Heterocyclic compounds as prmt5 inhibitors
AssigneeAngex Pharmaceutical, Inc.
InventorsWen-Lian Wu, Zhiqiang Yang, Francis Lee, John Qiang Tan
Life of this patent
Estimating the term…
Abstract
The present disclosure describes novel heterocyclic PRMT5 inhibitors and methods for preparing them. The pharmaceutical compositions comprising such PRMT5 inhibitors and methods of using them for treating cancer, infectious diseases, and other PRMT5 associated disorders are also described.
Claims19
A compound represented by a formula:
- or a pharmaceutically acceptable salt thereof;
- wherein
- (Ring A) is an optionally substituted 4-amino-7H-pyrrolo[2,3-d]pyrimidin-7-yl;
- (Ring B) is an optionally substituted fused tricyclic heterocyclic ring system containing 1, 2, 3, 4, or 5 ring N atoms, 0 or 1 ring O atom, and a fused benzene ring, wherein the fused benzene ring is directly attached to L;
- X is —O— or —CH2—;
- L is optionally substituted C1-3 hydrocarbylene, optionally substituted —O—C1-2 hydrocarbylene-, optionally substituted —S—C1-2 hydrocarbylene-, or optionally substituted —NRA—C1-2 hydrocarbylene-;
- and
- RA is H, C1-6 hydrocarbyl, C1-6 heteroaryl, C1-6 heterocycloalkyl, —C(O)—C1-6 alkyl, —C(O)NH—C1-6 alkyl, or —C(O)OC1-6 alkyl.
A compound, or a pharmaceutically acceptable salt thereof, wherein the compound is optionally substituted (1S,2R,3S,5R)-3-(2-(2,3-dihydro-1H-pyrrolo[2,3-b]quinolin-7-yl)ethyl)-5-(7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopentane-1,2-diol, optionally substituted (1S,2R,3S,5R)-3-(2-(2,3-dihydroimidazo[1,2-c]quinazolin-8-yl)ethyl)-5-(7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopentane-1,2-diol, optionally substituted (1S,2R,3S,5R)-3-(2-(imidazo[1,2-c]quinazolin-8-yl)ethyl)-5-(7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopentane-1,2-diol, optionally substituted (1S,2R,3S,5R)-3-(2-((1aS,7bR)-1a,7b-dihydro-1H-cyclopropa[c]quinolin-5-yl)ethyl)-5-(7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopentane-1,2-diol, optionally substituted (1S,2R,3S,5R)-3-(2-((1aR,7bS)-1a,7b-dihydro-1H-cyclopropa[c]quinolin-5-yl)ethyl)-5-(7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopentane-1,2-diol, optionally substituted (1S,2R,3S,5R)-3-(2-(1H-pyrazolo[3,4-b]quinolin-7-yl)ethyl)-5-(7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopentane-1,2-diol, optionally substituted (2R,3S,4R,5R)-2-(2-(2,3-dihydro-1H-pyrrolo[2,3-b]quinolin-7-yl)ethyl)-5-(7H-pyrrolo[2,3-d]pyrimidin-7-yl)tetrahydrofuran-3,4-diol, optionally substituted (2R,3S,4R,5R)-2-(2-(2,3-dihydroimidazo[1,2-c]quinazolin-8-yl)ethyl)-5-(7H-pyrrolo[2,3-d]pyrimidin-7-yl)tetrahydrofuran-3,4-diol, optionally substituted (2R,3S,4R,5R)-2-(2-(imidazo[1,2-c]quinazolin-8-yl)ethyl)-5-(7H-pyrrolo[2,3-d]pyrimidin-7-yl)tetrahydrofuran-3,4-diol, optionally substituted (1S,2R,3S,5R)-3-(2-(1H-pyrrolo[2,3-b]quinolin-7-yl)ethyl)-5-(7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopentane-1,2-diol, (1S,2R,3S,5R)-3-(2-(3,4-dihydro-1H-[1,2]oxazino[3,4-b]quinolin-8-yl)ethyl)-5-(7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopentane-1,2-diol, (1S,2R,3S,5R)-3-(2-(1,3-dihydroisoxazolo[3,4-b]quinolin-7-yl)ethyl)-5-(7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopentane-1,2-diol, optionally substituted (1R,2S,3R,5S)-3-(7H-pyrrolo[2,3-d]pyrimidin-7-yl)-5-(2-(1,3,4,5-tetrahydro-[1,2]oxazepino[3,4-b]quinolin-9-yl)ethyl)cyclopentane-1,2-diol, optionally substituted (1S,2R,3S,5R)-3-(2-(3H-imidazo[4,5-b]quinolin-6-yl)ethyl)-5-(7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopentane-1,2-diol, optionally substituted (1S,2R,3S,5R)-3-(2-(3H-[1,2,3]triazolo[4,5-b]quinolin-6-yl)ethyl)-5-(7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopentane-1,2-diol, optionally substituted (1S,2R,3S,5R)-3-(2-(2,3-dihydro-1H-pyrazolo[3,4-b]quinolin-7-yl)ethyl)-5-(7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopentane-1,2-diol, optionally substituted (1R,2S,3R,5S)-3-(7H-pyrrolo[2,3-d]pyrimidin-7-yl)-5-(2-(1,2,3,4-tetrahydrobenzo[b][1,8]naphthyridin-8-yl)ethyl)cyclopentane-1,2-diol, optionally substituted (1R,2S,3R,5S)-3-(7H-pyrrolo[2,3-d]pyrimidin-7-yl)-5-(2-(2,3,4,5-tetrahydro-1H-azepino[2,3-b]quinolin-9-yl)ethyl)cyclopentane-1,2-diol, optionally substituted (2R,3S,4R,5R)-2-(2-(1H-pyrazolo[3,4-b]quinolin-7-yl)ethyl)-5-(7H-pyrrolo[2,3-d]pyrimidin-7-yl)tetrahydrofuran-3,4-diol, optionally substituted (2R,3R,4S,5R)-2-(7H-pyrrolo[2,3-d]pyrimidin-7-yl)-5-(2-(1,2,3,4-tetrahydrobenzo[b][1,8]naphthyridin-8-yl)ethyl)tetrahydrofuran-3,4-diol, or optionally substituted (1R,2S,3R,5S)-3-(7H-pyrrolo[2,3-d]pyrimidin-7-yl)-5-(2-(1,2,3,4-tetrahydropyridazino[3,4-b]quinolin-8-yl)ethyl)cyclopentane-1,2-diol.
A compound, or a pharmaceutically acceptable salt thereof, wherein the compound is:
Dependencies are inferred from the claim text.