Heterocyclic compounds and uses thereof

A method for treating a disease or disorder selected from chronic myelogenous leukemia (CML), acute lymphocytic leukemia (ALL) and gastrointestinal stromal tumor (GIST) comprising the step of administering to a patient a compound of formula I:

• or a pharmaceutically acceptable salt thereof, wherein:
• T is —NHC(O)— or —C(O)NH—;
• W is CH or N;
• each of Ra, Rb, Rc, and Rd is independently selected from R, OR, or halogen;
• each R is independently hydrogen, lower alkyl, or lower haloalkyl;
• R1 is a warhead group—L-Y, wherein:
• L is a bivalent C2-8 straight or branched, hydrocarbon chain wherein L has at least one double bond and at least one methylene unit of L is replaced by cyclopropylene, —NRC(O)—, —C(O)NR—, —S—, —S(O)—, —SO2—, —C(═S)—, —C(═NR)—, —N═N—, or —C(═N2)—;
• and one or two additional methylene units of L are optionally and independently replaced by —O—, —N(R)—, or —C(O)—;
• or
• L is a bivalent C2-8 straight or branched, hydrocarbon chain wherein L has at least one triple bond and one or two methylene units of L are optionally and independently replaced by —NRC(O)—, —C(O)NR—, —S—, —S(O)—, —SO2—, —C(═S)—, —C(═NR)—, —O—, —N(R)—, or —C(O)—;
• or
• L is a bivalent C2-8 straight or branched, hydrocarbon chain wherein one methylene unit of L is replaced by cyclopropylene and one or two additional methylene units of L are independently replaced by —C(O)—, —NRC(O)—, —C(O)NR—, —N(R)SO2—, or —SO2N(R)—;
• or
• L is a bivalent C1-8, straight or branched, alkylene chain, wherein at least one methylene unit of L is replaced by —C(═N2)—, and one or two additional methylene units of L are optionally and independently replaced by —NRC(O)—, —C(O)NR—, —S—, —S(O)—, —SO2—, —C(═S)—, —C(═NR)—, —O—, —N(R)—, or —C(O)—;
• or
• L is —NHC(O)-cyclopropylene-SO2—;
• and
• Y is hydrogen, C1-6 aliphatic optionally substituted with oxo, halogen, or CN, or a 3-10 membered monocyclic or bicyclic, saturated, partially unsaturated, or aryl ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, and wherein said ring is substituted with 1-4 groups independently selected from —Q-Z, oxo, halogen, CN, or C1-6 aliphatic, wherein:
• Q is a covalent bond or a bivalent C1-6 saturated or unsaturated, straight or branched, hydrocarbon chain, wherein one or two methylene units of Q are optionally and independently replaced by —NR—, —NRC(O)—, —C(O)NR—, —S—, —O—, —C(O)—, —SO—, or —SO2—;
• and
• Z is hydrogen or C1-6 aliphatic optionally substituted with oxo, halogen, or CN;
• R2 is selected from R, halogen, —N(R)C(O)OR, or 1-imidazoyl substituted with R, or:
• R1 and R2 are taken together with their intervening atoms to form a 5-7 membered saturated, partially unsaturated, or aryl ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, wherein said ring is substituted with a warhead group and 0-3 groups independently selected from oxo, halogen, CN, or C1-6 aliphatic;
• and
• R3 is selected from hydrogen, lower alkyl, or halogen.