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US 2012/0238593 A1Published application
Heterocyclic compounds and uses thereof
AssigneeAvila Therapeutics, Inc.
InventorsJuswinder Singh, Shomir Ghosh, Arthur F. Kluge, Russell C. Petter
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Abstract
The present invention provides compounds, pharmaceutically acceptable compositions thereof, and methods of using the same.
Claims42
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;
- 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.
7 more elements
A method for treating a PDGFR-, c-KIT-, KDR-, or cFMS-mediated disorder in a patient in need thereof, comprising the step of irreversibly inhibiting PDGFR, c-KIT, KDR, or cFMS, by covalently modifying Cys814 of PDGFR-α, Cys822 of PDGFR-β, Cys1024 of KDR, Cys788 of c-KIT, or Cys774 of cFMS.
A conjugate selected from any of formulae:
- Cys814-linker-inhibitor moiety, wherein the Cys814 is Cys814 of PDGFR-α;
- Cys822-linker-inhibitor moiety, wherein the Cys822 is Cys822 of PDGFR-β;
- Cys788-linker-inhibitor moiety, wherein the Cys788 is Cys788 of c-KIT;
- Cys774-linker-inhibitor moiety, wherein the Cys774 is Cys774 of cFMS;
- or
- Cys1024-linker-inhibitor moiety, wherein the Cys 1024 is Cys 1024 of KDR.
3 more elements
A conjugate of any of the following formulae:
- wherein the Cys814 is Cys814 of PDGFR-α;
- the Cys822 is Cys822 of PDGFR-β;
- the Cys788 is Cys788 of c-KIT;
- the Cys774 is Cys774 of cFMS and the Cys1024 is Cys1024 of KDR, and:
- each T is —NHC(O)— or —C(O)NH—;
- each 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;
- each 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
- each R3 is selected from hydrogen, lower alkyl, or halogen.
9 more elements
Dependencies are inferred from the claim text.