US 12,338,255 B2
Bicyclic substituted sulfonylurea compounds as inhibitors of interleukin-1 activity
Ping Chen, Shanghai (CN); Hongjian Zhang, Plainsboro, NJ (US); Fei Jiang, Shanghai (CN); and Peihua Sun, Shanghai (CN)
Assigned to Viva Star Biosciences (Suzhou) Co., Ltd., Jiangsu (CN)
Filed by Viva Star Biosciences (Suzhou) Co., Ltd., Jiangsu (CN)
Filed on Feb. 17, 2023, as Appl. No. 18/111,283.
Claims priority of application No. PCT/CN2022/076992 (WO), filed on Feb. 21, 2022.
Prior Publication US 2023/0279026 A1, Sep. 7, 2023
Int. Cl. C07D 519/00 (2006.01)
CPC C07D 519/00 (2013.01) 19 Claims
 
1. A compound of Formulae (II)-(IV):

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt, tautomer or stereoisomer thereof,
wherein:
Ring Q is a fused 6,5-bicyclic heteroaryl or a fused 6,6-bicyclic heteroaryl ring system comprising 1, 2 or 3 nitrogen atoms as ring members and optionally comprising 1 or 2 ring members selected from O, S or S(═O2), wherein the Ring Q bears R1 and R2 substituents as indicated in Formulae (II)-(IV), and optionally bears 1 or 2 R12 substituents;
X1 and X5 are each independently N or C; and X2, X3, and X4 are each independently N or CR7, and the dashed circle denotes bonds forming a five-membered aromatic ring; provided that at least two but no more than three of X1, X2, X3, X4 and X5 are N;
Y1 is N or CH, Y2 is N, NR8 or CH, and Y3 is N, NR8 or CH, and

OG Complex Work Unit Chemistry
in Formula (III) denotes

OG Complex Work Unit Chemistry
provided that two of Y1, Y2, and Y3, are N;
Z1 is N or CH, Z2 is N or CR9, and Z3 is N or CH; provided that at least one of Z1, Z2, and Z3, are N;
each occurrence of R1 is independently hydrogen, C1-4alkyl, haloC1-4alkyl, C3-7cycloalkyl, C1-4alkoxy, C3-7cycloalkoxy, oxo (═O), NRaRb, C(═O)ORa, OC(═O)Ra, C(═O)NRaRb, NRbC(═O)Ra, C(═O)NHC(═O)Ra, or 4-6-membered heterocyclyl, each of which is optionally substituted with one to three R11;
each occurrence of R2 is independently C1-4alkyl, haloC1-4alkyl, C3-7cycloalkyl, halogen, CN, OH, C1-4alkoxy, NRaRb, C(═O)NRaRb, or 4-6-membered heterocyclyl, each of which is optionally substituted with one to two R11, or two R2 groups at geminal position may optionally form a spiro C3-5cycloalkyl;
R3, R4, R5, and R6 are each independently hydrogen, halogen, CN, C1-4alkyl, or haloC1-4alkyl;
each occurrence of R7 is independently hydrogen or C1-4alkyl;
each occurrence of R8 is independently hydrogen or C1-4alkyl;
each occurrence of R9 is independently hydrogen, C1-4alkyl or C1-4alkoxy;
each occurrence of R10 is independently hydrogen, C1-4alkyl, C3-7cycloalkyl, or 4-6-membered heterocyclyl optionally substituted with C1-4alkyl;
each occurrence of R11 is independently, C1-4alkyl, haloC1-4alkyl, halogen, CN, OH, C3-7cycloalkyl, C1-4alkoxy, C3-7cycloalkoxy, NRaRb, C(═O)ORa, OC(═O)Ra, C(═O)NRaRb, NRbC(═O)Ra, C(═O)NHC(═O)Ra, or 4-6-membered heterocyclyl;
each occurrence of R12 is independently hydrogen, C1-4alkyl, haloC1-4alkyl, C3-7cycloalkyl, C1-4alkyl-C3-7cycloalkyl, C1-4alkyl-NRaRb, C(═O)Ra, C(═O)NRaRb, or 4-6-membered heterocyclyl optionally substituted with one to three groups selected from C1-4alkyl, haloC1-4alkyl, C3-7cycloalkyl, halogen, CN, OH, C1-4alkoxy, C3-7cycloalkoxy, or NRaRb,
each occurrence of Ra and Rb is independently hydrogen, C1-4alkyl, C3-5cycloalkyl, or Ra and Rb, together with the nitrogen atom to which they are attached, form a saturated or unsaturated heterocyclic ring containing from three to seven ring atoms, which ring may optionally contain additional one or two heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur and may be optionally substituted by from one to three groups which may be the same or different selected from the group consisting of C1-4alkyl, phenyl and benzyl; and
each occurrence of n is independently 0, 1, or 2.