US 12,331,052 B2
Organic compounds
Peng Li, New Milford, NJ (US); Qiang Zhang, Somerset, NJ (US); and Hailin Zheng, New York, NY (US)
Assigned to INTRA-CELLULAR THERAPIES, INC., Bedminster, NJ (US)
Appl. No. 17/417,001
Filed by INTRA-CELLULAR THERAPIES, INC., New York, NY (US)
PCT Filed Dec. 20, 2019, PCT No. PCT/US2019/068109
§ 371(c)(1), (2) Date Jun. 21, 2021,
PCT Pub. No. WO2020/132605, PCT Pub. Date Jun. 25, 2020.
Claims priority of provisional application 62/783,618, filed on Dec. 21, 2018.
Prior Publication US 2022/0048910 A1, Feb. 17, 2022
This patent is subject to a terminal disclaimer.
Int. Cl. C07D 471/18 (2006.01); A61K 31/485 (2006.01); A61K 31/4985 (2006.01); A61K 31/4995 (2006.01); A61P 25/04 (2006.01); A61P 25/20 (2006.01); A61P 25/22 (2006.01); A61P 25/36 (2006.01); C07D 471/14 (2006.01)
CPC C07D 471/14 (2013.01) [A61K 31/485 (2013.01); A61K 31/4985 (2013.01); A61P 25/04 (2018.01); A61P 25/20 (2018.01); A61P 25/22 (2018.01); A61P 25/36 (2018.01)] 34 Claims
 
1. A compound of a Formula I:

OG Complex Work Unit Chemistry
wherein:
R1 is H, C1-6alkyl, —C(O)—O—C(Ra)(Rb)(Rc), —C(O)—O—CH2—O—C(Ra)(Rb)(Rc) or —C(R6) (R7)—O— C(O)—R8;
R2 and R3 are independently selected from H, D, C1-6alkyl, C1-6alkoxy, halo, cyano, or hydroxy;
or wherein R2 and R3 and the carbon to which they are attached collectively form a group —CH2CH2—, or
wherein R2 and R3 and the carbon to which they are attached are absent;
L is C1-6alkylene, C1-6alkoxy, C2-3alkoxyC1-3alkylene, C1-6alkylamino or N—C1-6alkyl C1-6alkylamino, C1-6alkylthio, C1-6alkylsulfonyl, each of which is unsubstituted;
each R4 is independently selected from C1-6alkyl, C1-6alkoxy, halo, cyano, or hydroxy;
Z is selected from aryl and heteroaryl, wherein said aryl or heteroaryl is optionally substituted with one or more R4 moieties, and wherein said heteroaryl is a monocyclic 5-membered or 6-membered heteroaryl or a bicyclic 9-membered or 10-membered heteroaryl selected from the group consisting of indolyl, benzfuranyl, benzthiophenyl, benzimidazolyl, benzoxazolyl, benzisoxazolyl, benzthiazolyl, quinolinyl, isoquinolinyl, quinoxalinyl, quinazolinyl, benzodioxolyl, and 2-oxo-tetrahydroquinolinyl;
R8 is —C(Ra)(Rb)(Rc), —O—C(Ra)(Rb)(Rc), or —N(Rd)(Re);
Ra, Rb and Rc are each independently selected from H and C1-24alkyl;
Rd and Re are each independently selected from H and C1-24alkyl; and
R6 and R7 are each independently selected from H, C1-6alkyl, carboxy and C1-6alkoxycarbonyl;
provided that the L-Z moiety is not 1-(4-fluoro-1-phenoxy) propyl); and
further provided that when R1 is H or CH3; then L-Z is not selected from:

OG Complex Work Unit Chemistry
in free or pharmaceutically acceptable salt form.