Tricyclic derivatives as potent and selective histone deacetylase inhibitors
AssigneeChipscreen Biosciences, Ltd.
InventorsXian-Ping LU, Zhi-Bin Li, Zhi-Qiang Ning
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Abstract
The present invention relates to certain tricyclic derivatives which are capable of inhibiting histone deacetylases. The compounds of this invention are therefore useful in treating diseases associated with abnormal histone deacetylase activities. Pharmaceutical compositions comprising these compounds, methods of treating diseases utilizing pharmaceutical compositions comprising these compounds, and methods of preparing these compounds are also disclosed.
Claims26
An isolated compound of formula I:
- X is a bond, —CH2CH2—, —CH═CH—, O or S;
- each ring A and ring B, independently of each other, represents a benzene ring, which is optionally substituted with one or more halogen, nitro, alkyl, alkoxy or amino groups;
- R1 is —NHOH or
- R2, R3, R4 and R5 are independently hydrogen, halo, alkyl, alkoxy or trifluoromethyl;
- and
- n is an integer ranging from 1 to 7.
A process for the preparation of a compound of formula I
- X is a bond, —CH2CH2—, —CH═CH—, O or S;
- each ring A and ring B, independently of each others represents a benzene ring, which is optionally substituted with one or more halogen, nitro, alkyl, alkoxy or amino groups;
- R1 is —NHOH
- n is an integer ranging from 1 to 7;
- or
- a stereoisomer, enantiomer, diastereomer, or pharmaceutically acceptable salts thereof comprising the steps of:
- (a) condensing compound 1 with compound 2 to give compound 3;
- (b) hydrolyzing compound 3 with lithium hydroxide to give compound 4;
- and
- (c) condensing compound 4 with hydroxylamine to give compound 5a;
An isolated compound of formula II:
- X is a bond, —CH2CH2—, —CH═CH—, O or S;
- each ring A and ring B, independently of each others represents a benzene ring, which is optionally substituted with one or more halogen, nitro, alkyl, alkoxy or amino groups;
- R1 is —NHOH or
- R2, R3, R4 and R5 are independently hydrogen, halo, alkyl, alkoxy or trifluoromethyl;
- R6 and R7 are independently hydrogen or alkyl;
- m is an integer ranging from 2 to 4;
- and
- n is an integer ranging from 1 to 7.
A process for the preparation of a compound of formula I
- X is a bond, —CH2CH2—, —CH═CH—, O or S;
- each ring A and ring B, independently of each other, represents a benzene ring, which is optionally substituted with one or more halogen, nitro, alkyl, alkoxy or amino groups;
- R1 is
- R2, R3, R4 and R5 are independently hydrogen, halo, alkyl, alkoxy or trifluoromethyl;
- n is an integer ranging from 1 to 7;
- a stereoisomer, enantiomer, diastereomer, or pharmaceutically acceptable salts thereof comprising the steps of:
- (a) condensing compound 1 with compound 2 to give compound 3;
- (b) hydrolyzing compound 3 with lithium hydroxide to give compound 4;
- and
- (d) condensing compound 4 with compound 6 to give compound 5b
Dependencies are inferred from the claim text.