Novel benzimidazole derivatives useful as selective androgen receptor modulators (sarms)

A method of treating a disorder mediated by an androgen receptor, in a subject in need thereof comprising administering to the subject a therapeutically effective amount of the compound of formula (I)

• wherein
• R1 is selected from the group consisting of hydrogen, C1-4alkyl, —C1-4alkyl-OH, —C1-4alkyl-CN, —C1-4alkyl-NO2, —C1-4alkyl-N(RARB), —C1-4alkyl-CO2H, —CH2-aryl and —CH2-heteroaryl;
• wherein the aryl or heteroaryl group (on the —CH2-aryl and —CH2-heteroaryl group) is optionally substituted with one or more substituents independently selected from halogen, C1-4alkyl, halogen substituted C1-4alkyl, C1-4alkoxy, halogen substituted C1-4alkoxy, —C1-4alkyl-OH, cyano, nitro, amino, C1-4alkylamino, di(C1-4alkyl)amino, —S—C1-4alkyl, —S-(halogen substituted C1-4alkyl), —SO—C1-4alkyl, —SO2—C1-4alkyl, —O-aralkyl, —C(O)O—C1-4alkyl, —CO2H, —C(O)H, heteroaryl or heterocycloalkyl;
• wherein RA and RB are independently selected from hydrogen or C1-4alkyl;
• alternatively, RA and RB are taken together with the nitrogen atom to which they are bound to form a five to seven membered aromatic, partially unsaturated or saturated ring structure, optionally containing one to two additional heteroatoms selected from O, S or N;
• and wherein the ring structure is optionally substituted with C1-4alkyl;
• wherein X is selected from the group consisting of —S—, —SO—, SO2—, —O—SO7—, —O—, —C(OH)—, —C(═N(OH))—, —C(O)—, —C(O)—O—, —NRC—, —NRC—C(O)—, —C(O)—NRC—, —NRC—SO2— and —SO2—NRC—;
• wherein RC is selected from hydrogen or C1-4alkyl;
• wherein R7 is selected from the group consisting of C1-4alkyl, halogen substituted C1-4alkyl, C2-4alkenyl, aryl, aralkyl, biphenyl, cycloalkyl, cycloalkyl-(C1-4alkyl)-, heteroaryl, heteroaryl-(C1-4-alkyl)-, heterocycloalkyl and heterocycloalkyl-(C1-4alkyl)-;
• wherein the cycloalkyl, aryl, heteroaryl or heterocycloalkyl group, whether alone or as part of a substituent group is optionally substituted with one or more substituents independently selected from halogen, hydroxy, carboxy, C1-4alkyl, halogen substituted C1-4alkyl, C1-4alkoxy, halogen substituted C1-4alkoxy, cyano, nitro, amino, C1-4alkylamino, di(C1-4alkyl)amino, —S(O)0-2—(C1-4alkyl), —SO2—N(RD)2, aryl, heteroaryl or heterocycloalkyl;
• wherein each RD is independently selected from hydrogen or C1-4alkyl;
• provided that when X is O or NRC, then R6 is other than C2-4alkenyl;
• R2 is selected from the group consisting of hydrogen, halogen, C1-4alkyl, halogen substituted C1-4alkyl, cyano, nitro, amino, C1-4alkylamino, di(C1-4alkyl)amino, —O—C1-4alkyl, —S—C1-4alkyl, —SO—C1-4alkyl, —SO2—C1-4alkyl and —NRE—C(O)—C1-4alkyl;
• wherein RE is selected from hydrogen or C1-4alkyl;
• R3 is selected from the group consisting of hydrogen, halogen, C1-4alkyl, halogen substituted C1-4alkyl, cyano, nitro, amino, C1-4alkylamino, di(C1-4alkyl)amino, —O—C1-4alkyl, —S—C1-4alkyl, —SO—C1-4alkyl, —SO2—C1-4alkyl and —NRF—C(O)—C1-4alkyl;
• wherein RF is selected from hydrogen or C1-4alkyl;
• provided that at least one of R2 or R3 is other than hydrogen;
• a is an integer from 0 to 1;
• R4 is selected from the group consisting of hydrogen, C1-4alkyl, halogen substituted C1-4alkyl and —C(O)—R8;
• wherein R8 is selected from the group consisting of C1-4alkyl, cycloalkyl, cycloalkyl-(C1-4alkyl)-, aryl, aralkyl, heteroaryl, heteroaryl-(C1-4alkyl)-, heterocycloalkyl and heterocycloalkyl-(C1-4alkyl)-;
• wherein the alkyl, cycloalkyl, aryl, heteroaryl or heterocycloalkyl group, whether alone or as part of a substituent group is optionally substituted with one or more substituents independently selected from halogen, hydroxy, carboxy, C1-4alkyl, halogen substituted C1-4alkyl, C1-4alkoxy, halogen substituted C1-4alkoxy, cyano, nitro, amino, C1-4alkylamino or di(C1-4alkyl)amino;
• R5 is selected from the group consisting of hydrogen, halogen, C1-4alkyl and halogen substituted C1-4alkyl;
• R6 is selected from the group consisting of C1-4alkyl, halogen substituted C1-4alkyl, —C1-4alkyl-OH, —C1-4alkyl-CN, —C1-4alkyl-NO2, —C1-4alkyl-N(RGRH), C1-4alkyl-CO2H, —(C1-4alkyl)-Y—R9, —CH2-aryl and —CH2-heteroaryl;
• wherein the aryl or heteroaryl (on the —CH2-aryl or —CH2-heteroaryl group) is optionally substituted with one or more substituents independently selected from halogen, hydroxy, C1-4alkyl, halogen substituted C1-4alkyl, C1-4alkoxy, halogen substituted C1-4alkoxy, cyano, nitro, amino, C1-4alkylamino, di(C1-4alkyl)amino, —S(O)0-2—C1-4alkyl or —SO2—N(RJ)2;
• wherein each RJ is independently selected from hydrogen or C1-4alkyl;
• wherein RG and RH are independently selected from hydrogen or C1-4alkyl;
• alternatively, RG and RH are taken together with the nitrogen atom to which they are bound to form a five to seven membered aromatic, partially unsaturated or saturated ring structure, optionally containing one to two additional heteroatoms selected from O, S or N;
• and wherein the ring structure is optionally substituted with C1-4alkyl;
• wherein Y is selected from the group consisting of —S—, —SO—, SO2—, —O—SO7—, —O—, —C(OH)—, —C(═N(OH))—, —C(O)—, —C(O)—O—, —NRK—, —NRK—C(O)—, —C(O)—NRK—, —NRK—SO2— and —SO2—NRK—;
• wherein RK (is selected from hydrogen or C1-4alkyl;
• wherein R9 is selected from the group consisting of C1-4alkyl, halogen substituted C1-4alkyl, C2-4alkenyl, aryl, aralkyl, biphenyl, cycloalkyl, cycloalkyl-(C1-4alkyl)-, heteroaryl, heteroaryl-(C1-4alkyl)-, heterocycloalkyl and heterocycloalkyl-(C1-4alkyl)-;
• wherein the cycloalkyl, aryl, heteroaryl or heterocycloalkyl group, whether alone or as part of a substituent group is optionally substituted with one or more substituents independently selected from halogen, hydroxy, carboxy, C1-4alkyl, halogen substituted C1-4alkyl, C1-4alkoxy, halogen substituted C1-4alkoxy, cyano, nitro, amino, C1-4alkylamino, di(C1-4alkyl)amino, —S(O)0-2—(C1-4alkyl), —SO2—N(RL)2, or —NRM—C(O)—C1-4alkyl;
• wherein each RL is independently selected from hydrogen or C1-4alkyl;
• and
• wherein RM is selected from hydrogen or C1-4alkyl;
• provided that when Y is O or NRK, then R9 is other than C2-4alkenyl;
• provided that when R4 is hydrogen and R5 is hydrogen, then R6 is other than C1-4alkyl;
• provided further that when R1 is hydrogen;
• a is 0;
• R4 is hydrogen and R5 is C1-4alkyl;
• then R6 is there than C1-4alkyl;
• provided further that when R1 is hydrogen;
• a is 0;
• R2 is —O—C1-4alkyl;
• R3 is hydrogen;
• R4 is hydrogen;
• R5 is hydrogen;
• then R6 is other than —CH2-phenyl, wherein the phenyl is substituted with —O—C1-4alkyl;
• provided further that when R1 is hydrogen, a is 0, R4 is hydrogen and R5 is hydrogen, then R6 is other than —CH2— (benzimidazolyl), wherein the benzimidazolyl is substituted with one to two substituents selected from halogen, C1-4alkyl or —O—C1-4alkyl;
• or a pharmaceutically acceptable salt thereof.

A method of treating a disorder mediated by an androgen receptor, in a subject in need thereof comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition of comprising a pharmaceutically acceptable carrier and a compound of formula (I)

• wherein
• R1 is selected from the group consisting of hydrogen, C1-4alkyl, —C1-4alkyl-OH, —C1-4alkyl-CN, —C1-4alkyl-NO2, —C1-4alkyl-N(RARB), —C1-4alkyl-CO2H, —(C1-4alkyl)-X—R7, —CH2-aryl and —CH2-heteroaryl;
• wherein the aryl or heteroaryl group (on the —CH2-aryl and —CH2-heteroaryl group) is optionally substituted with one or more substituents independently selected from halogen, C1-4alkyl, halogen substituted C1-4alkyl, C1-4alkoxy, halogen substituted C1-4alkoxy, —C1-4alkyl-CN, —C1-4alkyl-OH, cyano, nitro, amino, C1-4alkylamino, di(C1-4alkyl)amino, —S—C1-4alkyl, —S-(halogen substituted C1-4alkyl), —SO—C1-4alkyl, —SO2—C1-4alkyl, —O-aralkyl, —C(O)O—C1-4alkyl, —CO2H, —C(O)H, heteroaryl or heterocycloalkyl;
• wherein RA and RB are independently selected from hydrogen or C1-4alkyl;
• alternatively, RA and RB are taken together with the nitrogen atom to which they are bound to form a five to seven membered aromatic, partially unsaturated or saturated ring structure, optionally containing one to two additional heteroatoms selected from O, S or N;
• and wherein the ring structure is optionally substituted with C1-4alkyl;
• wherein X is selected from the group consisting of —S—, —SO—, SO2—, —O—SO7—, —O—, —C(OH)—, —C(═N(OH))—, —C(O)—, —C(O)—O—, —NRC—, —NRC—C(O)—, —C(O)—NRC—, —NRC—SO2— and —SO2—NRC—;
• wherein RC is selected from hydrogen or C1-4alkyl;
• wherein R7 is selected from the group consisting of C1-4alkyl, halogen substituted C1-4alkyl, C2-4alkenyl, aryl, aralkyl, biphenyl, cycloalkyl, cycloalkyl-4C1-4alkyl)-, heteroaryl, heteroaryl-(C1-4alkyl)-, heterocycloalkyl and heterocycloalkyl-(C1-4alkyl)-;
• wherein the cycloalkyl, aryl, heteroaryl or heterocycloalkyl group, whether alone or as part of a substituent group is optionally substituted with one or more substituents independently selected from halogen, hydroxy, carboxy, C1-4alkyl, halogen substituted C1-4alkyl, C1-4alkoxy, halogen substituted C1-4alkoxy, cyano, nitro, amino, C1-4alkylamino, di(C1-4alkyl)amino, —S(O)0-2—(C1-4alkyl), —SO2—N(RD)2, aryl, heteroaryl or heterocycloalkyl;
• wherein each RD is independently selected from hydrogen or C1-4alkyl;
• provided that when X is O or NRC, then R6 is other than C2-4alkenyl;
• R2 is selected from the group consisting of hydrogen, halogen, C1-4alkyl, halogen substituted C1-4alkyl, cyano, nitro, amino, C1-4alkylamino, di(C1-4alkyl)amino, —O—C1-4alkyl, —S—C1-4alkyl, —SO—C1-4alkyl, —SO2—C1-4alkyl and —NRE—C(O)—C1-4alkyl;
• wherein RE is selected from hydrogen or C1-4alkyl;
• R3 is selected from the group consisting of hydrogen, halogen, C1-4alkyl, halogen substituted C1-4alkyl, cyano, nitro, amino, C1-4alkylamino, di(C1-4alkyl)amino, —O—C1-4alkyl, —S—C1-4alkyl, —SO—C1-4alkyl, —SO2—C1-4alkyl and —NRF—C(O)—C1-4alkyl;
• wherein RF is selected from hydrogen or C1-4alkyl;
• provided that at least one of R2 or R3 is other than hydrogen;
• a is an integer from 0 to 1;
• R4 is selected from the group consisting of hydrogen, C1-4alkyl, halogen substituted C1-4alkyl and —C(O)—R8;
• wherein R8 is selected from the group consisting of C1-4alkyl, cycloalkyl, cycloalkyl-(C1-4alkyl)-, aryl, aralkyl, heteroaryl, heteroaryl-(C1-4alkyl)-, heterocycloalkyl and heterocycloalkyl-(C1-4alkyl)-;
• wherein the alkyl, cycloalkyl, aryl, heteroaryl or heterocycloalkyl group, whether alone or as part of a substituent group is optionally substituted with one or more substituents independently selected from halogen, hydroxy, carboxy, C1-4alkyl, halogen substituted C1-4alkyl, C1-4alkoxy, halogen substituted C1-4alkoxy, cyano, nitro, amino, C1-4alkylamino or di(C1-4alkyl)amino;
• R5 is selected from the group consisting of hydrogen, halogen, C1-4alkyl and halogen substituted C1-4alkyl;
• R6 is selected from the group consisting of C1-4alkyl, halogen substituted C1-4alkyl, OH, —C1-4alkyl-CN, —C1-4alkyl-NO2, —C1-4alkyl-N(RGRH), C1-4alkyl-CO2H, —(C1-4alkyl)-Y—R9, —CH2-aryl and —CH2-heteroaryl;
• wherein the aryl or heteroaryl (on the —CH2-aryl or —CH2-heteroaryl group) is optionally substituted with one or more substituents independently selected from halogen, hydroxy, C1-4alkyl, halogen substituted C1-4alkyl, C1-4alkoxy, halogen substituted C1-4alkoxy, cyano, nitro, amino, C1-4alkylamino, di(C1-4alkyl)amino, —S(O)0-2—C1-4alkyl or —SO2—N(RJ)2;
• wherein each RJ is independently selected from hydrogen or C1-4alkyl;
• wherein RG and RH are independently selected from hydrogen or C1-4alkyl;
• alternatively, RG and RH are taken together with the nitrogen atom to which they are bound to form a five to seven membered aromatic, partially unsaturated or saturated ring structure, optionally containing one to two additional heteroatoms selected from O, S or N;
• and wherein the ring structure is optionally substituted with C1-4alkyl;
• wherein Y is selected from the group consisting of —S—, —SO—, SO2—, —O—SO7—, —O—, —C(OH)—, —C(═N(OH))—, —C(O)—, —C(O)—O—, —NRK—, —NRK—C(O)—, —C(O)—NRK—, —NRK—SO2— and —SO2—NRK—;
• wherein RK (is selected from hydrogen or C1-4alkyl;
• wherein R9 is selected from the group consisting of C1-4alkyl, halogen substituted C1-4alkyl, C2-4alkenyl, aryl, aralkyl, biphenyl, cycloalkyl, cycloalkyl-4C1-4alkyl)-, heteroaryl, heteroaryl-(C1-4alkyl)-, heterocycloalkyl and heterocycloalkyl-(C1-4alkyl)-;
• wherein the cycloalkyl, aryl, heteroaryl or heterocycloalkyl group, whether alone or as part of a substituent group is optionally substituted with one or more substituents independently selected from halogen, hydroxy, carboxy, C1-4alkyl, halogen substituted C1-4alkyl, C1-4alkoxy, halogen substituted C1-4alkoxy, cyano, nitro, amino, C1-4alkylamino, di(C1-4alkyl)amino, —S(O)0-2—(C1-4alkyl), —SO2—N(RL)7 or —NRM—C(O)—C1-4alkyl;
• wherein each RL is independently selected from hydrogen or C1-4alkyl;
• and
• wherein RM is selected from hydrogen or C1-4alkyl;
• provided that when Y is O or NRK, then R9 is other than C2-4alkenyl;
• provided that when R4 is hydrogen and R5 is hydrogen, then R6 is other than C1-4alkyl;
• provided further that when R1 is hydrogen;
• a is 0;
• R4 is hydrogen and R5 is C1-4alkyl;
• then R6 is there than C1-4alkyl;
• provided further that when R1 is hydrogen;
• a is 0;
• R2 is —O—C1-4alkyl;
• R3 is hydrogen;
• R4 is hydrogen;
• R5 is hydrogen;
• then R6 is other than —CH2-phenyl, wherein the phenyl is substituted with —O—C1-4alkyl;
• provided further that when R1 is hydrogen, a is 0, R4 is hydrogen and R5 is hydrogen, then R6 is other than —CH2-(benzimidazolyl), wherein the benzimidazolyl is substituted with one to two substituents selected from halogen, C1-4alkyl or —O—C1-4alkyl;
• or a pharmaceutically acceptable salt thereof.

A method of treating a condition selected from the group consisting of prostate carcinoma, benign prostatic hyperplasia (BPH), hirsutism, alopecia, anorexia nervosa, breast cancer, acne, AIDS, cachexia, male contraception, and male performance, in a subject in need thereof comprising administering to the subject a therapeutically effective amount of the compound of formula (I)

• wherein
• R1 is selected from the group consisting of hydrogen, C1-4alkyl, —C1-4alkyl-OH, —C1-4alkyl-CN, —C1-4alkyl-NO2, —C1-4alkyl-N(RARB), —C1-4alkyl-CO2H, —(C1-4alkyl)-X—R7, —CH2-aryl and —CH2-heteroaryl;
• wherein the aryl or heteroaryl group (on the —CH2-aryl and —CH2-heteroaryl group) is optionally substituted with one or more substituents independently selected from halogen, C1-4alkyl, halogen substituted C1-4alkyl, C1-4alkoxy, halogen substituted C1-4alkoxy, —C1-4alkyl-OH, cyano, nitro, amino, C1-4alkylamino, di(C1-4alkyl)amino, —S—C1-4alkyl, —S-(halogen substituted C1-4alkyl), —SO—C1-4alkyl, —SO2—C1-4alkyl, —O-aralkyl, —C(O)O—C1-4alkyl, —CO2H, —C(O)H, heteroaryl or heterocycloalkyl;
• wherein RA and RB are independently selected from hydrogen or C1-4alkyl;
• alternatively, RA and RB are taken together with the nitrogen atom to which they are bound to form a five to seven membered aromatic, partially unsaturated or saturated ring structure, optionally containing one to two additional heteroatoms selected from O, S or N;
• and wherein the ring structure is optionally substituted with C1-4alkyl;
• wherein X is selected from the group consisting of —S—, —SO—, SO2—, —O—SO7—, —O—, —C(OH)—, —C(═N(OH))—, —C(O)—, —C(O)—O—, —NRC—, —NRC—C(O)—, —C(O)—NRC—, —NRC—SO2— and —SO2—NRC—;
• wherein RC is selected from hydrogen or C1-4alkyl;
• wherein R7 is selected from the group consisting of C1-4alkyl, halogen substituted C1-4alkyl, C2-4alkenyl, aryl, aralkyl, biphenyl, cycloalkyl, cycloalkyl-4C1-4alkyl)-, heteroaryl, heteroaryl-(C1-4alkyl)-, heterocycloalkyl and heterocycloalkyl-(C1-4alkyl)-;
• wherein the cycloalkyl, aryl, heteroaryl or heterocycloalkyl group, whether alone or as part of a substituent group is optionally substituted with one or more substituents independently selected from halogen, hydroxy, carboxy, C1-4alkyl, halogen substituted C1-4alkyl, C1-4alkoxy, halogen substituted C1-4alkoxy, cyano, nitro, amino, C1-4alkylamino, di(C1-4alkyl)amino, —S(O)0-2—(C1-4alkyl), —SO2—N(RD)2, aryl, heteroaryl or heterocycloalkyl;
• wherein each RD is independently selected from hydrogen or C1-4alkyl;
• provided that when X is O or NRC, then R6 is other than C2-4alkenyl;
• R2 is selected from the group consisting of hydrogen, halogen, C1-4alkyl, halogen substituted C1-4alkyl, cyano, nitro, amino, C1-4alkylamino, di(C1-4alkyl)amino, —O—C1-4alkyl, —S—C1-4alkyl, —SO—C1-4alkyl, —SO2—C1-4alkyl and —NRE—C(O)—C1-4alkyl;
• wherein RE is selected from hydrogen or C1-4 alkyl;
• R3 is selected from the group consisting of hydrogen, halogen, C1-4alkyl, halogen substituted C1-4 alkyl, cyano, nitro, amino, C1-4alkylamino, di(C1-4alkyl)amino, —O—C1-4alkyl, —S—C1-4alkyl, —SO—C1-4alkyl, —SO2—C1-4alkyl and —NRF—C(O)—C1-4alkyl;
• wherein RF is selected from hydrogen or C1-4 alkyl;
• provided that at least one of R2 or R3 is other than hydrogen;
• a is an integer from 0 to 1;
• R4 is selected from the group consisting of hydrogen, C1-4alkyl, halogen substituted C1-4alkyl and —C(O)—R8;
• wherein R8 is selected from the group consisting of C1-4alkyl, cycloalkyl, cycloalkyl-(C1-4alkyl)-, aryl, aralkyl, heteroaryl, heteroaryl-(C1-4alkyl)-, heterocycloalkyl and heterocycloalkyl-(C1-4-alkyl)-;
• wherein the alkyl, cycloalkyl, aryl, heteroaryl or heterocycloalkyl group, whether alone or as part of a substituent group is optionally substituted with one or more substituents independently selected from halogen, hydroxy, carboxy, C1-4alkyl, halogen substituted C1-4alkyl, C1-4alkoxy, halogen substituted C1-4alkoxy, cyano, nitro, amino, C1-4alkylamino or di(C1-4alkyl)amino;
• R5 is selected from the group consisting of hydrogen, halogen, C1-4alkyl and halogen substituted C1-4alkyl;
• R6 is selected from the group consisting of C1-4alkyl, halogen substituted C1-4alkyl, —C1-4alkyl-OH, —C1-4alkyl-CN, —C1-4alkyl-NO2, —C1-4alkyl-N(RGRH), C1-4alkyl-CO2H, —(C1-4alkyl)-Y—R9, —CH7-aryl and —CH2-heteroaryl;
• wherein the aryl or heteroaryl (on the —CH2-aryl or —CH2-heteroaryl group) is optionally substituted with one or more substituents independently selected from halogen, hydroxy, C1-4alkyl, halogen substituted C1-4alkyl, C1-4alkoxy, halogen substituted C1-4alkoxy, cyano, nitro, amino, C1-4alkylamino, di(C1-4alkyl)amino, —S(O)0-2—C1-4alkyl or —SO2—N(RJ)2;
• wherein each RJ is independently selected from hydrogen or C1-4alkyl;
• wherein RG and RH are independently selected from hydrogen or C1-4alkyl;
• alternatively, RG and RH are taken together with the nitrogen atom to which they are bound to form a five to seven membered aromatic, partially unsaturated or saturated ring structure, optionally containing one to two additional heteroatoms selected from O, S or N;
• and wherein the ring structure is optionally substituted with C1-4alkyl;
• wherein Y is selected from the group consisting of —S—, —SO—, SO2—, —O—SO7—, —O—, —C(OH)—, —C(═N(OH))—, —C(O)—, —C(O)—O—, —NRK—, —NRK—C(O)—, —C(O)—NRK—, —NRK—SO2— and —SO2—NRK—;
• wherein RK (is selected from hydrogen or C1-4alkyl;
• wherein R9 is selected from the group consisting of C1-4alkyl, halogen substituted C1-4alkyl, C2-4alkenyl, aryl, aralkyl, biphenyl, cycloalkyl, cycloalkyl-4C1-4alkyl)-, heteroaryl, heteroaryl-(C1-4alkyl)-, heterocycloalkyl and heterocycloalkyl-(C1-4alkyl)-;
• wherein the cycloalkyl, aryl, heteroaryl or heterocycloalkyl group, whether alone or as part of a substituent group is optionally substituted with one or more substituents independently selected from halogen, hydroxy, carboxy, C1-4alkyl, halogen substituted C1-4alkyl, C1-4alkoxy, halogen substituted C1-4alkoxy, cyano, nitro, amino, C1-4alkylamino, di(C1-4alkyl)amino, —S(O)0-2—(C1-4alkyl), —SO2—N(RJ)2, or —NRM—C(O)—C1-4alkyl;
• wherein each RL is independently selected from hydrogen or C1-4alkyl;
• and
• wherein RM is selected from hydrogen or C1-4alkyl;
• provided that when Y is O or NRK, then R9 is other than C2-4alkenyl;
• provided that when R4 is hydrogen and R5 is hydrogen, then R6 is other than C1-4alkyl;
• provided further that when R1 is hydrogen;
• a is 0;
• R4 is hydrogen and R5 is C1-4alkyl;
• then R6 is there than C1-4alkyl;
• provided further that when R1 is hydrogen;
• a is 0;
• R2 is —O—C1-4alkyl;
• R3 is hydrogen;
• R4 is hydrogen;
• R5 is hydrogen;
• then R6 is other than —CH2-phenyl, wherein the phenyl is substituted with —O—C1-4alkyl;
• provided further that when R1 is hydrogen, a is 0, R4 is hydrogen and R5 is hydrogen, then R6 is other than —CH2— (benzimidazolyl), wherein the benzimidazolyl is substituted with one to two substituents selected from halogen, C1-4alkyl or —O—C1-4alkyl;
• or a pharmaceutically acceptable salt thereof.