Substituted Amino-Compounds and Uses Thereof

A compound of formula Ia or formula Ib:

• or a pharmaceutically acceptable salt, tautomer or in vivo-hydrolysable precursor thereof, wherein:
• W is C or N;
• Q is selected from C3-12cycloalkyl, C3-12cycloalkenyl, C6-14aryl, or C5-15heterocyclyl;
• each R′ is, independently, selected from H, halogen, C2-6alkenyl, C1-6alkyl, C3-12cycloalkyl, C6-10aryl, C1-6alkyl-C6-10aryl, or C5-15heterocyclyl wherein said C1-6alkyl, said C3-12cycloalkyl, said C6-10aryl, said C1-6alkyl-C6-10aryl, or said C5-15heterocyclyl is optionally substituted by 1, 2, or 3 substitutents independently selected from:
• halogen, CN, NH2, OH, COOH, OC1-6alkyl, CH2OH, SO2H, S(═O), C2-6alkenyl, C1-6alkyl-Ra, OC1-6alkyl-Ra, C(═O)C1-6alkyl-Ra, C(═O)OC1-6alkyl-RaC(═O)NH2, C(═O)NHC1-6alkyl-Ra, C(═O)N(C1-6alkyl-Ra)2, S(═O)C1-6alkyl-Ra, S(═O)NHC1-6alkyl-Ra, S(═O)N(C1-6alkyl-Ra)2, SO2C1-6alkyl-Ra, SO2NHC1-6alkyl-Ra, SO2N(C1-6alkyl-Ra)2, NH(C1-6alkyl)-Ra, N(C1-6alkyl-Ra)2, NHC(═O)C1-6alkyl, C6-10aryl-Ra, OC6-10aryl-Ra, C(═O)C6-10aryl-Ra, C(═O)OC6-10aryl-Ra, C(═O)NHC6-10aryl-Ra, C(═O)N(C6-10aryl-Ra)2, S(═O)C6-10aryl-Ra, S(═O)NHC6-10aryl-Ra, S(═O)N(C6-10aryl-Ra)2, SO2C6-10aryl-Ra, SO2NHC6-10aryl-Ra, SO2N(C6-10aryl-Ra)2, NH(C6-10aryl)-Ra, N(C6-10aryl-Ra)2, NC(═O)C6-10aryl, C5-6heterocyclyl-Ra, OC5-6heterocyclyl-Ra, C(═O)C5-6heterocyclyl-Ra, C(═O)OC5-6heterocyclyl-Ra, C(═O)NHC5-6heterocyclyl Ra, C(═O)N(C5-6heterocyclyl Ra)2, S(═O)C5-6heterocyclyl-Ra, S(═O)NHC5-6heterocyclyl-Ra, S(═O)N(C5-6heterocyclyl-Ra)2, SO2C5-6heterocyclyl-Ra, SO2NHC5-6heterocyclyl-Ra, SO2N(C5-6heterocyclyl-Ra)2, NH(C5-6heterocyclyl-Ra), N(C5-6heterocyclyl-Ra)2, NHC(═O)C5-6heterocyclyl, SO2Ra, S(═O)Ra, N(C1-6alkyl-Ra)(C6-10aryl-Ra), N(C1-6alkyl-Ra)(C6-10heteroaryl-Ra), N(C6-10aryl-Ra)(C6-10heteroaryl-Ra), C(═O)(C1-6alkyl-Ra)(C6-10aryl-Ra), C(═O)(C1-6alkyl-Ra)(C6-10heteroaryl-Ra), C(═O)(C6-10aryl-Ra)(C6-10heteroaryl-Ra), C(═O)O(C1-6alkyl-Ra)(C6-10aryl-Ra), C(═O)O(C1-6alkyl-Ra)(C6-10heteroaryl-Ra), C(═O)O(C6-10aryl-Ra)(C6-10heteroaryl-Ra), S(═O)(C1-6alkyl-Ra)(C6-10aryl-Ra), S(═O)(C1-6alkyl-Ra)(C6-10heteroaryl-Ra), S(═O)(C6-10aryl-Ra)(C6-10heteroaryl-Ra), SO2(C1-6alkyl-Ra)(C6-10aryl-Ra), SO2(C1-6alkyl-Ra)(C6-10heteroaryl-Ra), or SO2(C6-10aryl-Ra)(C6-10heteroaryl-Ra);
• each Ra is, independently, selected from H, halogen, CN, NH2, OH, C1-6alkyl, OC1-6alkyl, C(═O)C1-6alkyl, C(═O)OC1-6alkyl, C(═O)NH2, C(═O)NHC1-6alkyl, C(═O)N(C1-6alkyl)2, SOC1-6alkyl, SONHC1-6alkyl, SON(C1-6alkyl)2, SO2C1-6alkyl, SO2NHC1-6alkyl, SO2N(C1-6alkyl)2, NH(C1-6alkyl), N(C1-6alkyl)2, NC(═O)C1-6alkyl, C5-6aryl, OC5-6aryl, C(═O)C5-6aryl, C(═O)OC5-6aryl, C(═O)NH2, C(═O)NHC5-6aryl, C(═O)N(C5-6aryl)2, SO2C5-6aryl, SO2NHC5-6aryl, SO2N(C5-6aryl)2, NH(C5-6aryl), N(C5-6aryl)2, NC(═O)C5-6aryl, C5-6heterocyclyl, OC5-6heterocyclyl, C(═O)C5-6heterocyclyl, C(═O)OC5-6heterocyclyl, C(═O)NH2, C(═O)NHC5-6heterocyclyl, C(═O)N(C5-6heterocyclyl)2, S(═O)C5-6heterocyclyl, S(═O)NHC5-6heterocyclyl, S(═O)N(C5-6heterocyclyl)2, SO2NHC5-6heterocyclyl, SO2N(C5-6heterocyclyl)2, NH(C5-6heterocyclyl), N(C5-6heterocyclyl)2, NC(═O)C5-6heterocyclyl, C(═O)NHC1-6alkylC5-6aryl, NRbRb, C(═O)Rb, C(═O)NRbRb, OC(═O)NRbRb, S(═O)Rb, S(═O)NRbRb, or SO2NRbRb;
• each Rb is, independently, selected from H, C1-6alkyl, C5-6aryl, or C5-6heterocyclyl;
• each V is, independently, selected from NH, O, S, S(═O), SO2, NHS(═O), NHSO2, S(═O)NH, SO2NH, NHC(═O), C(═O)NH, NRaSO2, NRaS(═O), NRaC(O), C(O)NRa, S(O)2NRa, S(═O)NRa, OC1-6alkylenyl, C2-6alkenylenyl or C1-6alkylenyl, wherein said OC1-6alkylenyl, C2-6alkenylenyl, and C1-6alkylenyl is optionally substituted by 1, 2, or 3 substitutents independently selected from Ra;
• X, Y, and Z are, independently, selected from NH, O, S, S(═O), SO2, NHS(═O), NHSO2, S(═O)NH, SO2NH, NHC(═O), C(═O)NH, NRaSO2, NRaS(═O), NRaC(O), C(O)NRa, S(O)2NRa, S(═O)NRa, or C1-6alkyl wherein said C1-6alkyl is optionally substituted by 1, 2, or 3 substituents independently selected from Ra;
• m is 0, 1, 2 or 3;
• n, q, r, s, and u are each, independently, 0 or 1;
• R2 is selected from H, halogen, C1-6alkyl, C3-12cycloalkyl, C6-10aryl, C1-6alkyl-C6-10aryl, C5-10heterocyclyl, or C1-6alkyl-C5-10heterocyclyl wherein said C1-6alkyl, C3-12cycloalkyl, C6-10aryl, C1-6alkyl-C6-10aryl, C5-10heterocyclyl, and C1-6alkyl-C5-10heterocyclyl is optionally substituted by 1, 2, or 3 substitutents independently selected from:
• halogen, CN, NH2, OH, C1-6alkyl-Ra, OC1-6alkyl-Ra, C(═O)C1-6alkyl-Ra, C(═O)OC1-6alkyl-Ra, C(═O)NH2, C(═O)NHC1-6alkyl-Ra, C(═O)N(C1-6alkyl-Ra)2 S(═O)C1-6alkyl-Ra, S(═O)NHC1-6alkyl-Ra, S(═O)N(C1-6alkyl-Ra)2, SO2C1-6alkyl-Ra, SO2NHC1-6alkyl-Ra, SO2N(C1-6alkyl-Ra)2, NH(C1-6alkyl)-Ra, N(C1-6alkyl-Ra)2, NHC(═O)C1-6alkyl, C5-6aryl-Ra, OC5-6aryl-Ra, C(═O)C5-6aryl-Ra, C(═O)OC5-6aryl-Ra, C(═O)NH2, C(═O)NHC5-6aryl-Ra, C(═O)N(C5-6aryl-Ra)2, S(═O)C5-6aryl-Ra, S(═O)NHC5-6aryl-Ra, S(═O)N(C5-6aryl-Ra)2, SO2C5-6aryl-Ra, SO2NHC5-6aryl-Ra, SO2N(C5-6aryl Ra)2, NH(C5-6aryl) Ra, N(C5-6aryl-Ra)2, NHC(═O)C5-6aryl, C5-6heterocyclyl-Ra, OC5-6heterocyclyl-Ra, C(═O)C5-6heterocyclyl-Ra, C(═O)OC5-6heterocyclyl-Ra, C(═O)NH2, C(═O)NHC5-6heterocyclyl-Ra, C(═O)N(C5-6heterocyclyl-Ra)2, SO2C5-6heterocyclyl-Ra, SO2NHC5-6heterocyclyl-Ra, SO2N(C5-6heterocyclyl-Ra)2 S(═O)C5-6heterocyclyl-Ra, S(═O)NHC5-6heterocyclyl-Ra, S(═O)N(C5-6heterocyclyl-Ra)2, NH(C5-6heterocyclyl)-Ra, N(C5-6heterocyclyl-Ra)2, or NHC(═O)C5-6heterocyclyl;
• R3 is selected from R1, C1-6alkylRc, C1-6alkylNRcRc, C1-6alkylORc, C1-6alkylSRc, C1-6alkylNHC1-6alkylC5-6arylRd, C1-6alkylNHC6-10arylRd, C1-6alkylNHC(O)C6-10arylRd, C1-6alkylOC1-6alkylC5-6arylRdC1-6alkylSC1-6alkylC5-6arylRdC1-6alkylC5-9heterocyclylRd, C1-6alkylC3-9cycloalkylRd, C1-6alkylNHC1-6alkylC5-9heterocyclylRd, C1-6alkylNHC5-9heterocyclyl(Rd)t, C1-6alkylNHC(O)C5-9heterocyclylRd, C1-6alkylOC1-6alkylC5-9heterocyclylRd, C1-6alkylSC1-6alkylC5-9heterocyclylRd, C1-6alkylNHC1-6alkylC3-9cycloalkylRd, C1-6alkylOC1-6alkylC3-9cycloalkylRd, or C1-6alkylSC1-6alkylC3-9cycloalkylRd;
• t is 0, 1, 2, 3, 4 or 5;
• each Rc is, independently, selected from H, C(═O)C1-4alkyl, C(═O)C1-4alkylOC1-4alkyl, C(═O)C1-4alkylC(═O)OC1-4alkyl, C(═O)C1-4alkylC(═O)OH, C(═O)C1-4alkylOC(═O)C1-4alkyl, C5-6arylRd, C5-9heterocyclylRd, C3-9cycloalkylRd, C(═O)C5-6arylRd, C(═O)C5-9heterocyclylRd, C(═O)C3-9cycloalkylRd, C1-4alkyl C5-6arylRd, C1-4alkyl-C5-9heterocyclylRd, or C1-4alkyl-C3-9cycloalkylRd;
• and
• Rd is selected from H, C1-3alkyl, NH2, OH, COOH, OC1-3alkyl, or OC1-3alkylOH;
• provided that:
• a) when the compound has formula Ia, W is N, R2 is C1-4alkyl, q is 0, r is 0, and s is 0, then [R1—V)n]m-Q is other than phenyl;
• b) when the compound has formula Ia, W is N, R2 is C1-4alkyl, q is 0, r is 0, s is 0, Q is phenyl, and m is 1, then R1—V)n— is other than bromo, pyridyl, or methoxyphenyl;
• c) when the compound has formula Ib, W is N, and —[X]q—[Y]r—[Z]s— is —H2—, then [R1—(V)n]m-Q is other than phenyl;
• d) when the compound has formula Ib, W is N, —[X]q—[Y]r—[Z]s— is —CH2— or —CH(CH3)—, Q is phenyl, and m is 2, then at least one of R1—V)n— is other than fluoro;
• e) when the compound has formula Ib, W is N, —[X]q—[Y]r—[Z]s— is —NH—, Q is phenyl, and m is 2, then at least one of R1(V)n— is other than C1-4alkyl;
• and
• f) when the compound has formula Ib, W is N, and —[X]q—[Y]r—[Z]s— is —O—, then [R1—(V)n]m-Q is other than phenyl.

A compound according to claim 1, or a pharmaceutically acceptable salt, tautomer or in vivo-hydrolysable precursor thereof, wherein:

• R1 is, independently, selected from H, halogen, C6aryl, or C5-6heterocyclyl wherein said C6aryl, or C5-6heterocyclyl is optionally substituted by 1, 2, or 3 substituents, independently, selected from:
• halogen, OH, NH2, CN, C(═O)NH2, C1-6alkyl, OC1-6alkyl, C1-4alkylOH, C1-4alkylOC1-3alkyl, CH2OH, SO2H, SO2NHC(CH3)3, SO2C1-6alkyl, SO2NHC1-6alkyl, OC1-3alkylOC1-3alkyl, OC1-3alkylOH, OC1-3alkylOC(═O)C1-3alkyl, C(═O)C1-6alkyl, C(═O)OC1-6alkyl, C(═O)NH2, C5-6heterocyclyl, OC5-6aryl, —C6aryl-OC1-4alkyl or OC1-6alkyl-C5-6aryl;
• and
• R2 is H or C1-6alkyl;
• and
• R3 is H or C1-3alkyl.

A compound according to claim 1, or a pharmaceutically acceptable salt, tautomer or in vivo-hydrolysable precursor thereof, wherein:

• Q is C6aryl or C5-9heterocyclyl;
• W is N;
• R1 is, independently, selected from H, halogen, C6aryl, or C5-6heterocyclyl wherein said C6aryl, or C5-6heterocyclyl is optionally substituted by 1, 2, or 3 substituents, independently, selected from:
• halogen, OH, NH2, CN, C(═O)NH2, C1-6alkyl, OC1-6alkyl, C1-4alkylOH, C1-4alkylOC1-3alkyl, CH2OH, SO2H, SO2NHC(CH3)3, SO2C1-6alkyl, SO2NHC1-6alkyl, OC1-3alkylOC1-3alkyl, OC1-3alkylOH, OC1-3alkylOC(═O)C1-3alkyl, C(═O)C1-6alkyl, C(═O)OC1-6alkyl, C(═O)NH2, C5-6heterocyclyl, OC5-6aryl, —C6aryl-OC1-4alkyl or OC1-6alkyl-C5-6aryl;
• and
• R2 is C1-3alkyl.

A compound according to claim 3, or a pharmaceutically acceptable salt, tautomer or in vivo-hydrolysable precursor thereof, wherein:

• Q is C6-10aryl;
• W is N;
• —[X]q—[Y]r—[Z]s— is OC1-3alkyl;
• m is 1;
• n is 0;
• and
• R′ is C6-10aryl optionally substituted by 1 or 2 substituents independently selected from:
• OC1-4alkyl and —C6aryl-OC1-4alkyl.

A compound according to claim 3, or a pharmaceutically acceptable salt, tautomer or in vivo-hydrolysable precursor thereof, wherein:

• Q is C3-10cycloalkenyl;
• W is N
• —[X]q—[Y]r—[Z]s— is absent;
• m is 1;
• n is 0;
• and
• R1 is C6-10aryl optionally substituted by 1 or 2 substituents independently selected from:
• OC1-4alkyl and —C6aryl-OC1-4alkyl.

A compound according to claim 2, or a pharmaceutically acceptable salt, tautomer or in vivo-hydrolysable precursor thereof, wherein:

• Q is C6-10aryl, C3-10cycloalkyl or C3-10cycloalkenyl;
• W is N;
• —[X]q—[Y]r—[Z]s— is OC1-3alkyl, N(C1-3alkyl)C1-3alkyl, C1-3alkylOC1-3alkyl, C1-3alkylN(H)C1-3alkyl or C1-3alkyl optionally substituted by OH;
• m is 1;
• V is S;
• n is 0 or 1;
• and
• R1 is C6-10aryl or C5-15heterocyclyl, wherein each said aryl and heterocyclyl is optionally substituted by 1 or 2 substituents independently selected from:
• halogen, CN, C1-4alkyl, C1-4haloalkyl, OC1-4alkyl, OC1-4haloalkyl, —C(O)H, COOH, OC1-4alkyl-C6-10aryl, OH, NHC(═O)C1-4alkyl and —C6aryl-OC1-4alkyl.

A compound according to claim 1 selected from:

• 2-amino-6-[[3-(3-methoxyphenyl)phenoxy]methyl]-3-methyl-3H-pyrimidin-4-one;
• and
• 2-amino-6-[2-[3-(3-methoxyphenyl)phenyl]-3-bicyclo[2.2.1]hept-5-enyl]-3-methyl-3H-pyrimidin-4-one,
• or a pharmaceutically acceptable salt, tautomer, or in vivo-hydrolysable precursor thereof.