Substituted pyrazole and pyrrole compounds and methods for using them for inhibition of initiation of translation and treatment of diseases and disorders relating thereto

A compound having the structural formula

• wherein
• L2 is selected from the group consisting of a bond, —CH2—, —CH(CH3)— or —CH2CH2—;
• Q is selected from the group consisting of
• —C(O)OH,
• —C(O)O(C1-C3 alkyl),
• —C(O)NR2BR2A, in which R2A is C1-C3 alkyl, C1-C3 hydroxyalkyl, C1-C3 aminoalkyl or C1-C3 thioalkyl and R2B is H or C1-C3 alkyl,
• —C(O)NR2BR2A, in which R2A and R2B come together with a nitrogen to which they are both directly bound to form a heterocycloalkyl optionally substituted with 1-3 substituents selected from C1-C3 alkyl, C1-C3 fluoroalkyl, hydroxyl, amino, thio, C1-C3 hydroxyalkyl, C1-C3 aminoalkyl, C1-C3 thioalkyl and —C(O)C1-C3 alkyl, and
• —C(O)NR2BR2A, in which R2A is —S(O)1-2(C1-C3 alkyl), —S(O)1-2(C1-C3 fluoroalkyl), or heteroaryl optionally substituted with 1-2 groups selected from substituents selected from C1-C3 alkyl, C1-C3 fluoroalkyl, hydroxyl, amino, thio, C1-C3 hydroxyalkyl, C1-C3 aminoalkyl, C1-C3 thioalkyl and —C(O)C1-C3 alkyl and R2B is H or C1-C3 alkyl;
• L1 is —S—, —S(O)— or —S(O)2—;
• R1 is selected from the group consisting of
• optionally substituted C1-C8 alkyl, optionally-substituted C1-C8 alkenyl, optionally substituted C1-C8 alkynyl, and hydrogen;
• L3 is a bond, —C(O)—, —S—, —S(O)1-2—, —O—, —NR6—, —CH2—, —CH(CH3)(OH)—, —CH(OH)—, —CH2CH2—, —C(O)NR6—, —NR6C(O)—, —C(S)NR6—, —NR6C(S)—, —C(O)O—, —OC(O)—, —S(O)1-2O—, —OS(O)1-2—, —S(O)1-2NR6—or —NR6S(O)1-2—;
• R3 is selected from the group consisting of
• phenyl and heteroaryl each (i) optionally substituted with a single substituent selected from -L3C-(phenyl optionally substituted with 1-5 R3D), -L3C-(heteroaryl optionally substituted with 1-5 R3D), -L3C-(cycloalkyl optionally substituted with 1-5 R3E), -L3C-(heterocycloalkyl optionally substituted with 1-5 R3E) and (ii) optionally substituted with 1-5 R3E,
• in which
• each L3C is a bond, methylene, ethylene, —C(O)—, —S—, —S(O)1-2—, —O—or —NR3G—;
• each R3D is independently selected from optionally-substituted C1-C4 alkyl, C1-C4 fluoroalkyl, halogen, —CN, SF5, —N3, —C(O)R3F, —SR3F, —S(O)1-2R3F, —OR3F, —NR3GR3F, —C(O)R3F, —C(O)NR3GR3F, —NR3GC(O)R3F, —C(S)NR3GR3F, —NR3GC(S)R3F, —C(O)OR3F, —OC(O)R3F, —C(O)SR3F, —SC(O)R3F, —C(S)OR3F, —OC(S)R3F, —C(S)SR3F, —SC(S)R3F, —S(O)1-2OR3F, —OS(O)1-2R3F, —S(O)1-2NR3GR3F, —NR3GS(O)1-2R3F, —OC(O)OR3F, —OC(O)NR3GR3F, —NR3GC(O)OR3F, —NR3GC(O)NR3GR3F, —SC(O)OR3F, —OC(O)SR3F, —SC(O)SR3F, —SC(O)NR3GR3F, —NR3GC(O)SR3F, —OC(S)OR3F, —OC(S)NR3GR3F, —NR3GC(S)OR3F, —NR3GC(S)NR3GR3F, —SC(S)OR3F, —OC(S)SR3F, —SC(S)SR3F, —SC(S)NR3GR3F, —NR3GC(S)SR3F, —NR3GC(NR3G)NR3GR3F and —NR3GS(O)1-2NR3GR3F;
• each R3E is independently selected from oxo, optionally-substituted C1—C4 alkyl, C1-C4 fluoroalkyl, halogen, —CN, SF5, —N3, —C(O)R3F, —SR3F, —S(O)1-2R3F, —OR3F, —NR3GR3F, —C(O)R3F, —C(O)NR3GR3F, —NR3GC(O)R3F, —C(S)NR3GR3F, —NR3GC(S)R3F, —C(O)OR3F, —OC(O)R3F, —C(O)SR3F, —SC(O)R3F, —C(S)OR3F, —OC(S)R3F, —C(S)SR3F, —SC(S)R3F, —S(O)1-2OR3F, —OS(O)1-2R3F, —S(O)1-2NR3GR3F, —NR3GS(O)1-2R3F, —OC(O)OR3F, —OC(O)NR3GR3F, —NR3GC(O)OR3F, —NR3GC(O)NR3GR3F, —SC(O)OR3F, —OC(O)SR3F, —SC(O)SR3F, —SC(O)NR3GR3F, —NR3GC(O)SR3F, —OC(S)OR3F, —OC(S)NR3GR3F, —NR3GC(S)OR3F, —NR3GC(S)NR3GR3F, —SC(S)OR3F, —OC(S)SR3F, —SC(S)SR3F, —SC(S)NR3GR3F, —NR3GC(S)SR3F, —NR3GC(NR3G)NR3GR3F and —NR3GS(O)1-2NR3GR3F;
• each R3F is independently selected from H, C1-C3 alkyl, C1-C3 fluoroalkyl and C1-C3 hydroxyalkyl and
• each R3G is independently selected from H, C1-C3 alkyl, C1-C3 fluoroalkyl, C1-C3 hydroxyalkyl, —S(O)1-2(C1-C3 alkyl), —C(O)(C1-C3 alkyl) and —C(O)O(C1-C3 alkyl);
• L4 is selected from the group consisting of a bond, —C(O)—, —S—, —S(O)1-2—, —O—, —NR6—, —C(O)NR6—, —NR6C(O)—, —C(S)NR6—, —NR6C(S)—, —C(O)O—, —OC(O)—, —C(O)S—, —SC(O)—, —C(S)O—, —OC(S)—, —C(S)S—, —SC(S)—, —S(O)1-2O—, —OS(O)1-2—, —S(O)1-2NR6—and —NR6S(O)1-2—;
• R4 is selected from the group consisting of optionally substituted C1-C8 alkyl, optionally-substituted C1-C8 alkenyl optionally substituted C1-C8 alkynyl, and hydrogen;
• L5 is a bond, —C(O)—, —S—, —S(O)1-2—, —O—, —NR6—, —CH2—, —CH(CH3)(OH)—, —CH(OH)—, —CH2CH2—, —CH═CH—, —C≡C—, —C(O)NR6—, —NR6C(O)—, —C(S)NR6—, —NR6C(S)—, —C(O)O—, —OC(O)—, —S(O)1-2O—, —OS(O)1-2—, —S(O)1-2NR6—or —NR6S(O)1-2—;
• R5 is selected from the group consisting of
• phenyl and heteroaryl each optionally substituted with 1-5 R5E, in which
• each R5E is independently selected from oxo, optionally-substituted C1—C4 alkyl, C1-C4 fluoroalkyl, halogen, —CN, —SF5, —N3, —C(O)R5F, —SR5F, —S(O)1-2R5F, —OR5F, —NR5GR5F, —C(O)R5F, —C(O)NR5GR5F, —NR5GC(O)R5F, —C(S)NR5GR5F, —NR1GC(S)R5F, —C(O)OR5F, —OC(O)R5F, —C(O)SR5F, —SC(O)R5F, —C(S)OR5F, —OC(S)R5F, —C(S)SR5F, —SC(S)R5F, —S(O)1-2OR5F, —OS(O)1-2R5F, —S(O)1-2NR5GR5F, —NR5GS(O)1-2R5F, —OC(O)OR5F, —OC(O)NR5GR5F, —NR5GC(O)OR5F, —NR5GC(O)NR5GR5F, —SC(O)OR5F, —OC(O)SR5F, —SC(O)SR5F, —SC(O)NR5GR5F, —NR5GC(O)SR5F, —OC(S)OR5F, —OC(S)NR5GR5F, —NR5G C(S)OR5F, —NR5GC(S)NR5GR5F, —SC(S)OR5F, —OC(S)SR5F, —SC(S)SR5F, —SC(S)NR5GR5F, —NR5GC(S)SR5F, —NR5GC(NR5G)NR5GR5F and —NR5GS(O)1-2NR5GR5F;
• each R5F is independently selected from H, C1-C3 alkyl, C1-C3 fluoroalkyl, C1-C3 hydroxyalkyl and (C1-C3 alkoxy)C1-C3 alkyl and
• each R5G is independently selected from H, C1-C3 alkyl, C1-C3 fluoroalkyl, C1-C3 hydroxyalkyl, and (C1-C3 alkoxy)C1-C3 alkyl, —S(O)1-2(C1-C3 alkyl), —C(O)(C1-C3 alkyl) and —C(O)O(C1-C3 alkyl);
• and
• in which
• R6 is selected from the group consisting of hydrogen, C1-C3 alkyl, C1-C3 fluoroalkyl, C1-C3 hydroxyalkyl, C1-C3 aminoalkyl, C1-C3 thioalkyl, (C1-C3 alkoxy)C1-C3 alkyl, —S(O)1-2(C1-C3 alkyl), —C(O)(C1-C3 alkyl) and —C(O)O(C1-C3 alkyl);
• each alkyl, alkylene, alkenyl, alkenylene, alkynyl and alkynylene is straight-chain or branched;
• each optionally substituted alkyl, alkene, alkyne, alkylene, alkenylene and alkynylene is unsubstituted or substituted with 1-5 substituents independently selected from oxo, halogen, —CN, —SF5, —N3, —C(O)R8, —SR8, —S(O)1-2R8, —OR8, —NR9R8, —C(O)NR9R8, —NR9C(O)R8, —C(S)NR9R8, —NR9C(S)R8, —C(O)OR8, —OC(O)R8, —C(O)SR8, —SC(O)R8, —C(S)OR8, —OC(S)R8, —C(S)SR8, —SC(S)R8, —S(O)1-2OR8, —OS(O)1-2R8, —S(O)1-2NR9R8, —NR9S(O)1-2R8, —OC(O)OR8, —OC(O)NR9R8, —NR9C(O)OR8, —NR9C(O)NR9R8, —SC(O)OR8, —OC(O)SR8, SC(O)SR8, —SC(O)NR9R8, —NR9C(O)SR8, —OC(S)OR8, —OC(S)NR9R8, —NR9C(S)OR8, —NR9C(S)NR9R8, —SC(S)OR8, —OC(S)SR8, —SC(S)SR8, —SC(S)NR9R8, —NR9C(S)SR8, —NR9C(NR9)NR9R8 and —NR9S(O)1-2NR9R8, in which
• each R8 is independently selected from H, C1-C3 alkyl, C1-C3 fluoroalkyl, C1-C3 hydroxyalkyl and (C1-C3 alkoxy)C1-C3 alkyl and
• each R9 is independently selected from H, C1-C3 alkyl, C1-C3 fluoroalkyl, C1-C3 hydroxyalkyl, and (C1-C3 alkoxy)C1-C3 alkyl, —S(O)1-2(C1-C3 alkyl), —C(O)(C1-C3 alkyl) and —C(O)O(C1-C3 alkyl);
• each cycloalkyl has 3-10 ring carbons and is unsaturated or partially unsaturated, and optionally includes one or two fused aryl or heteroaryl rings, each fused ring having 3-8 ring members;
• each heterocycloalkyl has 3-10 ring members and 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur and is unsaturated or partially unsaturated, and optionally includes one or two fused aryl or heteroaryl rings, each fused aryl or heteroaryl ring having 3-8 ring members;
• each optionally substituted heteroaryl is a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur or a 8-10 membered bicyclic heteroaryl having 1-5 heteroatoms independently selected from nitrogen, oxygen or sulfur, optionally includes one or two fused cycloalkyl or heterocycloalkyl rings, each fused cycloalkyl or heterocycloalkyl ring having 4—8 ring members,
• the compound being optionally in the form of a pharmaceutically acceptable salt or N-oxide, or a solvate or hydrate.