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US 2003/0119856 A1Published application
Thiazole compounds useful as inhibitors of protein kinase
AssigneeVertex Pharmaceuticals Incorporated
InventorsJohn Cochran, Suganthini Nanthakumar, Edmund Harrington, Jian Wang
Life of this patent
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Abstract
The present invention provides a compound of formula I: 1 or a pharmaceutically acceptable derivative thereof. These compounds are inhibitors of protein kinases, particularly inhibitors of GSK3, Aurora2, and Syk mammalian protein kinases. The invention also provides pharmaceutically acceptable compositions comprising the compounds of the invention and methods of utilizing those compounds and compositions in the treatment of various protein kinase mediated disorders.
Claims15
A compound of formula I:
- 180
- 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 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:
- 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;
- provided that:
- (a) when Ar1 is phenyl, two R2 are not simultaneously OR in the meta and para positions of Ar1;
- and
- (b) R1 is other than CN.
28 more elements
A compound selected from the following Table 1 compounds:
- 7 Cmpd I- Structure — — 2 181 3 182 4 183 5 184 6 185 7 186 8 187 9 188 10 189 11 190 12 191 13 192 14 193 15 194 16 195 17 196 18 197 19 198 20 199 21 200 22 201 23 202 24 203 25 204 26 205 27 206 28 207 29 208 30 209 31 210 — — 33 211 34 212 35 213 36 214 37 215 38 216 39 217 40 218 41 219 42 220 43 221 44 222 45 223 46 224 47 225 48 226 49 227 50 228 51 229 52 230 53 231 54 232 55 233 56 234 57 235 58 236 59 237 60 238 61 239 62 240 63 241 64 242 65 243 66 244 67 245 68 246 69 247 70 248 71 249 72 250 73 251 74 252 75 253 76 254 77 255 78 256 79 257 80 258 81 259 82 260 83 261 84 262 85 263 86 264 87 265 88 266 89 267 90 268 91 269 92 270 93 271 94 272 95 273 96 274 97 275 98 276 99 277 100 278 101 279 — — 103 280 104 281 105 282 106 283 107 284 108 285 109 286 110 287 111 288 112 289 113 290 114 291 115 292 116 293 117 294
A compound selected from the following Table 2 compounds:
- 295
Dependencies are inferred from the claim text.