Abstract: A compound of the Formula I and optionally a pharmaceutically acceptable salt thereof is provided: Formula I, wherein, R is one selected from the group consisting of H and CH3; n is an integer 4 when X is -CH2- and Ar is 1,4-phenyl, or n is an integer ranging from 1 to 4 when X is -CH2-and Ar is either 2'-fluoro-1,4-phenyl or 2,5-thienyl, or n is an integer ranging from 1 to 4 when X is one selected from the group consisting of O, S, -NH-, -NHCHO-, -NHCOCH3-, and -NHCOCF3- and Ar is one selected from the group consisting of (a) 1,4-phenyl, (b) 2'-fluoro-1,4-phenyl, and (c) 2,5-thienyl, or n is an integer 3 when X is -CH2-, R is CH3 and Ar is 1,4-phenyl.

Abstract: A compound of the Formula I and optionally a pharmaceutically acceptable salt thereof is provided: Formula I, wherein, R is one selected from the group consisting of H and CH3; n is an integer 4 when X is —CH2— and Ar is 1,4-phenyl, or n is an integer ranging from 1 to 4 when X is —CH2— and Ar is either 2?-fluoro-1,4-phenyl or 2,5-thienyl, or n is an integer ranging from 1 to 4 when X is one selected from the group consisting of O, S, —NH—, —NHCHO—, —NHCOCH3—, and —NHCOCF3— and Ar is one selected from the group consisting of (a) 1,4-phenyl, (b) 2?-fluoro-1,4-phenyl, and (c) 2,5-thienyl, or n is an integer 3 when X is —CH2—, R is CH3 and Ar is 1,4-phenyl.

Abstract: Fused cyclic pyrimidine compounds, including tautomers thereof, and pharmaceutically acceptable salts, prodrugs, solvates and hydrates thereof, are disclosed having the general Formula I: These compounds are useful in methods for treating cancer, selectively targeting cancerous cells via the proton coupled folate transporter, folate receptor alpha, and/or folate receptor beta pathways, inhibiting GARFTase in cancerous cells, and selectively targeting activated macrophages in a patient having an autoimmune disease, such as rheumatoid arthritis.

Abstract: A compound of the Formula I and optionally a pharmaceutically acceptable salt thereof is provided: Formula I, wherein, R is one selected from the group consisting of H and CH3; n is an integer 4 when X is —CH2— and Ar is 1,4-phenyl, or n is an integer ranging from 1 to 4 when X is —CH2— and Ar is either 2?-fluoro-1,4-phenyl or 2,5-thienyl, or n is an integer ranging from 1 to 4 when X is one selected from the group consisting of O, S, —NH—, —NHCHO—, —NHCOCH3—, and —NHCOCF3— and Ar is one selected from the group consisting of (a) 1,4-phenyl, (b) 2?-fluoro-1,4-phenyl, and (c) 2,5-thienyl, or n is an integer 3 when X is —CH2—, R is CH3 and Ar is 1,4-phenyl.

Abstract: A compound of the Formula I and optionally a pharmaceutically acceptable salt thereof is provided: Formula I, wherein, R is one selected from the group consisting of H and CH3; n is an integer ranging from 1 to 4; X is one selected from the group consisting of —CH2—, O, S, —NH—, —NHCHO—, —NHCOCH3—, and —NHCOCF3—; and Ar is one selected from the group consisting of (a) 1,4-phenyl, (b) 2?-fluoro-1,4-phenyl, and (c) 2,5-thienyl. Methods of treating a patient having cancer, targeting mitochondrial metabolism, and targeting SHMT2 and MTHFD2 using the compounds of this invention are disclosed.

Abstract: Fused cyclic pyrimidine compounds, including tautomers thereof, and pharmaceutically acceptable salts, prodrugs, solvates and hydrates thereof, are disclosed having the general Formula I: These compounds are useful in methods for treating cancer, selectively targeting cancerous cells via the proton coupled folate transporter, folate receptor alpha, and/or folate receptor beta pathways, inhibiting GARFTase in cancerous cells, and selectively targeting activated macrophages in a patient having an autoimmune disease, such as rheumatoid arthritis.

Abstract: Fused cyclic pyrimidine compounds, including tautomers thereof, and pharmaceutically acceptable salts, prodrugs, solvates and hydrates thereof, are disclosed having the general Formula I: These compounds are useful in methods for treating cancer, selectively targeting cancerous cells via the proton coupled folate transporter, folate receptor alpha, and/or folate receptor beta pathways, inhibiting GARFTase in cancerous cells, and selectively targeting activated macrophages in a patient having an autoimmune disease, such as rheumatoid arthritis.

Abstract: This invention provides substituted pyrimidine compounds having the formula: wherein X is absent, CH2, S, or O, and R is an alkyl group having from one to ten carbon atoms, and optionally salts, hydrates, or solvates thereof, that are useful in treating a patient having a disease or cancer. The compounds of this invention are useful as multi-enzyme antifolates selectively targeting the folate receptor (FR). Further, a method of making 5- and 6-substituted cyclopenta[d]pyrimidine for nonclassical and classical antifolates as TS and DHFR inhibitors is provided.

Abstract: A compound of the Formula I and optionally a pharmaceutically acceptable salt thereof is provided: Formula I, wherein, R is one selected from the group consisting of H and CH3; n is an integer ranging from 1 to 4; X is one selected from the group consisting of —CH2—, O, S, —NH—, —NHCHO—, —NHCOCH3—, and —NHCOCF3—; and Ar is one selected from the group consisting of (a) 1,4-phenyl, (b) 2?-fluoro-1,4-phenyl, and (c) 2,5-thienyl. Methods of treating a patient having cancer, targeting mitochondrial metabolism, and targeting SHMT2 and MTHFD2 using the compounds of this invention are disclosed.

Abstract: This invention provides substituted pyrimidine compounds having the formula: wherein X is absent, CH2, S, or O, and R is an alkyl group having from one to ten carbon atoms, and optionally salts, hydrates, or solvates thereof, that are useful in treating a patient having a disease or cancer. The compounds of this invention are useful as multi-enzyme antifolates selectively targeting the folate receptor (FR). Further, a method of making 5- and 6-substituted cyclopenta[d]pyrimidine for nonclassical and classical antifolates as TS and DHFR inhibitors is provided.

Abstract: Fused cyclic pyrimidine compounds, including tautomers thereof, and pharmaceutically acceptable salts, prodrugs, solvates and hydrates thereof, are disclosed having the general Formula I: These compounds are useful in methods for treating cancer, selectively targeting cancerous cells via the proton coupled folate transporter, folate receptor alpha, and/or folate receptor beta pathways, inhibiting GARFTase in cancerous cells, and selectively targeting activated macrophages in a patient having an autoimmune disease, such as rheumatoid arthritis.

Abstract: Fused cyclic pyrimidine compounds, including tautomers thereof, and pharmaceutically acceptable salts, prodrugs, solvates and hydrates thereof, are disclosed having the general Formula I: These compounds are useful in methods for treating cancer, selectively targeting cancerous cells via the proton coupled folate transporter, folate receptor alpha, and/or folate receptor beta pathways, inhibiting GARFTase in cancerous cells, and selectively targeting activated macrophages in a patient having an autoimmune disease, such as rheumatoid arthritis.

Abstract: This invention provides substituted pyrimidine compounds having the formula: wherein X is absent, CH2, S, or O, and R is an alkyl group having from one to ten carbon atoms, and optionally salts, hydrates, or solvates thereof, that are useful in treating a patient having a disease or cancer. The compounds of this invention are useful as multi-enzyme antifolates selectively targeting the folate receptor (FR). Further, a method of making 5- and 6-substituted cyclopenta[d]pyrimidine for nonclassical and classical antifolates as TS and DHFR inhibitors is provided.

Abstract: This invention provides substituted pyrimidine compounds having the formula: wherein X is absent, CH2, S, or O, and R is an alkyl group having from one to ten carbon atoms, and optionally salts, hydrates, or solvates thereof, that are useful in treating a patient having a disease or cancer. The compounds of this invention are useful as multi-enzyme antifolates selectively targeting the folate receptor (FR). Further, a method of making 5- and 6-substituted cyclopenta[d]pyrimidine for nonclassical and classical antifolates as TS and DHFR inhibitors is provided.

Abstract: Fused cyclic pyrimidine compounds, including tautomers thereof, and pharmaceutically acceptable salts, prodrugs, solvates and hydrates thereof, are disclosed having the general Formula I: These compounds are useful in methods for treating cancer, selectively targeting cancerous cells via the proton coupled folate transporter, folate receptor alpha, and/or folate receptor beta pathways, inhibiting GARFTase in cancerous cells, and selectively targeting activated macrophages in a patient having an autoimmune disease, such as rheumatoid arthritis.

Abstract: Pyrrolo[2,3-d]pyrimidine derivatives, and pharmaceutical acceptable salts thereof, useful in therapeutically treating patients with cancer are disclosed. These compounds selectively target folate receptors (FR) of cancerous tumor cells and inhibit purine synthesis and hence, DNA synthesis.

Abstract: Fused cyclic pyrimidine compounds, including tautomers thereof, and pharmaceutically acceptable salts, prodrugs, solvates and hydrates thereof, are disclosed having the general Formula 1: These compounds are useful in methods for treating cancer, selectively targeting cancerous cells via the proton coupled folate transporter, folate receptor alpha, and/or folate receptor beta pathways, inhibiting GARFTase in cancerous cells, and selectively targeting activated macrophages in a patient having an autoimmune disease, such as rheumatoid arthritis.

Abstract: Pyrrolo[2,3-d]pyrimidine derivatives, and pharmaceutical acceptable salts thereof, useful in therapeutically treating patients with cancer are disclosed. These compounds selectively target folate receptors (FR) of cancerous tumor cells and inhibit purine synthesis and hence, DNA synthesis.

Abstract: A method for treating cancer tumors, particularly ovarian cancer tumors, is described, where fused cyclic pyrimidine having a cancer treating ability is selectively delivered to an FR expressing cancerous tumor.

Abstract: Pyrrolo[2,3-d]pyrimidine derivatives, and pharmaceutical acceptable salts thereof, useful in therapeutically treating patients with cancer are disclosed. These compounds selectively target folate receptors (FR) of cancerous tumor cells and inhibit purine synthesis and hence, DNA synthesis.