US 12,325,702 B2
ATF6 inhibitors and uses thereof
Jennifer Alfaro, Santiago (CL); Sebastian Belmar, Santiago (CL); Gonzalo Esteban Núñez Vasquez, Santiago (CL); Brahmam Pujala, Greater Noida (IN); Balaji Dashrath Sathe, Greater Noida (IN); Pooja Thakral, New Delhi (IN); Rajesh Kumar Patidar, Uttar Pradesh (IN); Sebastian Bernales, San Francisco, CA (US); and Sarvajit Chakravarty, Edmond, OK (US)
Assigned to Altos Labs, Inc., Redwood City, CA (US)
Filed by Altos Labs, Inc., Redwood City, CA (US)
Filed on May 26, 2023, as Appl. No. 18/324,826.
Application 18/324,826 is a continuation of application No. 16/992,000, filed on Aug. 12, 2020, abandoned.
Application 16/992,000 is a continuation of application No. 16/377,156, filed on Apr. 6, 2019, granted, now 10,829,485, issued on Nov. 10, 2020.
Claims priority of provisional application 62/654,263, filed on Apr. 6, 2018.
Prior Publication US 2024/0124434 A1, Apr. 18, 2024
This patent is subject to a terminal disclaimer.
Int. Cl. C07D 413/14 (2006.01); A61P 35/00 (2006.01); C07D 401/12 (2006.01); C07D 401/14 (2006.01); C07D 405/12 (2006.01); C07D 405/14 (2006.01); C07D 413/12 (2006.01); C07D 417/14 (2006.01)
CPC C07D 413/14 (2013.01) [A61P 35/00 (2018.01); C07D 401/12 (2013.01); C07D 401/14 (2013.01); C07D 405/12 (2013.01); C07D 405/14 (2013.01); C07D 413/12 (2013.01); C07D 417/14 (2013.01)] 38 Claims
 
1. A method of treating a metabolic disorder in a subject in need thereof, comprising administering to the subject a compound of Formula (A):

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or a pharmaceutically acceptable salt thereof, wherein:
one of G1 and G2 is N and one of G1 and G2 is CRd,
wherein Rd is H or C1-C6alkyl;
R1 is H, C1-C6alkyl, or C3-C8cycloalkyl; or R1 is H, C1-C6alkyl, C3-C8cycloalkyl, or C1-C6 haloalkyl;
R8 is H or C1-C6alkyl,
n is 0 or 1;
L is —CH2— or is absent;
R2, R3, R4, R5, and R6 are each independently H, halo, CN, C1-C6alkyl, or C1-C6haloalkyl;
or R2, R4, R5, and R6 are each independently H, halo, CN, C1-C6alkyl, or C1-C6haloalkyl and R3 is taken together with an R1 and the atoms to which they are attached to form a 5- or 6-membered ring, wherein the 5- or 6-membered ring is unsubstituted or substituted with one to three groups selected from the group consisting of halo, CN, —OH, C1-C6alkyl, and C1-C6haloalkyl;
provided that either:
R3 is taken together with R1 and the atoms to which they are attached to form a 5- or 6-membered ring; or
at least two of R2, R3, R4, R5, and R6 are other than H; or
one of R2, R3, R4, R5, and R6 is cyano;

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wherein --- indicates that

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 or is attached in either an E or Z configuration;
Ra and Rb are each independently H, C1-C6alkyl, —C(O)C1-C6alkyl, 6-membered aryl, or 5- or 6-membered heteroaryl, wherein each C1-C6alkyl, —C(O)C1-C6alkyl, 6-membered aryl, or 5- or 6-membered heteroaryl of Ra and Rb are unsubstituted or substituted with one to four groups selected from the group consisting of OH, halo, and C1-C6alkyl;
Rc is C1-C6alkyl, —C(O)C1-C6alkyl, 6-membered aryl, or 5- or 6-membered heteroaryl, wherein each C1-C6alkyl, —C(O)C1-C6alkyl, 6-membered aryl, or 5- or 6-membered heteroaryl of Rc is unsubstituted or substituted with one to four groups selected from the group consisting of OH, halo, and C1-C6alkyl;
Re is H or C1-C6alkyl;
provided that when A is

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 and Ra is H, methyl, ethyl, n-Pr, i-Pr, i-Bu, 2-thiofuryl, 2-furyl, unsubstituted phenyl, 3-hydroxyphenyl, 4-hydroxyphenyl, 4-fluorophenyl, or 2,4-dichlorophenyl, at least one of (i)-(ix) applies:
(i) G2 is N;
(ii) n is 1, L is absent, and R1 is C1-C6alkyl;
(iii) n is 0, L is absent, and at least one of R2, R3, R4, R5, and R6 is halo, CN, or C1-C6haloalkyl;
(iv) n is 1, and R3 is taken together with R1 and the atoms to which they are attached to form a 5- or 6-membered ring;
(v) one of R2, R3, R4, R5, and R6 is CN; and
(vi) R4 and R5 are each independently Cl, Br, I, CN, C1-C6alkyl, or C1-C6haloalkyl;
(vii) one of Rd and R7 is C1-C6alkyl;
(viii) R2 and R3 are each Cl;
(ix) at least one of R2, R3, R4, R5, and R6 is F, Br, I, CN, or C1-C6haloalkyl and RE is H or 2-thiofuryl;
provided that when A is

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 and n is 1, then R1 is other than H;
provided that when A is

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 n is 0 and L is absent, then Ra is other than H;
provided that when A is

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 and Re is methyl, then Ra is other than unsubstituted phenyl;
provided that when A

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 n is 1 and L is absent, then R1 is other than H;
and
R7 is H, C1-C6alkyl or C1-C6haloalkyl,
provided that when Rd is C1-C6alkyl, R7 is H, and when R7 is C1-C6alkyl, Rd is H.