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US RE49,834 E1Granted
Jak1 selective inhibitors and uses thereof
AssigneeHangzhou Highlightll Pharmaceutical Co., Ltd
InventorCongxin Liang
Life of this patent
Estimating the term…
Abstract
The new 1H-furo[3,2-b]imidazo[4,5-d]pyridine derivatives are selective Jak1 kinase inhibitors useful in treating disorders related to Jak1 activities such as autoimmune diseases or disorders, inflammatory diseases or disorders, and cancer or neoplastic diseases or disorders.
Claims22
A compound of formula I:
- or a pharmaceutically acceptable salt thereof,
- wherein R1 is H, halo, or C1-3 alkyl optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halo, OH, CN, OR, NHR, NRR′, N(R)C(═O)R′, N(R)C(═O)(0)R′, N(R)C(═O)(O)R′, OC(═O)NRR′, C(═O)R, C(═O)NRR′, N(R)S(O)2R′, S(O)2R, and S(O)2NRR′;
- R2 is H, halo, or C1-3 alkyl;
- Cy is C3-7 cycloalkyl, 3-7 membered heterocyclyl, phenyl, or 5-6 membered heteroaryl, each optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of R3, oxo, halo, OH, CN, OR, NHR, NRR′, N(R)C(═O)R′, N(R)C(═O)(O)R′, OC(═O)NRR′, C(═O)R, C(═O)NRR′, N(R)S(O)2R′, S(O)2R, and S(O)2NRR′, wherein R3 is C1-3 alkyl optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halo, OH, CN, OR, NHR, NRR′, N(R)C(═O)R′, N(R)C(═O)(O)R′, OC(═O)NRR′, C(═O)R, C(═O)NRR′, N(R)S(O)2R′, S(O)2R, and S(O)2NRR′;
- and
- R and R′ are each independently H, or C1-3 alkyl optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halo, OH, and CN.
3 more elements
A compound of formula A1-14:
A process, comprising contacting a compound of formula V:
- and a compound of formula VI:
- in the presence of a (C1-6)3 alkyloxonium tetrafluoroborate at a sufficient temperature, and for a sufficient time to produce a compound of formula I:
- wherein R1 is H, halo, or C1-3 alkyl optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halo, OH, CN, OR, NHR, NRR′, N(R)C(═O)R′, N(R)C(═O)(O)R′, OC(═O)NRR′, C(═O)R, C(═O)NRR′, N(R)S(O)2R′, S(O)2R, and S(O)2NRR′;
- R2 is H;
- Cy is C3-7 cycloalkyl, 3-7 membered heterocyclyl, phenyl, or 5-6 membered heteroaryl, each optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of R3, oxo, halo, OH, CN, OR, NHR, NRR′, N(R)C(═O)R′, N(R)C(═O)(O)R′, OC(═O)NRR′, C(═O)R, C(═O)NRR′, N(R)S(O)2R′, S(O)2R, and S(O)2NRR′, wherein R3 is C1-3 alkyl optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halo, OH, CN, OR, NHR, NRR′, N(R)C(═O)R′, N(R)C(═O)(O)R′, OC(═O)NRR′, C(═O)R, C(═O)NRR′, N(R)S(O)2R′, S(O)2R, and S(O)2NRR′;
- and
- R and R′ are each independently H, or C1-3 alkyl optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halo, OH, and CN.
4 more elements
A compound that is 2-[(2R,5S)-5-[2-Methylfuro[3,2-b]imidazo[4,5-d]pyridin-1-yl]tetrahydropyran-2-yl]acetonitrile (11).
A pharmaceutically acceptable salt that is a pharmaceutically acceptable salt of 2-[(2R,5S)-5-[2-Methylfuro[3,2-b]imidazo[4,5-d]pyridin-1-yl]tetrahydropyran-2-yl]acetonitrile (11).
A compound of formula A1-14:
- or a pharmaceutically acceptable salt thereof.
A process, comprising contacting a compound of formula V:
- and a compound of formula VI:
- in the presence of a (C1-6 alkyl)3oxonium tetrafluoroborate at a sufficient temperature, and for a sufficient time to produce a compound of formula I:
- or a pharmaceutically acceptable salt thereof, wherein R1 is H, halo, or C1-3 alkyl optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halo, OH, CN, OR, NHR, NRR′, N(R)C(═O)R′, N(R)C(═O)(O)R′, OC(═O)NRR′, C(═O)R, C(═O)NRR′, N(R)S(O)2R′, S(O)2R, and S(O)2NRR′;
- R2 is H;
- Cy is C3-7 cycloalkyl, 3-7 membered heterocyclyl, phenyl, or 5-6 membered heteroaryl, each optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of R3, oxo, halo, OH, CN, OR, NHR, NRR′, N(R)C(═O)R′, N(R)C(═O)(O)R′, OC(═O)NRR′, C(═O)R, C(═O)NRR′, N(R)S(O)2R′, S(O)2R, and S(O)2NRR′, wherein R3 is C1-3 alkyl optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halo, OH, CN, OR, NHR, NRR′, N(R)C(═O)R′, N(R)C(═O)(O)R′, OC(═O)NRR′, C(═O)R, C(═O)NRR′, N(R)S(O)2R′, S(O)2R, and S(O)2NRR′;
- and
- R and R′are each independently H, or C1-3 alkyl optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halo, OH, and CN.
4 more elements
Dependencies are inferred from the claim text.