US 7,459,554 B2Granted

Imidazopyrazine tyrosine kinase inhibitors

AssigneeOSI Pharmaceuticals, Inc.

InventorsHan-Qing Dong, Kenneth Foreman, Mark Joseph Mulvihill, Anthony Innocenzo Nigro, Arno G. Steinig, Douglas Werner, Robin Wilkes

Life of this patent

Estimating the term…

Abstract

Compounds of the formula and pharmaceutically acceptable salts thereof, wherein Q1 and R1 are defined herein, inhibit the IGF-1R enzyme and are useful for the treatment and/or prevention of various diseases and conditions that respond to treatment by inhibition of tyrosine kinases.

Claims68

Dependent claims

A compound represented by Formula I:

or a pharmaceutically acceptable salt thereof, wherein:
Q1 is aryl1, heteroaryl1, cycloalkyl, heterocyclyl, cycloalkenyl, or heterocycloalkenyl, any of which is optionally substituted by one to five independent G1 substituents;
R1 is alkyl, cycloalkyl, bicycloalkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, heterocyclyl, or heterobicycloalkyl, any of which is optionally substituted by one or more independent G11 substituents;
G1 and G41 are each independently halo, oxo, —CF3, —OCF3, —OR2, —NR2R3(R3a)j1, —C(O)R2, —CO2R2, —CONR2R3, —NO2, —CN, —S(O)j1R2, —SO2NR2R3, NR2(C═O)R3, NR2(C═O)OR3, NR2(C═O)NR2R3, NR2S(O)j1R3, —(C═S)OR2, —(C═O)SR2, —NR2(C═NR3)NR2aR3a, —NR2(C═NR3)OR2a, —NR2(C═NR3)SR3a, —O(C═O)OR2, —O(C═O)NR2R3, —O(C═O)SR2, —S(C═O)OR2, —S(C═O)NR2R3, C0-10alkyl, C2-10alkenyl, C2-10alkynyl, C1-10alkoxyC1-10alkyl, C1-10alkoxyC2-10alkenyl, C1-10alkoxyC2-10alkynyl, C1-10alkylthioC1-10alkyl, C1-10alkylthioC2-10alkenyl, C1-10alkylthioC2-10alkynyl, cycloC3-8alkyl, cycloC3-8alkenyl, cycloC3-8alkylC1-10alkyl, cycloC3-8alkenylC1-10alkyl, cycloC3-8alkylC2-10alkenyl, cycloC3-8alkenylC2-10alkenyl, cycloC3-8alkylC2-10alkynyl, cycloC3-8alkenylC2-10alkynyl, heterocyclyl-C0-10alkyl, heterocyclyl-C2-10alkenyl, or heterocyclyl-C2-10alkynyl, any of which is optionally substituted with one or more independent halo, oxo, —CF3, —OCF3, —OR222, —NR222R333(R333a)j1a, —C(O)R222, —CO2R222, —CONR222R333, —NO2, —CN, —S(O)j1aR222, —SO2NR222R333, NR222(C═O)R333, NR222(C═O)OR333, NR222(C═O)NR222R333, NR222S(O)j1aR333, —(C═S)OR222, —(C═O)SR222, —NR222(C═NR333)NR222aR333a, —NR222(C═NR333)OR222a, —NR222(C═NR333)SR333a, —O(C═O)OR222, —O(C═O)NR222R333, —O(C═O)SR222, —S(C═O)OR222, or —S(C═O)NR222R333 substituents;
or —(X1)n—(Y1)m—R4;
or aryl-C0-10alkyl, aryl-C2-10alkenyl, or aryl-C2-10alkynyl, any of which is optionally substituted with one or more independent halo, —CF3, —OCF3, —OR222, —NR222R333(R333a)j2a, —C(O)R222, —CO2R222, —CONR222R333, —NO2, —CN, —S(O)j2aR222, —SO2NR222R333, NR222(C═O)R333, NR222(C═O)OR333, NR222(C═O)NR222R333, NR222S(O)j2aR333, —(C═S)OR222, —(C═O)SR222, —NR222(C═NR333)NR222aR333a, —NR222(C═NR333)OR222a, —NR222(C═NR333)SR333a, —O(C═O)OR222, —O(C═O)NR222R333, —O(C═O)SR222, —S(C═O)OR222, or —S(C═O)NR222R333 substituents;
or hetaryl-C0-10alkyl, hetaryl-C2-10alkenyl, or hetaryl-C2-10alkynyl, any of which is optionally substituted with one or more independent halo, —CF3, —OCF3, —OR222, —NR222R333(R333a)j3a, —C(O)R222, —CO2R222, —CONR222R333, —NO2, —CN, —S(O)j3aR222, —SO2NR222R333, NR222(C═O)R333, NR222(C═O)OR333, NR222(C═O)NR222R333, NR222S(O)j3aR333, —(C═S)OR222, —(C═O)SR222, —NR222(C═NR333)NR222aR333a, —NR222(C═NR333)OR222a, —NR222(C═NR333)SR333a, —O(C═O)OR222, —O(C═O)NR222R333, —O(C═O)SR222, —S(C═O)OR222, or —S(C═O)NR222R333 substituents;
G11 is halo, oxo, —CF3, —OCF3, —OR21, —NR21R31(R3a1)j4, —C(O)R21, —CO2R21, —CONR21R31, —NO2, —CN, —S(O)j4R21, —SO2NR21R31, NR21(C═O)R31, NR21(C═O)OR31, NR21(C═O)NR21R31, NR21S(O)j4R31, —(C═S)OR21, —(C═O)SR21, —NR21 (C═NR31)NR2a1R3a1, —NR21(C═NR31)OR2a1, —NR21(C═NR31)SR3a1, —O(C═O)OR21, —O(C═O)NR21R31, —O(C═O)SR21, —S(C═O)OR21, —S(C═O)NR21R31, —P(O)OR21OR31, C0-10alkyl, C2-10alkenyl, C2-10alkynyl, C1-10alkoxyC1-10alkyl, C1-10alkoxyC2-10alkenyl, C1-10alkoxyC2-10alkynyl, C1-10alkylthioC1-10alkyl, C1-10alkylthioC2-10alkenyl, C1-10alkylthioC2-10alkynyl, cycloC3-8alkyl, cycloC3-8alkenyl, cycloC3-8alkylC1-10alkyl, cycloC3-8alkenylC1-10alkyl, cycloC3-8alkylC2-10alkenyl, cycloC3-8alkenylC2-10alkenyl, cycloC3-8alkylC2-10alkynyl, cycloC3-8alkenylC2-10alkynyl, heterocyclyl-C0-10alkyl, heterocyclyl-C2-10alkenyl, or heterocyclyl-C2-10alkynyl, any of which is optionally substituted with one or more independent halo, oxo, —CF3, —OCF3, —OR2221, —NR2221R3331(R333a1)j4a, —C(O)R2221, —CO2R2221, —CONR2221R3331, —NO2, —CN, —S(O)j4aR2221, —SO2NR2221R3331, NR2221(C═O)R3331, NR2221(C═O)OR3331, NR2221(C═O)NR2221R3331, NR2221S(O)j4aR3331, —(C═S)OR2221, —(C═O)SR2221, —NR2221(C═NR3331)NR222a1R333a1, —NR2221(C═NR3331)OR222a1, —NR2221(C═NR3331)SR333a1, —O(C═O)OR2221, —O(C═O)NR2221R3331, —O(C═O)SR2221, —S(C═O)OR2221, —P(O)OR2221OR3331, or —S(C═O)NR2221R3331 substituents;
or aryl-C0-10alkyl, aryl-C2-10alkenyl, or aryl-C2-10alkynyl, any of which is optionally substituted with one or more independent halo, —CF3, —OCF3, —OR2221, —NR2221R3331(R333a1)j5a, —C(O)R2221, —CO2R2221, —CONR2221R3331, —NO2, —CN, —S(O)j5aR2221, —SO2NR2221R3331, NR2221(C═O)R3331, NR2221(C═O)OR3331, NR2221(C═O)NR2221R3331, NR2221S(O)j5aR3331, —(C═S)OR2221, —(C═O)SR2221, —NR2221(C═NR3331)NR222a1R333a1, —NR2221(C═NR3331)OR222a1, —NR2221(C═NR3331)SR333a1, —O(C═O)OR2221, —O(C═O)NR2221R3331, —O(C═O)SR2221, —S(C═O)OR2221, —P(O)OR2221R3331, or —S(C═O)NR2221R3331 substituents;
or hetaryl-C0-10alkyl, hetaryl-C2-10alkenyl, or hetaryl-C2-10alkynyl, any of which is optionally substituted with one or more independent halo, —CF3, —OCF3, —OR2221, —NR2221R3331(R333a1)j6a, —C(O)R2221, —CO2R2221, —CONR2221R3331, —NO2, —CN, —S(O)j6aR2221, —SO2NR2221R3331, NR2221(C═O)R3331, NR2221(C═O)OR3331, NR2221(C═O)NR2221R3331, NR2221S(O)j6aR3331, —(C═S)OR2221, —(C═O)SR2221, —NR2221(C═NR3331)NR222a1R333a1, —NR2221(C═NR3331)OR222a1, —NR2221(C═NR3331)SR333a1, —O(C═O)OR2221, —O(C═O)NR2221R3331, —O(C═O)SR2221, —S(C═O)OR2221, —P(O)OR2221OR3331, or —S(C═O)NR2221R3331 substituents;
or G11 is taken together with the carbon to which it is attached to form a double bond which is substituted with R5 and G111;
R2, R2a, R3, R3a, R222, R222a, R333, R333a, R21, R2a1, R31, R3a1, R2221, R222a1, R3331, and R333a1 are each independently equal to C0-10alkyl, C2-10alkenyl, C2-10alkynyl, C1-10alkoxyC1-10alkyl, C1-10alkoxyC2-10alkenyl, C1-10alkoxyC2-10alkynyl, C1-10alkylthioC1-10alkyl, C1-10alkylthioC2-10alkenyl, C1-10alkylthioC2-10alkynyl, cycloC3-8alkyl, cycloC3-8alkenyl, cycloC3-8alkylC1-10alkyl, cycloC3-8alkenylC1-10alkyl, cycloC3-8alkylC2-10alkenyl, cycloC3-8alkenylC2-10alkenyl, cycloC3-8alkylC2-10alkynyl, cycloC3-8alkenylC2-10alkynyl, heterocyclyl-C0-10alkyl, heterocyclyl-C2-10alkenyl, or heterocyclyl-C2-10alkynyl, any of which is optionally substituted by one or more G111 substituents;
or aryl-C0-10alkyl, aryl-C2-10alkenyl, or aryl-C2-10alkynyl, hetaryl-C0-10alkyl, hetaryl-C2-10alkenyl, or hetaryl-C2-10alkynyl, any of which is optionally substituted by one or more G111 substituents;
or in the case of —NR2R3(R3a)j1 or —NR222R333(R333a)j1a or —NR222R333(R333a)j2a or —NR2221R3331(R333a1)j3a or —NR2221R3331(R333a1)j4a or —NR2221R3331(R333a1)j5a or —NR2221R3331(R333a1)j6a, R2 and R3 or R222 and R3333 or R2221 and R3331 taken together with the nitrogen atom to which they are attached form a 3-10 membered saturated ring, unsaturated ring, heterocyclic saturated ring, or heterocyclic unsaturated ring, wherein said ring is optionally substituted by one or more G111 substituents;
X1 and Y1 are each independently —O—, —NR7—, —S(O)j7—, —CR5R6—, —N(C(O)OR7)—, —N(C(O)R7)—, —N(SO2R7)—, —CH2O—, —CH2S—, —CH2N(R7)—, —CH(NR7)—, —CH2N(C(O)R7)—, —CH2N(C(O)OR7)—, —CH2N(SO2R7)—, —CH(NHR7)—, —CH(NHC(O)R7)—, —CH(NHSO2R7)—, —CH(NHC(O)OR7)—, —CH(OC(O)R7)—, —CH(OC(O)NHR7)—, —CH═CH—, —C≡C—, —C(═NOR7)—, —C(O)—, —CH(OR7)—, —C(O)N(R7)—, —N(R7)C(O)—, —N(R7)S(O)—, —N(R7)S(O)2— —OC(O)N(R7)—, —N(R7)C(O)N(R7)—, —NR7C(O)O—, —S(O)N(R7)—, —S(O)2N(R7)—, —N(C(O)R7)S(O)—, —N(C(O)R7)S(O)2—, —N(R7)S(O)N(R7)—, —N(R7)S(O)2N(R7)—, —C(O)N(R7)C(O)—, —S(O)N(R7)C(O)—, —S(O)2N(R7)C(O)—, —OS(O)N(R7)—, —OS(O)2N(R7)—, —N(R7)S(O)O—, —N(R7)S(O)2O—, —N(R7)S(O)C(O)—, —N(R7)S(O)2C(O)—, —SON(C(O)R7)—, —SO2N(C(O)R7)—, —N(R7)SON(R7)—, —N(R7)SO2N(R7)—, —C(O)O—, —N(R7)P(OR8)O—, —N(R7)P(OR8)—, —N(R7)P(O)(OR8)O—, —N(R7)P(O)(OR8)—, —N(C(O)R7)P(OR8)O—, —N(C(O)R7)P(OR8)—, —N(C(O)R7)P(O)(OR8)O—, —N(C(O)R7)P(OR8)—, —CH(R7)S(O)—, —CH(R7)S(O)2—, —CH(R7)N(C(O)OR7)—, —CH(R7)N(C(O)R7)—, —CH(R7)N(SO2R7)—, —CH(R7)O—, —CH(R7)S—, —CH(R7)N(R7)—, —CH(R7)N(C(O)R7)—, —CH(R7)N(C(O)OR7)—, —CH(R7)N(SO2R7)—, —CH(R7)C(═NOR7)—, —CH(R7)C(O)—, —CH(R7)CH(OR7)—, —CH(R7)C(O)N(R7)—, —CH(R7)N(R7)C(O)—, —CH(R7)N(R7)S(O)—, —CH(R7)N(R7)S(O)2—, —CH(R7)OC(O)N(R7)—, —CH(R7)N(R7)C(O)N(R7)—, —CH(R7)NR7C(O)O—, —CH(R7)S(O)N(R7)—, —CH(R7)S(O)2N(R7)—, —CH(R7)N(C(O)R7)S(O)—, —CH(R7)N(C(O)R7)S(O)—, —CH(R7)N(R7)S(O)N(R7)—, —CH(R7)N(R7)S(O)2N(R7)—, —CH(R7)C(O)N(R7)C(O)—, —CH(R7)S(O)N(R7)C(O)—, —CH(R7)S(O)2N(R7)C(O)—, —CH(R7)OS(O)N(R7)—, —CH(R7)OS(O)2N(R7)—, —CH(R7)N(R7)S(O)O—, —CH(R7)N(R7)S(O)2O—, —CH(R7)N(R7)S(O)C(O)—, —CH(R7)N(R7)S(O)2C(O)—, —CH(R7)SON(C(O)R7)—, —CH(R7)SO2N(C(O)R7)—, —CH(R7)N(R7)SON(R7)—, —CH(R7)N(R7)SO2N(R7)—, —CH(R7)C(O)O—, —CH(R7)N(R7)P(OR8)O—, —CH(R7)N(R7)P(OR8)—, —CH(R7)N(R7)P(O)(OR8)O—, —CH(R7)N(R7)P(O)(OR8)—, —CH(R7)N(C(O)R7)P(OR8)O—, —CH(R7)N(C(O)R7)P(OR8)—, —CH(R7)N(C(O)R7)P(O)(OR8)O—, or —CH(R7)N(C(O)R7)P(OR8)—;
or X1 and Y1 are each independently represented by one of the following structural formulas:
R10, taken together with the phosphinamide or phosphonamide, is a 5-, 6-, or 7-membered aryl, heteroaryl or heterocyclyl ring system;
R5, R6, and G111 are each independently a C0-10alkyl, C2-10alkenyl, C2-10alkynyl, C1-10alkoxyC1-10alkyl, C1-10alkoxyC2-10alkenyl, C1-10alkoxyC2-10alkynyl, C1-10alkylthioC1-10alkyl, C1-10alkylthioC2-10alkenyl, C1-10alkylthioC2-10alkynyl, cycloC3-8alkyl, cycloC3-8alkenyl, cycloC3-8alkylC1-10alkyl, cycloC3-8alkenylC1-10alkyl, cycloC3-8alkylC2-10alkenyl, cycloC3-8alkenylC2-10alkenyl, cycloC3-8alkylC2-10alkynyl, cycloC3-8alkenylC2-10alkynyl, heterocyclyl-C0-10alkyl, heterocyclyl-C2-10alkenyl, or heterocyclyl-C2-10alkynyl, any of which is optionally substituted with one or more independent halo, —CF3, —OCF3, —OR77, —NR77R87, —C(O)R77, —CO2R77, —CONR77R87, —NO2, —CN, —S(O)j5aR77, —SO2NR77R87, NR77(C═O)R87, NR77(C═O)OR87, NR77(C═O)NR78R87, NR77S(O)j5aR87, —(C═S)OR77, —(C═O)SR77, —NR77(C═NR87)NR78R88, —NR77(C═NR87)OR78, —NR77(C═NR87)SR78, —O(C═O)OR77, —O(C═O)NR77R87, —O(C═O)SR77, —S(C═O)OR77, —P(O)OR77OR87, or —S(C═O)NR77R87 substituents;
or aryl-C0-10alkyl, aryl-C2-10alkenyl, or aryl-C2-10alkynyl, any of which is optionally substituted with one or more independent halo, —CF3, —OCF3, —OR77, —NR77R87, —C(O)R77, —CO2R77, —CONR77R87, —NO2, —CN, —S(O)j5aR77, —SO2NR77R87, NR77(C═O)R87, NR77(C═O)OR87, NR77(C═O)NR78R87, NR77S(O)j5aR87, —(C═S)OR77, —(C═O)SR77, —NR77(C═NR87)NR78R88, —NR77(C═NR87)OR78, —NR77(C═NR87)SR78, —O(C═O)OR77, —O(C═O)NR77R87, —O(C═O)SR77, —S(C═O)OR77, —P(O)OR77R87, or —S(C═O)NR77R87 substituents;
or hetaryl-C0-10alkyl, hetaryl-C2-10alkenyl, or hetaryl-C2-10alkynyl, any of which is optionally substituted with one or more independent halo, —CF3, —OCF3, —OR77, —NR77R87, —C(O)R77, —CO2R77, —CONR77R87, —NO2, —CN, —S(O)j5aR77, —SO2NR77R87, NR77(C═O)R87, NR77(C═O)OR87, NR77(C═O)NR78R87, NR77S(O)j5aR87, —(C═S)OR77, —(C═O)SR77, —NR77(C═NR87)NR78R88, —NR77(C═NR87)OR78, —NR77(C═NR87)SR78, —O(C═O)OR77, —O(C═O)NR77R87, —O(C═O)SR77, —S(C═O)OR77, —P(O)OR77OR87, or —S(C═O)NR77R87 substituents;
or R5 with R6 taken together with the respective carbon atom to which they are attached, form a 3-10 membered saturated or unsaturated ring, wherein said ring is optionally substituted with R69;
or R5 with R6 taken together with the respective carbon atom to which they are attached, form a 3-10 membered saturated or unsaturated heterocyclic ring, wherein said ring is optionally substituted with R69;
R7 and R8 are each independently H, acyl, alkyl, alkenyl, aryl, heteroaryl, heterocyclyl or cycloalkyl, any of which is optionally substituted by one or more G111 substituents;
R4 is H, alkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, heterocyclyl, cycloalkenyl, or heterocycloalkenyl, any of which is optionally substituted by one or more G41 substituents;
R69 is equal to halo, —OR78, —SH, —NR78R88, —CO2R78, —CONR78R88, —NO2, —CN, —S(O)j8R78, —SO2NR78R88, C0-10alkyl, C2-10alkenyl, C2-10alkynyl, C1-10alkoxyC1-10alkyl, C1-10alkoxyC2-10alkenyl, C1-10alkoxyC2-10alkynyl, C1-10alkylthioC1-10alkyl, C1-10alkylthioC2-10alkenyl, C1-10alkylthioC2-10alkynyl, cycloC3-8alkyl, cycloC3-8alkenyl, cycloC3-8alkylC1-10alkyl, cycloC3-8alkenylC1-10alkyl, cycloC3-8alkylC2-10alkenyl, cycloC3-8alkenylC2-10alkenyl, cycloC3-8alkylC2-10alkynyl, cycloC3-8alkenylC2-10alkynyl, heterocyclyl-C0-10alkyl, heterocyclyl-C2-10alkenyl, or heterocyclyl-C2-10alkynyl, any of which is optionally substituted with one or more independent halo, cyano, nitro, —OR778, —SO2NR778R888, or —NR778R888 substituents;
or aryl-C0-10alkyl, aryl-C2-10alkenyl, or aryl-C2-10alkynyl, any of which is optionally substituted with one or more independent halo, cyano, nitro, —OR778, C1-10alkyl, C2-10alkenyl, C2-10alkynyl, haloC1-10alkyl, haloC2-10alkenyl, haloC2-10alkynyl, —COOH, C1-4alkoxycarbonyl, —CONR778R888, —SO2NR778R888, or —NR778R888 substituents;
or hetaryl-C0-10alkyl, hetaryl-C2-10alkenyl, or hetaryl-C2-10alkynyl, any of which is optionally substituted with one or more independent halo, cyano, nitro, —OR778, C1-10alkyl, C2-10alkenyl, C2-10alkynyl, haloC1-10alkyl, haloC2-10alkenyl, haloC2-10alkynyl, —COOH, C1-4alkoxycarbonyl, —CONR778R888, —SO2NR778R888, or —NR778R888 substituents;
or mono(C1-6alkyl)aminoC1-6alkyl, di(C1-6alkyl)aminoC1-6alkyl, mono(aryl)aminoC1-6alkyl, di(aryl)aminoC1-6alkyl, or —N(C1-6alkyl)-C1-6alkyl-aryl, any of which is optionally substituted with one or more independent halo, cyano, nitro, —OR778, C1-10alkyl, C2-10alkenyl, C2-10alkynyl, haloC1-10alkyl, haloC2-10alkenyl, haloC2-10alkynyl, —COOH, C1-4alkoxycarbonyl, —CONR778R888 SO2NR778R888, or —NR778R888 substituents;
or in the case of —NR78R88, R78 and R88 taken together with the nitrogen atom to which they are attached form a 3-10 membered saturated ring, unsaturated ring, heterocyclic saturated ring, or heterocyclic unsaturated ring, wherein said ring is optionally substituted with one or more independent halo, cyano, hydroxy, nitro, C1-10alkoxy, —SO2NR778R888, or —NR778R888 substituents;
R77, R78, R87, R88, R778, and R888 are each independently C0-10alkyl, C2-10alkenyl, C2-10alkynyl, C1-10alkoxyC1-10alkyl, C1-10alkoxyC2-10alkenyl, C1-10alkoxyC2-10alkynyl, C1-10alkylthioC1-10alkyl, C1-10alkylthioC2-10alkenyl, C1-10alkylthioC2-10alkynyl, cycloC3-8alkyl, cycloC3-8alkenyl, cycloC3-8alkylC1-10alkyl, cycloC3-8alkenylC1-10alkyl, cycloC3-8alkylC2-10alkenyl, cycloC3-8alkenylC2-10alkenyl, cycloC3-8alkylC2-10alkynyl, cycloC3-8alkenylC2-10alkynyl, heterocyclyl-C0-10alkyl, heterocyclyl-C2-10alkenyl, heterocyclyl-C2-10alkynyl, C1-10alkylcarbonyl, C2-10alkenylcarbonyl, C2-10alkynylcarbonyl, C1-10alkoxycarbonyl, C1-10alkoxycarbonylC1-10alkyl, monoC1-6alkylaminocarbonyl, diC1-6alkylaminocarbonyl, mono(aryl)aminocarbonyl, di(aryl)aminocarbonyl, or C1-10alkyl(aryl)aminocarbonyl, any of which is optionally substituted with one or more independent halo, cyano, hydroxy, nitro, C1-10alkoxy, —SO2N(C0-4alkyl)(C0-4alkyl), or —N(C0-4alkyl)(C0-4alkyl) substituents;
or aryl-C0-10alkyl, aryl-C2-10alkenyl, or aryl-C2-10alkynyl, any of which is optionally substituted with one or more independent halo, cyano, nitro, —O(C0-4alkyl), C1-10alkyl, C2-10alkenyl, C2-10alkynyl, haloC1-10alkyl, haloC2-10alkenyl, haloC2-10alkynyl, —COOH, C1-4alkoxycarbonyl, —CON(C0-4alkyl)(C0-10alkyl), —SO2N(C0-4alkyl)(C0-4alkyl), or —N(C0-4alkyl)(C0-4alkyl) substituents;
or hetaryl-C0-10alkyl, hetaryl-C2-10alkenyl, or hetaryl-C2-10alkynyl, any of which is optionally substituted with one or more independent halo, cyano, nitro, —O(C0-4alkyl), C1-10alkyl, C2-10alkenyl, C2-10alkynyl, haloC1-10alkyl, haloC2-10alkenyl, haloC2-10alkynyl, —COOH, C1-4alkoxycarbonyl, —CON(C0-4alkyl)(C0-4alkyl), —SO2N(C0-4alkyl)(C0-4alkyl), or —N(C0-4alkyl)(C0-4alkyl) substituents;
or mono(C1-6alkyl)aminoC1-6alkyl, di(C1-6alkyl)aminoC1-6alkyl, mono(aryl)aminoC1-6alkyl, di(aryl)aminoC1-6alkyl, or —N(C1-6alkyl)-C1-6alkyl-aryl, any of which is optionally substituted with one or more independent halo, cyano, nitro, —O(C0-4alkyl), C1-10alkyl, C2-10alkenyl, C2-10alkynyl, haloC1-10alkyl, haloC2-10alkenyl, haloC2-10alkynyl, —COOH, C1-4alkoxycarbonyl, —CON(C0-4alkyl)(C0-4alkyl), —SO2N(C0-4alkyl)(C0-4alkyl), or —N(C0-4alkyl)(C0-4alkyl) substituents;
and
n, m, j1, j1a, j2a, j3a, j4, j4a, j5a, j6a, j7, and j8 are each independently equal to 0, 1, or 2.

32 more elements