Benzofuran and benzothiophene derivatives useful in the treatment of hyper-proliferative disorders

A compound of Formula I

• wherein
• X is selected from O and S;
• R1 is selected from H, (C1-C6)alkyl, C(O)(C1-C6)alkyl, and benzoyl;
• R2 is selected from
• phenyl and naphthyl, each optionally substituted with 1, 2, or 3 substituents each independently selected from
• OH, CN, NO2, (C1-C6)alkyl, (C1-C6)alkoxy, halo, halo(C1-C6)alkyl, halo(C1-C6)alkoxy, C(O)RA, C(O)NRBRB, NRBRB, NH[(C1-C6)alkyl,]0-1S(O)2RB, NH[(C1-C6)alkyl]0-1C(O)RA, and NH[(C1-C6)alkyl]0-1C(O)ORB,
• a heterocycle selected from a six membered heterocycle, a five membered heterocycle and a fused bicyclic heterocycle, each heterocycle being optionally substituted with 1, 2 or 3 substituents each independently selected from
• OH, CN, NO2, (C1-C6)alkyl, (C1-C6)alkoxy, halo, halo(C1-C6)alkyl, halo(C1-C6)alkoxy, C(O)RA, C(O)NRBRB, NRBRB, NH[(C1-C6)alkyl,]0-1S(O)2RB, NH[(C1-C6)alkyl]0-1C(O)RA, and NH[(C1-C6)alkyl]0-1C(O)ORB,
• RA is in each instance independently H, (C1-C6)alkyl, (C1-C6)alkoxy, NRBRB, or
• (C1-C6)alkyl, said alkyl being optionally substituted with OH, C(O)RB, halo, (C1-C3)alkoxy, and NRBRB;
• RB is in each instance independently H, (C3-C6)cycloalkyl, and
• (C1-C6)alkyl, said alkyl being optionally substituted with
• OH, ═O, halo, (C1-C6)alkoxy, NH(C1-C3)alkyl, N[(C1-C3)alkyl]2, and NC(O)(C1-C3)alkyl,
• and where RB, when it is attached to a N atom, is in each instance (C1-C4)alkyl, then the 2 (C1-C4)alkyl groups, taken together with the N atom to which they are attached, may be joined together to form a saturated ring,
• and where RB and RB together with the N to which they are attached may form a morpholinyl ring or a piperazinyl ring optionally substituted on the available N atom with (C1-C6)alkyl, said alkyl being optionally substituted with OH, ═O, NH2, (C1-C6)alkoxy, NH(C1-C3)alkyl, or N[(C1-C3)alkyl]2,
• and with the proviso that when RB is attached to S(O) or to S(O)2, it cannot be H;
• R3 is selected from from H, OH, CN, (C1-C3)alkyl, (C1-C3)alkoxy, halo, halo(C1-C3)alkyl, and halo(C1-C3)alkoxy;
• R4 is selected from
• piperonyl,
• Y where
• Y is a heterocycle optionally substituted with 1, 2, or 3 substituents each independently selected from
• ═O, N-oxide, H, CN, NO2, halo, halo(C1-C6)alkyl, OH, halo(C1-C6)alkoxy, C(O)ORB, C(NH)NRBRB, NRBRB, S(O)0-2RB, S(O)2NRBRB,
• (C1-C6)alkoxy, said alkoxy being optionally substituted with 1 or 2 substituents selected from OH, NRBRB, and (C1-C3)alkoxy,
• NRCRC where
• RC is selected from RB, C(O)RB, and S(O)2RB,
• C(O)RD where
• RD is selected from RA, (C3-C6)cycloalkyl, Z and N[(C1-C3)alkyl]Z where
• Z is in each instance a heterocycle independently optionally substituted with
• CN, ═O, OH, N-oxide, NO2, halo, (C1-C6)alkoxy, halo(C1-C3)alkoxy, halo(C1-C3)alkyl, S(O)2RB, S(O)2NRBRB, NRBRB, C(O)RA, and (C1-C6)alkyl,
• said alkyl being optionally substituted with OH, C(O)RB, (C1-C3)alkoxy and NRBRB;
• NRBRE where
• RE is selected from C(O)RA, C(O)RB, S(O)2RB, S(O)2NRBRB and C(O)[(C1-C6)alkyl]Z where Z is optionally substituted as described above,
• (C1-C6)alkyl, said alkyl being optionally substituted with
• CN, OH, ═O, halo, (C1-C6)alkoxy, C(O)RA, NRBRB, NRCRC, NRBRE, C(NH)NRBRB, S(O)0-2RB, S(O)2NRBRB, C(O)RB C(O)ORB, Z, C(O)Z, and C(O)N[(C1-C3)alkyl]Z, where Z in each instance is independently optionally substituted as described above,
• phenyl and naphthyl each optionally substituted with 1, 2, or 3 substituents each independently selected from
• OH, CN, NO2, halo, halo(C1-C6)alkyl, halo(C1-C6)alkoxy, C(O)ORB, C(NH)NRBRB, NRBRB, S(O)0-2RB, S(O)2NRBRB, Z, C(O)Z where Z is in each instance optionally substituted as described above,
• (C1-C6)alkoxy, said alkoxy being optionally substituted with 1 or 2 substituents selected from OH, NRBRB, and (C1-C3)alkoxy,
• NRCRC where
• RC is selected from RB, C(O)RB, and S(O)2RB,
• C(O)RD where
• RD is selected from RA, (C3-C6)cycloalkyl, and N[(C1-C3)alkyl]Z where Z is optionally substituted as described above,
• NRBRE where
• RE is selected from C(O)RA, C(O)RB, S(O)2RB, S(O)2NRBRB and C(O)[(C1-C6)alkyl]Z where Z is optionally substituted as described above,
• (C1-C6)alkyl, said alkyl being optionally substituted with
• CN, OH, ═O, halo, (C1-C6)alkoxy, C(O)RA, NRBRB, NRBRE, C(NH)NRBRB, S(O)0-2RB, S(O)2NRBRB, C(O)RB C(O)ORB, Z, C(O)Z, and C(O)N[(C1-C3)alkyl]Z, where Z in each instance is independently optionally substituted as described above;
• R5 and R6 are each independently selected from H, OH, CN, (C1-C3)alkyl, (C1-C3)alkoxy,
• halo, halo(C1-C3)alkyl, and halo(C1-C3)alkoxy;
• or a pharmaceutically acceptable salt or ester thereof.