapy including adminstration to a patient undergoing chemotherapy. This reduction in toxicity can be accomplished by administering an effective amount of S-3-(3-methylaminopropylamino)propyl dihydrogen phosphorothioate. Methods of inducing mucolytic activity and reducing toxicity of acetominophen overdose are also discussed. Such activities are induced through the administration of S-3-(3-methylaminopropylamino)propyl dihydrogen phosphorothioate.

Method of reducing chemotherapy toxicity using

5,10-Dialkyl substituted 5,10-dideazaaminopterins and a cyclized derivative thereof are disclosed as potent antineoplastic agents. Also disclosed is an improved process for the preparation of 10-ethyl-10-deazaaminopterin using the intermediate methyl 4-[[2-(2,4-diamino-6-pteridinyl)-1-ethyl]ethenyl]benzoate.

Cyclized 5,10-dideazaaminopterin compounds

It is disclosed that 5-methyl-5-deazamethotrexate and 5-methyl-5-deaza-10-ethylaminopterin are more than 10 times as potent as 5-deazamethotrexate in the L1210 cell growth inhibition test.

5-methyl-5-deaza analogues of methotrexate and N.sup.10 -ethylaminopterin

A system for supplying hot water into a dwelling or the like. The system includes a continuous circulating hydraulic loop for distribution to fixtures and heat exchange units. A storage circuit is employed to add heated water as needed to the loop. A water heating circuit supplies solar energy to the storage system for eventual use in the continuous loop. The storage circuit and the water heating circuit are controlled to provide water on an optimum efficiency basis. Feed water is also supplied to the system through the solar panels of the water heating system.

Hot water supply system

A solar energy system employing solar panels used to heat water. The system includes a boiler with the vent for the boiler being located beneath the solar panels to distribute exhaust heat thereto. A structure is defined to allow venting of the enclosed area behind the panels. The panels are constructed with multiple sheets of plastic as glazing which are retained by means of interlocking elements and adhesive.

A system for space heating for a building employing structural elements of the building as heating conduits. Girder pairs are employed as manifold conduits and joist pairs are employed as distribution conduits for the present system. The crawl space of the building is used for the return air and becomes a plenum therefor.

Heating system

There is disclosed an improved process for the preparation of 10-deazaaminopterin and related compounds. In accordance with this process, 6-(bromomethyl)-2,4-pteridinediamine hydrobromide is reacted with triphenylphosphine to form a phosphonium salt which is then treated with a base to yield the corresponding ylid (2,4-diamino-6-pteridinyl)methylenetriphenylphosphorane. This compound is reacted with an aromatic aldehyde such as diethyl 4-formylbenzoyl-L-glutamate to form an olefin which is then reduced catalytically to the tetrahydro derivative of the desired product. Oxidation of the tetrahydro derivative is accomplished with hydrogen peroxide.

Process for the preparation of 10-deazaaminopterin and related compounds

A method for the preparation of pteridine compounds such as methotrexate is disclosed. 2,4-diamino-6-pteridine-methanol.multidot.HBr is reacted with triphenylphosphine dibromide or phosphorus tribromide to form 6-(bromomethyl)-2,4-diamino-pteridine hydrobromide and the bromine atom in the molecule is then replaced with the functional group, N-[4-(methylamino)-benzoyl]-L-glutamic acid in the case of methotrexate and N-(4-aminobenzoyl)-L-glutamic acid in the case of aminopterin.

Method of making pteridine compounds

A pteridine compound having the formula of 6-(bromomethyl)-2,4-diaminopteridine hydrobromide. 2,4-diamino-6-pteridine-methanol.HBr is reacted with triphenylphosphine dibromide or phosphorus tribromide to form 6-(bromomethyl)-2,4-diaminopteridine hydrobromide. The bromine atom in the molecule can then be replaced with the functional group, N-[4-(methylamino)-benzoyl]-L-glutamic acid in the case of methotrexate and N-(4-aminobenzoyl)-L-glutamic acid in the case of aminopterin.

Growing community of inventors

Birmingham, AL, United States of America

James R Piper