MX2011010372A - Derivados de imidazo[2,1-b][1,3,4]tiadiazol. - Google Patents

Info

Publication number

MX2011010372A

MX2011010372A MX2011010372A MX2011010372A MX2011010372A MX 2011010372 A MX2011010372 A MX 2011010372A MX 2011010372 A MX2011010372 A MX 2011010372A MX 2011010372 A MX2011010372 A MX 2011010372A MX 2011010372 A MX2011010372 A MX 2011010372A

Authority

MX

Mexico

Prior art keywords

optionally substituted

substituents selected

mmol

alkyl

compound

Prior art date

2009-04-02

Links

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• UVNXNSUKKOLFBM-UHFFFAOYSA-N imidazo[2,1-b][1,3,4]thiadiazole Chemical class N1=CSC2=NC=CN21 UVNXNSUKKOLFBM-UHFFFAOYSA-N 0.000 title 1
• 150000001875 compounds Chemical class 0.000 claims abstract description 191
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 47
• 201000010099 disease Diseases 0.000 claims abstract description 34
• 150000002148 esters Chemical class 0.000 claims abstract description 33
• 206010028980 Neoplasm Diseases 0.000 claims abstract description 30
• 238000011282 treatment Methods 0.000 claims abstract description 30
• 150000001408 amides Chemical class 0.000 claims abstract description 27
• 150000003839 salts Chemical class 0.000 claims abstract description 25
• 201000011510 cancer Diseases 0.000 claims abstract description 24
• 239000012453 solvate Substances 0.000 claims abstract description 16
• 230000005764 inhibitory process Effects 0.000 claims abstract description 10
• 125000001424 substituent group Chemical group 0.000 claims description 129
• 239000000203 mixture Substances 0.000 claims description 101
• 125000001072 heteroaryl group Chemical group 0.000 claims description 69
• 125000003118 aryl group Chemical group 0.000 claims description 61
• 238000006243 chemical reaction Methods 0.000 claims description 60
• 125000000217 alkyl group Chemical group 0.000 claims description 59
• 229910052739 hydrogen Inorganic materials 0.000 claims description 58
• 239000001257 hydrogen Substances 0.000 claims description 47
• 125000005842 heteroatom Chemical group 0.000 claims description 40
• 238000000034 method Methods 0.000 claims description 38
• 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 37
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 36
• 229910052757 nitrogen Inorganic materials 0.000 claims description 30
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 29
• 125000005843 halogen group Chemical group 0.000 claims description 27
• 125000004429 atom Chemical group 0.000 claims description 26
• 125000001153 fluoro group Chemical group F* 0.000 claims description 26
• 229910052760 oxygen Inorganic materials 0.000 claims description 23
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 23
• 229910052717 sulfur Inorganic materials 0.000 claims description 19
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 18
• 239000001301 oxygen Substances 0.000 claims description 18
• 239000003814 drug Substances 0.000 claims description 17
• 238000002360 preparation method Methods 0.000 claims description 14
• 239000011593 sulfur Substances 0.000 claims description 14
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 13
• 208000035475 disorder Diseases 0.000 claims description 13
• 150000002431 hydrogen Chemical class 0.000 claims description 13
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 13
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• 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 6
• 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 5
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 5
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• LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 3
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• 125000004400 (C1-C12) alkyl group Chemical group 0.000 claims description 2
• 125000006582 (C5-C6) heterocycloalkyl group Chemical group 0.000 claims description 2
• 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 2
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• 102000020233 phosphotransferase Human genes 0.000 abstract description 19
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• 150000002632 lipids Chemical class 0.000 abstract description 12
• 102000038030 PI3Ks Human genes 0.000 abstract description 3
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 218
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 195
• -1 amino, sulfhydryl Chemical group 0.000 description 111
• 229910052796 boron Inorganic materials 0.000 description 106
• 229910001868 water Inorganic materials 0.000 description 101
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 94
• 239000000047 product Substances 0.000 description 93
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 92
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 90
• 238000000589 high-performance liquid chromatography-mass spectrometry Methods 0.000 description 79
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• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 60
• 238000005481 NMR spectroscopy Methods 0.000 description 56
• RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 50
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• 125000003762 3,4-dimethoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 description 33
• 239000012044 organic layer Substances 0.000 description 32
• 229910000027 potassium carbonate Inorganic materials 0.000 description 32
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• 101100030361 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) pph-3 gene Proteins 0.000 description 25
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• 238000004440 column chromatography Methods 0.000 description 24
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• 239000000243 solution Substances 0.000 description 22
• MQVHKBWFJUMWBG-UHFFFAOYSA-N 2-bromo-5-iodoimidazo[2,1-b][1,3,4]thiadiazole Chemical compound IC1=CN=C2SC(Br)=NN21 MQVHKBWFJUMWBG-UHFFFAOYSA-N 0.000 description 21
• 230000000694 effects Effects 0.000 description 21
• KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 20
• XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 20
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