US 11,679,107 B2
Certain aryl pladienolide compounds and methods of use
Andrew Cook, Stow, MA (US); Dominic Reynolds, Stoneham, MA (US); Cheng Zhong, Belmont, MA (US); Ryan Brawn, Sudbury, MA (US); Shelby Ellery, Boston, MA (US); Thiwanka Samarakoon, Westwood, MA (US); Xiang Liu, Winchester, MA (US); Sudeep Prajapati, Somerville, MA (US); Megan Sheehan, Allston, MA (US); Jason T. Lowe, East Bridgewater, MA (US); and James Palacino, Wellesley, MA (US)
Assigned to EISAI R&D MANAGEMENT CO., LTD., Tokyo (JP)
Appl. No. 17/46,528
Filed by Eisai R&D Management Co., Ltd., Tokyo (JP)
PCT Filed Apr. 11, 2019, PCT No. PCT/US2019/026992
§ 371(c)(1), (2) Date Oct. 9, 2020,
PCT Pub. No. WO2019/200100, PCT Pub. Date Oct. 17, 2019.
Claims priority of provisional application 62/814,824, filed on Mar. 6, 2019.
Claims priority of provisional application 62/814,828, filed on Mar. 6, 2019.
Claims priority of provisional application 62/679,658, filed on Jun. 1, 2018.
Claims priority of provisional application 62/656,865, filed on Apr. 12, 2018.
Prior Publication US 2021/0177837 A1, Jun. 17, 2021
Int. Cl. C07D 405/06 (2006.01); A61K 31/496 (2006.01); A61P 35/00 (2006.01); A61K 9/00 (2006.01); A61K 31/497 (2006.01); A61K 31/506 (2006.01); A61K 31/5377 (2006.01); A61K 31/5386 (2006.01); A61K 31/541 (2006.01); A61K 31/551 (2006.01); A61K 38/19 (2006.01); A61K 38/20 (2006.01); A61K 38/21 (2006.01); A61K 39/395 (2006.01); C07D 313/00 (2006.01); C07D 405/10 (2006.01); C07D 405/12 (2006.01); C07D 405/14 (2006.01); C07D 407/12 (2006.01); C07D 409/12 (2006.01); C07D 413/10 (2006.01); C07D 413/12 (2006.01); C07D 413/14 (2006.01); C07D 417/10 (2006.01); C07D 453/02 (2006.01); C07D 471/10 (2006.01); C07D 487/04 (2006.01); C07D 491/107 (2006.01); C07D 498/08 (2006.01)
CPC A61K 31/496 (2013.01) [A61K 9/0053 (2013.01); A61K 31/497 (2013.01); A61K 31/506 (2013.01); A61K 31/5377 (2013.01); A61K 31/5386 (2013.01); A61K 31/541 (2013.01); A61K 31/551 (2013.01); A61K 38/191 (2013.01); A61K 38/208 (2013.01); A61K 38/2013 (2013.01); A61K 38/2066 (2013.01); A61K 38/2086 (2013.01); A61K 38/217 (2013.01); A61K 39/3955 (2013.01); A61P 35/00 (2018.01); C07D 313/00 (2013.01); C07D 405/06 (2013.01); C07D 405/10 (2013.01); C07D 405/12 (2013.01); C07D 405/14 (2013.01); C07D 407/12 (2013.01); C07D 409/12 (2013.01); C07D 413/10 (2013.01); C07D 413/12 (2013.01); C07D 413/14 (2013.01); C07D 417/10 (2013.01); C07D 453/02 (2013.01); C07D 471/10 (2013.01); C07D 487/04 (2013.01); C07D 491/107 (2013.01); C07D 498/08 (2013.01); C07B 2200/05 (2013.01)] 19 Claims
 
1. A compound of Formula I:

OG Complex Work Unit Chemistry
and/or a pharmaceutically acceptable salt thereof,
wherein:
R1 is chosen from:

OG Complex Work Unit Chemistry
each of which may be optionally substituted with 1 to 3 groups independently chosen from halogens, hydroxyl groups, C1-C6 alkyl groups, C1-C6 alkoxy groups, C3-C8 cycloalkyl groups, hydroxy C1-C6 alkyl groups, dimethylamino groups, and methoxy C1-C6 alkyl groups;
R2, R4, and R6 are each independently chosen from hydrogen, hydroxyl groups, —O—R16 groups, and C1-C6 alkyl groups;
R5 is chosen from hydrogen, hydroxyl groups, and —O—R16 groups;
R9 and R13 are each independently chosen from hydrogen and C1-C6 alkyl groups;
R3, R7, and R8 are each independently chosen from hydrogen and C1-C3 alkyl groups;
R10 is chosen from hydrogen, C1-C6 alkyl groups, C1-C6 aminoalkyl groups, C1-C6 alkylamino groups, C1-C6 alkylcarboxylic acid groups, C3-C8 cycloalkyl groups, benzyl groups, C3-C8 heterocyclyl groups, —CH2—C3-C8-heterocyclyl groups, —C(O)—C3-C8 heterocyclyl groups, acyl groups, hydroxy C1-C6 alkyl groups, methoxy C1-C6 alkyl groups, —CD3, and —C(O)—NR11R12 groups;
R11 and R12 are independently chosen from hydrogen, C1-C6 alkyl groups, C1-C6 aminoalkyl groups, C1-C6 alkylamino groups, C3-C8 cycloalkyl groups, and C3-C8 heterocyclyl groups;
V is —CH2—;
W is chosen from 3 to 8 membered carbocycles and 3 to 10 membered heterocycles, each of which may be optionally substituted with 1 to 3 groups independently chosen from halogens, —NR8R9 groups, C1-C6 alkyl groups, C1-C6alkoxy groups, methoxy C1-C6 alkyl groups, hydroxy C1-C6 alkyl groups, and C3-C5 cycloalkyl groups;
X is chosen from a bond, hydrogen, 3 to 8 membered carbocycles, and 3 to 8 membered heterocycles, each of which may be optionally substituted with 1 to 3 groups independently chosen from halogens, hydroxyl groups, C1-C6 alkyl groups, hydroxy C1-C6 alkyl groups, C1-C6 alkoxy groups, methoxy C1-C6 alkyl groups, —SO2—C1-C6 alkyl groups, and —NR14R15 groups, wherein R14 and R15 are each independently chosen from hydrogen and C1-C6 alkyl groups;
Y is chosen from hydrogen, 3 to 8 membered carbocycles, and 3 to 8 membered heterocycles, each of which may be optionally substituted with 1 to 3 groups independently chosen from halogens, hydroxyl groups, C1-C6 alkyl groups, hydroxy C1-C6 alkyl groups, C1-C6 alkoxy groups, methoxy C1-C6 alkyl groups, —SO2—C1-C6 alkyl groups, and —NR14R15 groups, wherein R14 and R15 are each independently chosen from hydrogen and C1-C6 alkyl groups;
L1 and L2 are each independently chosen from a bond, —O—, —C(O)—, —C(O)O—, —N(R13)—C(O)—, —C(O)—N(R13)—, —N(R13)—S(O2)—, —S(O2)—N(R13)—, —S(O2)—, and —N(R13)—; and
each n is independently chosen from 0 to 4.