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US 7,119,095 B2Granted
Pharmaceutically active compounds and methods of use thereof
AssigneeDana-Farber Cancer Institute, Inc.
InventorsAndre Rosowsky, Ronald A. Forsch
Life of this patent
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Abstract
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.
Claims30
A compound according to Formula I:
- wherein:
- RA is Independently selected at each occurrence of RA from the group consisting of hydrogen, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-8cycloalkyl, chloro, fluoro, C1-4fluoroalkyl, amino, mono and di(C1-6alkyl)amino, nitrile, optionally substituted heteroaryloxy, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted arylamino, optionally substituted heteroarylamino, C1-6alkylthio, optionally substituted arylthio, optionally substituted heteroarylthio, optionally substituted aryl acetoxy or optionally substituted heteroaryl acetoxy;
- R1 and R2 are independently selected at each occurrence or R1, and R2 in Formula I from the group consisting of hydrogen, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, chloro, fluoro, C1-6fluoroalkyl, C1-6alkoxy, optionally substituted aryloxy, optionally substituted heteroaryloxy, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted arylamino, optionally substituted heteroarylamino, C1-6alkylthio, optionally substituted arylthio, optionally substituted heteroarylthio;
- R3 is selected from the group consisting of hydrogen, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and C1-6fluoroalkyl:
- W is hydroxyl, alkoxy, amino, carboxylate, C1-6alkylcarbonyloxy, sulfonate or carhoxamide;
- i is an integer from 0 to 3;
- and
- n Is an integer from about 1 to about 12.
5 more elements
A compound according to Formula III:
- wherein:
- RA is independently selected at each occurrence of RA from the group consisting of hydrogen, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-8cycloalkyl, C1-6alkoxy, chloro, fluoro, C1-4fluoroalkyl, amino, mono and di(C1-6alkyl)amino, nitrile, optionally substituted aryloxy, optionally substituted heteroaryloxy, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted arylamino, optionally substituted heteroarylamino, C1-6alkylthio, optionally substituted arylthio, optionally substituted heteroarylthio, optionally substituted aryl acetoxy or optionally substituted heteroaryl acetoxy;
- R1, R2, and R4 are independently selected at each occurrence of R1, R2, and R4 in Formula III from the group consisting of hydrogen, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, chioro, fluoro, C1-6fluoroalkyl, C1-6alkoxy, optionally substituted aryloxy, optionally substituted heteroaryloxy, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted arylamino, optionally substituted heteroarylamino, C1-6alkylthio, optionally substituted arylthio, optionally substituted heteroarylthio;
- R3 is selected from the group consisting of hydrogen, C1-6alkyl, C2-6alkenyl, C2-5alkynyl, and C1-6fluoroalkyl;
- W is hydroxy, alkoxy, amino, carboxylate, C1-6alkylcarbonyloxy or carboxamide;
- Z is N or CH;
- i is an integer from 0 to 5;
- and
- n is an integer from 1 to 12.
6 more elements
Dependencies are inferred from the claim text.