Back to results
US 6,440,965 B1Granted
Substituted pyrimidine derivatives, their preparation and their use in the treatment of neurodegenerative or neurological disorders of the central nervous system
AssigneeKrenitsky Pharmaceuticals, Inc.
InventorsJames L. Kelley, Thomas A. Krenitsky, Lilia M. Beauchamp
Life of this patent
Estimating the term…
Abstract
The present invention relates to novel derivatives of a series of substituted pyrimidines, to pharmaceutical compositions which contain them, to methods for their preparation and to their use in therapy, particularly in the treatment of neurodegenerative or other neurological disorders of the central and peripheral systems.
Claims18
A compound of Formula I
- wherein:
- R1 is hydroxyC1-C6alkyloxyC1-6alkylamino, morpholino, piperidino, piperazino, piperazinoamino, homopiperazino, homopiperidino, or homomorpholino, wherein C or N atoms of R1 may be substituted with one or more substituents selected from the group consisting of:
- NR4R5 (wherein R4 and R5 may be the same or different and are H, C1-6alkyl, hydroxyC1-6alkyl, C3-8cycloalkyl, C6-10aryl, C6-10arylC1-6alkyl, C1-6alkoxy, C6-10aryloxy or C6-10arylC1-6alkoxy);
- NR4R5carbonyC1-C6alkyl (wherein R4 and R5 may be the same or different);
- OH;
- CN;
- C1-6alkyl;
- C2-7alkenyl;
- C2-7alkynyl;
- C6-10aryl;
- C6-10heteroaryl;
- hydroxyC1-6alkyl;
- dihydroxyC1-6alkyl;
- C1-6alkoxy;
- C1-6aryloxy;
- C6-10heteroaryloxy;
- hydroxyC1-6alkoxy;
- C1-6alkoxyC1-6alkyl;
- C6-10aryloxyC1-6alkyl;
- C6-10heteroaryloxyC1-6alkyl;
- C3-8cycloalkyl;
- C6-10arylC1-6alkyl;
- C6-10heteroarylC1-6alkyl;
- C6-10arylC1-6alkoxy;
- and
- C6-10heteroarylC1-6alkoxy;
- R2 is selected from the group consisting of:
- H;
- halogen;
- NR7R8 (wherein R7 and R8 may be the same or different and are H, C1-6alkyl, C1-6alkyloxy, C1-6alkyl , C3-8cycloalkyl, C6-10arylC6-10arylC1-6alkyl, C1-6alkoxy, C6-10aryloxy, C6-C10arylC1-6alkoxy, or C(O)C1-6alkyl, each of which may be optionally substituted with one or more substituents selected from the group consisting of OH, halogen and C1-6alkyl);
- pyrrolidino;
- piperidino;
- hydroxypiperidino;
- heptamethyleneimino;
- piperazino;
- N-substituted piperazino (wherein the substituent may be C1-6alkyl, hydroxyC1-6alkyl, C6-10aryl, C6-10arylC1-6alkyl or C6-10heteroaryl);
- homopiperazino;
- N-substituted homopiperazino (wherein the substituent may be C1-6alkyl, hydroxyC1-6alkyl, C6-10aryl, C6-10arylC1-6alkyl or C6-10heteroaryl);
- morpholino;
- homomorpholino;
- and
- C-substituted piperidino (wherein the substituent may be C1-6alkyl, hydroxyC1-6alkyl, C6-10aryl, C6-10arylC1-6alkyl or C6-10heteroaryl);
- X is a C6-10 aryl ring optionally substituted with one or more suitable substituents for an aryl ring selected from the group consisting of:
- halogen;
- C1-6alkyl;
- C2-7alkenyl;
- C2-7alkynyl;
- C6-10aryl;
- C6-10heteroaryl;
- OR (wherein R is H, C1-6alkyl, C3-8cycloalkyl, C6-10aryl, or C6-10arylC1-6alkyl);
- NR9R10 (wherein R9 and R10 may be the same or different and are H, C1-6alkyl, C3-8cycloalkyl, C6-10aryl, or C6-10arylC1-6alkyl);
- NROR;
- C(O)NR9R10;
- C(O)OR;
- C(O)R;
- NRC(O)NR9R10;
- NRC(O)R;
- NRC(O)OR;
- CR(OH)R;
- OC(O)R;
- S(O)nR, wherein R is other than H and n is 0, 1, or 2;
- NRS(O)mR, wherein R is other than H and m is 1 or 2;
- S(O)2NR9R10;
- NO2;
- CN;
- CF3;
- and
- OCF3;
- and pharmaceutically acceptable esters, amides, salts and solvates thereof.
66 more elements
A compound of formula IA
- wherein
- R2 is selected from the group consisting of NH2, NHC1-6alkyl, NHC2H4OC2H4OC2H4OH,
- Y is any suitable substituent for an aryl ring;
- Y′ is selected from the group consisting of H, CH3, CH2CH3, CH2CH2OH, C(O)R, S(O)2R and C6H5;
- R is selected from the group consisting of H, C1-6alkyl, C3-8cycloalkyl, C6-C10aryl and C6-C10arylC1-6alkyl;
- and pharmaceutically acceptable esters, amides, salts and solvates thereof.
3 more elements
A compound of formula IB
- wherein
- R2 is selected from the group consisting of NH2, NHC1-6alkyl, NHC2H4OC2H4OC2H4OH,
- Y is any suitable substituent for an aryl ring;
- Y′ is selected from the group consisting of H, CH3, CH2CH3, CH2CH2OH, C(O)R, S(O)2R and C6H5;
- R is selected from the group consisting of H, C1-6alkyl, C3-8cycloalkyl, C6-C10aryl and C6-C10arylC1-6alkyl;
- and pharmaceutically acceptable esters, amides, salts and solvates thereof.
3 more elements
A compound of formula IC
- wherein
- R2 is selected from the group consisting of NH2, NHC1-6alkyl, NHC2H4OC2H4OC2H4OH,
- Y is any suitable substituent for an aryl ring;
- Y′ is selected from the group consisting of H, CH3, CH2CH3, CH2CH2OH, C(O)R, S(O)2R and C6H5;
- R is selected from the group consisting of H, C1-6alkyl, C3-8cycloalkyl, C6-C10aryl and C6-C10arylC1-6alkyl;
- and pharmaceutically acceptable esters, amides, salts and solvates thereof.
3 more elements
A compound of formula ID
- wherein
- R2 is selected from the group consisting of NH2, NHC1-6alkyl, and NHC2H4OC2H4OC2H4OH;
- Y is any suitable substituent for an aryl ring;
- and pharmaceutically acceptable esters, amides, salts and solvates thereof.
1 more element
Dependencies are inferred from the claim text.