US 11,667,649 B2
Heteroaromatic macrocyclic ether chemotherapeutic agents
Joshua Courtney Horan, Somerville, MA (US); Xinxing Tang, Pudong (CN); Scot Richard Mente, Arlington, MA (US); Henry Efrem Pelish, Newton, MA (US); Matthew D. Shair, Lexington, MA (US); and Anupong Tangpeerachaikul, Quincy, MA (US)
Assigned to Nuvalent, Inc., Cambridge, MA (US)
Filed by Nuvalent, Inc., Cambridge, MA (US)
Filed on Nov. 11, 2021, as Appl. No. 17/524,169.
Application 17/524,169 is a continuation of application No. PCT/US2021/030940, filed on May 5, 2021.
Claims priority of provisional application 63/125,747, filed on Dec. 15, 2020.
Claims priority of provisional application 63/060,331, filed on Aug. 3, 2020.
Claims priority of application No. PCT/CN2020/088589 (WO), filed on May 5, 2020.
Prior Publication US 2022/0098212 A1, Mar. 31, 2022
Prior Publication US 2022/0340586 A9, Oct. 27, 2022
Int. Cl. C07D 491/22 (2006.01)
CPC C07D 491/22 (2013.01) 31 Claims
 
1. A compound of Formula (I), or an enantiomer, a mixture of enantiomers, or a tautomer thereof, or a pharmaceutically acceptable salt thereof:

OG Complex Work Unit Chemistry
wherein
Q is CH;
Z is CR5;
X is a 5-membered heteroarylene selected from the group consisting of

OG Complex Work Unit Chemistry
wherein * indicates the point of attachment of X to the methylene group bonded to X and Y;
Y is a 5- membered heteroarylene selected from the group consisting of

OG Complex Work Unit Chemistry
wherein * indicates the point of attachment of Y to the methylene group bonded to X and Y;
R1 is selected from the group consisting of H, methyl, and hydroxymethyl;
each instance of R2 is independently selected from the group consisting of H, CN, halo, C1-4 alkoxy, C1-4 alkyl, halo-C1-4 alkyl, C3-4 cycloalkylmethyl, C3-6 cycloalkyl, and C3-6 heterocyclyl;
each instance of R3 is independently selected from the group consisting of H, halo, CN, C1-4 alkoxy, halo-C1-4 alkyl, and C1-4 alkyl; and
each of R4 and R5 is independently H or F.