CPC C07D 471/04 (2013.01) [A61K 45/06 (2013.01); C07D 405/14 (2013.01); C07D 417/14 (2013.01)] | 23 Claims |
1. A compound of Formula I:
or a pharmaceutically acceptable salt or solvate thereof, wherein:
indicates an optional single or double bond, as allowed by valence;
X3, X5, and X8 are C; X2 and X4 are N; X6 and X7 are CH; and X1 is CH or N;
T1 is C(═O)OH;
T2 is hydrogen or (C1-C6)alkyl which is optionally substituted with (C1-C6)alkoxy, (C1-C6)thioalkoxy, (C1-C6)haloalkoxy, S(O)2(C1-C6 alkyl), (C3-C6)cycloalkyl, 3- to 6-membered heterocycloalkyl, phenyl, or 5- to 6-membered heteroaryl, wherein each of the (C3-C6)cycloalkyl, 3- to 6-membered heterocycloalkyl, phenyl, or 5- to 6-membered heteroaryl is optionally substituted with 1-4 RT;
each RT is independently selected from the group consisting of OH, SH, CN, NO2, halogen,
(C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)haloalkyl, (C1-C6)cyanoalkyl,
(C1-C6)hydroxyalkyl, (C1-C6)alkoxy, (C1-C6)haloalkoxy, (C3-C6)cycloalkyl, amino,
(C1-C6)alkylamino, and di(C1-C6)alkylamino;
L1 is a bond or (C1-C3)alkylene which is optionally substituted with 1-3 RL;
L2 is a bond, —O—, —S(O)0-2—, or —NH—;
each RL is independently selected from the group consisting of: halogen, (C1-C3)alkyl, and
(C1-C3)haloalkyl; or a pair of RL on the same or on adjacent carbon atoms, taken together with the atom(s) to which each is attached, forms a (C3-C6)cycloalkyl ring;
Ring A is:
wherein mm represents the point of attachment to L2, and nn represents the point of attachment to L3;
n1 is 0, 1, or 2; m1 and m2 are independently 0 or 1;
W1 is CRY1 or N, provided that when L2 is —O—, —S—, or —N(H)—, then W1 is CRY1;
W2 is CRY2;
each occurrence of RY is independently selected from the group consisting of halogen, CN,
—OH, oxo, (C1-C6)alkyl, (C1-C3)haloalkyl, (C1-C3)alkoxy, and (C1-C3)haloalkoxy;
RY1 and RY2 are independently selected from the group consisting of hydrogen, halogen, CN, —OH, (C1-C6)alkyl, (C1-C3)haloalkyl, (C1-C3)alkoxy, and (C1-C3)haloalkoxy; or
when W1 is CRY1, the RY1 and RY2 groups taken together form (C1-C4)alkylene, wherein one of the CH2 units of the (C1-C4)alkylene is optionally replaced by a heteroatom selected from the group consisting of O, S, NH, and N(C1-3)alkyl;
L3 is —O—;
Ring B is:
wherein aa represents the point of attachment to L3;
each of B1, B2, B3, and B4 is independently selected from the group consisting of CR1 and N;
each R1 is selected from the group consisting of hydrogen, halogen, CN, (C1-C6)alkyl,
(C1-C6)haloalkyl; (C1-C3)alkyl(C3-C6)cycloalkyl, (C1-C3)alkyl(3- to 5-membered heterocycloalkyl), and
—C(O)NR2R3;
each R2 and R3 is independently selected from the group consisting of hydrogen and
(C1-C6)alkyl;
L4 is selected from the group consisting of: —C(RcRc)—; —O—; —S—; —N(C1-3 alkyl)-; —C(═O)—; and
—S(O)1-2—;
L5 is selected from the group consisting of: a bond; —C(RcRc)—; —O—; —S—; —N(H)—;
—N(C1-3 alkyl)-; —C(═O)—; and —S(O)1-2—;
provided that when L4 is —O—, —S—, or —N(C1-3 alkyl)-, then L5 is a bond, —C(RcRc)—, —C(═O), or
—S(O)1-2—, and
provided that when L5 is —O—, —S—, —N(H)—, or —N(C1-3 alkyl)-, then L4 is —C(RcRc)—, —C(═O), or
—S(O)1-2—,
each occurrence of R′ is independently selected from the group consisting of: hydrogen, halogen, CN, —OH, (C1-C6)alkyl, (C1-C3)haloalkyl, (C3-C8)cycloalkyl, (C1-C3)alkoxy, and (C1-C3)haloalkoxy; or
a pair of R′ taken together with the carbon atom to which each is attached forms a
(C3-C8)cycloalkyl ring;
Ring C is selected from the group consisting of phenyl, 5- to 6-membered heteroaryl,
(C3-C6)cycloalkyl, (C5-C10)bicycloalkyl, 5- to 10-membered bicycloheteroaryl, and 3- to 6-membered heterocycloalkyl;
each Rb is independently selected from the group consisting of (C1-C6)alkyl, (C1-C6)haloalkyl,
(C1-C6)alkoxy, (C1-C6)haloalkoxy, halogen, (C3-C6)cycloalkyl, and CN; and
b is an integer selected from 0-3.
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