US 12,338,241 B2
Bicyclic sulfones and sulfoxides and methods of use thereof
Snahel Patel, Foster City, CA (US); Gregory Hamilton, Atlanta, GA (US); Craig Stivala, San Mateo, CA (US); Huifen Chen, Burlingame, CA (US); and Blake Daniels, Oakland, CA (US)
Assigned to Genentech, Inc., South San Francisco, CA (US)
Filed by Genentech, Inc., South San Francisco, CA (US)
Filed on Jun. 6, 2021, as Appl. No. 17/340,082.
Application 17/340,082 is a division of application No. 16/175,206, filed on Oct. 30, 2018, granted, now 11,072,617.
Claims priority of provisional application 62/579,392, filed on Oct. 31, 2017.
Prior Publication US 2023/0002391 A1, Jan. 5, 2023
Int. Cl. C07D 487/04 (2006.01); A61P 25/00 (2006.01); C07D 231/54 (2006.01); C07D 249/16 (2006.01)
CPC C07D 487/04 (2013.01) [A61P 25/00 (2018.01); C07D 231/54 (2013.01); C07D 249/16 (2013.01)] 21 Claims
 
1. A method for the treatment of a disease or disorder in a human, the method comprising administration to the human of an effective treatment amount of a compound of, formula (I):

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt thereof, wherein
R1 is selected from the group consisting of C1-C6 alkyl, C3-C6 cycloalkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 haloalkoxy, C1-C6 hydroxyalkyl, C1-C6cyanoalkyl, C(O)C1-C6 cycloalkyl-C1-C3 alkyl, C1-C6 Alkyl-N(R2)2, C1-C6 alkoxy-C1-C6 alkyl, C1-C6haloalkoxy-C1-C6alkyl, phenyl, benzyl, difluoro(phenyl)methyl, 4 to 6 membered heteroaryl, 5 to 6 membered heteroaryl, and CH2-(5 to 6 membered heteroaryl); wherein
when R1 is phenyl, benzyl, difluoro(phenyl)methyl, 5 to 6 membered heteroaryl or CH2-(5 to 6 membered heteroaryl), the phenyl or heteroaryl moiety of R1 is optionally substituted by one or two substituents independently selected from the group consisting of hydrogen, C1-C6 alkyl, hydroxyl, hydroxymethyl, methoxymethyl, cyano, trifluoromethyl, difluoromethoxy, and trifluoromethoxy, and
when R1 is cycloalkyl, the cycloalkyl is optionally substituted by by one, two, or three substituents independently selected from the group consisting of fluoro C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 haloalkoxy, hydroxyl, C1-C6 hydroxyalkyl, and cyano;
n is 0, 1 or 2;
each R2 is independently selected from the group consisting of C1-C6 alkyl, C3-C6 cycloalkyl, C1-C6 alkoxy, and C1-C6 haloalkyl; or two R2 together with the nitrogen atom to which they are both attached from a 4-6 membered heteroaryl ring;
the A ring and the B together are selected from the group consisting of:

OG Complex Work Unit Chemistry
p is 2, and q is 1;
RB1 is independently R2a and R2b and each R2a and R2b is independently selected from the group consisting of hydrogen, halogen, deutero, hydroxyl, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 cycloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 thioalkyl, C1-C6 alkyl-N(R2)2, and cyano; and
RB2 is R4 and R4 is selected from the group consisting of C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 cycloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 thioalkyl, C1-C6 alkyl-N(R2)2, phenyl benzyl, CH2—(C3-C6 cycloalkyl), CH2CH2—(C3-C6 cycloalkyl), CH2-(4 to 6 membered heterocyclyl), CH2CH2-(4 to 6 membered heterocyclyl), 5 to 6 membered heteroaryl, and CH2-(5 to 6 membered heterocyclyl);
wherein when R4 is phenyl, heteroacyl, or benzyl, the phenyl or heteroacyl ring is optionally substituted by 1 to 3 substituents selected from the group consisting of halogen, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, and cyano;
wherein the disease or disorder is selected from the group consisting of Parkinson's Disease, Lewy body dementia, multiple system atrophy, Parkinson-plus syndrome, tauopathies tauopathy, Alzheimer's Disease, frontotemporal dementia, amyotrophic lateral sclerosis, spinal muscular atrophy, primary lateral sclerosis, Huntington's disease, ischemia, stroke, intracranial hemorrhage, cerebral hemorrhage, muscular dystrophy, progressive muscular atrophy, pseudobulbar palsy, progressive bulbar palsy, spinal muscular atrophy, inherited muscular atrophy, peripheral neuropathies neuropathy, progressive supranuclear palsy, corticobasal degeneration, and demyelinating disease.