Therapeutic pyrazoloquinoline derivatives

A compound of formula (I):

• or a tautomer thereof, or their pharmaceutically acceptable salts,
• wherein
• R is hydrogen, or oxide;
• each R1 is selected from the group consisting of hydrogen, hydroxy, halo, cyano, —CONRaRb, —NRaRb, hydroxy(C1-C6)alkyl, aryl, heteroaryl, heterocycle, amino(C1-C6)alkyl, (C1-C6)alkyl optionally substituted with up to 5 fluoro, and (C1-C6)alkoxy optionally substituted with up to 5 fluoro;
• R2 is selected from the group consisting of hydrogen, hydroxy, halo, hydroxy(C1-C6)alkyl, (C1-C6)alkyl optionally substituted with up to 5 fluoro, and (C1-C6)alkoxy optionally substituted with up to 5 fluoro;
• each Ra and Rb is independently hydrogen, (C1-C6)alkyl, aryl, heteroaryl, heterocycle, (C1-C6)alkylaryl, —S(O)z(C1-C6)alkyl, —S(O)zaryl, —C(O)(C1-C6)alkyl, —C(O)NRg(C1-C6)alkyl, —C(O)NRgaryl, —C(O)O(C1-C6)alkyl, arylOC(O)— or arylC(O)—, or Ra together with Rb form a heterocycle group optionally substituted with one or more Rd;
• wherein the heterocycle group optionally include one or more groups selected from O (oxygen), S (sulfur), and NRc;
• each Rc is independently hydrogen, (C2-C6)alkenyl, (C2-C6)alkynyl, —C(O)O(C1-C6)alkyl, —C(O)Oaryl, (C1-C6)alkoxy(C1-C6)alkyl, hydroxy(C1-C6)alkyl, aryl, heteroaryl, heterocycle, arylO(C1-C6)alkyl, —C(O)NRg(C1-C6)alkyl, —C(O)NRgaryl, —S(O)z(C1-C6)alkyl, —S(O)zaryl, —C(O)(C1-C6)alkyl, arylC(O)—, (C1-C6)alkyl optionally substituted with up to 5 fluoro, or (C1-C6)alkoxy optionally substituted with up to 5 fluoro;
• each Rd is independently selected from the group consisting of hydrogen, halo, oxo, hydroxy, —C(O)NRaRb, —NRaRb, hydroxy(C1-C6)alkyl, aryl, aryl(C1-C6)alkyl, (C1-C6)alkyl optionally substituted with up to 5 fluoro, and (C1-C6)alkoxy optionally substituted with up to 5 fluoro;
• each Re and Rf is independently selected from hydrogen, (C1-C6)alkyl, aryl, heteroaryl, heterocycle, (C1-C6)alkylaryl, aryl(C1-C6)alkyl, —C(O)(C1-C6)alkyl, —S(O)z(C1-C6)alkyl, —S(O)zNRg(C1-C6)alkyl, —S(O)zaryl, —C(O)NRg(C1-C6)alkyl, —C(O)(C1-C6)alkyl, arylC(O)—, arylOC(O)—, or —C(O)O(C1-C6)alkyl;
• Rg is hydrogen, aryl, heteroaryl, heterocycle or (C1-C6)alkyl optionally substituted with up to 5 fluoro;
• Ar is aryl optionally substituted with one or more M or heteroaryl optionally substituted with one or more M;
• each Q is independently hydrogen, halo, oxo, hydroxy, —C(O)NRaRb, —NRaRb, (C1-C6)alkyl optionally substituted with up to 5 fluoro, (C1-C6)alkoxy optionally substituted with up to 5 fluoro, (C1-C6)alkyl optionally substituted with one or more Rd, hydroxy(C1-C6)alkyl optionally substituted with one or more Rd, aryl optionally substituted with one or more Rd, or aryl(C1-C6)alkyl optionally substituted with one or more Rd;
• each M is independently hydrogen, halo, CF3, CF2H, hydroxy, cyano, nitro, (C1-C6)alkyl, hydroxy(C1-C6)alkyl, (C1-C6)alkoxy, —NRaRb, aryl, heteroaryl or heterocycle;
• each X is independently NL, oxygen, C(O)2, or S(O)z;
• each L is independently hydrogen, (C2-C6)alkenyl, (C2-C6)alkynyl, —C(O)O(C1-C6)alkyl, —C(O)Oaryl, (C1-C6)alkoxy(C1-C6)alkyl, hydroxy(C1-C6)alkyl, aryl, heteroaryl, heterocycle, arylO(C1-C6)alkyl, —CONReRf, —S(O)z(C1-C6)alkyl, —S(O)zaryl, —C(O)(C1-C6)alkyl, arylC(O)—, —C(O)NRg(C1-C6)alkyl, (C1-C6)alkyl optionally substituted with up to 5 fluoro, or (C1-C6)alkoxy optionally substituted with up to 5 fluoro;
• p is an integer selected from 0, 1, 2 and 3,
• z is an integer selected from 0, 1, and 2;
• and
• n is an integer selected from 0, 1, and 2.