US 12,084,420 B2
Indoline compounds for inhibiting KIF18A
Derek A. Cogan, New York, NY (US)
Assigned to Volastra Therapeutics, Inc., New York, NY (US)
Filed by Volastra Therapeutics, Inc., New York, NY (US)
Filed on Aug. 25, 2022, as Appl. No. 17/896,037.
Claims priority of provisional application 63/344,435, filed on May 20, 2022.
Claims priority of provisional application 63/306,452, filed on Feb. 3, 2022.
Claims priority of provisional application 63/237,275, filed on Aug. 26, 2021.
Prior Publication US 2023/0147507 A1, May 11, 2023
Int. Cl. C07D 209/96 (2006.01); A61P 35/00 (2006.01); C07D 401/06 (2006.01); C07D 401/12 (2006.01); C07D 401/14 (2006.01); C07D 403/06 (2006.01); C07D 403/12 (2006.01); C07D 403/14 (2006.01); C07D 405/06 (2006.01); C07D 405/12 (2006.01); C07D 405/14 (2006.01); C07D 409/06 (2006.01); C07D 409/12 (2006.01); C07D 409/14 (2006.01); C07D 413/12 (2006.01); C07D 491/107 (2006.01); C07D 491/113 (2006.01); C07F 9/572 (2006.01)
CPC C07D 209/96 (2013.01) [A61P 35/00 (2018.01); C07D 401/06 (2013.01); C07D 401/12 (2013.01); C07D 401/14 (2013.01); C07D 403/06 (2013.01); C07D 403/12 (2013.01); C07D 403/14 (2013.01); C07D 405/06 (2013.01); C07D 405/12 (2013.01); C07D 405/14 (2013.01); C07D 409/06 (2013.01); C07D 409/12 (2013.01); C07D 409/14 (2013.01); C07D 413/12 (2013.01); C07D 491/107 (2013.01); C07D 491/113 (2013.01); C07F 9/5728 (2013.01)] 35 Claims
 
1. A compound of Formula (I):

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt thereof, wherein:
ring A is C6-14 aryl optionally substituted with one or more substituents independently selected from the group consisting of halo, —OH, C1-6 alkyl, 3- to 10-membered heterocycloalkyl, —NRa1C(O)NRa2Ra3, —NRa4C(O)ORa5, —NRa6Ra7, —N═S(O)Ra8Ra9, —ORa10, —S(O)Ra11, —S(O)(NRa12)Ra13, —S(O)2NRa14Ra15, —S(O)2Ra16, —(CRa17Ra18)0-1C(O)NRa19Ra20, —SRa21, —C(O)Ra22, and C1-6 alkyl substituted with one or more substituents independently selected from the group consisting of —OH, cyano, C3-10 cycloalkyl, and 3- to 10-membered heterocycloalkyl optionally substituted with one or more halo;
Ra1-Ra22 are each independently hydrogen, C1-6 alkyl, C2-6 alkenyl, C3-10 cycloalkyl, C3-10 cycloalkenyl, 3- to 10-membered heterocycloalkyl, 3- to 10-membered heterocycloalkenyl, C6-14 aryl, or 5- to 12-membered heteroaryl, each optionally substituted with one or more substituents independently selected from the group consisting of halo, cyano, —OH, —O(C1-6 alkyl), C2-6 alkenyl, C3-10 cycloalkyl, —S(C1-6 alkyl), ═CR1a1R1a2, and C1-6 alkyl optionally substituted with one or more substituents independently selected from the group consisting of halo, —OH, and —O(C1-6 alkyl), wherein R1a1 and R1a2 are each independently hydrogen or C1-6 alkyl;
ring B is C5-7 cycloalkyl, C5-7 cycloalkenyl, or 5- to 7-membered heterocycloalkyl wherein one or two of the ring atoms are each oxygen and the remaining ring atoms are each carbon;
each RB group is independently halo, C1-6 alkyl optionally substituted with one or more halo, or C2-6 alkenyl; or two vicinal RB groups are taken together with the carbon atoms to which they are attached to form C3-10 cycloalkyl; or two geminal RB groups are taken together with the carbon atom to which they are attached to form C3-10 cycloalkyl;
m is 0, 1, 2, 3, or 4;
Y1 is N or CRC1;
Y2 is N or CRC2;
Y3 is N or CRC3;
Y4 is N or CRC4;
wherein no more than three of Y1, Y2, Y3, and Y4 are N;
RC1, RC3, and RC4 are each independently hydrogen, halo, cyano, —OH, —NO2, —C(O)NRc1Rc2, —NRc3Rc4, —NRc5S(O)2Rc6, —P(O)Rc7Rc8, —N═S(O)Rc9Rc10, —S(O)(NRc11)Rc12, —S(O)2Rc13, —NRc14C(O)ORc15, —NRc16S(O)2(CH2)1-6NRc17C(O)Rc18, or C1-6 alkyl optionally substituted with one or more substituents independently selected from the group consisting of halo and —OH;
RC2 is halo, cyano, —OH, —NO2, —C(O)NRc1Rc2, —NRc3Rc4, —NRc5S(O)2Rc6, —P(O)Rc7Rc8, —N═S(O)Rc9Rc10, —S(O)(NRc11)Rc12, —S(O)2Rc13, —NRc14C(O)ORc15, —NRc16S(O)2(CH2)1-6NRc17C(O)Rc18, or C1-6 alkyl optionally substituted with one or more substituents independently selected from the group consisting of halo and —OH; and
Rc1-Rc18 are each independently hydrogen, C3-10 cycloalkyl, or C1-6 alkyl optionally substituted with one or more substituents independently selected from the group consisting of halo and —OH.