SG184870A1 - 5, 7-substituted-imidazo [1, 2-c] pyrimidines as inhibitors of jak kinases - Google Patents

Info

Publication number

SG184870A1

SG184870A1 SG2012076493A SG2012076493A SG184870A1 SG 184870 A1 SG184870 A1 SG 184870A1 SG 2012076493 A SG2012076493 A SG 2012076493A SG 2012076493 A SG2012076493 A SG 2012076493A SG 184870 A1 SG184870 A1 SG 184870A1

Authority

SG

Singapore

Prior art keywords

alkyl

formula

ring

pyrazol

hetar

Prior art date

2010-04-14

Links

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• -1 7-substituted-imidazo [1, 2-c] pyrimidines Chemical class 0.000 title claims description 253
• 239000003112 inhibitor Substances 0.000 title abstract description 23
• 108091000080 Phosphotransferase Proteins 0.000 title description 5
• 102000020233 phosphotransferase Human genes 0.000 title description 5
• 150000001875 compounds Chemical class 0.000 claims abstract description 335
• 150000003839 salts Chemical class 0.000 claims abstract description 39
• 238000011282 treatment Methods 0.000 claims abstract description 37
• 208000023275 Autoimmune disease Diseases 0.000 claims abstract description 23
• 230000036210 malignancy Effects 0.000 claims abstract description 19
• 210000000056 organ Anatomy 0.000 claims abstract description 15
• 239000012453 solvate Substances 0.000 claims abstract description 15
• 125000000217 alkyl group Chemical group 0.000 claims description 609
• 125000001424 substituent group Chemical group 0.000 claims description 195
• 238000002360 preparation method Methods 0.000 claims description 156
• 229910052799 carbon Inorganic materials 0.000 claims description 129
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 104
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 97
• 229910052739 hydrogen Inorganic materials 0.000 claims description 73
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 71
• 229910052757 nitrogen Inorganic materials 0.000 claims description 69
• 125000001153 fluoro group Chemical group F* 0.000 claims description 65
• 239000001257 hydrogen Substances 0.000 claims description 65
• PQIOSYKVBBWRRI-UHFFFAOYSA-N methylphosphonyl difluoride Chemical group CP(F)(F)=O PQIOSYKVBBWRRI-UHFFFAOYSA-N 0.000 claims description 62
• 125000003545 alkoxy group Chemical group 0.000 claims description 60
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 49
• 238000000034 method Methods 0.000 claims description 48
• 239000002585 base Substances 0.000 claims description 43
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 42
• 125000004432 carbon atom Chemical group C* 0.000 claims description 40
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 38
• 229910052786 argon Inorganic materials 0.000 claims description 37
• 125000000623 heterocyclic group Chemical group 0.000 claims description 35
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 35
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• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 30
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• 150000002431 hydrogen Chemical group 0.000 claims description 28
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 28
• 125000000304 alkynyl group Chemical group 0.000 claims description 26
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 25
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• 125000005842 heteroatom Chemical group 0.000 claims description 24
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 23
• 125000001072 heteroaryl group Chemical group 0.000 claims description 23
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 22
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 21
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 21
• 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims description 20
• 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 20
• 229910052760 oxygen Inorganic materials 0.000 claims description 18
• 229910052731 fluorine Inorganic materials 0.000 claims description 17
• 125000000714 pyrimidinyl group Chemical group 0.000 claims description 16
• WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 claims description 16
• 239000003153 chemical reaction reagent Substances 0.000 claims description 15
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 15
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• 125000002883 imidazolyl group Chemical group 0.000 claims description 5
• 125000002757 morpholinyl group Chemical group 0.000 claims description 5
• 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 5
• 125000002971 oxazolyl group Chemical group 0.000 claims description 5
• 125000004193 piperazinyl group Chemical group 0.000 claims description 5
• 238000002560 therapeutic procedure Methods 0.000 claims description 5
• 125000001113 thiadiazolyl group Chemical group 0.000 claims description 5
• 125000000335 thiazolyl group Chemical group 0.000 claims description 5
• 125000004484 1-methylpiperidin-4-yl group Chemical group CN1CCC(CC1)* 0.000 claims description 4
• 235000015854 Heliotropium curassavicum Nutrition 0.000 claims description 4
• 244000301682 Heliotropium curassavicum Species 0.000 claims description 4
• 125000006380 bromopyridyl group Chemical group 0.000 claims description 4
• DOBRDRYODQBAMW-UHFFFAOYSA-N copper(i) cyanide Chemical compound [Cu+].N#[C-] DOBRDRYODQBAMW-UHFFFAOYSA-N 0.000 claims description 4
• 230000008569 process Effects 0.000 claims description 4
• 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims description 4
• 125000000168 pyrrolyl group Chemical group 0.000 claims description 4
• 229910052717 sulfur Inorganic materials 0.000 claims description 4
• RCPFKNIWFCVDLQ-UHFFFAOYSA-N 4-oxa-3-azabicyclo[3.2.1]octane Chemical compound C1C2CCC1ONC2 RCPFKNIWFCVDLQ-UHFFFAOYSA-N 0.000 claims description 3
• 125000002393 azetidinyl group Chemical group 0.000 claims description 3
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• 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 3
• 125000001544 thienyl group Chemical group 0.000 claims description 3
• KLNXUTSCUIBQGB-UHFFFAOYSA-N 2-bromo-2-fluoroacetaldehyde Chemical compound FC(Br)C=O KLNXUTSCUIBQGB-UHFFFAOYSA-N 0.000 claims description 2
• AVAHZUUYBFUOPN-UHFFFAOYSA-N 2-chloro-2-fluoroacetaldehyde Chemical compound FC(Cl)C=O AVAHZUUYBFUOPN-UHFFFAOYSA-N 0.000 claims description 2
• DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 claims description 2
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• 108010024121 Janus Kinases Proteins 0.000 abstract description 31
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