US 11,999,727 B2
Compounds and methods of use
Kevin M. Cottrell, Arlington, MA (US); and John P. Maxwell, Hingham, MA (US)
Assigned to Tango Therapeutics, Inc., Boston, MA (US)
Filed by Tango Therapeutics, Inc., Boston, MA (US)
Filed on Apr. 29, 2022, as Appl. No. 17/732,846.
Application 17/732,846 is a continuation of application No. 17/525,692, filed on Nov. 12, 2021, granted, now 11,492,350.
Application 17/525,692 is a continuation of application No. PCT/US2021/044004, filed on Jul. 30, 2021.
Claims priority of provisional application 63/059,959, filed on Jul. 31, 2020.
Prior Publication US 2023/0113778 A1, Apr. 13, 2023
This patent is subject to a terminal disclaimer.
Int. Cl. C07D 417/14 (2006.01); A61P 35/00 (2006.01)
CPC C07D 417/14 (2013.01) [A61P 35/00 (2018.01)] 30 Claims
 
1. A compound of Formula (I) or a pharmaceutically acceptable salt thereof;
wherein:

OG Complex Work Unit Chemistry
each R1 is independently selected from H, -D, halo, —CN, —C1-C6 alkyl, —C1-C6 heteroalkyl, —C1-C6 haloalkyl, —C3-C9 cycloalkyl, 3-10 membered heterocyclyl, heterocyclylalkyl, heteroarylalkyl, arylalkyl, cycloalkylalkyl, —N(Ra1)2, —C(═O)Ra1, —C(═O)ORa1, —NRa1C(═O)Ra1, —NRa1C(═O)ORa1, —C(═O)N(Ra1)2, —OC(═O)N(Ra1)2, —S(═O)Ra1, —S(═O)2Ra1, —SRa1, —S(═O)(═NRa1)Ra1, —NRa1S(═O)2Ra1 and —S(═O)2N(Ra1)2;
each R2 is independently selected from halo, —CN, —C1-C6 alkyl, —C1-C6 heteroalkyl, —C1-C6 haloalkyl, —C1-C6 haloalkoxy, —C3-C9 cycloalkyl, 3-10 membered heterocyclyl, heterocyclylalkyl, heteroarylalkyl, arylalkyl, cycloalkylalkyl, —ORa2, —N(Ra2)2, —C(═O)Ra2, —C(═O)ORa2, —NRa2C(═O)Ra2, —NRa2C(═O)ORa2, —C(═O)N(Ra2)2, —C(═O)N(ORa2)(Ra2), —OC(═O)N(Ra2)2, —S(═O)Ra2, —S (═O)2Ra2, —SRa2, —S(═O)(═NRa2)Ra2, NRa2S(═O)2Ra2, —S(═O)2N(Ra2)2;
each R3 is independently selected from H, -D, halo, —CN, —C1-C6 alkyl, —C1-C6 heteroalkyl, —C1-C6 haloalkyl, —C3-C9 cycloalkyl, 3-10 membered heterocyclyl, heterocyclylalkyl, heteroarylalkyl, arylalkyl, cycloalkylalkyl, —ORa3, —N(Ra3)2, —C(═O)Ra3, —C(═O)ORa3, —NRa3C(═O)Ra3, —NRa3C(═O)ORa3, —C(═O)N(Ra3)2, —OC(═O)N(Ra3)2, —S(═O)Ra3, —S(═O)2Ra3, —SRa3, —S(═O)(═NRa3)Ra3, —NRa3S(═O)2Ra3 and —S(═O)2N(Ra3)2;
each R4 is independently selected from H, -D, halo, —CN, —C1-C6 alkyl, —C1-C6 heteroalkyl, —C1-C6 haloalkyl, —C3-C9 cycloalkyl, 3-10 membered heterocyclyl, heterocyclylalkyl, heteroarylalkyl, arylalkyl, cycloalkylalkyl, —ORa4, —N(Ra4)2, —C(═O)Ra4, —C(═O)ORa4, —NRa4C(═O)Ra4, —NRa4C(═O)ORa4, —C(═O)N(Ra4)2, —OC(═O)N(Ra4)2, —S(═O)Ra4, —S(═O)2Ra4, —SRa4, —S(═O)(═NRa4)Ra4, —NRa4 and —S(═O)2N(Ra4)2;
each R6 is independently absent or selected from H, -D, halo, —CN, —C1-C6 alkyl, —C1-C6 heteroalkyl, —C1-C6 haloalkyl, —C3-C10 carbocyclyl, 3-10 membered heterocyclyl, heterocyclylalkyl, C6-C10 aryl, 5-10 member heteroaryl, heteroarylalkyl, arylalkyl, cycloalkylalkyl, —ORa6, —N(Ra6)2, —C(═O)Ra6, —C(═O)ORa6, —NRa6C(═O)Ra6, NRa6C(═O)ORa6, —C(═O)N(Ra6)2, —OC(═O)N(Ra6)2, —S(═O)Ra6, —S(═O)2Ra6, —SRa6, —S(═O)(═NRa6)Ra6, NRa6S(═O)2Ra6 and —S(═O)2N(Ra6)2, wherein each alkyl, carbocyclyl, heterocyclyl, cycloalkylalkyl, heterocyclylalkyl, aryl, heteroaryl, arylalkyl and heteroarylalkyl is optionally substituted at any available position;
each R7 is independently absent or selected from H, -D, halo, —CN, —C1-C6 alkyl, —C1-C6 hydroxyalkyl, haloalkyl, —C3-C9 cycloalkyl, 3-10 membered heterocyclyl, 5-6-membered monocyclic heteroaryl, heterocyclylalkyl, heteroarylalkyl, arylalkyl, cycloalkylalkyl, —ORa7, —N(Ra7)2, —C(═O)Ra7, —C(═O)ORa7, —NRa7C(═O)Ra7, —NRa7C(═O)ORa7, —C(═O)N(Ra7)2, —OC(═O)N(Ra7)2, —S(═O)Ra7, —S(═O)2Ra7, —SRa7, —S(═O)(═NRa7)Ra7, —NRa7S(═O)2Ra7 and —S(═O)2N(Ra7)2;
each R8 is independently selected from H, -D, ═O, halo, —CN, —C1-C6 alkyl, —C1-C6 heteroalkyl, —C1-C6 haloalkyl, —C3-C9 cycloalkyl, 3-10 membered heterocyclyl, heterocyclylalkyl, heteroarylalkyl, arylalkyl, cycloalkylalkyl, —ORa8, —N(Ra8)2, —C(═O)Ra8, C(═O)ORa8, —NRa8C(═O)Ra8, —ORa8, —CH2C(═O)N(Ra8)2, —C(═O)N(Ra8)2, —OC(═O)N(Ra8)2, —CH2C(═O)N(Ra8)2, —S(═O)Ra8, —S(═O)2Ra8, —SRa8, —S(═O)(═NRa8)Ra8, —NRa8S(═O)2Ra and —S(═O)2N(Ra8)2;
each Ra1, Ra2, Ra3, Ra4, Ra6, Ra7 and Ra8 is independently selected from H, C1-C6 alkyl, —C1-C6 heteroalkyl, C3-C9 cycloalkyl, 3-7 membered heterocyclyl, cycloalkylalkyl, heterocyclylalkyl, aryl, 5-6 membered heteroaryl, arylalkyl and heteroarylalkyl wherein each alkyl, cycloalkyl, heterocyclyl, cycloalkylalkyl, heterocyclylalkyl, aryl, heteroaryl, arylalkyl and heteroarylalkyl is optionally substituted at any available position; and
n is 0, 1, 2 or 3 provided that:
(i) when R1 is H, R2 is not halo, —OPr, —N(CH3)2 or —CF3;
(ii) when R1 is ORa1, R2 is not —ORa2;
(iii) when R1 is H and R2 is —CH3, R8 groups cannot be taken together to form a ring and R6 is not absent or H, and is not thiazolyl, furanyl or pyrrolyl;
(iv) when R2 is Me, R1 is not piperidine
(v) the compound is not:
A. 5-(2-(5-methyl-2-(p-tolyl)piperidin-1-yl)-2-oxoacetamido)nicotinamide or any of its enantiomers or diastereomers;
B. 2-(2-(4-(2H-tetrazol-5-yl)phenyl)-5-methylpiperidin-1-yl)-N-(5,6-dimethylpyridin-3-yl)-2-oxoacetamide or any of its enantiomers or diastereomers;
C. 2-cyano-5-(2-(5-methyl-2-phenylpiperidin-1-yl)-2-oxoacetamido)nicotinamide or any of its enantiomers or diastereomers.