US 6,583,148 B1Granted

Neurotrophic substituted pyrimidines

AssigneeKrenitsky Pharmaceuticals, Inc.

InventorsJames L. Kelley, Thomas A. Krenitsky, Lilia M. Beauchamp

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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.

Claims30

Dependent claims

A compound of the formula

wherein:
X is a C6-10 aryl ring or a C6-10 heteroaryl ring optionally substituted with one or more substituents selected from the group consisting of halogen, C1-6 alkyl, C2-7alkenyl, C2-7alkynyl, C6-10aryl, C6-10heteroaryl, OR, 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 n is 0, 1 or 2, NR′S(O)mR′ wherein m is 1 or 2, S(O)2NR9R10, NO2, CN, CF3, and OCF3, wherein R is H, C1-6alkyl, C3-8cycloalkyl, C6-10aryl or C6-10arylC1-6alkyl and R′ is C1-6alkyl, C3-8cycloalkyl, C6-10aryl or C6-10arylC1-6alkyl;
R1 is pyrrolidino, 3-oxopiperidino, 4-oxopiperidino, or NR4R5, wherein R4 and R5 are independently H, C3-11alkenyl, C3-11alkynyl, dihydroxyC3-10alkyl, hydroxyC2-10alkyl, C1-6alkyloxyC2-6alkyl, C1-6alkylthioC2-6alkyl, (C1-6alkyl)j(C3-9cycloalkyl)(CH2)q (wherein j is 0 or 1 and q is 0-6), (C1-6alkyl)j(C4-9heterocycloalkyl)(CH2)q (wherein j and q are as above and the heterocyclic ring contains one heteroatom which is O, S or N), oxo(C3-8cycloalkyl)(CH2)q (wherein q is 0-6), hydroxy(CH2)p(C3-8cycloalkyl)(CH2)q (wherein p and q are independently 0-6), or C2-6alkyl, provided that both R4 and R5 are not H or C2-6alkyl and that if R4 is H, R5 is not hydroxyC1-6alkyloxyC2-6alkyl;
wherein C or N atoms of R4 and R5 may be substituted with one or more substituents selected from the group consisting of OH, oxo, 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, C6-10heteroarylC1-6alkoxy, C1-6alkylcarbonylC1-6alkyl, C6-10arylcarbonylC1-6alkyl, carboxyC1-6alkyl, C1-6alkoxycarbonylC1-6alkyl, C6-10aryloxycarbonylC1-6alkyl, C6-10arylC1-6alkyloxycarbonylC1-6alkyl, cyanoC1-6alkyl, C1-6alkylthioC1-6alkyl, C1-6alkylsulfinylC1-6alkyl, C1-6alkylsulfonylC1-6alkyl, C6-10arylthioC1-6alkyl, C6-10arylsulfinylC1-6alkyl, C6-10arylsulfonylC1-6alkyl, C6-10arylC1-6alkylthioC1-6alkyl, C6-10arylC1-6alkylsulfinylC1-6alkyl, C6-10arylC1-6alkylsulfonylC1-6alkyl, C6-10heteroarylthioC1-6alkyl, C6-10heteroarylsulfinylC1-6alkyl, C6-10heteroarylsulfonylC1-6alkyl, aziridino, azetidino, pyrrolidino, piperidino, heptamethyleneimino, homopiperazino, N-substituted homopiperazino (wherein the substituent may be C1-6alkyl, C6-10aryl, C6-10arylC1-6alkyl or C6-10heteroaryl), piperazino, N-substituted piperazino (wherein the substituent may be C1-6alkyl, C6-10aryl, C6-10arylC1-6alkyl or C6-10heteroaryl), morpholino, homomorpholino, thiomorpholino, aminoC1-6alkyl, C1-6alkylaminoC1-6alkyl, di(C1-6alkyl)aminoC1-6alkyl (wherein the alkyl groups may be the same or different), C6-10arylaminoC1-6alkyl, C6-10arylC1-6alkylaminoC1-6alkyl, di(C6-10aryl)aminoC1-6alkyl (wherein the aryl groups may be the same or different), di(C6-10arylC1-6alkyl)aminoC1-6alkyl (wherein the arylalkyl groups may be the same or different), R12C(O)C1-6alkyl (wherein R12 is aziridino, azetidino, pyrrolidino, piperidino, heptamethyleneimino, piperazino, homopiperazino, morpholino, homomorpholino, or thiomorpholino), C(O)R6, C(O)C(O)R6, C(S)R6, S(O)2R6, and C(NR11)R6 (wherein R11 is hydrogen, C1-6alkyl or C6-10aryl and R6 may be H, C1-6alkyl, C6-10aryl, C6-10arylC1-6alkyl or C6-10heteroaryl);
or a pharmaceutically acceptable ester, amide, salt or solvate thereof.

2 more elements

A compound selected from:

2-Amino-5-(4-chlorophenoxy)-4-(trans-4-hydroxycyclohexylamino)pyrimidine;
2-Amino-5-(4-chlorophenoxy)-4-(trans-3-hydroxycyclohexylamino)pyrimidine;
2-Amino-5-(4-chlorophenoxy)-4-(trans-2-hydroxycyclohexylamino)pyrimidine;
2-Amino-5-(4-chlorophenoxy)-4-(cis-4-hydroxycyclohexylamino)pyrimidine;
2-Amino-5-(4-chlorophenoxy)-4-(cyclohexylamino)pyrimidine;
2-Amino-5-(4-chlorophenoxy)-4-(cis-3-hydroxycyclohexylamino)pyrimidine;
2-Amino-5-(4-chlorophenoxy)-4-(cis-2-hydroxycyclohexylamino)pyrimidine;
2-Amino-5-(4-chlorophenoxy)-4-(4-oxocyclohexylamino)pyrimidine;
2-Amino-5-(4-chlorophenoxy)-4-(3-oxocyclohexylamino)pyrimidine;
2-Amino-5-(4-chlorophenoxy)-4-(2-oxocyclohexylamino)pyrimidine;
2-Amino-5-(4-chlorophenoxy)-4-(trans-4-(hydroxymethyl)cyclohexylamino)pyrimidine;
2-Amino-5-(4-chlorophenoxy)-4-(trans-3-(hydroxymethyl)cyclohexylamino)pyrimidine;
2-Amino-5-(4-chlorophenoxy)-4-(trans-2-(hydroxymethyl)cyclohexylamino)pyrimidine;
2-Amino-5-(4-chlorophenoxy)-4-(cis-4-(hydroxymethyl)cyclohexylamino)pyrimidine;
2-Amino-5-(4-chlorophenoxy)-4-(cis-3-(hydroxymethyl)cyclohexylamino)pyrimidine;
2-Amino-5-(4-chlorophenoxy)-4-(cis-2-(hydroxymethyl)cyclohexylamino)pyrimidine;
2-Amino-5-(4-chlorophenoxy)-4-(trans-4-(2-hydroxyethyl)cyclohexylamino)pyrimidine;
2-Amino-5-(4-chlorophenoxy)-4-(trans-3-(2-hydroxyethyl)cyclohexylamino)pyrimidine;
2-Amino-5-(4-chlorophenoxy)-4-(trans-2-(2-hydroxyethyl)cyclohexylamino)pyrimidine;
2-Amino-5-(4-chlorophenoxy)-4-(cis-4-(2-hydroxyethyl)cyclohexylamino)pyrimidine;
2-Amino-5-(4-chlorophenoxy)-4-(cis-3-(2-hydroxyethyl)cyclohexylamino)pyrimidine;
2-Amino-5-(4-chlorophenoxy)-4-(cis-2-(2-hydroxyethyl)cyclohexylamino)pyrimidine;
2-Amino-5-(4-chlorophenoxy)-4-(trans-4-hydroxycyclohexylmethylamino)pyrimidine;
2-Amino-5-(4-chlorophenoxy)-4-(trans-3-hydroxycyclohexylmethylamino)pyrimidine;
2-Amino-5-(4-chlorophenoxy)-4-(trans-2-hydroxycyclohexylmethylamino)pyrimidine;
2-Amino-5-(4-chlorophenoxy)-4-(cis-4-hydroxycyclohexylmethylamino)pyrimidine;
2-Amino-5-(4-chlorophenoxy)-4-(cis-3-hydroxycyclohexylmethylamino)pyrimidine;
2-Amino-5-(4-chlorophenoxy)-4-(cis-2-hydroxycyclohexylmethylamino)pyrimidine;
2-Amino-5-(4-chlorophenoxy)-4-(trans-3-hydroxycyclopentylamino)pyrimidine;
2-Amino-5-(4-chlorophenoxy)-4-(trans-2-hydroxycyclopentylamino)pyrimidine;
2-Amino-5-(4-chlorophenoxy)-4-(cis-3-hydroxycyclopentylamino)pyrimidine;
2-Amino-5-(4-chlorophenoxy)-4-(cis-2-hydroxycyclopentylamino)pyrimidine;
2-Amino-5-(4-chlorophenoxy)-4-(3-oxocyclopentylamino)pyrimidine;
2-Amino-5-(4-chlorophenoxy)-4-(2-oxocyclopentylamino)pyrimidine;
2-Amino-5-(4-chlorophenoxy)-4-(trans-3-(hydroxymethyl)cyclopentylamino)pyrimidine;
2-Amino-5-(4-chlorophenoxy)-4-(trans-2-(hydroxymethyl)cyclopentylamino)pyrimidine;
2-Amino-5-(4-chlorophenoxy)-4-(cis-3-(hydroxymethyl)cyclopentylamino)pyrimidine;
2-Amino-5-(4-chlorophenoxy)-4-(cis-2-(hydroxymethyl)cyclopentylamino)pyrimidine;
2-Amino-5-(4-chlorophenoxy)-4-(trans-3-(2-hydroxyethyl)cyclopentylamino)pyrimidine;
2-Amino-5-(4-chlorophenoxy)-4-(trans-2-(2-hydroxyethyl)cyclopentylamino)pyrimidine;
2-Amino-5-(4-chlorophenoxy)-4-(cis-3-(2-hydroxyethyl)cyclopentylamino)pyrimidine;
2-Amino-5-(4-chlorophenoxy)-4-(cis-2-(2-hydroxyethyl)cyclopentylamino)pyrimidine;
2-Amino-5-(4-chlorophenoxy)-4-(trans-3-hydroxycyclopentylmethylamino)pyrimidine;
2-Amino-5-(4-chlorophenoxy)-4-(trans-2-hydroxycyclopentylmethylamino)pyrimidine;
2-Amino-5-(4-chlorophenoxy)-4-(cis-3-hydroxycyclopentylmethylamino)pyrimidine;
2-Amino-5-(4-chlorophenoxy)-4-(cis-2-hydroxycyclopentylmethylamino)pyrimidine;
2-Amino-5-(4-chlorophenoxy)-4-(trans-2-(hydroxymethyl)cyclobutylmethylamino)pyrimidine;
2-Amino-5-(4-chlorophenoxy)-4-(trans-3-(hydroxymethyl)cyclobutylmethylamino)pyrimidine;
2-Amino-5-(4-chlorophenoxy)-4-(cis-2-(hydroxymethyl)cyclobutylmethylamino)pyrimidine;
2-Amino-5-(4-chlorophenoxy)-4-(cis-3-(hydroxymethyl)cyclobutylmethylamino)pyrimidine;
2-Amino-5-(4-chlorophenoxy)-4-(trans-2-hydroxycyclobutylmethylamino)pyrimidine;
2-Amino-5-(4-chlorophenoxy)-4-(trans-3-hydroxycyclobutylmethylamino)pyrimidine;
2-Amino-5-(4-chlorophenoxy)-4-(cis-2-hydroxycyclobutylmethylamino)pyrimidine;
2-Amino-5-(4-chlorophenoxy)-4-(cis-3-hydroxycyclobutylmethylamino)pyrimidine;
2-Amino-5-(4-chlorophenoxy)-4-(trans-2-(hydroxymethyl)cyclopropylmethylamino)pyrimidine;
2-Amino-5-(4-chlorophenoxy)-4-(cis-2-(hydroxymethyl)cyclopropylmethylamino)pyrimidine;
2-Amino-5-(4-chlorophenoxy)-4-(1-hydroxycyclopropylmethylamino)pyrimidine;
2-Amino-5-(4-chlorophenoxy)-4-(1-hydroxycyclobutylmethylamino)pyrimidine;
2-Amino-5-(4-chlorophenoxy)-4-(1-hydroxycyclopentylmethylamino)pyrimidine;
2-Amino-5-(4-chlorophenoxy)-4-(1-hydroxycyclohexylmethylamino)pyrimidine;
2-Amino-5-(4-chlorophenoxy)-4-(2-hydroxyethylamino)pyrimidine;
2-Amino-5-(4-chlorophenoxy)-4-(3-hydroxypropylamino)pyrimidine;
2-Amino-5-(4-chlorophenoxy)-4-(4-hydroxybutylamino)pyrimidine;
2-Amino-5-(4-chlorophenoxy)-4-(5-hydroxypentylamino)pyrimidine;
2-Amino-5-(4-chlorophenoxy)-4-(6-hydroxyhexylamino)pyrimidine;
2-Amino-5-(4-chlorophenoxy)-4-(2-hydroxy-1-methyl(ethylamino))pyrimidine;
2-Amino-5-(4-chlorophenoxy)-4-(1,1-dimethyl-2-hydroxy(ethylamino))pyrimidine;
2-Amino-5-(4-chlorophenoxy)-4-(1-hydroxymethyl-2-hydroxy(ethylamino))pyrimidine;
2-Amino-5-(4-chlorophenoxy)-4-(2-hydroxy-1-hydroxymethyl-1-methyl(ethylamino))pyrimidine;
2-Amino-5-(4-chlorophenoxy)-4-(tris(hydroxymethyl)methylamino)pyrimidine;
2-Amino-5-(4-chlorophenoxy)-4-(2,3-dihydroxypropylamino)pyrimidine;
2-Amino-5-(4-chlorophenoxy)-4-(3,4-dihydroxybutylamino)pyrimidine;
2-Amino-5-(4-chlorophenoxy)-4-(bis(2-hydroxyethyl)amino)pyrimidine;
2-Amino-5-(4-chlorophenoxy)-4-(bis(3-hydroxypropyl)amino)pyrimidine;
2-Amino-5-(4-chlorophenoxy)-4-(2-methoxyethylamino)pyrimidine;
2-Amino-5-(4-chlorophenoxy)-4-(3-methoxypropylamino)pyrimidine;
2-Amino-5-(4-chlorophenoxy)-4-(3-hydroxypyrrolidino)pyrimidine;
2-Amino-5-(4-chlorophenoxy)-4-(2-hydroxymethylpyrrolidino)pyrimidine;
2-Amino-5-(4-chlorophenoxy)-4-(2-hydroxyethylpyrrolidino)pyrimidine;
2-Amino-5-(4-chlorophenoxy)-4-(3-hydroxymethylpyrrolidino)pyrimidine;
2-Amino-5-(4-chlorophenoxy)-4-(3-(2-hydroxyethyl)pyrrolidino)pyrimidine;
5-(4-Chlorophenoxy)-4-(trans-4-hydroxycyclohexylamino)pyrimidine;
5-(4-Chlorophenoxy)-4-(cis-4-hydroxycyclohexylamino)pyrimidine;
5-(4-Chlorophenoxy)-4-(cis-3-hydroxycyclohexylamino)pyrimidine;
5-(4-Chlorophenoxy)-4-(4-oxocyclohexylamino)pyrimidine;
5-(4-Chlorophenoxy)-4-(trans-4-(hydroxymethyl)cyclohexylamino)pyrimidine;
5-(4-Chlorophenoxy)-4-(trans-3-(hydroxymethyl)cyclohexylamino)pyrimidine;
5-(4-Chlorophenoxy)-4-(trans-3-hydroxycyclopentylamino)pyrimidine;
5-(4-Chlorophenoxy)-4-(trans-2-hydroxycyclopentylamino)pyrimidine;
5-(4-Chlorophenoxy)-4-(trans-3-(hydroxymethyl)cyclopentylamino)pyrimidine;
5-(4-Chlorophenoxy)-4-(trans-2-(hydroxymethyl)cyclopentylamino)pyrimidine;
5-(4-Chlorophenoxy)-4-(trans-2-(hydroxymethyl)cyclopropylmethylamino)pyrimidine;
5-(4-Chlorophenoxy)-4-(2-hydroxyethylamino)pyrimidine;
5-(4-Ethylphenoxy)-4-(trans-4-hydroxycyclohexylamino)pyrimidine;
5-(2,4-Dichlorophenoxy)-4-(trans-4-hydroxycyclohexylamino)pyrimidine;
4-(trans-4-Hydroxycyclohexylamino)-5-(4-trifluoromethylphenoxy)pyrimidine;
5-(4-Chloro-2-fluorophenoxy)-4-(trans-4-hydroxycyclohexylamino)pyrimidine;
2-Amino-5-(4-ethylphenoxy)-4-(trans-4-hydroxycyclohexylamino)pyrimidine;
2-Amino-5-(2,4-dichlorophenoxy)-4-(trans-4-hydroxycyclohexylamino)pyrimidine;
2-Amino-5-(4-chloro-2-methylphenoxy)-4-(trans-4-hydroxycyclohexylamino)pyrimidine;
2-Amino-5-(2-chlorophenoxy)-4-(trans-4-hydroxycyclohexylamino)pyrimidine;
2-Amino-5-(4-bromophenoxy)-4-(trans-4-hydroxycyclohexylamino)pyrimidine;
2-Amino-5-(4-fluorophenoxy)-4-(trans-4-hydroxycyclohexylamino)pyrimidine;
2-Amino-4-(trans-4-hydroxycyclohexylamino)-5-(4-trifluoromethylphenoxy)pyrimidine;
2-Amino-4-(trans-4-hydroxycyclohexylamino)-5-(4-methylphenoxy)pyrimidine;
2-Amino-4-(trans-4-hydroxycyclohexylamino)-5-(2-methylphenoxy))pyrimidine;
2-Amino-4-(trans-4-hydroxycyclohexylamino)-5-(4-isopropylphenoxy)pyrimidine;
2-Amino-5-(4-butylphenoxy)-4-(trans-4-hydroxycyclohexylamino)pyrimidine;
2-Amino-4-(trans-4-hydroxycyclohexylamino)-5-(4-methoxyphenoxy)pyrimidine;
2-Amino-4-(trans-4-hydroxycyclohexylamino)-5-(2-methoxyphenoxy)pyrimidine;
2-Amino-4-(trans-4-hydroxycyclohexylamino)-5-(4-(trifluoromethoxy)phenoxy)pyrimidine;
2-Amino-5-(2,3-difluorophenoxy)-4-(trans-4-hydroxycyclohexylamino)pyrimidine;
2-Amino-5-(2,4-difluorophenoxy)-4-(trans-4-hydroxycyclohexylamino)pyrimidine;
2-Amino-5-(2,6-difluorophenoxy)-4-(trans-4-hydroxycyclohexylamino)pyrimidine;
2-Amino-5-(4-chloro-2-fluorophenoxy)-4-(trans-4-hydroxycyclohexylamino)pyrimidine;
2-Amino-5-(2-chloro-4-fluorophenoxy)-4-(trans-4-hydroxycyclohexylamino)pyrimidine;
2-Amino-5-(2-chloro-4-ethylphenoxy)-4-(trans-4-hydroxycyclohexylamino)pyrimidine;
2-Amino-5-(2,4,6-trichlorophenoxy)-4-(trans-4-hydroxycyclohexylamino)pyrimidine;
or a pharmaceutically acceptable ester, amide, salt or solvate thereof.

116 more elements

A compound selected from:

2-Amino-4-(trans-4-hydroxycyclohexylamino)-5-(4-methylbenzyl)pyrimidine;
2-Amino-5-(4-chlorobenzyl)-4-(trans-4-hydroxycyclohexylamino)pyrimidine;
2-Amino-4-(trans-4-hydroxycyclohexylamino)-5-(4-trifluoromethylbenzyl)pyrimidine;
2-Amino-4-(trans-4-hydroxycyclohexylamino)-5-(isopropylbenzyl)pyrimidine;
2-Amino-5-(4-chlorobenzyl)-4-(4-oxopiperidino)pyrimidine;
2-Amino-5-(4-bromobenzyl)-4-(4-oxopiperidino)pyrimidine;
2-Amino-4-(4-oxopiperidino)-5-(4-trifluoromethylbenzyl)pyrimidine;
2-Amino-5-(4-methylbenzyl)-4-(4-oxopiperidino)pyrimidine;
2-Amino-5-(4-ethylbenzyl)-4-(4-oxopiperidino)pyrimidine;
2-Amino-5-(4-chlorobenzyl)-4-(3-oxopiperidino)pyrimidine;
2-Amino-5-(4-bromobenzyl)-4-(3-oxopiperidino)pyrimidine;
2-Amino-4-(4-oxopiperidino)-5-(3-trifluoromethylbenzyl)pyrimidine;
2-Amino-5-(4-methylbenzyl)-4-(3-oxopiperidino)pyrimidine;
2-Amino-5-(4-ethylbenzyl)-4-(3-oxopiperidino)pyrimidine;
2-Amino-5-(2,4-dichlorobenzyl)-4-(4-oxopiperidino)pyrimidine;
2-Amino-5-(2-chloro-4-bromobenzyl)-4-(4-oxopiperidino)pyrimidine;
2-Amino-5-(2-chloro-4-trifluoromethylbenzyl)-4-(4-oxopiperidino)pyrimidine;
2-Amino-5-(2-chloro-4-methylbenzyl)-4-(4-oxopiperidino)pyrimidine;
2-Amino-5-(2-chloro-4-ethylbenzyl)-4-(4-oxopiperidino)pyrimidine;
2-Amino-5-(2,4-dichlorobenzyIl)-4-(3-oxopiperidino)pyrimidine;
2-Amino-5-(2-chloro-4-bromobenzyl)-4-(3-oxopiperidino)pyrimidine;
2-Amino-5-(2-chloro-4-trifluoromethylbenzyl)-4-(3-oxopiperidino)pyrimidine;
2-Amino-5-(2-chloro-4-methylbenzyl)-4-(3-oxopiperidino)pyrimidine;
2-Amino-5-(2-chloro-4-ethylbenzyl)-4-(3-oxopiperidino)pyrimidine;
5-Benzyl-4-(trans-4-hydroxycyclohexylamino)pyrimidine;
5-(4-Chlorobenzyl)-4-(4-oxopiperidino)pyrimidine;
5-(4-Bromobenzyl)-4-(4-oxopiperidino)pyrimidine;
4-(4-Oxopiperidino)-5-(4-trifluoromethylbenzyl)pyrimidine;
5-(4-Mthylbenzyl)-4-(4-oxopiperidino)pyrimidine;
5-(4-Ethylbenzyl)-4-(4-oxopiperidino)pyrimidine;
5-(4-Chlorobenzyl)-4-(3-oxopiperidino)pyrimidine;
5-(4-Bromobenzyl)-4-(3-oxopiperidino)pyrimidine;
4-(4-Oxopiperidino)-5-(3-trifluoromethylbenzyl)pyrimidine;
5-(4-Methylbenzyl)-4-(3-oxopiperidino)pyrimidine;
5-(4-Ethylbenzyl)-4-(3-oxopiperidino)pyrimidine;
5-(2,4-Dichlorobenzyl)-4-(4-oxopiperidino)pyrimidine;
5-(2-Chloro-4-bromobenzyl)-4-(4-oxopiperidino)pyrimidine;
5-(2-Chloro-4-trifluoromethylbenzyl)-4-(4-oxopiperidino)pyrimidine;
5-(2-Chloro-4-methylbenzyl)-4-(4-oxopiperidino)pyrimidine;
5-(2-Chloro-4-ethylbenzyl)-4-(4-oxopiperidino)pyrimidine;
5-(2,4-Dichlorobenzyl)-4-(3-oxopiperidino)pyrimidine;
5-(2-Chloro-4-bromobenzyl)-4-(3-oxopiperidino)pyrimidine;
5-(2-Chloro-4-trifluoromethylbenzyl)-4-(3-oxopiperidino)pyrimidine;
5-(2-Chloro-4-methylbenzyl)-4-(3-oxopiperidino)pyrimidine;
5-(2-Chloro-4-ethylbenzyl)-4-(3-oxopiperidino)pyrimidine;
2-Amino-5-(4-chlorophenethyl)-4-(trans-4-hydroxycyclohexylamino)pyrimidine;
2-Amino-5-(4-chlorobenzyloxy)-4-(trans-4-hydroxycyclohexylamino)pyrimidine;
or a pharmaceutically acceptable ester, amide, salt or solvate thereof.

45 more elements

Dependencies are inferred from the claim text.

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Abstract

A compound of the formula

wherein:
X is a C6-10 aryl ring or a C6-10 heteroaryl ring optionally substituted with one or more substituents selected from the group consisting of halogen, C1-6 alkyl, C2-7alkenyl, C2-7alkynyl, C6-10aryl, C6-10heteroaryl, OR, 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 n is 0, 1 or 2, NR′S(O)mR′ wherein m is 1 or 2, S(O)2NR9R10, NO2, CN, CF3, and OCF3, wherein R is H, C1-6alkyl, C3-8cycloalkyl, C6-10aryl or C6-10arylC1-6alkyl and R′ is C1-6alkyl, C3-8cycloalkyl, C6-10aryl or C6-10arylC1-6alkyl;
R1 is pyrrolidino, 3-oxopiperidino, 4-oxopiperidino, or NR4R5, wherein R4 and R5 are independently H, C3-11alkenyl, C3-11alkynyl, dihydroxyC3-10alkyl, hydroxyC2-10alkyl, C1-6alkyloxyC2-6alkyl, C1-6alkylthioC2-6alkyl, (C1-6alkyl)j(C3-9cycloalkyl)(CH2)q (wherein j is 0 or 1 and q is 0-6), (C1-6alkyl)j(C4-9heterocycloalkyl)(CH2)q (wherein j and q are as above and the heterocyclic ring contains one heteroatom which is O, S or N), oxo(C3-8cycloalkyl)(CH2)q (wherein q is 0-6), hydroxy(CH2)p(C3-8cycloalkyl)(CH2)q (wherein p and q are independently 0-6), or C2-6alkyl, provided that both R4 and R5 are not H or C2-6alkyl and that if R4 is H, R5 is not hydroxyC1-6alkyloxyC2-6alkyl;
wherein C or N atoms of R4 and R5 may be substituted with one or more substituents selected from the group consisting of OH, oxo, 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, C6-10heteroarylC1-6alkoxy, C1-6alkylcarbonylC1-6alkyl, C6-10arylcarbonylC1-6alkyl, carboxyC1-6alkyl, C1-6alkoxycarbonylC1-6alkyl, C6-10aryloxycarbonylC1-6alkyl, C6-10arylC1-6alkyloxycarbonylC1-6alkyl, cyanoC1-6alkyl, C1-6alkylthioC1-6alkyl, C1-6alkylsulfinylC1-6alkyl, C1-6alkylsulfonylC1-6alkyl, C6-10arylthioC1-6alkyl, C6-10arylsulfinylC1-6alkyl, C6-10arylsulfonylC1-6alkyl, C6-10arylC1-6alkylthioC1-6alkyl, C6-10arylC1-6alkylsulfinylC1-6alkyl, C6-10arylC1-6alkylsulfonylC1-6alkyl, C6-10heteroarylthioC1-6alkyl, C6-10heteroarylsulfinylC1-6alkyl, C6-10heteroarylsulfonylC1-6alkyl, aziridino, azetidino, pyrrolidino, piperidino, heptamethyleneimino, homopiperazino, N-substituted homopiperazino (wherein the substituent may be C1-6alkyl, C6-10aryl, C6-10arylC1-6alkyl or C6-10heteroaryl), piperazino, N-substituted piperazino (wherein the substituent may be C1-6alkyl, C6-10aryl, C6-10arylC1-6alkyl or C6-10heteroaryl), morpholino, homomorpholino, thiomorpholino, aminoC1-6alkyl, C1-6alkylaminoC1-6alkyl, di(C1-6alkyl)aminoC1-6alkyl (wherein the alkyl groups may be the same or different), C6-10arylaminoC1-6alkyl, C6-10arylC1-6alkylaminoC1-6alkyl, di(C6-10aryl)aminoC1-6alkyl (wherein the aryl groups may be the same or different), di(C6-10arylC1-6alkyl)aminoC1-6alkyl (wherein the arylalkyl groups may be the same or different), R12C(O)C1-6alkyl (wherein R12 is aziridino, azetidino, pyrrolidino, piperidino, heptamethyleneimino, piperazino, homopiperazino, morpholino, homomorpholino, or thiomorpholino), C(O)R6, C(O)C(O)R6, C(S)R6, S(O)2R6, and C(NR11)R6 (wherein R11 is hydrogen, C1-6alkyl or C6-10aryl and R6 may be H, C1-6alkyl, C6-10aryl, C6-10arylC1-6alkyl or C6-10heteroaryl);
or a pharmaceutically acceptable ester, amide, salt or solvate thereof.

2 more elements