主权项 |
1. A compound represented by Formula Ia or a pharmaceutically acceptable salt thereof, wherein
R′ is H, C1-C8 alkyl optionally substituted by one or more halogen atoms;R1 is H, C1-C8 alkyl optionally substituted by one or more halogen atoms, C1-C4 alkyl, OH, OR′, —NR19R21, CN or C3-C7 cycloalkyl; orR1 is —X—Y; orR1 is —W—R7—X—Y; orR1 is —S(O)2—W—X—Y; orR1 is —S(O)2—W—R7—X—Y;R2 is H, C1-C8 alkyl optionally substituted by one or more halogen atoms, C1-C4 alkyl, OH, OR′, —NR19R21, CN or C3-C7 cycloalkyl; orR2 is —X—Y; orR2 is —W—R7—X—Y; orR2 is —S(O)2—W—X—Y;R2 is —S(O)2—W—R7—X—Y;wherein either R1 or R2 is —X—Y, —S(O)2—W—X—Y; or —S(O)2—W—R7—X—Y;R2a is hydrogen;R2 and R2a taken together are oxo;R3 is H, C1-C4 alkoxy, OH, —NR19R21, CN, halogen, C3-C7 cycloalkyl or C1-C8 alkyl optionally substituted by one or more halogen atoms;R4 is H, C1-C4 alkoxy, OH, —NR19R21, CN, halogen, C3-C7 cycloalkyl or C1-C8 alkyl optionally substituted by one or more halogen atoms;R5 is C1-C8 alkyl optionally substituted by one or more halogen atoms, C1-C4 alkyl, OH, OR′, —NR19R21, CN or C3-C7 cycloalkyl; C1-C8 alkoxy optionally substituted by one or more halogen atoms; C6-C14 aryl; —(C0-C4 alkyl)-4 to 14 membered heteroaryl, or —(C0-C4 alkyl)-3 to 14 membered heterocyclyl wherein the heteroaryl and heterocyclyl contain at least one heteroatom selected from N, O and S, wherein the aryl, heteroaryl and heterocyclyl are each optionally substituted by one or more Z substituents;R6 is C8-C14 aryl; —(C0-C4 alkyl)-4 to 14 membered heteroaryl, —(C0-C4 alkyl)-3 to 14 membered heterocyclyl wherein the heteroaryl and heterocyclyl contain at least one heteroatom selected from N, O and S, wherein the aryl, heteroaryl and heterocyclyl are each optionally substituted by one or more Z substituents;W is C1-C8 alkylene optionally substituted by hydroxy, halogens or C1-C4 alkyl;X is C1-C8 alkylene optionally substituted by hydroxy, halogens or C1-C4 alkyl;Y is carboxy, alkoxycarbonyl, tetrazolyl, carbamoyl, monoalkylcarbamoyl, dialkylcarbamoyl, or —CONH—S(O)q—Rx, wherein Rx is —C1-C4 alkyl or —NR19R21;q is 0, 1 or 2;R7 is a divalent moiety represented by —O—, —NHC(O)—, —CH2═CH2—, —C8-C14 aryl-D-; -3 to 14 membered heterocyclyl-D-, wherein the heterocyclyl contains at least one heteroatom selected from N, O and S, wherein D is O, S, NH or not present;Z is independently OH, aryl, O-aryl, benzyl, O-benzyl, C1-C6 alkyl optionally substituted by one or more OH groups or NH2 groups, C1-C6 alkyl optionally substituted by one or more halogen atoms, C1-C6 alkoxy optionally substituted by one or more OH groups, C1-C6 alkoxy optionally substituted by one or more halogen, C1-C6 alkoxy R21, (SO2)R21, optionally substituted by C1-C4 alkoxy, NR18(SO2)R21, (SO2)NR19R21, (SO2)R21, NR18C(O)R21, C(O)NR19R21, NR18C(O)NR19R21, NR18C(O)OR19, NR19R21, C(O)OR19, C(O)R19, SR19, OR19, oxo, CN, NO2, halogen or a 3 to 14 membered heterocyclyl, wherein the heterocyclyl contains at least one heteroatom selected from N, O and S;R18 is independently H or C1-C6 alkyl;R19 and R21 are each independently H; C1-C8 alkyl; C3-C8 cycloalkyl; C1-C4 alkoxy-C1-C4 alkyl; (C0-C4 alkyl)-aryl optionally substituted by one or more groups selected from C1-C6 alkyl, C1-C6 alkoxy and halogen; (C0-C4 alkyl)-3- to 14-membered heterocyclyl, the heterocyclyl including one or more heteroatoms selected from N, O and S, optionally substituted by one or more groups selected from halogen, oxo, C1-C6 alkyl and C(O)C1-C6 alkyl; (C0-C4 alkyl)-O-aryl optionally substituted by one or more groups selected from C1-C6 alkyl, C1-C6 alkoxy and halogen; and (C0-C4 alkyl)-O-3- to 14-membered heterocyclyl, the heterocyclyl including one or more heteroatoms selected from N, O and S, optionally substituted by one or more groups selected from halogen, C1-C6 alkyl or C(O)C1-C6 alkyl; wherein the alkyl groups are optionally substituted by one or more halogen atoms, C1-C4 alkoxy, C(O)NH2, C(O)NHC1-C6 alkyl or C(O)N(C1-C6 alkyl)2; orR19 and R21 together with the nitrogen atom to which they attached form a 5- to 10-membered heterocyclyl, the heterocyclyl including one or more further heteroatoms selected from N, O and S, the heterocyclyl being optionally substituted by one or more substituents selected from OH; halogen; aryl; 5- to 10-membered heterocyclyl including one or more heteroatoms selected from N, O and S; S(O)2-aryl; S(O)2—C1-C6 alkyl; C1-C6 alkyl optionally substituted by one or more halogen atoms; C1-C6 alkoxy optionally substituted by one or more OH groups or C1-C4 alkoxy; and C(O)OC1-C6 alkyl, wherein the aryl and heterocyclyl substituent groups are themselves optionally substituted by C1-C6 alkyl, C1-C6 haloalkyl or C1-C6 alkoxy. |