Compounds for the treatment of medical disorders

A method for the treatment of a disorder mediated by the complement factor D pathway, comprising administering an effective amount to a host in need thereof a compound of the formula

• or a pharmaceutically acceptable salt or composition thereof, wherein:
• Q1 is C(R1R1′);
• Q2 is C(R2R2′);
• Q3 is C(R3R3′);
• X1 is N and X2 is CH;
• R1, R1′, R2, R2′, R3, and R3′ are independently selected from hydrogen, halogen, hydroxyl, nitro, cyano, amino, C1-C6alkyl, C2-C6alkenyl, C1-C6alkoxy, C2-C6alkynyl, C2-C6alkanoyl, C1-C6thioalkyl, hydroxyC1-C6alkyl, aminoC1-C6alkyl, —C0-C4alkylNR9R10, —C(O)OR9, —OC(O)R9, —NR9C(O)R1, —C(O)NR9R10, —OC(O)NR9R10, —O(heteroaryl), —NR9C(O)OR10, C1-C2haloalkyl, —C0-C4alkyl(C3-C7cycloalkyl), —O—C0-C4alkyl(C3-C7cycloalkyl), and C1-C2haloalkoxy;
• R9 and R10 are independently selected at each occurrence from hydrogen, C1-C6alkyl, and (C3-C7cycloalkyl)C0-C4alkyl;
• or R1 and R1′ or R3 and R3′ may be taken together to form a 3- to 6-membered carbocyclic spiro ring or a 3- to 6-membered heterocyclic spiro ring containing 1 or 2 heteroatoms independently selected from N, O, or S,
• or R2 and R2′ may be taken together to form a 3- to 6-membered carbocyclic spiro ring;
• or R2 and R2′ may be taken together to form a 3- to 6-membered heterocyclic spiro ring;
• each of which spiro rings is unsubstituted or substituted with 1 or more substituents independently selected from halogen, hydroxyl, cyano, —COOH, C1-C4alkyl, C2-C4alkenyl, C2-C4alkynyl, C1-C4alkoxy, C2-C4alkanoyl, hydroxyC1-C4alkyl, (mono- and di-C1-C4alkylamino)C0-C4alkyl, —C0-C4alkyl(C3-C7cycloalkyl), —O—C0-C4alkyl(C3-C7cycloalkyl), C1-C2haloalkyl, and C1-C2haloalkoxy;
• or R1 and R2 may be taken together to form a 3-membered carbocyclic ring;
• or R1 and R2 may be taken together to form a 4- to 6-membered carbocyclic ring or a 4- to 6-membered heterocyclic ring containing 1 or 2 heteroatoms independently selected from N, O, and S;
• or R2 and R3, if bound to adjacent carbon atoms, may be taken together to form a 3- to 6-membered carbocyclic ring or a 3- to 6-membered heterocyclic ring, each of which non-spiro ring may be unsubstituted or substituted with 1 or more substituents independently selected from halogen, hydroxyl, cyano, —COOH, C1-C4alkyl, C2-C4alkenyl, C2-C4alkynyl, C1-C4alkoxy, C2-C4alkanoyl, hydroxyC1-C4alkyl, (mono- and di-C1-C4alkylamino)C0-C4alkyl, —C0-C4alkyl(C3-C7cycloalkyl), —O—C0-C4alkyl(C3-C7cycloalkyl), C1-C2haloalkyl, and C1-C2haloalkoxy;
• A is
• R5 and R6 are independently selected from —CHO, —C(O)NH2, —C(O)NH(CH3), C2-C6alkanoyl, hydrogen, hydroxyl, halogen, cyano, nitro, —COOH, —SO2NH2, —C(NH2)C1-C3alkyl, —C(NH2)C1-C3haloalkyl, —CF(C═CH2), —C(═NCN)C1-C6alkyl, C1-C6alkyl, C2-C6alkenyl, C1-C6alkoxy, —C0-C4alkyl(C3-C7cycloalkyl), —C(O)C0-C4alkyl(C3-C7cycloalkyl), —P(O)(OR9)2, —OC(O)R9, —C(O)OR9, —C(O)N(CH2CH2R9)(R10), —NR9C(O)R10, phenyl, and 5- to 6-membered heteroaryl;
• Each R5 and R6 other than hydrogen, hydroxyl, cyano, and —COOH is unsubstituted or substituted with one or more substituents independently selected from halogen, hydroxyl, amino, imino, cyano, cyanoimino, C1-C2alkyl, C1-C4alkoxy, —C0-C2alkyl(mono- and di-C1-C4alkylamino), C1-C2haloalkyl, C1-C2haloalkoxy, C(O)alkyl, C(O)cycloalkyl, C(O)aryl, C(O)heterocycle, and C(O)heteroaryl;
• R8 and R8′ are independently selected from hydrogen, halogen, hydroxyl, C1-C6alkyl, C1-C6alkoxy, and (C1-C4alkylamino)C0-C2alkyl, or R8 and R8′ are taken together to form an oxo group, or can be taken together with the carbon that they are bonded to form a 3-membered carbocyclic ring;
• X12 is N or CR12;
• X13 is N or CR13;
• R12 and R13 are independently selected at each occurrence from (q) and (r);
• (q) hydrogen, halogen, hydroxyl, nitro, cyano, amino, —COOH, C1-C2haloalkyl, C1-C2haloalkoxy;
• (r) 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 (r) is unsubstituted or substituted with one or more substituents independently selected from halogen, hydroxyl, nitro, cyano, amino, —COOH, —CONH2, C1-C2haloalkyl, and C1-C2haloalkoxy, and each of which (r) is also optionally substituted with one substituent selected from phenyl and 4- to 7-membered heterocycle containing 1, 2, or 3 heteroatoms independently selected from N, O, and S;
• which phenyl or 4- to 7-membered heterocycle is unsubstituted or 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-C2haloalkyl, and C1-C2haloalkoxy;
• L is
• where R17 is hydrogen or C1-C6alkyl and R18 and R18′ are independently selected from hydrogen, halogen, hydroxymethyl, and methyl;
• and m is 0, 1, 2, or 3;
• B is a monocyclic, bicyclic carbocyclic or carbocyclic-oxy group or a monocyclic, bicyclic, or tricyclic heterocyclic group having 1, 2, 3, or 4 heteroatoms independently selected from N, O, and S and from 4 to 7 ring atoms per ring, or B is a C2-C6alkenyl or C2-C6alkynyl group, or B is —(C0-C4alkyl)(aryl), —(C0-C4alkyl)(heteroaryl), or —(C0-C4alkyl)(biphenyl),
• and B is unsubstituted or substituted with one or more substituents independently selected from (w) and (x) and 0 or 1 substituents selected from (y) and (z):
• (w) halogen, hydroxyl, —COOH, cyano, C1-C6alkyl, C2-C6alkanoyl, C1-C6alkoxy, —C0-C4alkylNR9R10, —SO2R9, C1-C2haloalkyl, and C1-C2haloalkoxy;
• (x) nitro, C2-C6alkenyl, C2-C6alkynyl, C1-C6thioalkyl, -JC3-C7cycloalkyl, —B(OH)2, -JC(O)NR9R23, -JOSO2OR21, —C(O)(CH2)1-4S(O)R21, SR9, —O(CH2)1-4S(O)NR21R22, -JOP(O)(OR21)(OR22), -JP(O)(OR21)(OR22), -JOP(O)(OR2′)R22, -JP(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)NR9R22, -JNR9SO2NR9R22, -JSO2NR9COR22, -JSO2NR9CONR21R22, -JNR21SO2R22, -JC(O)NR21SO2R22, -JC(NH2)NR22, -JC(NH2)NR9S(O)2R22, -JOC(O)NR21R22, -JNR21C(O)OR22, -JNR21OC(O)R22, —(CH2)1-4C(O)NR21R22, -JNR9C(O)R21, -JC(O)R21, -JNR9C(O)NR10R22, —CCR21, —(CH2)1-4OC(O)R21, and -JC(O)OR23;
• each of which (x) may be unsubstituted or substituted with one or more substituents independently selected from halogen, hydroxyl, nitro, cyano, amino, oxo, —B(OH)2, —Si(CH3)3, —COOH, —CONH2, —P(O)(OH)2, C1-C6alkyl, C1-C6alkoxy, —C0-C2alkyl(mono- and di-C1-C4alkylamino), C1-C6alkylester, C1-C4alkylamino, C1-C4hydroxylalkyl, C1-C2haloalkyl, and C1-C2haloalkoxy;
• (y) naphthyl, naphthyloxy, indanyl, (4- to 7-membered heterocycloalkyl)C0-C4alkyl containing 1 or 2 heteroatoms selected from N, O, and S, and bicyclic heterocycle containing 1, 2, or 3 heteroatoms independently selected from N, O, and S, and containing 4- to 7-ring atoms in each ring;
• each of which (y) is unsubstituted or 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), —SO2R9, C1-C2haloalkyl, and C1-C2haloalkoxy;
• and
• (z) tetrazolyl, (phenyl)C0-C2alkyl, (phenyl)C1-C2alkoxy, phenoxy, and 5- or 6-membered heteroaryl containing 1, 2, or 3 heteroatoms independently selected from N, O, B, and S, each of which (z) is unsubstituted or 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), —SO2R9, —OSi(CH3)2C(CH3)3, —Si(CH3)2C(CH3)3, C1-C2haloalkyl, and C1-C2haloalkoxy;
• J is independently selected at each occurrence from a covalent bond, C1-C4alkylene, —OC1-C4alkylene, C2-C4alkenylene, and C2-C4alkynylene;
• R21 and R22 are 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
• R23 is independently selected at each occurrence from (C3-C7cycloalkyl)C0-C4alkyl, (phenyl)C0-C4alkyl, (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.