US 12,465,590 B2
Oxalamido-substituted tricyclic inhibitors of hepatitis b virus
Raffaele De Francesco, Milan (IT); Lorena Donnici, Milan (IT); Luca Guidotti, Milan (IT); Matteo Iannacone, Milan (IT); Romano Di Fabio, Pomezia (IT); Vincenzo Summa, Pomezia (IT); Adolfo Prandi, Milan (IT); Pietro Randazzo, Milan (IT); Leda Ivanova Bencheva, Milan (IT); Marilenia De Matteo, Milan (IT); Luca Ferrante, Milan (IT); Davide Gornati, Milan (IT); and Alessandro Grillo, Milan (IT)
Assigned to OSPEDALE SAN RAFFAELE S.R.L., Milan (IT); IRBM S.P.A., Pomezia (IT); and ISTITUTO NAZIONALE DI GENETICA MOLECOLARE—INGM, Milan (IT)
Appl. No. 17/611,777
Filed by Antios Therapeutics, Inc., Mendham, NJ (US)
PCT Filed May 25, 2020, PCT No. PCT/EP2020/064424
§ 371(c)(1), (2) Date Nov. 16, 2021,
PCT Pub. No. WO2020/234483, PCT Pub. Date Nov. 26, 2020.
Claims priority of application No. 19176238 (EP), filed on May 23, 2019; and application No. 19211249 (EP), filed on Nov. 25, 2019.
Prior Publication US 2022/0241241 A1, Aug. 4, 2022
Int. Cl. C07D 513/14 (2006.01); A61K 31/407 (2006.01); A61K 31/437 (2006.01); A61K 31/445 (2006.01); A61K 31/506 (2006.01); A61K 31/513 (2006.01); A61K 31/522 (2006.01); A61K 31/675 (2006.01); A61K 31/7072 (2006.01); A61K 31/7084 (2006.01); A61K 38/21 (2006.01); A61K 39/29 (2006.01); A61K 39/395 (2006.01); A61P 31/20 (2006.01); C07D 515/14 (2006.01)
CPC A61K 31/407 (2013.01) [A61K 31/437 (2013.01); A61K 31/445 (2013.01); A61K 31/506 (2013.01); A61K 31/513 (2013.01); A61K 31/522 (2013.01); A61K 31/675 (2013.01); A61K 31/7072 (2013.01); A61K 31/7084 (2013.01); A61K 38/212 (2013.01); A61K 39/292 (2013.01); A61K 39/3955 (2013.01); A61P 31/20 (2018.01); C07D 513/14 (2013.01); C07D 515/14 (2013.01)] 7 Claims
 
1. A compound of general formula (I):

OG Complex Work Unit Chemistry
wherein:
Cy is aryl or heteroaryl;
A is C—R3;
X is O or S;
Y, Y′, Y″ are each methanediyl;
Y′″ is absent;
R1 is H or C1-6 alkyl;
R2 is selected from H, OH, halogen and C1-6 alkyl;
R3 is selected from H, C1-6 alkyl, C3-8 cycloalkyl, haloC1-6 alkyl and halogen;
R5 is H or C1-6 alkyl;
R6 is selected from H, C1-6 alkyl, C3-8 cycloalkyl, C3-8 heterocycloalkyl, C1-6 alkylaryl, C1-6 alkylheteroaryl and C1-6 alkyl-C3-8 cycloalkyl wherein each of said C1-6 alkyl, C3-8 cycloalkyl, C3-8 heterocycloalkyl, C1-6 alkylaryl, C1-6 alkylheteroaryl or C1-6 alkyl-C3-8 cycloalkyl is optionally substituted with one or more substituents each independently selected from: OH, halogen, halo-C1-6 alkyl, cyano and NH2;
each of R7 and R8 are independently selected from:
hydrogen;
C1-12 alkyl optionally substituted with one or more substituents each independently selected from the group consisting of: OH, halogen, CN, NH2, NH(R9), N(R9)2, haloC1-6alkyl, aryl, heteroaryl, 3-7 membered saturated ring and 5-7 membered partially saturated ring, each of said saturated or partially saturated ring optionally containing one or more heteroatoms selected from the group consisting of O, N and S and each of said aryl, heteroaryl, 3-7 membered saturated ring or 5-7 membered partially saturated ring being optionally substituted with one or more substituents each independently selected from: OH, halogen, C1-6 alkyl, haloC1-6 alkyl, CN, haloC1-6 alkoxy and C1-6 alkoxy;
aryl or heteroaryl, each of said aryl or heteroaryl being optionally substituted with one or more substituents each independently selected from: OH, halogen, haloC1-6 alkyl, CN, haloC1-6 alkoxy and C1-6 alkoxy; and
a 3-8 membered saturated or partially saturated cyclic or bicyclic ring optionally containing one or more heteroatoms each independently selected from the group consisting of: O, S and N, the 3-8 membered saturated or partially saturated cyclic or bicyclic ring being optionally substituted with one, two or more substituents each independently selected from the group consisting of: OH, halogen, CN, C1-6 alkyl, hydroxyC1-6 alkyl, C(O)OR9, C(O)R9, halo-C1-6 alkyl, haloC1-6 alkoxy and C1-6 alkoxy;
or R7 and R8 form together with the nitrogen atom to which they are attached a cyclic amine selected from: aziridine, azetidine, pyrrolidine, piperidine, azepane, morpholine, thiomorpholine and piperazine each of said cyclic amine being optionally substituted with one or more substituents each independently selected from the group consisting of: OH, halogen, CN, C1-6 alkyl, hydroxyC1-6 alkyl, haloC1-6 alkyl, haloC1-6 alkoxy and C1-6 alkoxy;
Ra, Rb, Rc and Rd are each independently selected from the group consisting of: hydrogen, halogen, CN, C1-6 alkyl, C1-6 alkoxy, haloC1-6 alkyl, haloC1-6 alkoxy, C(O)OR9, C(O)R9, NH2, NH(R9), N(R9)2;
each R9 is independently selected from C1-6 alkyl, haloC1-6 alkyl, C1-6 alkylaryl, C1-6 alkylheteroaryl and C1-6 alkyl-C3-8cycloalkyl;
or a pharmaceutically acceptable salt, tautomer, solvate or stereoisomer thereof.