US 11,697,652 B2
Tetracyclic compounds and uses thereof
Lan Jiang, Foster City, CA (US); David W. Lin, Berkeley, CA (US); Michael L. Mitchell, Castro Valley, CA (US); Ezra Roberts, San Francisco, CA (US); and Gregg M. Schwarzwalder, Redwood City, CA (US)
Assigned to Gilead Sciences, Inc., Foster City, CA (US)
Filed by Gilead Sciences, Inc., Foster City, CA (US)
Filed on Feb. 23, 2021, as Appl. No. 17/182,559.
Claims priority of provisional application 63/128,670, filed on Dec. 21, 2020.
Claims priority of provisional application 63/036,268, filed on Jun. 8, 2020.
Claims priority of provisional application 62/980,857, filed on Feb. 24, 2020.
Prior Publication US 2021/0284642 A1, Sep. 16, 2021
Int. Cl. C07D 471/22 (2006.01); A61P 31/18 (2006.01)
CPC C07D 471/22 (2013.01) [A61P 31/18 (2018.01)] 52 Claims
 
1. A compound of Formula I:

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt thereof, wherein
R1 is H, C6-10aryl or C6-10heteroaryl, wherein the C6-10aryl or C6-10heteroaryl are optionally substituted with one to four RA1, wherein each RA1 is independently halo, C1-6alkyl, C1-4haloalkyl, C3-6cycloalkyl, cyano, —O—C1-4alkyl, —O—C3-6cycloalkyl, or C1-4alkyl-O—C1-4alkyl;
Y is selected from the group consisting of —C(O)NH—,

OG Complex Work Unit Chemistry
L is —CR3aR3b—, —C(O)—, —SO2—, —CR3aR3b—CR3cR3d—, or —N(Ra)—;
W1 is a bond or —CR4aR4b—;
W2 is —CR5aR5b—, —CR5aR5bCR5cR5d—, —CR6a═CR6b—, —N(R7)—, —O—, —S(O)n—, —C(O)NRe—, —CR5aR5b—N(R7)—, —CR5aR5b—O—, —CR5aR5b—S(O)n—, —CR5aR5b—C(O)NRe—, —CR5aR5b—NRe—C(O)—, —S(O)nN(Re)—CR5aR5b—, or —N(Re)—S(O)n—CR5aR5b—;
X is a bond or —CR8aR8b—;
Z is —CR9aR9b—, —CR9aR9bCR9cR9d—, or —CR10a═CR10b—;
T is CR2aR2b— or —CR2aR2b—CR2cR2d—; U is —NR11—, —CR12aR12b—, —S(O)n—, —C(O)—, or —O—; or T and U together are

OG Complex Work Unit Chemistry
R2a, R2b, R2c, R2d, R12a, and R12b are independently H, C1-6alkyl, C1-6haloalkyl, C3-6cycloalkyl, C3-6halocycloalkyl, halo, cyano, —CH2Ra, —CH2ORa, —CH2—S(O)nRa, —ORa, —O—C(O)—NHRa, —NHRa, —C(O)—NH(Ra), —NRe—C(O)Ra, —NRe—S(O)nRa, —S(O)n—NH(Ra), or —S(O)n—Ra;
R3a, R3b, R3c, and R3d are independently H, C1-6alkyl, C1-4haloalkyl, or —O—C1-4alkyl;
R4a, R4b, R5a, R5b, R5c, R5d, R8a, R8b, R9a, R9b, R9c, and R9d are independently H, C1-6alkyl, C1-4haloalkyl, C3-6cycloalkyl, C3-6halocycloalkyl, halo, hydroxyl, cyano, —O—C1-4alkyl, or C1-4alkylene-O—C1-4alkyl;
each R6a, R6b, R10a, and R10b is independently H, halo, C1-4haloalkyl, or C1-6alkyl;
R7 is H, C1-6alkyl, C1-4haloalkyl, C3-6cycloalkyl, C3-6halocycloalkyl, C(O)Rc, or SO2Rc;
R11 is H, C1-4alkyl, C1-4haloalkyl, C3-6cycloalkyl, C3-6halocycloalkyl, —C(O)—Ra, —S(O)n—Ra, —CH2—Ra;
each Ra is independently (i) H, (ii) C1-6alkyl, (iii) C3-6cycloalkyl, (iv) a 5 to 10 membered carbocyclic ring, (v) 5 to 10 membered heterocyclic ring containing 1 or 2 heteroatom selected from N, O, and S, (vi) a 6 to 10 membered aromatic ring, or (iv) a 5 to 10 membered heteroaromatic ring containing 1 to 3 heteroatoms selected from N, O and S;
wherein the C1-6alkyl, C3-6cycloalkyl, 5 to 10 membered carbocyclic ring, 5 to 10 membered heterocyclic ring, 6 to 10 membered aromatic ring or 5 to 10 membered heteroaromatic ring of Ra is optionally substituted with 0 to 4 substituents independently selected from the group consisting of (i) oxo (ii) halo, (iii) cyano, (iv) —O—C1-4alkyl, (v) C1-6alkyl, (vi) —ORe (vii) 3 to 10 membered carbocyclic ring, (viii) 5 to 10 membered heterocyclic ring containing 1 or 2 heteroatom selected from N, O, and S, (ix) 6 to 10 membered aromatic ring, or (x) a 5 to 10 membered heteroaromatic ring containing 1 to 3 heteroatoms selected from N, O and S; wherein the 3 to 10 membered carbocyclic ring, 5 to 10 membered heterocyclic ring, 6 to 10 membered aromatic ring, or 5 to 10 membered heteroaromatic ring is optionally substituted with one to four RA5, wherein each RA5 is independently oxo, halo, cyano, C1-6alkyl, C3-6cycloalkyl or —ORe;
Rb is H, C1-4alkyl, C1-4haloalkyl or C3-6cycloalkyl;
Rf is H, halo, C1-4alkyl, or C1-4haloalkyl;
each Rc is independently, H, C1-4alkyl, C1-4haloalkyl, C3-6cycloalkyl, C3-6halocycloalkyl; C(O)Rd, or —SO2Rd;
each Rd is independently C1-4alkyl, C1-4haloalkyl, C3-6cycloalkyl, C3-6halocycloalkyl, —NRe2, or —ORe;
each Re is independently H, C1-4alkyl or C3-6cycloalkyl wherein each C1-4alkyl or C3-6cycloalkyl is optionally substituted by a halo or a cyano; and
each n is 0, 1, or 2.