PT2414369E - Derivados de imidazo[2,1-b][1,3,4]tiadiazol - Google Patents

Info

Publication number

PT2414369E

PT2414369E PT107153181T PT10715318T PT2414369E PT 2414369 E PT2414369 E PT 2414369E PT 107153181 T PT107153181 T PT 107153181T PT 10715318 T PT10715318 T PT 10715318T PT 2414369 E PT2414369 E PT 2414369E

Authority

PT

Portugal

Prior art keywords

imidazo

optionally substituted

thiadiazol

mmol

substituents selected

Prior art date

2009-04-02

Links

• Espacenet
• Global Dossier
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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 description 3
• 150000001875 compounds Chemical class 0.000 claims description 190
• 125000001424 substituent group Chemical group 0.000 claims description 125
• 239000000047 product Substances 0.000 claims description 96
• -1 Tert-Butyl-2- (4- (5- (6-amino-5- (trifluoromethyl) pyridin-3-yl) -6-methylimidazo [2,1- b] [1,3,4 ] thiadiazol-2-yl) -2-methoxyphenoxy) ethyl Chemical group 0.000 claims description 81
• 125000001072 heteroaryl group Chemical group 0.000 claims description 71
• 125000003118 aryl group Chemical group 0.000 claims description 58
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 52
• 229910052739 hydrogen Inorganic materials 0.000 claims description 52
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 51
• 239000001257 hydrogen Substances 0.000 claims description 48
• 238000006243 chemical reaction Methods 0.000 claims description 41
• 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 38
• 125000005842 heteroatom Chemical group 0.000 claims description 35
• 238000000034 method Methods 0.000 claims description 34
• 238000011282 treatment Methods 0.000 claims description 29
• 206010028980 Neoplasm Diseases 0.000 claims description 28
• 125000000217 alkyl group Chemical group 0.000 claims description 28
• 201000010099 disease Diseases 0.000 claims description 28
• 229910052757 nitrogen Inorganic materials 0.000 claims description 28
• 150000002148 esters Chemical class 0.000 claims description 27
• 125000004429 atom Chemical group 0.000 claims description 26
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 25
• 150000001408 amides Chemical class 0.000 claims description 25
• 125000002619 bicyclic group Chemical group 0.000 claims description 23
• 208000035475 disorder Diseases 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
• 150000003839 salts Chemical class 0.000 claims description 23
• 125000002950 monocyclic group Chemical group 0.000 claims description 22
• 201000011510 cancer Diseases 0.000 claims description 20
• 125000004122 cyclic group Chemical group 0.000 claims description 20
• 125000001153 fluoro group Chemical group F* 0.000 claims description 20
• 125000005843 halogen group Chemical group 0.000 claims description 20
• 229910052760 oxygen Inorganic materials 0.000 claims description 19
• 239000003814 drug Substances 0.000 claims description 17
• 150000002431 hydrogen Chemical class 0.000 claims description 16
• 230000008569 process Effects 0.000 claims description 16
• 229910052717 sulfur Inorganic materials 0.000 claims description 16
• 239000012453 solvate Substances 0.000 claims description 15
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 13
• 239000002671 adjuvant Substances 0.000 claims description 12
• 239000003085 diluting agent Substances 0.000 claims description 12
• 239000008194 pharmaceutical composition Substances 0.000 claims description 12
• 229940124597 therapeutic agent Drugs 0.000 claims description 10
• 238000004519 manufacturing process Methods 0.000 claims description 9
• 230000002062 proliferating effect Effects 0.000 claims description 9
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 7
• 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 claims description 7
• 201000001320 Atherosclerosis Diseases 0.000 claims description 7
• 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 6
• 230000004663 cell proliferation Effects 0.000 claims description 6
• 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 6
• 238000002360 preparation method Methods 0.000 claims description 6
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• 210000000988 bone and bone Anatomy 0.000 claims description 4
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• AKQNKCWKASWGJF-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-(2-methylsulfanylpyrimidin-5-yl)imidazo[2,1-b][1,3,4]thiadiazole Chemical compound C1=C(OC)C(OC)=CC=C1C(S1)=NN2C1=NC=C2C1=CN=C(SC)N=C1 AKQNKCWKASWGJF-UHFFFAOYSA-N 0.000 claims description 3
• RWWQTLSCTIVVRI-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-(2-methylsulfinylpyrimidin-5-yl)imidazo[2,1-b][1,3,4]thiadiazole Chemical compound C1=C(OC)C(OC)=CC=C1C(S1)=NN2C1=NC=C2C1=CN=C(S(C)=O)N=C1 RWWQTLSCTIVVRI-UHFFFAOYSA-N 0.000 claims description 3
• RIEWWHCPDPFGRL-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-(2-piperazin-1-ylpyrimidin-5-yl)imidazo[2,1-b][1,3,4]thiadiazole Chemical compound C1=C(OC)C(OC)=CC=C1C(S1)=NN2C1=NC=C2C1=CN=C(N2CCNCC2)N=C1 RIEWWHCPDPFGRL-UHFFFAOYSA-N 0.000 claims description 3
• ZMXPAPWWMBZNTB-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-(6-methoxypyridin-3-yl)-6-methylimidazo[2,1-b][1,3,4]thiadiazole Chemical compound C1=NC(OC)=CC=C1C1=C(C)N=C2N1N=C(C=1C=C(OC)C(OC)=CC=1)S2 ZMXPAPWWMBZNTB-UHFFFAOYSA-N 0.000 claims description 3
• 125000000041 C6-C10 aryl group Chemical group 0.000 claims description 3
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• 230000001066 destructive effect Effects 0.000 claims description 3
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• 208000015768 polyposis Diseases 0.000 claims description 3
• 208000037803 restenosis Diseases 0.000 claims description 3
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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
• 229960004072 thrombin Drugs 0.000 claims description 3
• 238000002054 transplantation Methods 0.000 claims description 3
• 125000004400 (C1-C12) alkyl group Chemical group 0.000 claims description 2
• 125000006582 (C5-C6) heterocycloalkyl group Chemical group 0.000 claims description 2
• YBPINIBANNZBJJ-UHFFFAOYSA-N 2,4-difluoro-n-[2-methoxy-5-(5-pyridazin-4-ylimidazo[2,1-b][1,3,4]thiadiazol-2-yl)pyridin-3-yl]benzenesulfonamide Chemical compound COC1=NC=C(C=2SC3=NC=C(N3N=2)C=2C=NN=CC=2)C=C1NS(=O)(=O)C1=CC=C(F)C=C1F YBPINIBANNZBJJ-UHFFFAOYSA-N 0.000 claims description 2
• ZUQBOFLJCDUPLL-UHFFFAOYSA-N 2,5-bis(3,4-dimethoxyphenyl)-6-methylimidazo[2,1-b][1,3,4]thiadiazole Chemical compound C1=C(OC)C(OC)=CC=C1C(S1)=NN2C1=NC(C)=C2C1=CC=C(OC)C(OC)=C1 ZUQBOFLJCDUPLL-UHFFFAOYSA-N 0.000 claims description 2
• RSFFPCCWMHUQLL-UHFFFAOYSA-N 2,5-bis(3,4-dimethoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazole Chemical compound C1=C(OC)C(OC)=CC=C1C(S1)=NN2C1=NC=C2C1=CC=C(OC)C(OC)=C1 RSFFPCCWMHUQLL-UHFFFAOYSA-N 0.000 claims description 2
• HUTMTGYICXIPIA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-(3-fluoro-4-methylsulfonylphenyl)-6-methylimidazo[2,1-b][1,3,4]thiadiazole Chemical compound C1=C(OC)C(OC)=CC=C1C(S1)=NN2C1=NC(C)=C2C1=CC=C(S(C)(=O)=O)C(F)=C1 HUTMTGYICXIPIA-UHFFFAOYSA-N 0.000 claims description 2
• LZOMSHMFRHDKIM-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-(5-methoxypyridin-3-yl)imidazo[2,1-b][1,3,4]thiadiazole Chemical compound COC1=CN=CC(C=2N3N=C(SC3=NC=2)C=2C=C(OC)C(OC)=CC=2)=C1 LZOMSHMFRHDKIM-UHFFFAOYSA-N 0.000 claims description 2
• IAGZELQWGJLYMJ-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-[2-(4-methylpiperazin-1-yl)pyrimidin-5-yl]imidazo[2,1-b][1,3,4]thiadiazole Chemical compound C1=C(OC)C(OC)=CC=C1C(S1)=NN2C1=NC=C2C1=CN=C(N2CCN(C)CC2)N=C1 IAGZELQWGJLYMJ-UHFFFAOYSA-N 0.000 claims description 2
• TYUAFSOVSKDGIB-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-[6-(4-methylpiperazin-1-yl)-5-(trifluoromethyl)pyridin-3-yl]imidazo[2,1-b][1,3,4]thiadiazole Chemical compound C1=C(OC)C(OC)=CC=C1C(S1)=NN2C1=NC=C2C(C=C1C(F)(F)F)=CN=C1N1CCN(C)CC1 TYUAFSOVSKDGIB-UHFFFAOYSA-N 0.000 claims description 2
• OMOMOEILAGAXCG-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-[6-piperazin-1-yl-5-(trifluoromethyl)pyridin-3-yl]imidazo[2,1-b][1,3,4]thiadiazole Chemical compound C1=C(OC)C(OC)=CC=C1C(S1)=NN2C1=NC=C2C(C=C1C(F)(F)F)=CN=C1N1CCNCC1 OMOMOEILAGAXCG-UHFFFAOYSA-N 0.000 claims description 2
• RSNYNBZETHZDBU-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-6-methyl-5-pyridin-3-ylimidazo[2,1-b][1,3,4]thiadiazole Chemical compound C1=C(OC)C(OC)=CC=C1C(S1)=NN2C1=NC(C)=C2C1=CC=CN=C1 RSNYNBZETHZDBU-UHFFFAOYSA-N 0.000 claims description 2
• NWZFUZORNWLJOQ-UHFFFAOYSA-N 2-(3-methoxy-4-piperidin-4-yloxyphenyl)-5-(6-methoxypyridin-3-yl)imidazo[2,1-b][1,3,4]thiadiazole Chemical compound C1=NC(OC)=CC=C1C1=CN=C2N1N=C(C=1C=C(OC)C(OC3CCNCC3)=CC=1)S2 NWZFUZORNWLJOQ-UHFFFAOYSA-N 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
• QWFJSMCERPTIKB-UHFFFAOYSA-N 5-[2-(3,4-dimethoxyphenyl)-6-methylimidazo[2,1-b][1,3,4]thiadiazol-5-yl]-1h-pyridin-2-one Chemical compound C1=C(OC)C(OC)=CC=C1C(S1)=NN2C1=NC(C)=C2C1=CC=C(O)N=C1 QWFJSMCERPTIKB-UHFFFAOYSA-N 0.000 claims description 2
• BYZDTGPFYDEWOP-UHFFFAOYSA-N 5-[2-(3,4-dimethoxyphenyl)-6-methylimidazo[2,1-b][1,3,4]thiadiazol-5-yl]-3-(trifluoromethyl)pyridin-2-amine Chemical compound C1=C(OC)C(OC)=CC=C1C(S1)=NN2C1=NC(C)=C2C1=CN=C(N)C(C(F)(F)F)=C1 BYZDTGPFYDEWOP-UHFFFAOYSA-N 0.000 claims description 2
• AENJYOUQPLPPMH-UHFFFAOYSA-N 5-[2-(3,4-dimethoxyphenyl)-6-methylimidazo[2,1-b][1,3,4]thiadiazol-5-yl]pyridine-2-carbonitrile Chemical compound C1=C(OC)C(OC)=CC=C1C(S1)=NN2C1=NC(C)=C2C1=CC=C(C#N)N=C1 AENJYOUQPLPPMH-UHFFFAOYSA-N 0.000 claims description 2
• LQKQKJIRALJYEC-UHFFFAOYSA-N 5-[2-(3,4-dimethoxyphenyl)-6-methylimidazo[2,1-b][1,3,4]thiadiazol-5-yl]pyrimidin-2-amine Chemical compound C1=C(OC)C(OC)=CC=C1C(S1)=NN2C1=NC(C)=C2C1=CN=C(N)N=C1 LQKQKJIRALJYEC-UHFFFAOYSA-N 0.000 claims description 2
• NJNVCRQDBBXSPC-UHFFFAOYSA-N 5-[2-(3,4-dimethoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl]pyridine-2-carbonitrile Chemical compound C1=C(OC)C(OC)=CC=C1C(S1)=NN2C1=NC=C2C1=CC=C(C#N)N=C1 NJNVCRQDBBXSPC-UHFFFAOYSA-N 0.000 claims description 2
• UAQOVZOKHHGSKX-UHFFFAOYSA-N 5-[5-(4-methylsulfonylphenyl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl]-3-(trifluoromethyl)pyridin-2-amine Chemical compound C1=CC(S(=O)(=O)C)=CC=C1C1=CN=C2N1N=C(C=1C=C(C(N)=NC=1)C(F)(F)F)S2 UAQOVZOKHHGSKX-UHFFFAOYSA-N 0.000 claims description 2
• USYWDCIKSBYJOL-UHFFFAOYSA-N 5-[5-(6-fluoropyridin-3-yl)imidazo[2,1-b][1,3,4]thiadiazol-2-yl]-3-(trifluoromethyl)pyridin-2-amine Chemical compound C1=C(C(F)(F)F)C(N)=NC=C1C(S1)=NN2C1=NC=C2C1=CC=C(F)N=C1 USYWDCIKSBYJOL-UHFFFAOYSA-N 0.000 claims description 2
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• KDUXFZBQLUGABF-UHFFFAOYSA-N n-[3-[5-[6-amino-5-(trifluoromethyl)pyridin-3-yl]imidazo[2,1-b][1,3,4]thiadiazol-2-yl]phenyl]methanesulfonamide Chemical compound CS(=O)(=O)NC1=CC=CC(C=2SC3=NC=C(N3N=2)C=2C=C(C(N)=NC=2)C(F)(F)F)=C1 KDUXFZBQLUGABF-UHFFFAOYSA-N 0.000 claims description 2
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• BRXLDWIKOGTBQT-UHFFFAOYSA-N 2-[4-[5-[6-amino-5-(trifluoromethyl)pyridin-3-yl]-6-methylimidazo[2,1-b][1,3,4]thiadiazol-2-yl]-2-methoxyphenoxy]-n,n-dimethylacetamide Chemical compound C1=C(OCC(=O)N(C)C)C(OC)=CC(C=2SC3=NC(C)=C(N3N=2)C=2C=C(C(N)=NC=2)C(F)(F)F)=C1 BRXLDWIKOGTBQT-UHFFFAOYSA-N 0.000 claims 1
• QXVYXFLTVOHZHN-UHFFFAOYSA-N 5-[2-(3-methoxy-4-piperidin-4-yloxyphenyl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl]-3-(trifluoromethyl)pyridin-2-amine Chemical compound COC1=CC(C=2SC3=NC=C(N3N=2)C=2C=C(C(N)=NC=2)C(F)(F)F)=CC=C1OC1CCNCC1 QXVYXFLTVOHZHN-UHFFFAOYSA-N 0.000 claims 1
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• OCSQYJPBIKNLOZ-UHFFFAOYSA-N 5-[2-[3-methoxy-4-(2-morpholin-4-ylethoxy)phenyl]-6-methylimidazo[2,1-b][1,3,4]thiadiazol-5-yl]-3-(trifluoromethyl)pyridin-2-amine Chemical compound COC1=CC(C=2SC3=NC(C)=C(N3N=2)C=2C=C(C(N)=NC=2)C(F)(F)F)=CC=C1OCCN1CCOCC1 OCSQYJPBIKNLOZ-UHFFFAOYSA-N 0.000 claims 1
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