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US 11,236,088 B2Granted
Heterocyclic compounds and their application in medicine
AssigneeKind Pharmaceutical
InventorDong Liu
Life of this patent
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Abstract
This invention relates to heterocyclic compounds and their use in medicine. In particular, the present invention discloses heterocyclic compound of formula I, or an isotopically labeled compound thereof, or an optical isomer thereof, a geometric isomer thereof, a tautomer thereof or a mixture of various isomers, or a pharmaceutically acceptable salt thereof, or a prodrug thereof. The invention also relates to the use of these compounds in medicine.
Claims18
A compound of Formula I,
- or an isotopically labeled compound thereof, or an optical isomer thereof, a geometric isomer thereof, a tautomer thereof or a mixture of various isomers, or a pharmaceutically acceptable salt thereof, or a prodrug thereof,
- in which
- R1 and R2 are each independently selected from the group consisting of hydrogen, halo, cyano, C1 to C4 alkyl and substituted alkyl;
- n is 1, 2, 3, or 4;
- R3, R4, R6 are each independently selected from the group consisting of hydrogen, C1 to C6 alkyl and substituted alkyl, aryl and heteroaryl;
- R5 is selected from the group consisting of C1 to C6 alkyl and substituted alkyl, aryl and heteroaryl;
- R7 is selected from the group consisting of C1 to C6 alkyl and substituted alkyl, C2 to C6 alkenyl and substituted alkenyl, C2 to C6 alkynyl and substituted alkynyl, and acyl having 1 to 6 carbon atoms;
- Z is selected from the group consisting of O, S, C(═O), C (R9)(R10), wherein, R9 and R10 are each independently selected from hydrogen, C1 to C6 alkyl and substituted alkyl;
- A is a saturated four to six membered ring, which is a full carbocyclic ring or a heterocyclic ring containing one oxygen atom, one nitrogen atom, or two nitrogen atoms as ring atoms.
6 more elements
A compound of Formula I, or an isotopically labeled compound thereof, or an optical isomer thereof, a geometric isomer thereof, a tautomer thereof or a mixture of various isomers, or a pharmaceutically acceptable salt thereof, or a prodrug thereof, wherein the compound is selected from the group consisting of:
- 1-(3-fluoropropyl)-N-(4-((6R, 7S)-7-isobutyl-8-methyl-6,7,8,9-tetrahydro-3H-pyrazolo [3,4-h] isoquinolin-6-yl) phenyl) azetidin-3-amine;
- N-(3,5-difluoro-4-((6S, 7S)-7-isobutyl-8-methyl-6,7,8,9-tetrahydro-3H-pyrazolo [3,4 h] isoquinolin-6-yl) phenyl)-1-(3-fluoropropyl) azetidin-3-amine;
- N-(3,5-difluoro-4-((6S, 7S)-7-isobutyl-8-methyl-6,7,8,9-tetrahydro-3H-pyrazolo [3,4 h] isoquinolin-6-yl) phenyl)-1-(2,3-difluoropropyl) azetidin-3-amine;
- N-(3,5-difluoro-4-((6S, 7S)-7-isobutyl-8-methyl-6,7,8,9-tetrahydro-3H-pyrazolo [3,4-h] isoquinolin-6-yl) phenyl)-1-(3,3,3-trifluoropropyl) azetidin-3-amine;
- N-(4-((6S, 7S)-7-cyclopropylmethyl-8-methyl-6,7,8,9-tetrahydro-3H-pyrazolo [3,4-h] isoquinolin-6-yl)-3,5-difluorophenyl)-1-(3-fluoropropyl) azetidin-3-amine;
- N-(3,5-difluoro-4-((6S, 7S)-7-isobutyl-8-methyl-6,7,8,9-tetrahydro-3H-pyrazolo [3,4-h] isoquinolin-6-yl) phenyl)-1-propylazetidin-3-amine;
- 1-butyl-N-(3,5-difluoro-4-((6S, 7S)-7-isobutyl-8-methyl-6,7,8,9-tetrahydro-3H-pyrazolo [3,4-h] isoquinolin-6-yl) phenyl) azetidin-3-amine;
- N-(3,5-difluoro-4-((6S, 7S)-7-isobutyl-8-methyl-6,7,8,9-tetrahydro-3H-pyrazolo [3,4-h] isoquinolin-6-yl) phenyl)-1-isobutylazetidin-3-amine;
- N-(3,5-difluoro-4-((6S, 7S)-7-isobutyl-8-methyl-6,7,8,9-tetrahydro-3H-pyrazolo [3,4-h] isoquinolin-6-yl) phenyl)-1-pentylazetidin-3-amine;
- (6S, 7S)-6-(2,6-difluoro-4-((1-(3-fluoropropyl) azetidin-3-yl) thio) phenyl)-7-isobutyl-8-methyl-6,7,8,9-tetrahydro-3H-pyrazolo [3,4-h] isoquinoline;
- (6S, 7S)-6-(2,6-difluoro-4-((1-propyl) azetidin-3-yl) thio) phenyl)-7-isobutyl-8-methyl-6,7,8,9-tetrahydro-3H-pyrazolo [3,4-h] isoquinoline;
- (6S, 7S)-6-(4-((1-butylazetidin-3-yl) thio)-2,6-difluorophenyl)-7-isobutyl-8-methyl-6,7,8,9-tetrahydro-3H-pyrazolo [3,4-h] isoquinoline;
- (6S, 7S)-6-(2,6-difluoro-4-((1-isobutylazetidin-3-yl) thio) phenyl)-7-isobutyl-8-methyl-6,7,8,9-tetrahydro-3H-pyrazolo [3,4-h] isoquinoline;
- (6S, 7S)-6-(2,6-difluoro-4-((1-pentylazetidin-3-yl) thio) phenyl)-7-isobutyl-8-methyl-6,7,8,9-tetrahydro-3H-pyrazolo [3,4-h] isoquinoline;
- (6S, 7S)-6-(2,6-difluoro-4-((1-(3-fluoropropyl) azetidin-3-yl) oxy) phenyl)-7-isobutyl-8-methyl-6,7,8,9-tetrahydro-3H-pyrazolo [3,4-h] isoquinoline;
- (6S, 7S)-6-(2,6-difluoro-4-((1-propylazetidin-3-yl) oxy) phenyl)-7-isobutyl-8-methyl-6,7,8,9-tetrahydro-3H-pyrazolo [3,4-h] isoquinoline;
- (6S, 7S)-6-(2,6-difluoro-4-((1-isobutylazetidin-3-yl) oxy) phenyl)-7-isobutyl-8-methyl-6,7,8,9-tetrahydro-3H-pyrazolo [3,4-h] isoquinoline;
- (6S, 7S)-6-(4-((1-butylazetidin-3-yl) oxy) phenyl)-7-isobutyl-8-methyl-6,7,8,9-tetrahydro-3H-pyrazolo [3,4-h] isoquinoline;
- (6S, 7S)-6-(4-((1-pentylazetidin-3-yl) oxy) phenyl)-7-isobutyl-8-methyl-6,7,8,9-tetrahydro-3H-pyrazolo [3,4-h] isoquinoline;
- (6S, 7S)-7-(cyclopropylmethyl)-6-(2,6-difluoro-4-((1-(3-fluoropropyl) azetidin-3-yl) oxy) phenyl)-8-methyl-6,7,8,9-tetrahydro-3H-pyrazolo [3,4-h] isoquinoline;
- (6S, 7S)-7-cyclopropylmethyl-6-(2,6-difluoro-4-((1-propylazetidin-3-yl) oxy) phenyl)-8-methyl-6,7,8,9-tetrahydro-3H-pyrazolo [3,4-h] isoquinoline;
- (6S, 7S)-7-cyclopropylmethyl-6-(2,6-difluoro-4-((1-isobutylazetidin-3-yl) oxy) phenyl)-8-methyl-6,7,8,9-tetrahydro-3H-pyrazolo [3,4-h] isoquinoline;
- (6S, 7S)-6-(4-((1-butylazetidin-3-yl) oxy)-2,6-difluorophenyl)-7-cyclopropylmethyl-8-methyl-6,7,8,9-tetrahydro-3H-pyrazolo [3,4-h] isoquinoline;
- (6S, 7S)-7-cyclopropylmethyl-6-(2,6-difluoro-4-((1-pentylazetidin-3-yl) oxy) phenyl)-8-methyl-6,7,8,9-tetrahydro-3H-pyrazolo [3,4-h] isoquinoline;
- (6S, 7S)-7-cyclopropylmethyl-6-(2,6-difluoro-4-((1-(3-fluoropropyl) azetidin-3-yl) thio) phenyl)-8-methyl-6,7,8,9-tetrahydro-3H-pyrazolo [3,4-h] isoquinoline;
- (6S, 7S)-7-cyclopropylmethyl-6-(2,6-difluoro-4-((1-propylazetidin-3-yl) thio) phenyl)-8-methyl-6,7,8,9-tetrahydro-3H-pyrazolo [3,4-h] isoquinoline;
- (6S, 7S)-6-(4-((1-butylazetidin-3-yl) thio)-2,6-difluorophenyl)-7-cyclopropylmethyl-8-methyl-6,7,8,9-tetrahydro-3H-pyrazolo [3,4-h] isoquinoline;
- (6S, 7S)-6-(4-((1-isobutylazetidin-3-yl) thio)-2,6-difluorobenzene)-7-cyclopropylmethyl-8-methyl-6,7,8,9-tetrahydro-3H-pyrazolo [3,4-h] isoquinoline;
- (6S, 7S)-7-cyclopropylmethyl-6-(2,6-difluoro-4-((1-pentylazetidin-3-yl) thio) phenyl)-8-methyl-6,7,8,9-tetrahydro-3H-pyrazolo [3,4-h] isoquinoline;
- 3-(3,5-difluoro-4-((6S, 7S)-7-isobutyl-8-methyl-6,7,8,9-tetrahydro-3H-pyrazolo [3,4-h] isoquinolin-6-yl) phenoxy) azetidin-1-aldehyde;
- 1-(3-(3,5-difluoro-4-((6S, 7S)-7-isobutyl-8-methyl-6,7,8,9-tetrahydro-3H-pyrazolo [3,4-h] isoquinolin-6-yl) phenoxy) azetidin-1-yl) ethan-1-one;
- 1-(3-(3,5-difluoro-4-((6S, 7S)-7-isobutyl-8-methyl-6,7,8,9-tetrahydro-3H-pyrazolo [3,4-h] isoquinolin-6-yl) phenoxy) azetidin-1-yl) propan-1-one;
- 1-(3-(3,5-difluoro-4-((6S, 7S)-7-isobutyl-8-methyl-6,7,8,9-tetrahydro-3H-pyrazolo [3,4-h] isoquinolin-6-yl) phenoxy) azetidin-1-yl) butan-1-one;
- 1-(3-(3,5-difluoro-4-((6S, 7S)-7-isobutyl-8-methyl-6,7,8,9-tetrahydro-3H-pyrazolo [3,4-h] isoquinolin-6-yl) phenoxy) azetidin-1-yl)-2-methylpropan-1-one.
31 more elements
Dependencies are inferred from the claim text.