US 7,488,727 B2
Thiazole compounds useful as inhibitors of protein kinase
John Cochran, Marshfield, Mass. (US); Suganthini Nanthakumar, Newton, Mass. (US); Edmund Harrington, South Boston, Mass. (US); and Jian Wang, Boston, Mass. (US)
Assigned to Vertex Pharmaceuticals Incorporated, Cambridge, Mass. (US)
Filed on Jun. 15, 2007, as Appl. No. 11/763,693.
Application 11/763693 is a division of application No. 10/891912, filed on Jul. 13, 2004, granted, now 7,256,190.
Application 10/891912 is a division of application No. 10/154118, filed on May 23, 2002, granted, now 6,762,179.
Claims priority of provisional application 60/295158, filed on Jun. 01, 2001.
Prior Publication US 2007/0249645 A1, Oct. 25, 2007
This patent is subject to a terminal disclaimer.
Int. Cl. C07D 417/04 (2006.01); C07D 417/14 (2006.01); A61K 31/506 (2006.01)
U.S. Cl. 514—235.8  [514/252.14; 514/275; 544/60; 544/330; 544/331; 544/332] 11 Claims
 
1. A compound of formula I:

OG Complex Work Unit Drawing
or a pharmaceutically acceptable derivative thereof, wherein:
R1 is selected from R, halogen, CN, NO2, or TR;
T is an optionally substituted C1-C4 alkylidene chain wherein up to two methylene units of T are optionally and independently replaced by O, N(R), C(O), S, SO, or SO2;
each R is independently selected from hydrogen or an optionally substituted C1-6 aliphatic group, wherein:
two R bound to the same nitrogen atom are optionally taken together with the nitrogen to form a 3-7 membered saturated, partially unsaturated, or fully unsaturated ring having 0-2 heteroatoms, in addition to the nitrogen bound thereto, independently selected from nitrogen, oxygen, or sulfur;
Ar1 is an optionally substituted ring selected from:
(a) a 3-8 membered monocyclic saturated or partially unsaturated ring; or 8-10 membered bicyclic saturated or partially unsaturated ring, or a naphthyl ring;
(b) a 3-7 membered heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur; or
(c) a 5-6 membered monocyclic or 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, wherein:
Ar1 is optionally substituted by one to four substituents selected from the group consisting of:
(a) one group selected from QR, Ar2, or QAr2; and
(b) up to four R2 groups;
each Q is independently selected from a valence bond or an optionally substituted C1-6 alkylidene chain, wherein:
one or two non-adjacent methylene units of Q are optionally and independently replaced by —O—, —S—, —NR—, —C(O)—, —CO2—, —C(O)NR—, —OC(O)NR—, —C(O)C(O)—, —NRC(O)—, NRCO2—, —NRC(O)NR—, —S(O)—, —SO2—, —NRSO2—, —SO2NR—, or —NRSO2NR—;
each Ar2 is an optionally substituted ring independently selected from:
(a) a 3-8 membered monocyclic or 8-10 membered bicyclic saturated, partially unsaturated, or aryl ring;
(b) a 3-7 membered heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur; or
(c) a 5-6 membered monocyclic or 8-10 membered bicyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, wherein:
Ar2 is optionally substituted by one to four R2 groups; and
each R2 is independently selected from R, halogen, NO2, CN, OR, SR, N(R)2, NRCOR, NRCON(R)2, NRCO2R, C(O)R, CO2R, CON(R)2, OC(O)N(R)2, SOR, SO2R, SO2N(R)2, NRSO2R, NRSO2N(R)2, C(O)C(O)R, or C(O)CH2C(O)R; wherein:
two R2 on adjacent positions on Ar1 or Ar2 are optionally taken together to form a saturated, partially unsaturated, or fully unsaturated 4-6 membered ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur.