US 12,275,707 B2
Modulators of mas-related g-protein receptor X2 and related products and methods
Marion Lanier, San Diego, CA (US); Marcus Boehm, San Diego, CA (US); Liming Huang, San Diego, CA (US); Esther Martinborough, San Diego, CA (US); Marcos Sainz, San Diego, CA (US); Brandon Selfridge, San Diego, CA (US); and Adam Yeager, San Diego, CA (US)
Assigned to Escient Pharmaceuticals, Inc., San Diego, CA (US)
Filed by Escient Pharmaceuticals, Inc., San Diego, CA (US)
Filed on Nov. 30, 2023, as Appl. No. 18/525,253.
Application 18/525,253 is a continuation of application No. 17/484,993, filed on Sep. 24, 2021, granted, now 11,919,864.
Claims priority of provisional application 63/211,987, filed on Jun. 17, 2021.
Claims priority of provisional application 63/145,407, filed on Feb. 3, 2021.
Claims priority of provisional application 63/083,638, filed on Sep. 25, 2020.
Prior Publication US 2024/0336570 A1, Oct. 10, 2024
This patent is subject to a terminal disclaimer.
Int. Cl. C07D 215/46 (2006.01); C07D 401/12 (2006.01); C07D 401/14 (2006.01); C07D 405/12 (2006.01); C07D 405/14 (2006.01); C07D 417/12 (2006.01); C07D 471/04 (2006.01); C07D 495/04 (2006.01); C07D 513/04 (2006.01)
CPC C07D 215/46 (2013.01) [C07D 401/12 (2013.01); C07D 401/14 (2013.01); C07D 405/12 (2013.01); C07D 405/14 (2013.01); C07D 417/12 (2013.01); C07D 471/04 (2013.01); C07D 495/04 (2013.01); C07D 513/04 (2013.01)] 42 Claims
 
1. A method of treating an itch associated condition by administering to a subject in need thereof an effective amount of a compound having structure (Ic):

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt, isomer, hydrate, solvate or isotope thereof, wherein:
W is N and Z is CRz or W is CRw and Z is N;
R1c is heterocyclyl and where R1c is optionally substituted with one or more Rq;
R2, R3, R4, R5, and R6 are independently H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, aryl, cycloalkyl, heteroaryl, heterocyclyl, —OR, —C(O)OR, —OC(O)R, —X, —CX3, —CX2H, —C(X)H2, C(X)2R, —C(X)(R)2, —CN, —N(R)2, —N(R)C(O)R, —N(R)S(O)2R, or —S(O)2R;
each Rq is independently C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, aryl, cycloalkyl, heteroaryl, heterocyclyl, —OR, —O(CH2)nR, —OX3, —OX2H, —O(X)H2, —C(O)OR, —C(O)R, —OC(O)R, —X, —CX3, —CX2H, —C(X)H2, —CN, —N(R)2, —N(R)C(O)R, —N(R)S(O)2R, S(O)2R, —B(OR)2, —C(H)Q′R, or —(CH2)nQ′,
Q′ is C1-6 alkyl, aryl, cycloalkyl, heterocyclyl, —OR′, —C(O)OR′, —OC(O)R′, —X, —CX3, —CX2H, —C(X)H2, —CN, —N(R′)2, —N(R′)C(O)R′, or —N(R′)S(O)2R′;
each R is independently H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, alkylamino, —(CH2)nR′, X, aryl, cycloalkyl, heteroaryl, or heterocyclyl, or two R groups together with the atom to which it is attached forms a carbocycle or heterocycle, wherein C1-6 alkyl is optionally substituted with one or more of X, haloalkyl, or haloalkoxy;
each Rx is independently H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, aryl, cycloalkyl, heteroaryl, heterocyclyl, —OR, —C(O)OR, —OC(O)R, —X, —CX3, —CX2H, —C(X)H2, —CN, —N(R)2, —N(R)C(O)R, —N(R)S(O)2R, or —S(O)2R;
Rw is H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, aryl, cycloalkyl, heteroaryl, or heterocyclyl;
Rz is H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, aryl, cycloalkyl, heteroaryl, or heterocyclyl;
each R′ is independently H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, aryl, cycloalkyl, heteroaryl, or heterocyclyl;
each X is independently F, Cl, Br, or I; and
each n is independently 0, 1, 2, 3, 4 or 5;
wherein the itch associated condition is atopic dermatitis, chronic urticaria, contact dermatitis, drug allergy, prurigo nodularis, pruritus, psoriasis, or urticaria.