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US 8,802,657 B2Granted
Compounds useful as Raf kinase inhibitors
AssigneesMillennium Pharmaceuticals, Inc., Sunesis Pharmaceuticals, Inc.
InventorsJennifer Cossrow, Bing Guan, John Howard Jones, Gnanasambandam Kumaravel, Alexey Lugovskoy, Hairuo Peng, Noel Powell, Brian C. Raimundo, Hiroko Tanaka, Jeffrey Vessels, Thomas Wynn, Zhili Xin
Life of this patent
Estimating the term…
Abstract
The present invention provides compounds useful as inhibitors of Raf protein kinase. The present invention also provides compositions thereof, and methods of treating Raf-mediated diseases.
Claims19
A compound of formula I:
- or a pharmaceutically acceptable salt thereof, wherein:
- Cy1 is an optionally substituted 5-6 membered partially unsaturated or aromatic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
- Cy2 is an optionally substituted 5-14 membered saturated, partially unsaturated, or aromatic monocyclic, bicyclic, or tricyclic ring having 0-4 heteroatoms, independently selected from nitrogen, oxygen, and sulfur;
- L1 is a direct bond or an optionally substituted, straight or branched C1-6 alkylene chain;
- L2 is a direct bond, or is an optionally substituted, straight or branched C1-6 alkylene chain wherein 1 or 2 methylene units of L2 are optionally and independently replaced by —O—, —S—, —N(R)—, —C(O)—, —C(O)N(R)—, —N(R)C(O)N(R)—, —N(R)C(O)—, —N(R)C(O)O—, —OC(O)N(R)—, —SO2—, —SO2N(R)—, —N(R)SO2—, —OC(O)—, —C(O)O—, or a 3-6 membered cycloalkylene;
- each R is independently hydrogen or an optionally substituted C1-6 aliphatic group;
- R1 is hydrogen or an optionally substituted C1-6 aliphatic group;
- each of Rx and Ry is independently selected from —R2, -halo, —NO2, —CN, —OR2, —SR2, —N(R2)2, —C(O)R2, —CO2R2, —C(O)C(O)R2, —C(O)CH2C(O)R2, —S(O)R2, —S(O)2R2, —SO2N(R2)2, —OC(O)R2, —N(R2)C(O)R2, —N(R2)N(R2)2, —N(R2)—C(═NR2)N(R2)2, —C(═NR2)N(R2)2, —C═NOR2, —N(R2)C(O)N(R2)2, —N(R2)SO2N(R2)2, —N(R2)SO2R2, and —OC(O)N(R2)2;
- and
- each R2 is independently hydrogen or an optionally substituted group selected from C1-6 aliphatic, a C6-10 monocyclic or bicyclic aryl ring, and a 5-10 membered saturated, partially unsaturated, or aromatic monocyclic or bicyclic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or
- two R2 on the same nitrogen are taken together with the nitrogen to form an optionally substituted 5-8 membered saturated, partially unsaturated, or aromatic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur.
8 more elements
A compound of formula II:
- or a pharmaceutically acceptable salt thereof, wherein:
- Cy1 is an optionally substituted 5-6 membered, partially unsaturated, or aromatic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur;
- Cy2 is an optionally substituted 5-14 membered saturated, partially unsaturated, or aromatic monocyclic, bicyclic, or tricyclic ring having 0-4 heteroatoms, independently selected from nitrogen, oxygen, and sulfur;
- R1 is hydrogen or an optionally substituted C1-6 aliphatic group;
- each of Rx and Ry is independently selected from —R2, -halo, —NO2, —CN, —OR2, —SR2, —N(R2)2, —C(O)R2, —CO2R2, —C(O)C(O)R2, —C(O)CH2C(O)R2, —S(O)R2, —S(O)2R2, —SO2N(R2)2, —OC(O)R2, —N(R2)C(O)R2, —N(R2)N(R2)2, —N(R2)—C(═NR2)N(R2)2, —C(═NR2)N(R2)2, —C═NOR2, —N(R2)C(O)N(R2)2, —N(R2)SO2N(R2)2, —N(R2)SO2R2, and —OC(O)N(R2)2;
- and
- each R2 is independently hydrogen or an optionally substituted group selected from C1-6 aliphatic, a C6-10 monocyclic or bicyclic aryl ring, and a 5-10 membered saturated, partially unsaturated, or aromatic monocyclic or bicyclic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or
- two R2 on the same nitrogen are taken together with the nitrogen to form an optionally substituted 5-8 membered saturated, partially unsaturated, or aromatic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur.
5 more elements
Dependencies are inferred from the claim text.