US 11,878,975 B2
Substituted indole compounds useful as TLR inhibitors
Alaric J. Dyckman, Lawrenceville, NJ (US); Dharmpal S. Dodd, Monmouth Junction, NJ (US); Christopher P. Mussari, Princeton, NJ (US); John L. Gilmore, Yardley, PA (US); Tasir Shamsul Haque, Yardley, PA (US); Trevor C. Sherwood, West Windsor, NJ (US); Brian K. Whiteley, Lebanon, NJ (US); Shoshana L. Posy, Highland Park, NJ (US); Sreekantha Ratna Kumar, Bangalore (IN); Laxman Pasunoori, Waranagal (IN); Srinivasan Kunchithapatham Duraisamy, Hosur (IN); Subramanya Hegde, Bangalore (IN); Rushith Kumar Anumula, Secunderabad (IN); and Pitani Veera Venkata Srinivas, West Godawri (IN)
Assigned to Bristol-Myers Squibb Company, Princeton, NJ (US)
Appl. No. 16/955,097
Filed by BRISTOL-MYERS SQUIBB COMPANY, Princeton, NJ (US)
PCT Filed Dec. 18, 2018, PCT No. PCT/US2018/066149
§ 371(c)(1), (2) Date Jun. 18, 2020,
PCT Pub. No. WO2019/126113, PCT Pub. Date Jun. 27, 2019.
Claims priority of provisional application 62/607,472, filed on Dec. 19, 2017.
Prior Publication US 2020/0308172 A1, Oct. 1, 2020
Int. Cl. C07D 471/08 (2006.01); C07D 487/08 (2006.01); C07D 519/00 (2006.01); C07D 471/04 (2006.01); C07D 401/04 (2006.01); C07D 401/10 (2006.01); C07D 401/14 (2006.01); C07D 405/14 (2006.01); C07D 413/14 (2006.01); C07D 417/14 (2006.01); C07D 453/02 (2006.01); C07D 487/04 (2006.01); C07D 491/08 (2006.01)
CPC C07D 471/04 (2013.01) [C07D 401/04 (2013.01); C07D 401/10 (2013.01); C07D 401/14 (2013.01); C07D 405/14 (2013.01); C07D 413/14 (2013.01); C07D 417/14 (2013.01); C07D 453/02 (2013.01); C07D 487/04 (2013.01); C07D 491/08 (2013.01)] 14 Claims
 
1. A compound of Formula (I)

OG Complex Work Unit Chemistry
N-oxide, or a salt thereof, wherein:
G is:

OG Complex Work Unit Chemistry
(iv) a 9-membered heterocyclic ring selected from:

OG Complex Work Unit Chemistry

OG Complex Work Unit Chemistry
A is: —CHR12R13, wherein R12 and R13 together with the carbon atom to which they are attached and the hydrogen atom attached to the carbon atom, form a cyclic group selected from azabicyclo[4.1.1]octanyl, azetidinyl, C3-6 cycloalkyl, diazaspiro[4.5]decanonyl, morpholinyl, octahydrocyclopenta[c]pyrrolyl, or quinuclidinyl, each substituted with zero to 3 R12a;
R1 is —CH2CH3 or —CH(CH3)2;
each R2 is independently —CH3 or —OCH3;
R2a is —CH3;
each R2b is independently H or —CH3;
each R12a is independently —OH, —CH3, —CH2CH2CH3, —CH(CH3)2, —CH2CH(CH3)2, —CF3, —CH2CH2CH2CF3, —CH2CN, —CH2C(CH3)2OH, —CH2CH2OCH3, —CH2C(O)NH(CH3), —CH2C(O)N(CH3)2, —CH2C(O)NH2, —CH2CH2S(O)2CH3, —CH2CH2NHS(O)2CH3, —OCH3, —NRxRx, —N(CH3)(CH2CH3), —N(CH3)(CH(CH3)2), —NRx(CH2CHF2)—NH(CH2CF3), —N(CH3)(CH2CH2CF3), —N(CH3)(CH2CH2OCH3), —NH(CH2CN), —N(CH3)CH2N(CH3)2, —NH(CH2C(CH3)2OH), —NH(CH2C(O)NH2), —N(CH3)(OCH3), —NRxCH2CH2S(O)2CH3, —NHC(O)CH3, —NHC(O)CH2CF3, —NHC(O)CHRxNH(CH3), —NRxC(O)CH2N(CH3)2, —NHC(O)CH2N(CH3)(CH2CH3), —NHC(O)CH2N(CH2CH3)2, —NHC(O)CH2NH(CH2C(CH3)2OH), —NHCH2C(O)NRx(CH3), —NHS(O)2CH3, —C(O)C(CH3)3, —C(O)CH(CH2CH3)2, —C(O)CH2OCH3, —C(O)CH2CH2OCH3, —C(O)CH2NH(CH3), —C(O)CH2N(CH3)2, —C(O)CH(CH3)NH(CH3), —C(O)CH2N(CH3)(CH2CH3), —C(O)CH2N(CH2CH3)2, R12b, —CH2R12b, —C(O)R12b, —C(O)CH2R12b, —C(O)CH2NHR12b, —C(O)NRxR12b, —NRxC(O)CH2R12b, —NRxR12b, —NRxCH2R12b, —NHC(O)CH2NRxR12b, —NHC(O)CH2NRxCH2R12b, —NHCH2C(O)NHR12b, or —OR12b;
R12b is azetidinyl, cyclopropyl, diazabicyclo[2.2.1]heptanyl, dioxolanyl, dioxidotetrahydrothiopyranyl, dioxidothiomorpholinyl, imidazolyl, morpholinyl, octahydrocyclopenta[c]pyrrolyl, octahydropyrrolo[3,4-c]pyrrolyl, oxaazaspiro[3.3]heptanyl, oxetanyl, phenyl, piperazinyl, piperazinonyl, piperidinyl, pyridinyl, pyrrolidinyl, quinuclidinyl, tetrahydrofuranyl, tetrahydropyranyl, or triazolyl, each substituted with zero to 4 substituents independently selected from F, —OH, —CH3, —CH(CH3)2, —CH2OH, —OCH3, —CH2CH2OCH3, —NRxRx, and —C(O)NH2;
each Rx is independently H or —CH3;
n is zero; and
p is zero, 1, 2, or 3.