Compounds as modulators of a mutant cftr protein and their use for treating diseases associated with cftr protein malfunction

A method of treating cystic fibrosis in a patient comprising the step of:

• administrating to a therapeutically effective amount of a compound of general formula (II), as a modulator of a mutant CFTR protein to a living organism having cystic fibrosis:
• its tautomers, E and Z geometrical isomers, optically active forms such as enantiomers, diastereomers and their racemate forms or a mixture of stereoisomeric forms or its pharmaceutically acceptable salts thereof or complexes thereof;
• wherein Q1 and Q2 are independently selected from the group consisting of:
• C, CH, N, NH;
• wherein A is a fused five-membered ring having 0-3 independently selected heteroatoms wherein the heteroatoms comprise nitrogen, sulfur or oxygen;
• wherein R4, R5 and R6 represent optional substituents, which are independently selected from:
• —ORB, —OC(═O)RC, —OC(═O)ORB, —OC(═O)N(RA)RA′, —C(═O)RC, —C(═O)N(RA)RA′, —C(═O)N(ORB)RA, —C(═O)ORB, —C(═S)RC, —C(═O)C(═O)RC, —CH2ORB, —CH2CH2ORB, —CH2N(RA)RA′, —CH2CH2N(RA)RA′, —CH2OCH2RC, —CH2N(RA)CH2RC, —SRD, —S(═O)RD, —SO2RD, —SO2N(RA)RA′, —SO3RB, —N(RA)C(═O)RC, —N(RA)C(═O)ORB, —N(RA)C(═O)N(RA′)RA″, —N(RA)SO2RD, —N(RA)SO2N(RA′)RA″, —N(RA)RA′, —N(RA)C(═O)RC, —N(RA)C(═O)ORB, —N(RA)N(RA′)RA″, —N(RA′)N(RA)C(═O)RC, —CN, —CF3, —CHF2, —CH2F, —NH2, —SCN,
• —SO2CN, —F, Cl, —Br, —I, —PO3H2, —OPO3H2, which may be optionally preceded by:
• —CnH(2n−1)RC which is branched or unbranched wherein n is an integer from 1 to 4;
• —CnH(2n−3)Rc in E or Z geometrical conformation which is branched or unbranched wherein n is an integer from 2 to 5;
• —CnH(2n−5)RC which is branched or unbranched wherein n is an integer from 2 to 5;
• wherein Z2 is selected from:
• a single bond, —N(RA′)—, —S—, —S-alkil-, —O—, —O-alikil-, —C(═O)—, —S(═O)—, —OC(═O)—, —C(═O)N(RA′)—, —OC(═O)N(RA′)—, —C(═O)O—, —SO2—, —SO2N(RA′)—, —N(RA′)SO2—, —N(RA′)SO2N(RA″)—, —CH2O—, —N(RA′)C(═O)—, —N(RA′)C(═O)O—, —N(RA′)C(═O)N(RA)—, —C(═O)C(═O)—, —N(RA′)C(═O)O—, —N(RA′)N(RA″)—, —N(RA′)N(RA″)C(═O)—, —C(═O)N(RA′)N(RA″)—, —CH2N(RA′)—, —CH2CH2O—, —CH2CH2N(RA′)—, —CH2OCH2—, —CH2N(RA′)CH2—, —CnH2n which is branched or unbranched wherein n is an integer from 1 to 5;
• —CnH(2n−2) in E or Z geometrical conformation which is branched or unbranched wherein n is an integer from 2 to 5;
• —CnH(2n−4) which is branched or unbranched wherein n is an integer from 2 to 5;
• wherein R7 are independently selected from the group consisting of:
• —H, aromatic ring or heteroaromatic ring;
• wherein Z3 is selected from:
• a single bond, double bond, —N(RA′)—, —S—, —S-alkyl-,
• —O—, —O-alkyl- —C(═O)—, —C(═S)—, —OC(═O)—, —C(═O)N(RA′)—, —OC(═O)N(RA′)—, —C(═O)O—, —SO2—, —SO2N(RA′)—, —N(RA′)SO2—, —N(RA′)SO2N(RA′)—, —CH2O—, —N(RA′)C(═O)—, —N(RA′)C(═O)O—, —N(RA′)C(═O)N(RA′)—, —C(═O)C(═O)—, —N(RA′)C(═O)O—, —N(RA′)N(RA″)—, —N(RA′)N(RA″)C(═O)—, —C(═O)N(RA′)N(RA″)—, —CH2N(RA′)—, —CH2CH2O—, —CH2CH2N(RA′)—, —CH2OCH2—, —CH2N(RA′)CH2—, —CnH2n— which is branched or unbranched wherein n is an integer from 1 to 5;
• —CnH(2n−2) in E or Z geometrical conformation which is branched or unbranched wherein n is an integer from 2 to 5;
• —CnH(2n−4) which is branched or unbranched wherein n is an integer from 2 to 5;
• wherein R8 is selected from:
• H, O, S, aromatic ring or heteroaromatic ring;
• —CnH(2n+1) which is branched or unbranched wherein n is an integer from 1 to 5;
• —CnH(2n−1) in E or Z geometrical conformation which is branched or unbranched wherein n is an integer from 2 to 5;
• —CnH(2n−3) which is branched or unbranched wherein n is an integer from 2 to 5;
• wherein RA, RA′, RA″ are each independently selected from the group consisting of:
• —H, lower alkyl group, —CN, —CF3, —CHF2, —CH2F, —OH;
• wherein RB is independently selected from the group consisting of:
• —H, lower alkyl group, —CN, —CF3, —CHF2, —CH2F, —CH2Cl, —CH2Br, —CH2I;
• wherein Rc is independently selected from the group consisting of:
• —H, lower alkyl group, —CN, —CF3, —CHF2, —CH2F, —CH2Cl, —CH2Br, —CH2I, —F, —Cl, —Br, —I, —NH2;
• wherein RD is independently selected from the group consisting of:
• —H, lower alkyl group;
• wherein the 5-membered ring A is moiety selected from the group consisting of:
• and wherein compound 6-[(4-oxo-1H-quinolin-3-yl)carbonylamino]-1H-indole-4-carboxylic acid ethyl ester is excluded.