2-(amino-substituted)-4-aryl pyrimidines and related compounds useful for treating inflammatory diseases

A compound of formula I-A-i:

• or a pharmaceutically acceptable salt thereof, wherein:
• a. Cy2 is phenyl, pyridyl, naphthyl, thienyl, benzo[1,3]dioxolyl, benzo[1,3]dioxinyl, indolyl, or tetrazole, optionally substituted by one to three occurrences of R9 and one occurrence of R10 wherein:
• each occurrence of R9 is independently —ORB, —N(RB)C(O)RA, —N(RB)2, halo, C1-4aliphatic optionally substituted by halo, —NO2, —OS(O)2RC, —S(O)RC, —N(RB)SO2RA, or —S(O)2N(RB)2;
• R10 is phenyl, or a 5-6 membered heterocyclyl or heteroaryl ring;
• each occurrence of RA is independently 1-1, C1-3alkyl or C3-5cycloalkyl;
• each occurrence of RB is independently H or C1-4 aliphatic;
• and each occurrence of RC is independently C1-4 aliphatic;
• b. ring A is optionally substituted with one or two occurrences of R5, wherein each occurrence of R5 on ring A, when present, is independently F, Cl, Br, or methyl;
• c. W is:
• wherein:
• m is 1, 2, or 3;
• each occurrence of RF is independently H or C1-3alkyl;
• RE is H, C1-3alkyl, or SO2CH3;
• each of the foregoing pyridyl, pyrrolidinyl, piperidinyl, and piperazinyl groups is optionally substituted at one or more carbon atoms with 1, 2, or 3 occurrences of R11;
• each of the foregoing pyridyl, pyrrolidinyl, piperidinyl, and piperazinyl groups is optionally substituted at one or more substitutable nitrogen atoms with R12;
• each occurrence of R11 is independently optionally substituted C1-6aliphatic, optionally substituted 6-10-membered aryl, optionally substituted 5-10-membered heteroaryl, —N(RB)2, ═O, halo, —NO2, —CN, —ORB, —C(O)RA, —CO2RA, SRC, —S(O)RC, —S(O)2RC, —OS(O)2RC, —N(RB)C(O)RA, —N(RB)CO2RA, —N(RB)SO2RA, —C(O)N(RB)2, —SO2N(RB)2, —N(RB)C(O)N(RB)2, or —OC(O)RA;
• each occurrence of R12 is independently H, optionally substituted C1-6 aliphatic, optionally substituted 6-10-membered aryl, optionally substituted 5-10-membered heteroaryl, —C(═O)RB, —C(O)ORB or —SO2RB;
• ii) —V—R8, wherein V is —CH2— and R8 is:
• wherein each of the foregoing pyrrolidinyl, piperidinyl, and pyridyl groups are unsubstituted, or are substituted on one or two carbon atoms with one or two independent occurrences of C1-4alkyl, phenyl, heteroaryl, halo, —COOH, —COO(C1-4alkyl), —CONH2, —CONH(C1-4alkyl), —CON(C1-4alkyl)2, —CONH(heteroaryl), —CN, —NH2, —OH, —O(C1-4alkyl), —NH(C1-4alkyl), —N(C1-4alkyl)2, ═O, or C1-4alkyl substituted with one or two independent occurrences of phenyl, heteroaryl, halo, —COOH, —COO(C1-4alkyl), —CONH2, —CONH(C1-4alkyl), —CON(C1-4alkyl)2, —CONH(heteroaryl), —CN, —NH2, —OH, —O(C1-4alkyl), —NH(C1-4alkyl), or —N(C1-4alkyl)2;
• and wherein each of the foregoing pyrrolidinyl, piperidinyl, and pyridyl groups are optionally substituted on one substitutable nitrogen atom with —C1-4alkyl, —COO(C1-4alkyl), —SO2(C1-4alkyl), benzyl, or —CH2(heteroaryl);
• and
• d) Ring B is optionally substituted by one to three occurrences of R6, wherein each occurrence of R6 is independently —OMe, methyl, ethyl, F, or Cl.

A compound of formula I-B-i:

• or a pharmaceutically acceptable salt thereon wherein:
• a. Cy2 is a C6-10aryl or a 5-10-membered heteroaryl ring optionally substituted by one to three occurrences of R9 and one occurrence of R10, wherein:
• each occurrence of 1(9 is independently —ORB, —N(RB)C(O)RA, —N(RB)2, halo, C1-4aliphatic optionally substituted by halo, —NO2, —OS(O)2RC, —S(O)RC, —N(RB)SO2RA, or —S(O)2N(RB)2;
• R10 is phenyl, or a 5-6 membered heterocyclyl or heteroaryl ring;
• each occurrence of RA is independently H, C1-3alkyl or C3-5cycloalkyl;
• each occurrence of RB is independently H or C1-4 aliphatic;
• and each occurrence of RC is independently C1-4 aliphatic;
• b. ring A is optionally substituted with 1 or 2 occurrences of R5, wherein each occurrence of R5 on ring A, when present, is independently halo or optionally substituted C1-4 aliphatic;
• c. W is -L1-V—R8, wherein L1 is —CH2—, V is —NRE— or —NRECO—, wherein:
• each occurrence of RE is independently H, C1-6 aliphatic, —C(═O)RB, —C(O)OR8 or —SO2RB;
• R8 is C1-6alkyl, a 5-6-membered heteroaryl group, or a 3-7-membered heterocyclyl group;
• wherein R8 is unsubstituted, or R8 is substituted on one or two carbon atoms with one or two independent occurrences of C1-4alkyl, phenyl, heteroaryl, halo, —COOH, —COO(C1-4alkyl), —CONH2, —CONH(C1-4alkyl), —CON(C1-4alkyl)2, —CONH(heteroaryl), —CN, —NH12, —OH, —O(C1-4alkyl), —NH(C1-4alkyl), —N(C1-4alkyl)2, —O, or C1-4alkyl substituted with one or two independent occurrences of phenyl, heteroaryl, halo, —COOH, —COO(C1-4alkyl), —CONH2, —CONH(C1-4alkyl), —CON(C1-4alkyl)2, —CONH(heteroaryl), —CN, —NH2, —OH, —O(C1-4alkyl), —NH(C1-4alkyl), or —N(C1-4alkyl)2;
• and R8 is optionally substituted on one substitutable nitrogen atom with —C1-4alkyl, —COO(C1-4alkyl), —SO2(C1-4alkyl), benzyl, or —CH2(heteroaryl);
• and
• d) Ring B is optionally substituted by one occurrence of R6, wherein R6 is independently —ORB, C1-3aliphatic, or halo.