Azoaryls as reversibly modulatable tubulin inhibitors

Compounds corresponding to one of the following formulae:

• wherein:
• the aryl ring bearing R3 is denoted the “south ring”,
• dotted lines indicate sites where a fused ring may be present;
• R2 is chosen among —OCH3, —OCF3, —F, —CH3, —CF3, —CH2CH3, —OCH2CH3, —SCH3, —SCF3, NHCH3, —N(CH3)2 and —CN;
• and
• R1, R6 and R7 are defined as follows:
• R1 is chosen among hydrogen, —Y1Ra, —S2Rb, —NHRd, —ORe, —OPO3H2, —NO2, —B(OH)2, —B(ORb)2, —B(ORbO), —N3, —F, —Cl, —Br, —I, —CHO, —CO2H, —CONH2, —CN, —NC, —SO3H, —CO2Rb, —SO2NH2 and —Rb;
• R7, and when R6 is not linked to R5, R6 also, identical or different, are chosen among hydrogen, —Y2Rf, —S2Rg, —NHRi, —ORj, —OPO3H2, —NO2, —B(OH)2, —B(ORg)2, —B(ORgO), —N3, —F, —Cl, —Br, —I, —CHO, —CO2H, —CONH2, —CN, —NC, —SO3H, —CO2Rg, —SO2NH2, —Rg, —CO2NHRg, —CO2NRgRh, —N-piperazinyl, —N-morpholinyl, —N-pyrrolidinyl, —N-piperidinyl, and -linker-reporter units;
• and when R6 is linked to R5 then they are linked together forming a fused phenyl, 2-pyridinyl or 3-pyridinyl ring, the said phenyl, 2-pyridinyl or 3-pyridinyl being unsubstituted or substituted with one or several groups Rn, identical or different, such that the south ring is respectively a naphthalene, quinoline or isoquinoline;
• considering that at least one of the substituents R6, R7 and R1 is different from hydrogen;
• and
• R3 is chosen among —OCH3, —OCF3, —F, —CH3, —CF3, —CH2CH3, —OCH2CH3, —SCH3, —SCF3, —NHCH3, —N(CH3)2 and —CN;
• R4 and, when R6 is not linked to R5, R5 also, identical or different, are chosen among —OCH3, —OCF3, —F, —CH3, —CF3, —CH2CH3, —OCH2CH3, —SCH3, —SCF3, —NH2, —NHCH3, —N(CH3)2 and —CN;
• Y1═O, S, NH or NRk;
• Y2═O, S, NH or NR1;
• Ra is chosen among hydrogen, —Rb, —CORb, —CO2Rb, —CONH2, —CONRbRc, —CONHRb, —CH2OC(O)Rb, and cleavable groups which after cleavage, for instance in vivo, lead either to R1═—OH when Y1═O, or to R1═—NH2 when Y1═NH, or to R1═—NHRk when Y1═NRk, or to R1═—SH when Y1═S;
• Rb, Rc, Rg, Rh, Rk and Rl, identical or different, are chosen among (C1-C6)alkyl, (C1-C6)alkyl-OH, (C1-C6)alkenyl, (C1-C6)alkynyl, (C3-C7)cycloalkyl, aryl, heteroaryl, heterocycle, (C1-C6)alkyl(C3-C7)cycloalkyl, (C1-C6)alkylaryl, (C1-C6)alkylheteroaryl, and (C1-C6)alkylheterocycle;
• Rd and Ri are identical or different, and are a peptidic group attached via its carboxyl terminus;
• Re and Rj are identical or different, and are a glycosidyl group;
• Rf is chosen among hydrogen, —Rg, —CORg, —CO2Rg, —CONH2, —CONRgRh, —CONHRg, —OCH2OC(O)Rg, and cleavable groups which after, for instance in vivo, lead either to R6 or R7═—OH when Y2═O, to R6 or R7═—NH2 when Y2═NH, or to R6 or R7═—NHR1 when Y2═NR1, or to R6 or R7═—SH when Y2═S;
• Rn is chosen among —CH3, —OH, —NH2, —NHCOCH3, —SO3H, —CO2H, —CONH2, —CO2CH3, —PO3H2, —NO2, —B(OH)2, —N3, —CN, —C≡CH, and —SO2NH2;
• and their hydrates, pharmaceutically acceptable salts and solvates, as a mixture of isomers in any proportions and also as pure isomer.