68 results about "Antifolate" patented technology

A method for the assessment of the responsiveness of a cancer patient to antifolate-containing chemotherapy, the method is effected by searching for a mutation or mutations in a reduced folate carrier (RFC) gene in cells derived from the patient.

The present invention provides compositions and methods for the treatment of disorders of abnormal cell proliferation and / or inflammation, such as psoriasis and inflammatory bowel disease, in a human or other host animals.

The invention claimed herein relates to an improvement in a process for synthesizing a compound of formula Ib:wherein R1 and R2 are each individually amino or N-alkyl substituted amino; hydroxy; alkoxy; keto; lower alkyl; or a nitrogen or oxygen protecting group;R3 is hydrogen; hydroxy; alkoxy; trifluoromethyl alkoxy; halo; sulfhydryl or alkylthio;R4 is —C(O)—X;X is hydroxy; alkoxy; or an amino acid residue;in which process a 2-amino-5-nitro-benzonitrile starting reagent is cyclized to form 2,4-diamino-6-nitro-quinazoline, which is converted to 2,4,6-triamino-quinazoline, which is converted to 2,4-diamino-6-cyano-quinazoline, which is converted to 2,4-diamino-6-formyl-quinazoline;in which the improvement includes:reacting an R4-p-benzoic acid alkylene moiety with triethyl phosphite to form a 4-R4-carbonyloxyalkyl-phenyl-alkyldiethylphosphite; andreacting the 2,4-diamino-6-formyl-quinazoline with the 4-R4-carbonyloxyalkyl-phenyl-alkyldiethylphosphite to form the compound of formula Ib.

The disclosure relates generally to polyglutamated antifolates, formulations containing liposomes filled with alpha or D-gamma polyglutamated antifolates, methods of making the polyglutamated antifolates and liposome containing formulations, and methods of using polyglutamated antifolates and liposome containing formulations to treat hyerproliferative disorders (e.g., cancer) and disorders of the immune system (e.g., an autoimmune disease such as rheumatoid arthritis).

Conjugates of antifolates, releasable linkers, and drugs, and pharmaceutical compositions containing them are described. The conjugates are useful for treating diseases arising from pathogenic cell populations. Methods for treating such diseases are also described.

The present invention relates to pharmaceutical compositions containing the antifolate aminopterin, processes for making the compositions, and methods of using them to treat disorders in adult and pediatric patients. Pharmaceutical compositions substantially free of impurities are provided comprising a therapeutically effective amount of aminopterin, or a pharmaceutically acceptable salt thereof. Relative to the teachings of the prior art, the disclosed methods and compositions provide unexpected improvements that include a greater interpatient oral bioavailability in pediatric patients, a smaller interpatient coefficient of variation of oral bioavailability, a smaller mean intrapatient coefficient of variation of oral bioavailability, a greater therapeutic index, a smaller coefficient of variation of toxicity, efficacy in combination therapy, and efficacy of certain polyglutamated metabolites.

The invention is based on the discovery that GM-CSF antagonists can be used for the treatment of chronic inflammatory disease, such as rheumatoid arthritis. Accordingly, the invention provides methods of administering a GM-CSF antagonist, e.g., a GM-CSF antibody, and an anti-folate compounds, e.g., methotrexate, to a patient that has RA and pharmaceutical compositions comprising such antagonists.

The present invention provides compositions and methods for the treatment of disorders of abnormal cell proliferation and / or inflammation, such as psoriasis and inflammatory bowel disease, in a human or other host animals.

Compositions and methods for the treatment of arthritis, particularly rheumatoid arthritis and osteoarthritis. These compositions include at least one antifolate and at least one bisphosphonate, or pharmaceutically acceptable salts thereof.

Methods and kits for predicting the efficacy of antifolate (e.g., methotrexate) treatment of rheumatoid arthritis by detecting polymorphisms, particularly single nucleotide polymorphisms, in adenosine pathway genes.

The present application relates to a series of novel sulfonic acid metal cation salts of formula which are useful intermediates to prepare antifolate 5-substituted pyrrolo[2,3-d]pyrimidines. The present invention also relates to a novel process for preparing the sulfonic acid metal cation salts and to a novel process for preparing aldehydes of formula from the corresponding sulfonic acid metal cation salts.

Methods and kits for predicting the efficacy of antifolate (e.g., methotrexate) treatment of rheumatoid arthritis by detecting polymorphisms, particularly single nucleotide polymorphisms, in adenosine pathway genes.

The present application relates to a series of novel sulfonic acid metal cation salts of formula (I) which are useful intermediates to prepare antifolate 5-substituted pyrrolo[2,3-d]pyrimidines. The present invention also relates to a novel process for preparing the sulfonic acid metal cation salts and to a novel process for preparing aldehydes of formula (II) from the corresponding sulfonic acid metal cation salts.

The invention is based on the discovery that GM-CSF antagonists can be used for the treatment of chronic inflammatory disease, such as rheumatoid arthirtis. Accordingly, the invention provides methods of administering a GM-CSF antagonist, e.g., a GM-CSF antibody, and an anti-folate compounds, e.g., methotrexate, to a patient that has RA and pharmaceutical compositions comprising such antagonists.