US 12,391,695 B2
PRMT5 inhibitors
Prathap Sreedharan Nair, Pune (IN); Ganesh Bhausaheb Gudade, Pune (IN); Mahadeo Bhaskar Tryambake, Pune (IN); Chetan Sanjay Pawar, Pune (IN); Dipak Raychand Lagad, Pune (IN); Chaitanya Prabhakar Kulkarni, Pune (IN); Milind Dattatraya Sindkhedkar, Pune (IN); Venkata P. Palle, Pune (IN); and Rajender Kumar Kamboj, Pune (IN)
Assigned to Lupin Limited, Mumbai (IN)
Appl. No. 17/618,042
Filed by Lupin Limited, Mumbai (IN)
PCT Filed Jun. 9, 2020, PCT No. PCT/IB2020/055401
§ 371(c)(1), (2) Date Dec. 10, 2021,
PCT Pub. No. WO2020/250123, PCT Pub. Date Dec. 17, 2020.
Claims priority of application No. 201921022971 (IN), filed on Jun. 10, 2019; and application No. 201921022972 (IN), filed on Jun. 10, 2019.
Prior Publication US 2022/0315589 A1, Oct. 6, 2022
This patent is subject to a terminal disclaimer.
Int. Cl. C07D 487/04 (2006.01); A61P 35/00 (2006.01); C07D 401/12 (2006.01); C07D 487/14 (2006.01); C07D 519/00 (2006.01)
CPC C07D 487/04 (2013.01) [A61P 35/00 (2018.01); C07D 401/12 (2013.01); C07D 487/14 (2013.01); C07D 519/00 (2013.01)] 11 Claims
 
1. A compound of general formula (I), its stereoisomer, or its pharmaceutically acceptable salt,

OG Complex Work Unit Chemistry
wherein,
L1 is selected from bond, —CRaRb and O;
Ra and Rb are hydrogen;
ring A is selected from formula (i), (ii), (iii) and (iv), wherein the substituent R3 on ring A may be substituted on any of the ring carbon atoms,

OG Complex Work Unit Chemistry
Hy is selected from formula (a-1) to (h-1), provided that when Hy is (h-1) then ring A cannot be formula (i),

OG Complex Work Unit Chemistry
R is selected from —NR4R5, and hydrogen Z is selected from CR10 and N;
R1 and R2 together with the carbon atoms to which they are attached form a bond in order to form a —C═C—; or R1 and R2 together with the carbon atoms to which they are attached form a cyclopropane ring;
R2′ and R2a are hydrogen;
R3 is independently selected at each occurrence from halogen, substituted or unsubstituted alkyl, and —NR7R8
R4 and R5 are hydrogen;
R6 is selected from hydrogen, unsubstituted alkyl, and unsubstituted cycloalkyl;
R7 and R8 are hydrogen;
R10 is selected from hydrogen, halogen, and substituted or unsubstituted alkyl;
‘n’ is an integer ranging from 0 to 4, both inclusive;
‘m’ is an integer ranging from 0 to 1, both inclusive;
when an alkyl group is substituted, it is substituted with 1 to 4 substituents independently selected from oxo (═O), halogen, cyano, cycloalkyl, aryl, heteroaryl, heterocyclyl, —OR7a, —C(═O) OH, —C(═O)O(alkyl), —NR8aR8b, —NR8aC(═O)R9a, and —C(═O)NR8aR8b;
when the heteroaryl group is substituted, it is substituted with 1 to 4 substituents independently selected from halogen, cyano, alkyl, haloalkyl, cycloalkyl, heterocyclyl, —OR7a, —NR8aR8b, —NR7aC(═O)R9a, and —C(═O)NR8aR8b;
when the heterocylyl group is substituted, it is substituted with 1 to 4 substituents independently selected from halogen, cyano, alkyl, haloalkyl, cycloalkyl, heterocyclyl, —OR7a, —NR8aR8b, —NR7aC(═O)R9a, and —C(═O)NR8aR8b;
when the aryl group is substituted, it is substituted with 1 to 4 substituents independently selected from halogen, cyano, alkyl, haloalkyl, cycloalkyl, heterocyclyl, —OR7a, —NR8aR8b, —NR7aC(═O)R9a, and —C(═O)NR8aR8b;
when the cycloalkyl group is substituted, it is substituted with 1 to 4 substituents independently selected from halogen, cyano, alkyl, haloalkyl, —OR7a, —NR8aR8b, —NR7aC(═O)R9a, and —C(═O)NR8aR8b;
R7a is selected from hydrogen, alkyl, haloalkyl, and cycloalkyl;
R8a and R8b are each independently selected from hydrogen, alkyl, and cycloalkyl; and
R9a is selected from alkyl and cycloalkyl.