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US 9,808,447 B2Granted
Inhibitors of Rho associated protein kinases (ROCK) and methods of use
AssigneeH. Lee Moffitt Cancer Center and Research Institute, Inc.
InventorsErnst Schonbrunn, Rongshi Li, Said M. Sebti
Life of this patent
Estimating the term…
Abstract
Compounds and compositions having activity as inhibitors of Rho-associated proteinkinases (ROCKs), and methods of making and using the subject compounds are disclosed.
Claims21
A method of reducing or inhibiting tumor growth in a subject with breast cancer, comprising:
- administering to the subject an effective amount of a composition comprising a compound having the chemical structure shown in Formula IV
- wherein
- R is H, alkyl, acetyl, or heteroalkyl;
- R1 is H, alkyl, acetyl, or heteroalkyl;
- R8 and R9 are, independently of one another, H, —OH, acetyl, —C(O)NH2, alkyl, cycloalkyl, hereterocycloalkyl, aryl, or heteroaryl, wherein any one of the alkyl, cycloalkyl, hereterocycloalkyl, aryl, or heteroaryl groups is optionally substituted with one or more of —OH, —NO2, —NH2, —NR6R7, carbonyl, alkoxy, alkyl, —OCX3, —OCHX2, —OCH2X, or halogen, or both R8 together form a carbonyl;
- and
- R10 is cycloalkyl, aryl, or heteroaryl, any of which is optionally substituted with one or more of —OH, —C(O)NH2, —C(O)CH3, —NO2, —NH2, —NR6R7, carbonyl, alkyl, alkoxy, alkylalkoxy, alkoxylalkoxy, halogenated alkoxyl, cycloalkyl, heterocycloalkyl, heteroarylcarbonyl, aryl, heteroaryl, —OCX3, —OCHX2, —OCH2X, —OSO2CH3, or -tosyl;
- R6 and R7 are, independently, H, alkyl, —SO2CH3, —C(O)CH3, or —C(O)NH2;
- X is independently H or halogen;
- and
- n is 2 or 3,
- or a pharmaceutically acceptable salt thereof.
9 more elements
A method of reducing or inhibiting tumor growth in a subject with breast cancer, comprising:
- administering to the subject an effective amount of a composition comprising a compound having the chemical structure shown in Formula I
- wherein
- Z is CR or N;
- R is H, alkyl, acetyl, or heteroalkyl;
- R1 is H, alkyl, acetyl, or heteroalkyl;
- R2 is alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, or alkylaryl, any of which can be optionally substituted with one or more of —OH, —CH2OH, —C(O)NH2, acetyl, carbonyl, alkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl, any of which can be optionally substituted with one or more of —OH, —NO2, —NH2, —NR6R7, alkyl, alkoxy, alkylalkoxy, alkoxylalkoxy, halogenated alkoxy, heteroarylcarbonyl, heteroaryl, —OCX3, —OCHX2, —OCH2X, —OSO2CH3, tosyl, or halogen;
- or
- R1 and R2 can together form a cycloalkyl or heterocycloalkyl
- R6 and R7 are, independently, H, alkyl, —SO2CH3, —C(O)CH3, or —C(O)NH2;
- X is independently H or halogen;
- with the proviso that R and R1 are not both H when R2 is CH(CH2OH)Ph;
- or a pharmaceutically acceptable salt or hydrate thereof.
9 more elements
Dependencies are inferred from the claim text.