Pharmaceutical compounds for treatment of medical disorders

A compound of Formula:

• or a pharmaceutically acceptable salt thereof;
• wherein:
• A is selected from A1 and A3;
• C5 is selected from:
• L is
• L3 is —C(O)—;
• A1 is selected from:
• A3 is selected from:
• X51, X52, and X53 are independently selected from N, CR31, and CR201;
• wherein at least one of X51, X52, and X53 is selected from CR201;
• X54, X55, and X56 are independently selected from N, CR31, and CR201;
• R201 is selected from aminoalkyl-, alkylaminoalkyl-, heterocycloalkyl-, hydroxyalkyl, -alkyl-O-alkyl, -alkyl-S-alkyl, -alkyl-N(alkyl)-alkyl, -alkyl-NH-alkyl, -aliphatic-O-aliphatic, -aliphatic-S-aliphatic, -aliphatic-N(aliphatic)-aliphatic, -aliphatic-NH-aliphatic, -aliphatic-O-heterocycle, -aliphatic-S-heterocycle, -aliphatic-N(aliphatic)-heterocycle, -aliphatic-NH-heterocycle, -alkyl-NHC(O)haloalkyl, -alkyl-NR9C(O)haloalkyl, -alkyl-C(O)NHhaloalkyl, -alkyl-C(O)NR9haloalkyl, -alkyl-NHC(O)haloalkyl, -alkyl-NR9C(O)aliphatic, -alkyl-C(O)NHaliphatic, -alkyl-NR9C(O)aliphatic, -alkyl-NHC(O)aliphatic, -substituted alkyl-N(R9)-substituted alkyl, alkyl-heteroaryl, -alkyl-O-haloalkyl, heteroaryl, heterocycle, alkyl-heterocycle, and —N(aliphatic)2;
• R202 is selected from aryl and heteroaryl, wherein the aryl and heteroaryl groups are substituted with R201;
• R5 and R6 are independently selected from hydrogen, halogen, —CHO, —C(O)NH2, —C2-C6alkanoyl, —C(O)NH(CH3), —COOH, —P(O)(OR9)2, —OC(O)R9, —C(O)OR9, nitro, hydroxyl, phenyl, 5- to 6-membered heteroaryl, cyano, amino, and C1-C6alkyl;
• R8 and R8′ are hydrogen;
• R9 and R10 are independently selected from hydrogen, C1-C6alkyl, (C3-C7cycloalkyl)C0-C4alkyl, —C0-C4alkyl(C3-C7cycloalkyl), and —O—C0-C4alkyl(C3-C7cycloalkyl);
• X11 is N or CR11;
• X12 is N or CR12;
• X13 is N or CR13;
• X14 is N or CR14;
• wherein no more than 2 of X11, X12, X13, and X14 are N;
• wherein one of R12 and R13 is R32 and the other is R31 or R32;
• and wherein if there is no R13 and no R32 on the A ring then R12 is R32;
• and wherein if there is no R12 and no R32 on the A ring then R13 is R32;
• R31 is independently selected from hydrogen, halogen, hydroxyl, nitro, cyano, amino, —COOH, C1-C6haloalkyl, C1-C6haloalkoxy, C1-C6alkyl, —C0-C4alkyl(C3-C7cycloalkyl), C2-C6alkenyl, C2-C6alkanoyl, C1-C6alkoxy, C2-C6alkenyloxy, —C(O)OR9, C1-C6thioalkyl, —C0-C4alkylNR9R10, —C(O)NR9R10, —SO2R9, —SO2NR9R10, —OC(O)R9, and —C(NR9)NR9R10, each of which R31 other than hydrogen, halogen, hydroxyl, nitro, cyano, C1-C6haloalkyl, and C1-C6haloalkoxy is optionally substituted with one or more substituents independently selected from halogen, hydroxyl, nitro, cyano, amino, —COOH, —C(O)NR9R10, C1-C6haloalkyl, C1-C6haloalkoxy, phenyl, and 4- to 7-membered heterocycle containing 1, 2, or 3 heteroatoms independently selected from N, O, and S;
• each of which phenyl or 4- to 7-membered heterocycle is optionally substituted with one or more substituents independently selected from halogen, hydroxyl, nitro, cyano, C1-C6alkyl, C2-C6alkenyl, C2-C6alkanoyl, C1-C6alkoxy, (mono- and di-C1-C6alkylamino)C0-C4alkyl, C1-C6alkylester, —C0-C4alkyl)(C3-C7cycloalkyl), C1-C6haloalkyl, and C1-C6haloalkoxy;
• R32 is selected from C(O)NR21R71, —C(O)NR9R71, —NR9C(O)OR10, —NR9C(O)OR23, —NR9C(O)R21, —NR9C(O)NR9R10, and —NR9C(O)NR10R23;
• or R32 is selected from NR72R73, NR9SO2R73, and N(SO2R9)CH2C(O)R74;
• or R32 is selected from —OC(O)(CH2)1-4R21, —OC(O)NR21R22, —OC(O)(C1-6alkyl or C3-6cycloalkyl)(aryl), —OC(O)(C1-6alkyl or C3-6cycloalkyl)(heteroaryl), —OC(O)(C1-6alkyl or C3-6cycloalkyl)(heterocycle), —OC(O)(heteroaryl), —OC(O)(aryl), —OC(O)(C1-6alkyl or C3-6cycloalkyl), —OC(O)NR9(CH2)1-4P(O)(OR21)(OR22), —C(O)(C1-6alkyl or C3-6cycloalkyl)(aryl), —C(O)(C1-6alkyl or C3-6cycloalkyl)(heteroaryl), —C(O)(C1-6alkyl or C3-6cycloalkyl)(heterocycle), —C(O)(heteroaryl), —C(O)(heterocycle), —C(O)(aryl), —C(O)(C1-6alkyl or C3-6cycloalkyl), —C(O)(CH2)S(O)R21, O-heteroalkyl, and O-heteroaliphatic;
• or R32 is selected from —O(CH2)1-4R23a, —OC2-C4alkenylR23a, —OC2-C4alkynylR23, —O(CH2)1-4paracyclophane, —O(CH2)1-4P(O)R23bR23b, —O(CH2)1-4S(O)NR21R22, —O(CH2)1-4SO2NR21R22, —O(C3-C7cycloalkyl), —O(aryl), —O(heteroaryl), and —O residue of a carbohydrate;
• or R32 is selected from R48, S(O)═NHR21, S(O)═N(R21)R21, SF5, S═NHR21, S═N(R21)R21, JC(R9)═NR21, and SO2OR21;
• or R32 is selected from —O(CH2)1-4S(O)NR24R30 and —O(CH2)1-4SO2NR24R30;
• R11 and R14 are independently selected from hydrogen, halogen, hydroxyl, nitro, cyano, —O(PO)(OR9)2, —(PO)(OR9)2, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl, C2-C6alkenyl(aryl), C2-C6alkenyl(cycloalkyl), C2-C6alkenyl(heterocycle), C2-C6alkenyl(heteroaryl), C2-C6alkynyl(aryl), C2-C6alkynyl(cycloalkyl), C2-C6alkynyl(heterocycle), C2-C6alkynyl(heteroaryl), C2-C6alkanoyl, C1-C6alkoxy, C1-C6thioalkyl, —C0-C4alkyl(mono- and di-C1-C6alkylamino), —C0-C4alkyl(C3-C7cycloalkyl), —C0-C4alkoxy(C3-C7cycloalkyl), C1-C6haloalkyl, and C1-C6haloalkoxy;
• B is selected from:
• wherein R25, R26, and R27 are independently selected from halogen and C1-C6alkyl optionally substituted with one or more halogen atoms;
• and R28 is C1-C6alkyl or cyclopropyl;
• or
• B is
• wherein R26 is halogen or C1-C6alkyl optionally substituted with one or more halogen atoms, and R27 is C1-C6alkyl or cyclopropyl;
• J is independently selected from a covalent bond, C1-C4alkylene, —OC1-C4alkylene, C2-C4alkenylene, and C2-C4alkynylene;
• R21 and R22 are independently selected from hydrogen, hydroxyl, cyano, amino, C1-C6alkyl, C1-C6haloalkyl, C1-C6alkoxy, (C3-C7cycloalkyl)C0-C4alkyl, (phenyl)C0-C4alkyl, —C1-C4alkylOC(O)OC1-C6alkyl, —C1-C4alkylOC(O)C1-C6alkyl, —C1-C4alkylC(O)OC1-C6alkyl, (4- to 8-membered heterocycloalkyl)C0-C4alkyl having 1, 2, or 3 heteroatoms independently selected from N, O, and S, and (5- or 6-membered unsaturated or aromatic heterocycle)C0-C4alkyl having 1, 2, or 3 heteroatoms independently selected from N, O, and S;
• or R21 and R22 can be taken together to form a carbocyclic or heterocyclic ring;
• R23 is independently selected at each occurrence from C1-C6alkyl, C1-C6haloalkyl, (aryl)C0-C4alkyl, (C3-C7cycloalkyl)C0-C4alkyl, (phenyl)C0-C4alkyl, (4- to 8-membered heterocycle)C0-C4alkyl having 1, 2, or 3 heteroatoms independently selected from N, O, and S, and (5- or 6-membered unsaturated or aromatic heterocycle)C0-C4alkyl having 1, 2, or 3 heteroatoms independently selected from N, O, and S;
• R23a is independently selected at each occurrence from C3-C7cycloalkyl;
• R23b is independently selected at each occurrence from hydroxyl, C1-C6alkoxy, C1-C6alkyl, (C3-C7cycloalkyl)C0-C4alkyl, (phenyl)C0-C4alkyl, —O(CH2)2-4O(CH2)8-18, —OC(R23c)2OC(O)OR23d, —OC(R23c)2OC(O)R23d, an N-linked amino acid, or an N-linked amino acid ester;
• R23c is independently selected at each occurrence from hydrogen, C1-C8alkyl, C2-C8alkenyl, C2-C8alkynyl, (aryl)C0-C4alkyl, (aryl)C2-C8alkenyl- or (aryl)C2-C8alkynyl;
• or two R23c groups can be taken together with the carbon that they are bonded to form a 3-6 membered heterocycloalkyl having 1, 2, or 3 heteroatoms independently selected from N, O, and S, or a 3-6 membered carbocyclic ring;
• R23d is independently selected at each occurrence from C1-C8alkyl, C2-C8alkenyl, C2-C8alkynyl, (aryl)C0-C4alkyl, (aryl)C2-C8alkenyl, or (aryl)C2-C8alkynyl;
• R24 and R30 are taken together with the nitrogen to which they are attached to form a 4- to 7-membered monocyclic heterocycle, or a 6- to 10-membered bicyclic heterocycle group having fused, spiro, or bridged rings;
• R48 is selected from halogen, hydroxyl, nitro, cyano, amino, C1-C6haloalkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6thioalkyl, C1-C6alkoxy, -JC3-C7cycloalkyl, —B(OH)2, -JC(O)NR9R23, -JOSO2OR21, —C(O)(CH2)1-4S(O)R21, —O(CH2)1-4S(O)NR21R22, -JOP(O)(OR21)(OR22), -JP(O)(OR21)(OR22), -JOP(O)(OR21)R22, -JOP(O)R21R22, -JP(O)R21R22, -JSP(O)(OR21)(OR22), -JSP(O)(OR21)(R22), -JSP(O)(R21)(R22), -JNR9P(O)(NHR21)(NHR22), -JNR9P(O)(OR21)(NHR22), -JNR9P(O)(OR21)(OR22), -JC(S)R21, -JNR21SO2R22, -JNR9S(O)NR10R22, -JNR9SO2NR1OR22, -JSO2NR9COR22, -JSO2NR9CONR21R22, -JNR21SO2R22, -JC(O)NR21SO2R22, -JC(NH2)═NR22, -JCH(NH2)NR9S(O)2R22, -JOC(O)NR21R22, -JNR21C(O)OR22, -JNR21OC(O)R22, —(CH2)1-4C(O)NR21R22, -JC(O)NR24R30, -JNR9C(O)R21, -JC(O)R21, -JNR9C(O)NR10R22, —CCR21, —(CH2)1-4OC(O)R21, -JC(O)OR23, and R103;
• each of which R48 may be optionally substituted with one or more substituents selected from halogen, hydroxyl, nitro, cyano, amino, oxo, —B(OH)2, —Si(CH3)3, —COOH, —CONR9R10, —P(O)(OH)2, C1-C6alkyl, —C0-C4alkyl(C3-C7cycloalkyl), C1-C6alkoxy, —C0-C4alkyl(mono- and di-C1-C4alkylNR9R10), C1-C6alkyl ester, C1-C4alkylamino, C1-C4hydroxylalkyl, —OC(O)R9, —NR9C(O)R10, —C(O)NR9R10, —OC(O)NR9R10, —NR9C(O)OR10, C1-C6haloalkyl, S(O)═NHR21, SF5, JC(R9)═NR21, SO2OR21, and C1-C6haloalkoxy;
• R103 is C1-C4alkyl, C3-C6cycloalkyl, fluorine, chlorine, or bromine;
• R71 is independently selected at each occurrence from hydroxyl, C1-C6alkoxy, (C3-C7cycloalkyl)C0-C4alkyl, (phenyl)C0-C4alkyl, —C1-C4alkylOC(O)OC1-C6alkyl, —C1-C4alkylOC(O)C1-C6alkyl, —C1-C4alkylC(O)OC1-C6alkyl, (4- to 7-membered heterocycloalkyl)C0-C4alkyl having 1, 2, or 3 heteroatoms independently selected from N, O, and S, and (5- or 6-membered unsaturated or aromatic heterocycle)C0-C4alkyl having 1, 2, or 3 heteroatoms independently selected from N, O, and S;
• R72 is independently selected at each occurrence from aryl, heterocycle, alkynyl, hydroxyl, C1-C6alkoxy, (C3-C7cycloalkyl)C0-C4alkyl, (aryl)C0-C4alkyl, (heterocycle)C0-C4alkyl, (heteroaryl)C0-C4alkyl, —C1-C6alkylOC(O)OC1-C6alkyl, —C1-C4alkylOC(O)C1-C6alkyl, —C1-C4alkylC(O)OC1-C6alkyl, —S(O)(O)(alkyl), —S(O)(alkyl), —S(O)(O)(heteroalkyl), —S(O)(heteroalkyl), —S(O)(O)(aryl), —S(O)(aryl), —S(O)(O)(heteroaryl), and —S(O)(heteroaryl);
• R73 is independently selected at each occurrence from hydrogen, hydroxyl, cyano, amino, C1-C6alkyl, C1-C6haloalkyl, C1-C6alkoxy, (C3-C7cycloalkyl)C0-C4alkyl, (phenyl)C0-C4alkyl, —C1-C4alkylOC(O)OC1-C6alkyl, —C1-C4alkylOC(O)C1-C6alkyl, —C1-C4alkylC(O)OC1-C6alkyl, (4- to 7-membered heterocycloalkyl)C0-C4alkyl having 1, 2, or 3 heteroatoms independently selected from N, O, and S, and (5- or 6-membered unsaturated or aromatic heterocycle)C0-C4alkyl having 1, 2, or 3 heteroatoms independently selected from N, O, and S;
• and
• R74 is proline substituted with a —C(O)NR9R10.