US 12,466,800 B2
N-((1,2,3,5,6,7-hexahydro-S-indacen-4-yl)carbamoyl)-4, 5, 6, 7-tetrahydrobenzofuran-2-sulfonamide derivatives and related compounds as NLPR3 modulators for the treatment of multiple sclerosis (MS)
Raju Mohan, Encinitas, CA (US); John Nuss, Encinitas, CA (US); Jason Harris, Encinitas, CA (US); and Shendong Yuan, Encinitas, CA (US)
Assigned to ZOMAGEN BIOSCIENCES LTD, Encinitas, CA (US)
Appl. No. 17/627,082
Filed by Zomagen Biosciences Ltd, Encinitas, CA (US)
PCT Filed Jul. 16, 2020, PCT No. PCT/IB2020/000634
§ 371(c)(1), (2) Date Jan. 13, 2022,
PCT Pub. No. WO2021/009566, PCT Pub. Date Jan. 21, 2021.
Claims priority of provisional application 62/875,402, filed on Jul. 17, 2019.
Prior Publication US 2022/0396559 A1, Dec. 15, 2022
Int. Cl. C07D 307/935 (2006.01); A61K 31/343 (2006.01); A61K 31/4355 (2006.01); A61K 31/4365 (2006.01); A61P 25/16 (2006.01); A61P 25/28 (2006.01); A61P 37/02 (2006.01); C07D 307/82 (2006.01); C07D 307/93 (2006.01); C07D 333/62 (2006.01); C07D 491/04 (2006.01); C07D 491/048 (2006.01); C07D 495/04 (2006.01)
CPC C07D 307/82 (2013.01) [C07D 307/935 (2013.01); C07D 333/62 (2013.01); C07D 491/048 (2013.01); C07D 495/04 (2013.01)] 19 Claims
 
1. A compound having the structure of Formula (I):

OG Complex Work Unit Chemistry
wherein:
X1 is O, S, N(R3), or C(NO2)(R4);
X2 is —N(R5)— or —C(R5)2—;
X3 is —N(R5)— or —C(R5)2—;
X4 is —C(O)— or —CH2—;
Y1 is O;
Y2 is N or C(R9);
Y3 is O or N(R10);
Z is N or C(R19);
R1 is

OG Complex Work Unit Chemistry
R2 is

OG Complex Work Unit Chemistry
R3 is —OR14, —CN, —NO2, or —S(═O)2R15;
R4 is hydrogen, C1-C6alkyl, or C1-C6heteroalkyl;
each R5 is independently selected from hydrogen, C1-C6alkyl, and C1-C6heteroalkyl;
R6 is —OH, —C1-C6alkyl-OH, or —NH(R16);
each R7 is independently selected from C1-C6alkyl, —C1-C6alkyl-CO2R18, C1-C6haloalkyl, and C1-C6heteroalkyl; or R6 and R7 are combined to form a 5- or 6-membered heteroaryl ring;
R9 is hydrogen, halogen, C1-C6alkyl, C1-C6haloalkyl, or C1-C6heteroalkyl;
R10 is —OH or —O—C1-C6alkyl;
R11 is C1-C6alkyl;
R12 is C1-C6alkyl;
each R13 is independently selected from halogen, C1-C6alkyl, C1-C6haloalkyl, and C1-C6heteroalkyl;
R14 is hydrogen or C1-C6alkyl;
R15 is C1-C6alkyl;
R16 is hydrogen, C1-C6alkyl or —C(O)—C1-C6alkyl;
R17 is hydrogen or C1-C6alkyl;
R18 is hydrogen or C1-C6alkyl;
R19 is hydrogen, halogen, —CN, C1-C6alkyl, C1-C6haloalkyl, or C1-C6heteroalkyl;
n is 1 or 2;
p is 0, 1, 2, 3, or 4;
q is 0, 1, or 2;
s is 1, 2, or 3; and
t is 1, 2, or 3;
or a pharmaceutically acceptable salt or solvate thereof.