Back to results
US 2010/0075952 A1Published application
Pyrrolo-nitrogenous heterocyclic derivaties,the preparation and the pharmcetical use theeof
AssigneeShanghai Hengrui Pharmaceutical Co., Ltd.
InventorsPeng Cho ChoTang, Yidong Su, Yali Li, Lei Zhang, Fuqiang Zhao, Jialiang Yang, Ying Zhou, Pingyan Bie, Guangtao Qian, Minggang Ju
Life of this patent
Estimating the term…
Abstract
The invention provides new pyrrolo-nitrogenous heterocyclic derivatives represented by formula (I) or their salts, the preparation thereof, pharmaceutical compositions containing such derivatives and the use of such derivatives as therapeutic agents, especially as protein kinase inhibitors, wherein each substituent in formula (I) is same as defined in the description.
Claims19
A compound having the formula (I) or pharmaceutically acceptable salts thereof:
- Wherein:
- X is selected from the group consisting of carbon and nitrogen;
- R1 and R2 are each independently selected from the group consisting of hydrogen and alkyl;
- R3 is selected from the group consisting of alkyl, trifluoromethyl, aryl and aralkyl, wherein said alkyl, aryl or aralkyl is further substituted by one or more halogen;
- R4 is selected from the group consisting of alkyl, cycloalkyl, heterocyclo alkyl, aryl, heteroaryl, —(CH2)n(OCH2CH2)rR11, —[CH2CH(OH)]rCH2NR9R10 and —(CH2)nNR9R10, wherein said alkyl, cylcoalkyl, heterocyclo alkyl, aryl or heteroaryl is further substituted by one or more groups selected from the group consisting of aryl, hydroxyl, amino, amide group, aminocarbonyl, alkoxyl, aryloxy, aminoalkyl, hydroxyalkyl, heterocyclo alkyl, carboxylic acid, carboxylic ester and —NR9R10;
- when X is nitrogen, R5 is absent, R6, R7, R8 are each independently selected from the group consisting of hydrogen and halogen;
- when X is carbon, R5, R6, R7, R8 are each independently selected from the group consisting of hydrogen, halogen, hydroxyalkyl, alkyl, cycloalkyl, heterocyclo alkyl, aryl, heteroaryl, hydroxyl, cyano, nitro, —OR9, —O[CH2CH2O]rR11, —NR9R10, —(CH2)nCO2R9, —(CH2)nCONR9R10, —COR9, —NR9COR10, —SO2R9 and —NHCO2R10, wherein said aryl, heteroaryl, cycloalkyl or heterocyclo alkyl is further substituted by one or more groups selected from the group consisting of alkyl, alkoxyl and halogen;
- R9 and R10 are each independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, heterocyclo alkyl and heteroaryl, wherein said alkyl, cycloalkyl, aryl, heterocyclo alkyl or heteroaryl further substituted by one or more groups selected from the group consisting of alkyl, aryl, haloaryl, hydroxyl, amino, cyano, alkoxyl, aryloxy, hydroxyalkyl, heterocyclo alkyl, carboxylic acid, carboxylic ester and —NR9R10;
- R9 and R10 are taken together with the attached atom to form 4 to 8 membered hetero rings, wherein said 5 to 8 membered hetero rings may contain one to more heteroatoms selected from the group consisting of N, O and S, and said 4 to 8 membered rings are further substituted by one or more groups consisting of alkyl, halogen, aryl, heteroaryl, haloalkyl, hydroxyl, cyano, alkoxyl, aryloxy, aminoalkyl, hydroxyalkyl, heterocyclo alkyl, carboxylic acid, carboxylic ester and —NR9R10;
- R11 is selected from the group consisting of hydrogen and alkyl;
- n is an integer from 2 to 6;
- z is an integer from 1 to 4;
- and
- r is an integer from 1 to 6.
11 more elements
A compound having the following formula (IC) or (ID), which is an intermediate in the synthesis of the compound of formula (I):
- Wherein:
- R2 is selected from the group consisting of hydrogen and alkyl;
- R3 is selected from the group consisting of alkyl, trifluoromethyl, aryl and aralkyl, wherein said alkyl, aryl or aralkyl is further substituted by one or more halogen;
- R4 is selected from the group consisting of alkyl, cycloalkyl, heterocyclo alkyl, aryl, heteroaryl, —(CH2)n(OCH2CH2), —R11, —[CH2CH(OH)]rCH2NR9R10 and —(CH2)nNR9R10, wherein said alkyl, cylcoalkyl, heterocyclo alkyl, aryl or heteroaryl is further substituted by one or more groups selected from the group consisting of aryl, hydroxyl, amino, amide group, aminocarbonyl, alkoxyl, aryloxy, aminoalkyl, hydroxyalkyl, heterocyclo alkyl, carboxylic acid, carboxylic ester and —NR9R10;
- R9 and R10 are each independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, heterocyclo alkyl and heteroaryl, wherein said alkyl, cycloalkyl, aryl, heterocyclo alkyl or heteroaryl is further substituted by one or more groups selected from the group consisting of alkyl, aryl, haloaryl, hydroxyl, amino, cyano, alkoxyl, aryloxy, hydroxyalkyl, heterocyclo alkyl, carboxylic acid, carboxylic ester and —NR9R10;
- R9 and R10 are taken together with the attached atom to form 4 to 8 membered hetero rings, wherein said 5 to 8 membered hetero rings may contain one to more heteroatoms selected from the group consisting of N, O and S, and said 4 to 8 membered rings are further substituted by one or more groups consisting of alkyl, halogen, aryl, heteroaryl, haloalkyl, hydroxyl, cyano, alkoxyl, aryloxy, aminoalkyl, hydroxyalkyl, heterocyclo alkyl, carboxylic acid, carboxylic ester, and —NR9R10;
- R11 is selected from the group consisting of hydrogen and alkyl;
- n is an integer from 2 to 6;
- z is an integer from 1 to 4;
- and
- r is an integer from 1 to 6.
8 more elements
Dependencies are inferred from the claim text.