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US 10,703,759 B2Granted
8,9-dihydroimidazo[1,2-a]pyrimido[5,4-e]pyrimidin-5(6H)-ones
AssigneeImpact Therapeutics, Inc.
InventorsSui Xiong Cai, Ye Edward Tian
Life of this patent
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Abstract
Disclosed are 8,9-dihydroimidazo[1,2-a]pyrimido[5,4-e]pyrimidin-5(6H)-one compounds, specifically represented by the Formula I: or a pharmaceutically acceptable salt or prodrug thereof, wherein A and R1-R7 are defined herein. Compounds having Formula I are Wee1 kinase inhibitors. Therefore, compounds of the disclosure may be used to treat diseases caused by abnormal Wee1 activity.
Claims18
A compound having the Formula I:
- or a pharmaceutically acceptable salt thereof, wherein:
- A is N or CR15;
- R1 is H, optionally substituted C1-8 alkyl, optionally substituted C2-8 alkenyl, optionally substituted C3-8 cycloalkyl, optionally substituted aryl, or optionally substituted heteroaryl;
- R2 is an optionally substituted heterocyclic group, optionally substituted aryl, or optionally substituted heteroaryl;
- R3, R4, R5, R6, R7, and R15 are each independently H, halo, optionally substituted amino, optionally substituted alkoxy, optionally substituted C1-10 alkyl, haloalkyl, alkenyl, alkynyl, hydroxyalkyl, aminoalkyl, carboxyalkyl, nitro, cyano, acylamido, hydroxy, thiol, acyloxy, azido, carboxy, ethylenedioxo, hydroxyacylamido or optionally substituted alkylthiol,
- with the proviso that the compound is not 6-(2,6-dimethylphenyl)-2-((4-(4-methylpiperazin-1-yl)phenyl)amino)-8,9-dihydroimidazo[1,2-a]pyrimido[5,4-e]pyrimidin-5(6H)-one.
3 more elements
A compound having Formula III:
- or a pharmaceutically acceptable salt thereof, wherein;
- Ar1 is selected from phenyl substituted by 2 substituents selected from halo, and C1-C6 alkyl;
- and
- Ar2 is selected from:
- substituted phenyl, of which the substituents are selected from:
- halo;
- halo C1-C6 alkyl;
- C1-C6 alkyl;
- C1-C6 alkoxy;
- hydroxyl C1-C6 alkyl;
- NRaRb—C1-C6 alkyl;
- C1-C4 alkyl substituted by piperazinyl which is optionally substituted by 1-3 C1-C4 alkyl;
- piperidinyl —O— optionally substituted by 1-3 C1-C4 alkyl;
- NRaRb—C1-C6 alkoxy;
- NRaRb—C1-C6 alkyl-NRa—;
- piperazinyl substituted by 1-3 substituents selected from C1-C6 alkyl, hydroxy C1-C6 alkyl and C1-C6 acyl piperidinyl substituted by 1 substituent selected from C1-C6 alkyl and —NRaRb;
- 1,4-diazacyclopentan-1-yl optionally substituted by 1-3 C1-C6 alkyl;
- and morpholinyl optionally substituted by 1-3 C1-C6 alkyl;
- wherein Ra and Rb are independently H and C1-C4 alkyl;
- tetrahydroisoquinolinyl substituted by 1-3 substituents selected from C1-C6 alkyl and halo;
- 2′,3′-dihydro-1′H-spiro[cyclopropane-1,4′-isoquinolin]-7′-yl substituted by 1-3 substituents selected from C1-C6 alkyl, C1-C4 acyl and halo;
- and
- 4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-yl substituted by 1-3 C1-C6 alkyl.
20 more elements
A compound having Formula III:
- or a pharmaceutically acceptable salt thereof, wherein;
- Ar1 is disubstituted phenyl substituted by substituents selected from halo, C1-C3 alkyl, halo C1-C3 alkyl and C1-C3 alkoxy at two meta-positions;
- Ar2 is:
- phenyl substituted by 1, 2 or 3 substituents, and the substituents are selected from halo;
- halo C1-C6 alkyl;
- C1-C6 alkyl;
- C1-C6 alkoxy;
- hydroxy C1-C6 alkyl;
- NRaRb—C1-C6 alkyl;
- C1-C4 alkyl substituted by piperazinyl optionally substituted by 1-3 C1-C4 alkyl;
- piperidinyl —O— optionally substituted by 1-3 C1-C4 alkyl NRaRb—C1-C6 alkoxy;
- NRaRb—C1-C6 alkyl-NRa—;
- piperazinyl optionally substituted by 1-3 substituents selected from C1-C6 alkyl and hydroxy C1-C6 alkyl;
- piperidinyl substituted by 1 substituent selected from C1-C6 alkyl and —NRaRb;
- 1,4-diazacyclopentan-1-yl optionally substituted by 1-3 C1-C6 alkyl;
- and morpholinyl optionally substituted by 1-3 C1-C6 alkyl;
- wherein Ra and Rb are independently H and C1-C4 alkyl;
- tetrahydroisoquinolinyl substituted by 1-3 substituents selected from C1-C6 alkyl and halo;
- or
- 2′,3′-dihydro-1′H-spiro[cyclopropane-1,4′-isoquinolin]-7′-yl substituted by 1-3 substituents selected from C1-C6 alkyl, C1-C4 acyl and halo.
17 more elements
A compound having Formula III:
- or a pharmaceutically acceptable salt thereof, wherein:
- Ar1 is
- and
- Ar2 is
- wherein
- R8 is independently H, fluoro, chloro, bromo, methyl and trifluoromethyl;
- R9 is independently H, fluoro, chloro, bromo, methyl and trifluoromethyl;
- R10 is independently H, fluoro, chloro, bromo, methyl and methoxy;
- R11 is independently H, fluoro, chloro, bromo, methyl and trifluoromethyl;
- R12 is independently chloro, fluoro, bromo, methyl and methoxy;
- R13 is independently H, chloro, methyl, methoxy and hydroxymethyl;
- R14 is independently H, chloro, bromo and methyl.
9 more elements
Dependencies are inferred from the claim text.