Heterocyclic inhibitors of Rho GTPases for the treatment of disease

1 . A pharmaceutical composition comprising a compound of structural Formula II:

or a salt, ester, or prodrug thereof, wherein:

W 1, W 2, and W 3 are independently chosen from CH and N;

W 1, W 2, and W 3 and the intervening atoms combine to form a five-membered heteroaryl substituted by R 6b and R 6b ;

X and Y are independently chosen from CH and N

R 1 is chosen from alkyl and cycloalkyl, either one of which is optionally substituted with one or more R 5;

R 3 and R 4 are independently chosen from H, alkyl, cycloalkyl, heterocycloalkyl, alkenyl, and alkynyl, any one of which is optionally substituted with one or more R 7,

or R 3 and R 4, together with the intervening atoms, combine to form a 5-to 7-membered aryl or heteroaryl, either one of which is optionally substituted with one or more R 7 ;

R 6a and R 6b are independently chosen from from cyano, halo, hydroxy, oxo, alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl, or

R 6b and R 6b , together with the intervening atoms, combine to form a 5-or 6-membered heterocycloalkyl or a 5-or 6-membered heteroaryl; and

each R 5 and R 7 is independently chosen from from cyano, halo, hydroxy, alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl,

together with a pharmaceutically acceptable carrier.

2 . A method of inhibition of Rho GTPase comprising contacting Rho GTPase with a pharmaceutical composition as recited in claim 1 .

3 . A method of treating a Rho GTPase-mediated disease comprising administering a therapeutically effective amount of a pharmaceutical composition as recited in claim 1 to a patient in need thereof wherein the disease is chosen from oral squamous cell carcinoma, gastric cell carcinoma, breast cancer, lung cancer, testicular cancer, prostate cancer, colorectal cancer, melanoma, non-small cell lung cancer, or head and neck squamous cell carcinoma.