EA022753B1 - Имидазотиадиазолы для применения в качестве ингибиторов киназ - Google Patents

Info

Publication number

EA022753B1

EA022753B1 EA201101435A EA201101435A EA022753B1 EA 022753 B1 EA022753 B1 EA 022753B1 EA 201101435 A EA201101435 A EA 201101435A EA 201101435 A EA201101435 A EA 201101435A EA 022753 B1 EA022753 B1 EA 022753B1

Authority

EA

Eurasian Patent Office

Prior art keywords

imidazo

thiadiazol

trifluoromethylpyridin

mmol

dimethoxyphenyl

Prior art date

2009-04-02

Links

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• 108091000080 Phosphotransferase Proteins 0.000 title abstract description 24
• 102000020233 phosphotransferase Human genes 0.000 title abstract description 24
• BOXRDDIXJOUZLV-UHFFFAOYSA-N 2h-imidazo[4,5-d]thiadiazole Chemical class N1SC2=NC=NC2=N1 BOXRDDIXJOUZLV-UHFFFAOYSA-N 0.000 title description 11
• 239000003112 inhibitor Substances 0.000 title description 7
• 150000001875 compounds Chemical class 0.000 claims abstract description 191
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 34
• 206010028980 Neoplasm Diseases 0.000 claims abstract description 30
• 150000002148 esters Chemical class 0.000 claims abstract description 29
• 150000001408 amides Chemical class 0.000 claims abstract description 28
• 150000003839 salts Chemical class 0.000 claims abstract description 26
• 201000011510 cancer Diseases 0.000 claims abstract description 24
• 201000010099 disease Diseases 0.000 claims abstract description 24
• 238000011282 treatment Methods 0.000 claims abstract description 18
• 239000012453 solvate Substances 0.000 claims abstract description 14
• 230000005764 inhibitory process Effects 0.000 claims abstract description 9
• 125000001424 substituent group Chemical group 0.000 claims description 107
• 239000000203 mixture Substances 0.000 claims description 99
• -1 fluorine) Chemical class 0.000 claims description 75
• 125000000217 alkyl group Chemical group 0.000 claims description 67
• 125000001072 heteroaryl group Chemical group 0.000 claims description 50
• 229910052739 hydrogen Inorganic materials 0.000 claims description 49
• 239000001257 hydrogen Substances 0.000 claims description 45
• 125000003118 aryl group Chemical group 0.000 claims description 38
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 37
• 125000005842 heteroatom Chemical group 0.000 claims description 35
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 30
• 238000000034 method Methods 0.000 claims description 28
• 229910052757 nitrogen Inorganic materials 0.000 claims description 28
• 229910052700 potassium Inorganic materials 0.000 claims description 28
• 125000004429 atom Chemical group 0.000 claims description 26
• 229910052736 halogen Inorganic materials 0.000 claims description 25
• 150000002367 halogens Chemical class 0.000 claims description 25
• 230000015572 biosynthetic process Effects 0.000 claims description 22
• 229910052760 oxygen Inorganic materials 0.000 claims description 22
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 21
• 229910052731 fluorine Inorganic materials 0.000 claims description 21
• 239000011737 fluorine Substances 0.000 claims description 21
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 21
• 125000002619 bicyclic group Chemical group 0.000 claims description 20
• 125000002950 monocyclic group Chemical group 0.000 claims description 19
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 16
• 239000001301 oxygen Substances 0.000 claims description 16
• 102000001253 Protein Kinase Human genes 0.000 claims description 15
• 108060006633 protein kinase Proteins 0.000 claims description 15
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 13
• 239000008194 pharmaceutical composition Substances 0.000 claims description 12
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 11
• 239000003814 drug Substances 0.000 claims description 11
• 229910052717 sulfur Inorganic materials 0.000 claims description 11
• 239000011593 sulfur Substances 0.000 claims description 11
• 239000002671 adjuvant Substances 0.000 claims description 10
• 239000003085 diluting agent Substances 0.000 claims description 10
• 125000001153 fluoro group Chemical group F* 0.000 claims description 10
• 150000002431 hydrogen Chemical class 0.000 claims description 7
• 230000003993 interaction Effects 0.000 claims description 7
• 125000006273 (C1-C3) alkyl group Chemical group 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
• 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 5
• 125000004432 carbon atom Chemical group C* 0.000 claims description 5
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 4
• 238000004519 manufacturing process Methods 0.000 claims description 4
• 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
• 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 3
• 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims description 3
• XGDIPYSICGUMJK-UHFFFAOYSA-N tert-butyl 5-[5-[6-amino-5-(trifluoromethyl)pyridin-3-yl]imidazo[2,1-b][1,3,4]thiadiazol-2-yl]-2-oxospiro[1h-indole-3,4'-piperidine]-1'-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC21C1=CC(C=3SC4=NC=C(N4N=3)C=3C=C(C(N)=NC=3)C(F)(F)F)=CC=C1NC2=O XGDIPYSICGUMJK-UHFFFAOYSA-N 0.000 claims description 3
• 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
• 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
• PZUXOIHEQQTURR-UHFFFAOYSA-N 2-amino-5-[2-(3,4-dimethoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl]pyridine-3-carbonitrile Chemical compound C1=C(OC)C(OC)=CC=C1C(S1)=NN2C1=NC=C2C1=CN=C(N)C(C#N)=C1 PZUXOIHEQQTURR-UHFFFAOYSA-N 0.000 claims description 2
• UWARFAZJBCXUAH-UHFFFAOYSA-N 3-[5-[6-amino-5-(trifluoromethyl)pyridin-3-yl]imidazo[2,1-b][1,3,4]thiadiazol-2-yl]benzamide Chemical compound NC(=O)C1=CC=CC(C=2SC3=NC=C(N3N=2)C=2C=C(C(N)=NC=2)C(F)(F)F)=C1 UWARFAZJBCXUAH-UHFFFAOYSA-N 0.000 claims description 2
• VCDSWCOJROIKSV-UHFFFAOYSA-N 3-[5-[6-amino-5-(trifluoromethyl)pyridin-3-yl]imidazo[2,1-b][1,3,4]thiadiazol-2-yl]benzonitrile Chemical compound C1=C(C(F)(F)F)C(N)=NC=C1C1=CN=C2N1N=C(C=1C=C(C=CC=1)C#N)S2 VCDSWCOJROIKSV-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
• KZGFUDRECRXYET-UHFFFAOYSA-N 5-[2-(1-ethylpyrazol-4-yl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl]-3-(trifluoromethyl)pyridin-2-amine Chemical compound C1=NN(CC)C=C1C(S1)=NN2C1=NC=C2C1=CN=C(N)C(C(F)(F)F)=C1 KZGFUDRECRXYET-UHFFFAOYSA-N 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
• 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 description 2
• ZOLVBLFHQQAYHY-UHFFFAOYSA-N 5-[2-(3-methoxy-4-piperidin-4-yloxyphenyl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl]pyrimidin-2-amine Chemical compound COC1=CC(C=2SC3=NC=C(N3N=2)C=2C=NC(N)=NC=2)=CC=C1OC1CCNCC1 ZOLVBLFHQQAYHY-UHFFFAOYSA-N 0.000 claims description 2
• KWRFIVPQEUSIQV-UHFFFAOYSA-N 5-[2-(3-methoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl]-3-(trifluoromethyl)pyridin-2-amine Chemical compound COC1=CC=CC(C=2SC3=NC=C(N3N=2)C=2C=C(C(N)=NC=2)C(F)(F)F)=C1 KWRFIVPQEUSIQV-UHFFFAOYSA-N 0.000 claims description 2
• QWSACUPFDITMLU-UHFFFAOYSA-N 5-[2-(3-methylsulfonylphenyl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl]-3-(trifluoromethyl)pyridin-2-amine Chemical compound CS(=O)(=O)C1=CC=CC(C=2SC3=NC=C(N3N=2)C=2C=C(C(N)=NC=2)C(F)(F)F)=C1 QWSACUPFDITMLU-UHFFFAOYSA-N 0.000 claims description 2
• LJYVZFARGSUJCH-UHFFFAOYSA-N 5-[2-(4-methoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl]-3-(trifluoromethyl)pyridin-2-amine Chemical compound C1=CC(OC)=CC=C1C(S1)=NN2C1=NC=C2C1=CN=C(N)C(C(F)(F)F)=C1 LJYVZFARGSUJCH-UHFFFAOYSA-N 0.000 claims description 2
• COZZXMRJMOFWRL-UHFFFAOYSA-N 5-[2-(4-methylpyridin-3-yl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl]-3-(trifluoromethyl)pyridin-2-amine Chemical compound CC1=CC=NC=C1C(S1)=NN2C1=NC=C2C1=CN=C(N)C(C(F)(F)F)=C1 COZZXMRJMOFWRL-UHFFFAOYSA-N 0.000 claims description 2
• IADDDQNVAOFGGG-UHFFFAOYSA-N 5-[2-(4-morpholin-4-ylsulfonylphenyl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl]-3-(trifluoromethyl)pyridin-2-amine Chemical compound C1=C(C(F)(F)F)C(N)=NC=C1C1=CN=C2N1N=C(C=1C=CC(=CC=1)S(=O)(=O)N1CCOCC1)S2 IADDDQNVAOFGGG-UHFFFAOYSA-N 0.000 claims description 2
• UPYPASZOSPAMEB-UHFFFAOYSA-N 5-[2-(5-methoxypyridin-3-yl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl]-3-(trifluoromethyl)pyridin-2-amine Chemical compound COC1=CN=CC(C=2SC3=NC=C(N3N=2)C=2C=C(C(N)=NC=2)C(F)(F)F)=C1 UPYPASZOSPAMEB-UHFFFAOYSA-N 0.000 claims description 2
• IPSDTCAVEMBNQA-UHFFFAOYSA-N 5-[2-(6-methylpyridin-3-yl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl]-3-(trifluoromethyl)pyridin-2-amine Chemical compound C1=NC(C)=CC=C1C(S1)=NN2C1=NC=C2C1=CN=C(N)C(C(F)(F)F)=C1 IPSDTCAVEMBNQA-UHFFFAOYSA-N 0.000 claims description 2
• LLSSEDSCHHDSLG-UHFFFAOYSA-N 5-[2-[3-(dimethylamino)phenyl]imidazo[2,1-b][1,3,4]thiadiazol-5-yl]-3-(trifluoromethyl)pyridin-2-amine Chemical compound CN(C)C1=CC=CC(C=2SC3=NC=C(N3N=2)C=2C=C(C(N)=NC=2)C(F)(F)F)=C1 LLSSEDSCHHDSLG-UHFFFAOYSA-N 0.000 claims description 2
• 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 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
• JNIZCLWHOMQGII-UHFFFAOYSA-N 5-[5-[6-amino-5-(trifluoromethyl)pyridin-3-yl]imidazo[2,1-b][1,3,4]thiadiazol-2-yl]spiro[1h-indole-3,4'-piperidine]-2-one Chemical compound C1=C(C(F)(F)F)C(N)=NC=C1C1=CN=C2N1N=C(C=1C=C3C4(CCNCC4)C(=O)NC3=CC=1)S2 JNIZCLWHOMQGII-UHFFFAOYSA-N 0.000 claims description 2
• GHWVXCQZPNWFRO-UHFFFAOYSA-N butane-2,3-diamine Chemical compound CC(N)C(C)N GHWVXCQZPNWFRO-UHFFFAOYSA-N 0.000 claims description 2
• DHYKYBOWIVIKSA-UHFFFAOYSA-N tert-butyl n-[2-[4-[5-[6-amino-5-(trifluoromethyl)pyridin-3-yl]-6-methylimidazo[2,1-b][1,3,4]thiadiazol-2-yl]-2-methoxyphenoxy]ethyl]carbamate Chemical compound C1=C(OCCNC(=O)OC(C)(C)C)C(OC)=CC(C=2SC3=NC(C)=C(N3N=2)C=2C=C(C(N)=NC=2)C(F)(F)F)=C1 DHYKYBOWIVIKSA-UHFFFAOYSA-N 0.000 claims description 2
• JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 claims 3
• 125000006168 tricyclic group Chemical group 0.000 claims 2
• YDATXJNKCGEXCJ-UHFFFAOYSA-N 5-(2-pyridin-3-ylimidazo[2,1-b][1,3,4]thiadiazol-5-yl)-3-(trifluoromethyl)pyridin-2-amine Chemical compound C1=C(C(F)(F)F)C(N)=NC=C1C1=CN=C2N1N=C(C=1C=NC=CC=1)S2 YDATXJNKCGEXCJ-UHFFFAOYSA-N 0.000 claims 1
• RVPDONJLFXIZQS-UHFFFAOYSA-N 5-[2-(1h-indol-5-yl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl]-3-(trifluoromethyl)pyridin-2-amine Chemical compound C1=C(C(F)(F)F)C(N)=NC=C1C1=CN=C2N1N=C(C=1C=C3C=CNC3=CC=1)S2 RVPDONJLFXIZQS-UHFFFAOYSA-N 0.000 claims 1
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 1
• 230000002401 inhibitory effect Effects 0.000 claims 1
• IQFGMQLPJKPSCL-UHFFFAOYSA-N n-(trifluoromethyl)pyridin-2-amine Chemical compound FC(F)(F)NC1=CC=CC=N1 IQFGMQLPJKPSCL-UHFFFAOYSA-N 0.000 claims 1
• 239000008177 pharmaceutical agent Substances 0.000 claims 1
• 150000002632 lipids Chemical class 0.000 abstract description 12
• 102000004169 proteins and genes Human genes 0.000 abstract description 4
• 108090000623 proteins and genes Proteins 0.000 abstract description 4
• 102000038030 PI3Ks Human genes 0.000 abstract 1
• 108091007960 PI3Ks Proteins 0.000 abstract 1
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 180
• 229910052796 boron Inorganic materials 0.000 description 108
• 239000000047 product Substances 0.000 description 107
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 97
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 90
• 238000000589 high-performance liquid chromatography-mass spectrometry Methods 0.000 description 77
• 239000002904 solvent Substances 0.000 description 66
• 239000007787 solid Substances 0.000 description 64
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 59
• 238000006243 chemical reaction Methods 0.000 description 47
• 239000011541 reaction mixture Substances 0.000 description 46
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 42
• 239000000543 intermediate Substances 0.000 description 38
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