EA017406B1 - Производные индола в качестве агонистов рецептора s1p1 - Google Patents

Info

Publication number

EA017406B1

EA017406B1 EA200970612A EA200970612A EA017406B1 EA 017406 B1 EA017406 B1 EA 017406B1 EA 200970612 A EA200970612 A EA 200970612A EA 200970612 A EA200970612 A EA 200970612A EA 017406 B1 EA017406 B1 EA 017406B1

Authority

EA

Eurasian Patent Office

Prior art keywords

indol

oxadiazol

phenyl

chloro

oxy

Prior art date

2006-12-21

Links

• Espacenet
• Global Dossier
• Discuss

• 239000000018 receptor agonist Substances 0.000 title claims description 6
• 229940044601 receptor agonist Drugs 0.000 title claims description 6
• 102000011011 Sphingosine 1-phosphate receptors Human genes 0.000 title abstract 2
• 108050001083 Sphingosine 1-phosphate receptors Proteins 0.000 title abstract 2
• 229940054051 antipsychotic indole derivative Drugs 0.000 title 1
• 150000002475 indoles Chemical class 0.000 title 1
• 150000001875 compounds Chemical class 0.000 claims abstract description 269
• 238000000034 method Methods 0.000 claims abstract description 49
• 238000011282 treatment Methods 0.000 claims abstract description 15
• 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 14
• 239000001257 hydrogen Substances 0.000 claims abstract description 8
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 7
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 7
• 230000001404 mediated effect Effects 0.000 claims abstract description 6
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 41
• 150000003839 salts Chemical class 0.000 claims description 40
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 20
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 12
• 229910052736 halogen Inorganic materials 0.000 claims description 12
• 125000000217 alkyl group Chemical group 0.000 claims description 10
• 230000000694 effects Effects 0.000 claims description 10
• 150000002367 halogens Chemical class 0.000 claims description 10
• 201000006417 multiple sclerosis Diseases 0.000 claims description 9
• CYJOQZWKLYLDNB-UHFFFAOYSA-N 3-[5-[5-[4-phenyl-5-(trifluoromethyl)thiophen-2-yl]-1,2,4-oxadiazol-3-yl]indol-1-yl]propanoic acid Chemical compound C=1C=C2N(CCC(=O)O)C=CC2=CC=1C(N=1)=NOC=1C(SC=1C(F)(F)F)=CC=1C1=CC=CC=C1 CYJOQZWKLYLDNB-UHFFFAOYSA-N 0.000 claims description 7
• FLERAFQOOGRXHE-UHFFFAOYSA-N 3-[4-[5-(5-chloro-6-propan-2-yloxypyridin-3-yl)-1,2,4-oxadiazol-3-yl]indol-1-yl]propanoic acid Chemical compound C1=C(Cl)C(OC(C)C)=NC=C1C1=NC(C=2C=3C=CN(CCC(O)=O)C=3C=CC=2)=NO1 FLERAFQOOGRXHE-UHFFFAOYSA-N 0.000 claims description 6
• QFOCXKVUZZDCDL-UHFFFAOYSA-N 3-[5-[5-(3-chloro-4-propan-2-yloxyphenyl)-1,2,4-oxadiazol-3-yl]indol-1-yl]propanoic acid Chemical compound C1=C(Cl)C(OC(C)C)=CC=C1C1=NC(C=2C=C3C=CN(CCC(O)=O)C3=CC=2)=NO1 QFOCXKVUZZDCDL-UHFFFAOYSA-N 0.000 claims description 5
• 125000003545 alkoxy group Chemical group 0.000 claims description 5
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 5
• CFVKJJOPIKDXIF-UHFFFAOYSA-N 3-[4-[5-[3-chloro-4-(trifluoromethoxy)phenyl]-1,2,4-oxadiazol-3-yl]indol-1-yl]propanoic acid Chemical compound C1=CC=C2N(CCC(=O)O)C=CC2=C1C(N=1)=NOC=1C1=CC=C(OC(F)(F)F)C(Cl)=C1 CFVKJJOPIKDXIF-UHFFFAOYSA-N 0.000 claims description 4
• ISNSOGPOJKUJJB-UHFFFAOYSA-N 3-[4-[5-[4-phenyl-5-(trifluoromethyl)thiophen-2-yl]-1,2,4-oxadiazol-3-yl]indol-1-yl]propanoic acid Chemical compound C1=CC=C2N(CCC(=O)O)C=CC2=C1C(N=1)=NOC=1C(SC=1C(F)(F)F)=CC=1C1=CC=CC=C1 ISNSOGPOJKUJJB-UHFFFAOYSA-N 0.000 claims description 4
• HCWIAVVSUBERJZ-UHFFFAOYSA-N 3-[5-[5-(3-chloro-4-propan-2-yloxyphenyl)-1,2,4-oxadiazol-3-yl]indol-1-yl]-2,2,3-trifluoropropanoic acid Chemical compound C1=C(Cl)C(OC(C)C)=CC=C1C1=NC(C=2C=C3C=CN(C3=CC=2)C(F)C(F)(F)C(O)=O)=NO1 HCWIAVVSUBERJZ-UHFFFAOYSA-N 0.000 claims description 4
• RAXQVKOQRHWHOU-UHFFFAOYSA-N 3-[5-[5-[3-phenyl-4-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-3-yl]indol-1-yl]propanoic acid Chemical compound C=1C=C2N(CCC(=O)O)C=CC2=CC=1C(N=1)=NOC=1C(C=1)=CC=C(C(F)(F)F)C=1C1=CC=CC=C1 RAXQVKOQRHWHOU-UHFFFAOYSA-N 0.000 claims description 4
• NFIGDBFIDKDNIG-UHFFFAOYSA-N 4-[4-[5-(5-chloro-6-propan-2-yloxypyridin-3-yl)-1,2,4-oxadiazol-3-yl]indol-1-yl]butanoic acid Chemical compound C1=C(Cl)C(OC(C)C)=NC=C1C1=NC(C=2C=3C=CN(CCCC(O)=O)C=3C=CC=2)=NO1 NFIGDBFIDKDNIG-UHFFFAOYSA-N 0.000 claims description 4
• 239000003814 drug Substances 0.000 claims description 4
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
• CDRBYCWJUGAZCB-UHFFFAOYSA-N 3-[3-chloro-5-[5-[4-phenyl-5-(trifluoromethyl)thiophen-2-yl]-1,2,4-oxadiazol-3-yl]indol-1-yl]propanoic acid Chemical compound C=1C=C2N(CCC(=O)O)C=C(Cl)C2=CC=1C(N=1)=NOC=1C(SC=1C(F)(F)F)=CC=1C1=CC=CC=C1 CDRBYCWJUGAZCB-UHFFFAOYSA-N 0.000 claims description 3
• JWIKJHGBIFHLPM-UHFFFAOYSA-N 3-[4-[5-(3-chloro-4-propan-2-yloxyphenyl)-1,2,4-oxadiazol-3-yl]indol-1-yl]propanoic acid Chemical compound C1=C(Cl)C(OC(C)C)=CC=C1C1=NC(C=2C=3C=CN(CCC(O)=O)C=3C=CC=2)=NO1 JWIKJHGBIFHLPM-UHFFFAOYSA-N 0.000 claims description 3
• 241000124008 Mammalia Species 0.000 claims description 3
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 3
• 239000003937 drug carrier Substances 0.000 claims description 3
• 238000004519 manufacturing process Methods 0.000 claims description 3
• 125000004076 pyridyl group Chemical group 0.000 claims description 3
• 125000001544 thienyl group Chemical group 0.000 claims description 3
• JDKAJAKVJGLQIO-UHFFFAOYSA-N 2,2-dimethyl-3-[5-[5-[4-phenyl-5-(trifluoromethyl)thiophen-2-yl]-1,2,4-oxadiazol-3-yl]indol-1-yl]propanoic acid Chemical class C=1C=C2N(CC(C)(C)C(O)=O)C=CC2=CC=1C(N=1)=NOC=1C(SC=1C(F)(F)F)=CC=1C1=CC=CC=C1 JDKAJAKVJGLQIO-UHFFFAOYSA-N 0.000 claims description 2
• QDKQSBXYKYZLMW-UHFFFAOYSA-N 2-[4-[5-(3-chloro-4-propan-2-yloxyphenyl)-1,2,4-oxadiazol-3-yl]indol-1-yl]acetic acid Chemical compound C1=C(Cl)C(OC(C)C)=CC=C1C1=NC(C=2C=3C=CN(CC(O)=O)C=3C=CC=2)=NO1 QDKQSBXYKYZLMW-UHFFFAOYSA-N 0.000 claims description 2
• JNCSFNYUKWYUDF-UHFFFAOYSA-N 2-[4-[5-(3-cyano-4-propan-2-yloxyphenyl)-1,2,4-oxadiazol-3-yl]indol-1-yl]acetic acid Chemical compound C1=C(C#N)C(OC(C)C)=CC=C1C1=NC(C=2C=3C=CN(CC(O)=O)C=3C=CC=2)=NO1 JNCSFNYUKWYUDF-UHFFFAOYSA-N 0.000 claims description 2
• JQVFIRYJMBZLQN-UHFFFAOYSA-N 2-[5-[5-[4-phenyl-5-(trifluoromethyl)thiophen-2-yl]-1,2,4-oxadiazol-3-yl]indol-1-yl]acetic acid Chemical compound C=1C=C2N(CC(=O)O)C=CC2=CC=1C(N=1)=NOC=1C(SC=1C(F)(F)F)=CC=1C1=CC=CC=C1 JQVFIRYJMBZLQN-UHFFFAOYSA-N 0.000 claims description 2
• GZCAFNMJWRFCPB-UHFFFAOYSA-N 3-[3-bromo-5-[5-(3-chloro-4-propan-2-yloxyphenyl)-1,2,4-oxadiazol-3-yl]indol-1-yl]propanoic acid Chemical compound C1=C(Cl)C(OC(C)C)=CC=C1C1=NC(C=2C=C3C(Br)=CN(CCC(O)=O)C3=CC=2)=NO1 GZCAFNMJWRFCPB-UHFFFAOYSA-N 0.000 claims description 2
• IHFJSTWVWRLHRP-UHFFFAOYSA-N 3-[3-chloro-4-[5-[4-phenyl-5-(trifluoromethyl)thiophen-2-yl]-1,2,4-oxadiazol-3-yl]indol-1-yl]propanoic acid Chemical compound C1=CC=C2N(CCC(=O)O)C=C(Cl)C2=C1C(N=1)=NOC=1C(SC=1C(F)(F)F)=CC=1C1=CC=CC=C1 IHFJSTWVWRLHRP-UHFFFAOYSA-N 0.000 claims description 2
• ATRHHCBTXLJODU-UHFFFAOYSA-N 3-[3-chloro-5-[5-(3-chloro-4-ethoxyphenyl)-1,2,4-oxadiazol-3-yl]indol-1-yl]propanoic acid Chemical compound C1=C(Cl)C(OCC)=CC=C1C1=NC(C=2C=C3C(Cl)=CN(CCC(O)=O)C3=CC=2)=NO1 ATRHHCBTXLJODU-UHFFFAOYSA-N 0.000 claims description 2
• OQZVKFALLQGNLN-UHFFFAOYSA-N 3-[3-chloro-5-[5-(3-chloro-4-methoxyphenyl)-1,2,4-oxadiazol-3-yl]indol-1-yl]propanoic acid Chemical compound C1=C(Cl)C(OC)=CC=C1C1=NC(C=2C=C3C(Cl)=CN(CCC(O)=O)C3=CC=2)=NO1 OQZVKFALLQGNLN-UHFFFAOYSA-N 0.000 claims description 2
• NSXLYJQAZFEOGH-UHFFFAOYSA-N 3-[3-chloro-5-[5-(3-chloro-4-propan-2-yloxyphenyl)-1,2,4-oxadiazol-3-yl]indol-1-yl]propanoic acid Chemical class C1=C(Cl)C(OC(C)C)=CC=C1C1=NC(C=2C=C3C(Cl)=CN(CCC(O)=O)C3=CC=2)=NO1 NSXLYJQAZFEOGH-UHFFFAOYSA-N 0.000 claims description 2
• HVTSNKVSHMFPKV-UHFFFAOYSA-N 3-[3-chloro-5-[5-(3-chloro-4-propoxyphenyl)-1,2,4-oxadiazol-3-yl]indol-1-yl]propanoic acid Chemical compound C1=C(Cl)C(OCCC)=CC=C1C1=NC(C=2C=C3C(Cl)=CN(CCC(O)=O)C3=CC=2)=NO1 HVTSNKVSHMFPKV-UHFFFAOYSA-N 0.000 claims description 2
• KOHQHMAPKUTNNE-UHFFFAOYSA-N 3-[3-chloro-5-[5-(3-cyano-4-propan-2-yloxyphenyl)-1,2,4-oxadiazol-3-yl]indol-1-yl]propanoic acid Chemical class C1=C(C#N)C(OC(C)C)=CC=C1C1=NC(C=2C=C3C(Cl)=CN(CCC(O)=O)C3=CC=2)=NO1 KOHQHMAPKUTNNE-UHFFFAOYSA-N 0.000 claims description 2
• VWGIWRCFAHCBKK-UHFFFAOYSA-N 3-[3-chloro-5-[5-(4-methoxy-3-phenylphenyl)-1,2,4-oxadiazol-3-yl]indol-1-yl]propanoic acid Chemical compound COC1=CC=C(C=2ON=C(N=2)C=2C=C3C(Cl)=CN(CCC(O)=O)C3=CC=2)C=C1C1=CC=CC=C1 VWGIWRCFAHCBKK-UHFFFAOYSA-N 0.000 claims description 2
• SJDIWNCKZJNHPE-UHFFFAOYSA-N 3-[3-chloro-5-[5-[4-methoxy-3-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-3-yl]indol-1-yl]propanoic acid Chemical compound C1=C(C(F)(F)F)C(OC)=CC=C1C1=NC(C=2C=C3C(Cl)=CN(CCC(O)=O)C3=CC=2)=NO1 SJDIWNCKZJNHPE-UHFFFAOYSA-N 0.000 claims description 2
• YOCISYLTMKQWMT-UHFFFAOYSA-N 3-[3-chloro-5-[5-[4-nitro-3-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-3-yl]indol-1-yl]propanoic acid Chemical compound C=1C=C2N(CCC(=O)O)C=C(Cl)C2=CC=1C(N=1)=NOC=1C1=CC=C([N+]([O-])=O)C(C(F)(F)F)=C1 YOCISYLTMKQWMT-UHFFFAOYSA-N 0.000 claims description 2
• XAJVGJHOAIETSC-UHFFFAOYSA-N 3-[4-[5-(3-cyano-4-propan-2-yloxyphenyl)-1,2,4-oxadiazol-3-yl]indol-1-yl]propanoic acid Chemical compound C1=C(C#N)C(OC(C)C)=CC=C1C1=NC(C=2C=3C=CN(CCC(O)=O)C=3C=CC=2)=NO1 XAJVGJHOAIETSC-UHFFFAOYSA-N 0.000 claims description 2
• ZDNCNPFZPVFQLU-UHFFFAOYSA-N 3-[4-[5-(3-ethyl-4-piperidin-1-ylphenyl)-1,2,4-oxadiazol-3-yl]indol-1-yl]propanoic acid Chemical compound CCC1=CC(C=2ON=C(N=2)C=2C=3C=CN(CCC(O)=O)C=3C=CC=2)=CC=C1N1CCCCC1 ZDNCNPFZPVFQLU-UHFFFAOYSA-N 0.000 claims description 2
• ZRMYIOJUUABNBB-UHFFFAOYSA-N 3-[4-[5-(4-cyclohexyl-3-ethylphenyl)-1,2,4-oxadiazol-3-yl]indol-1-yl]propanoic acid Chemical compound CCC1=CC(C=2ON=C(N=2)C=2C=3C=CN(CCC(O)=O)C=3C=CC=2)=CC=C1C1CCCCC1 ZRMYIOJUUABNBB-UHFFFAOYSA-N 0.000 claims description 2
• NCIWSEFHPINPAQ-UHFFFAOYSA-N 3-[4-[5-(5-chloro-6-pyrrolidin-1-ylpyridin-3-yl)-1,2,4-oxadiazol-3-yl]indol-1-yl]propanoic acid Chemical compound C1=CC=C2N(CCC(=O)O)C=CC2=C1C(N=1)=NOC=1C(C=C1Cl)=CN=C1N1CCCC1 NCIWSEFHPINPAQ-UHFFFAOYSA-N 0.000 claims description 2
• QIHAASGINXICIX-UHFFFAOYSA-N 3-[4-[5-[4-(2-fluorophenyl)-3-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-3-yl]indol-1-yl]propanoic acid Chemical compound C1=CC=C2N(CCC(=O)O)C=CC2=C1C(N=1)=NOC=1C(C=C1C(F)(F)F)=CC=C1C1=CC=CC=C1F QIHAASGINXICIX-UHFFFAOYSA-N 0.000 claims description 2
• BGXPNVXUXLUWGQ-UHFFFAOYSA-N 3-[4-[5-[4-(2-methylpropyl)-3-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-3-yl]indol-1-yl]propanoic acid Chemical compound C1=C(C(F)(F)F)C(CC(C)C)=CC=C1C1=NC(C=2C=3C=CN(CCC(O)=O)C=3C=CC=2)=NO1 BGXPNVXUXLUWGQ-UHFFFAOYSA-N 0.000 claims description 2
• FONMSGPEBHUUIV-UHFFFAOYSA-N 3-[4-[5-[4-cyclohexyl-3-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-3-yl]indol-1-yl]propanoic acid Chemical compound C1=CC=C2N(CCC(=O)O)C=CC2=C1C(N=1)=NOC=1C(C=C1C(F)(F)F)=CC=C1C1CCCCC1 FONMSGPEBHUUIV-UHFFFAOYSA-N 0.000 claims description 2
• XKKBKGRBVYJKEQ-UHFFFAOYSA-N 3-[4-[5-[4-methoxy-3-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-3-yl]indol-1-yl]propanoic acid Chemical compound C1=C(C(F)(F)F)C(OC)=CC=C1C1=NC(C=2C=3C=CN(CCC(O)=O)C=3C=CC=2)=NO1 XKKBKGRBVYJKEQ-UHFFFAOYSA-N 0.000 claims description 2
• NORSCQNGKKVMIO-UHFFFAOYSA-N 3-[4-[5-[4-phenyl-3-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-3-yl]indol-1-yl]propanoic acid Chemical compound C1=CC=C2N(CCC(=O)O)C=CC2=C1C(N=1)=NOC=1C(C=C1C(F)(F)F)=CC=C1C1=CC=CC=C1 NORSCQNGKKVMIO-UHFFFAOYSA-N 0.000 claims description 2
• GVFAFIKUOWUAIQ-UHFFFAOYSA-N 3-[4-[5-[4-propan-2-yloxy-3-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-3-yl]indol-1-yl]propanoic acid Chemical compound C1=C(C(F)(F)F)C(OC(C)C)=CC=C1C1=NC(C=2C=3C=CN(CCC(O)=O)C=3C=CC=2)=NO1 GVFAFIKUOWUAIQ-UHFFFAOYSA-N 0.000 claims description 2
• JXFAYGCVJMEDKI-UHFFFAOYSA-N 3-[5-[5-(3-cyano-4-propan-2-yloxyphenyl)-1,2,4-oxadiazol-3-yl]indol-1-yl]propanoic acid Chemical compound C1=C(C#N)C(OC(C)C)=CC=C1C1=NC(C=2C=C3C=CN(CCC(O)=O)C3=CC=2)=NO1 JXFAYGCVJMEDKI-UHFFFAOYSA-N 0.000 claims description 2
• WHHGUZLUCIYBPL-UHFFFAOYSA-N 4-[4-[5-(3-bromo-4-propan-2-yloxyphenyl)-1,2,4-oxadiazol-3-yl]indol-1-yl]butanoic acid Chemical compound C1=C(Br)C(OC(C)C)=CC=C1C1=NC(C=2C=3C=CN(CCCC(O)=O)C=3C=CC=2)=NO1 WHHGUZLUCIYBPL-UHFFFAOYSA-N 0.000 claims description 2
• SKMHVWFGAFXNPS-UHFFFAOYSA-N 4-[4-[5-(3-chloro-4-propan-2-yloxyphenyl)-1,2,4-oxadiazol-3-yl]indol-1-yl]butanoic acid Chemical compound C1=C(Cl)C(OC(C)C)=CC=C1C1=NC(C=2C=3C=CN(CCCC(O)=O)C=3C=CC=2)=NO1 SKMHVWFGAFXNPS-UHFFFAOYSA-N 0.000 claims description 2
• APHXDFHTQCIQBC-UHFFFAOYSA-N 4-[4-[5-(3-cyano-4-phenylphenyl)-1,2,4-oxadiazol-3-yl]indol-1-yl]butanoic acid Chemical compound C1=CC=C2N(CCCC(=O)O)C=CC2=C1C(N=1)=NOC=1C(C=C1C#N)=CC=C1C1=CC=CC=C1 APHXDFHTQCIQBC-UHFFFAOYSA-N 0.000 claims description 2
• UHURKDFLIMINLN-UHFFFAOYSA-N 4-[4-[5-(3-cyano-4-propan-2-yloxyphenyl)-1,2,4-oxadiazol-3-yl]indol-1-yl]butanoic acid Chemical compound C1=C(C#N)C(OC(C)C)=CC=C1C1=NC(C=2C=3C=CN(CCCC(O)=O)C=3C=CC=2)=NO1 UHURKDFLIMINLN-UHFFFAOYSA-N 0.000 claims description 2
• ZOAACYIIORBWGO-UHFFFAOYSA-N 4-[4-[5-[3-chloro-4-(2-methylpropyl)phenyl]-1,2,4-oxadiazol-3-yl]indol-1-yl]butanoic acid Chemical compound C1=C(Cl)C(CC(C)C)=CC=C1C1=NC(C=2C=3C=CN(CCCC(O)=O)C=3C=CC=2)=NO1 ZOAACYIIORBWGO-UHFFFAOYSA-N 0.000 claims description 2
• NCZWOHWUDJLURH-UHFFFAOYSA-N 4-[4-[5-[3-chloro-4-(trifluoromethoxy)phenyl]-1,2,4-oxadiazol-3-yl]indol-1-yl]butanoic acid Chemical compound C1=CC=C2N(CCCC(=O)O)C=CC2=C1C(N=1)=NOC=1C1=CC=C(OC(F)(F)F)C(Cl)=C1 NCZWOHWUDJLURH-UHFFFAOYSA-N 0.000 claims description 2
• GJFQCFCPADTPMV-UHFFFAOYSA-N 4-[4-[5-[3-cyano-4-(2-methylpropyl)phenyl]-1,2,4-oxadiazol-3-yl]indol-1-yl]butanoic acid Chemical compound C1=C(C#N)C(CC(C)C)=CC=C1C1=NC(C=2C=3C=CN(CCCC(O)=O)C=3C=CC=2)=NO1 GJFQCFCPADTPMV-UHFFFAOYSA-N 0.000 claims description 2
• LMXLJFSUXSWIFZ-UHFFFAOYSA-N 4-[4-[5-[4-phenyl-3-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-3-yl]indol-1-yl]butanoic acid Chemical compound C1=CC=C2N(CCCC(=O)O)C=CC2=C1C(N=1)=NOC=1C(C=C1C(F)(F)F)=CC=C1C1=CC=CC=C1 LMXLJFSUXSWIFZ-UHFFFAOYSA-N 0.000 claims description 2
• CRVGFMNPKAVZLK-UHFFFAOYSA-N 4-[4-[5-[4-phenyl-5-(trifluoromethyl)thiophen-2-yl]-1,2,4-oxadiazol-3-yl]indol-1-yl]butanoic acid Chemical compound C1=CC=C2N(CCCC(=O)O)C=CC2=C1C(N=1)=NOC=1C(SC=1C(F)(F)F)=CC=1C1=CC=CC=C1 CRVGFMNPKAVZLK-UHFFFAOYSA-N 0.000 claims description 2
• HLDBXISXBVARTO-UHFFFAOYSA-N 4-[5-[5-(3-chloro-4-propan-2-yloxyphenyl)-1,2,4-oxadiazol-3-yl]indol-1-yl]butanoic acid Chemical compound C1=C(Cl)C(OC(C)C)=CC=C1C1=NC(C=2C=C3C=CN(CCCC(O)=O)C3=CC=2)=NO1 HLDBXISXBVARTO-UHFFFAOYSA-N 0.000 claims description 2
• VXNIDFMYHIAKQT-UHFFFAOYSA-N 5-[5-[5-(3-chloro-4-propan-2-yloxyphenyl)-1,2,4-oxadiazol-3-yl]indol-1-yl]pentanoic acid Chemical compound C1=C(Cl)C(OC(C)C)=CC=C1C1=NC(C=2C=C3C=CN(CCCCC(O)=O)C3=CC=2)=NO1 VXNIDFMYHIAKQT-UHFFFAOYSA-N 0.000 claims description 2
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 2
• 125000005843 halogen group Chemical group 0.000 claims 2
• XHSNHDLFBNSHHH-UHFFFAOYSA-N 3-[3-chloro-5-[5-[3-chloro-4-(trifluoromethoxy)phenyl]-1,2,4-oxadiazol-3-yl]indol-1-yl]propanoic acid Chemical compound C=1C=C2N(CCC(=O)O)C=C(Cl)C2=CC=1C(N=1)=NOC=1C1=CC=C(OC(F)(F)F)C(Cl)=C1 XHSNHDLFBNSHHH-UHFFFAOYSA-N 0.000 claims 1
• 125000004093 cyano group Chemical group *C#N 0.000 claims 1
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims 1
• 230000008520 organization Effects 0.000 claims 1
• 238000002360 preparation method Methods 0.000 abstract description 15
• 230000008569 process Effects 0.000 abstract description 7
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 172
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 135
• 239000000203 mixture Substances 0.000 description 125
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Natural products CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 122
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 118
• 239000007787 solid Substances 0.000 description 115
• 239000011541 reaction mixture Substances 0.000 description 114
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 112
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 87
• 239000000243 solution Substances 0.000 description 85
• 239000002904 solvent Substances 0.000 description 75
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Natural products CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 70
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 65
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 60
• 235000019441 ethanol Nutrition 0.000 description 58
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 53
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 43
• 239000000047 product Substances 0.000 description 43
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 36
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 33
• 238000006243 chemical reaction Methods 0.000 description 32
• 239000012043 crude product Substances 0.000 description 30
• 239000012071 phase Substances 0.000 description 30
• -1 cyano, nitro, phenyl Chemical group 0.000 description 28
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 27
• 239000012074 organic phase Substances 0.000 description 26
• 239000003921 oil Substances 0.000 description 24
• 235000019198 oils Nutrition 0.000 description 24
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 23
• 108020003175 receptors Proteins 0.000 description 22
• 102000005962 receptors Human genes 0.000 description 21
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 19
• 235000017557 sodium bicarbonate Nutrition 0.000 description 19
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 19
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical group CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 18
• 239000010410 layer Substances 0.000 description 18
• XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 17
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 16
• FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 16
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 16
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 16
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 15
• 239000000377 silicon dioxide Substances 0.000 description 15
• WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 14
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
• 239000000556 agonist Substances 0.000 description 14
• 210000004027 cell Anatomy 0.000 description 14
• HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 14
• 239000012044 organic layer Substances 0.000 description 13
• FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 12
• DQWJQKYJKIYMDT-UHFFFAOYSA-N ethyl 3-[4-(n'-hydroxycarbamimidoyl)indol-1-yl]propanoate Chemical compound C1=CC=C2N(CCC(=O)OCC)C=CC2=C1C(=N)NO DQWJQKYJKIYMDT-UHFFFAOYSA-N 0.000 description 12
• 238000012360 testing method Methods 0.000 description 12
• FQTIYMRSUOADDK-UHFFFAOYSA-N ethyl 3-bromopropanoate Chemical compound CCOC(=O)CCBr FQTIYMRSUOADDK-UHFFFAOYSA-N 0.000 description 11
• 238000001704 evaporation Methods 0.000 description 11
• 230000008020 evaporation Effects 0.000 description 11
• 239000000284 extract Substances 0.000 description 11
• 239000000706 filtrate Substances 0.000 description 11
• 150000002500 ions Chemical class 0.000 description 11
• 239000002244 precipitate Substances 0.000 description 11
• 238000010992 reflux Methods 0.000 description 11
• 125000001766 1,2,4-oxadiazol-3-yl group Chemical group [H]C1=NC(*)=NO1 0.000 description 10
• 101000587820 Homo sapiens Selenide, water dikinase 1 Proteins 0.000 description 10
• 101000701815 Homo sapiens Spermidine synthase Proteins 0.000 description 10
• 102100031163 Selenide, water dikinase 1 Human genes 0.000 description 10
• 239000007864 aqueous solution Substances 0.000 description 10
• 235000010334 sodium propionate Nutrition 0.000 description 10
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 10
• 239000000725 suspension Substances 0.000 description 10
• 240000004808 Saccharomyces cerevisiae Species 0.000 description 9
• 239000002253 acid Substances 0.000 description 9
• FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 9
• 229910000024 caesium carbonate Inorganic materials 0.000 description 9
• 238000010438 heat treatment Methods 0.000 description 9
• 238000006460 hydrolysis reaction Methods 0.000 description 9
• 239000012528 membrane Substances 0.000 description 9
• 229910000027 potassium carbonate Inorganic materials 0.000 description 9
• 239000011734 sodium Substances 0.000 description 9
• JXKPEJDQGNYQSM-UHFFFAOYSA-M sodium propionate Chemical compound [Na+].CCC([O-])=O JXKPEJDQGNYQSM-UHFFFAOYSA-M 0.000 description 9
• OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 8
• JFDZBHWFFUWGJE-UHFFFAOYSA-N benzenecarbonitrile Natural products N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 8
• 239000012267 brine Substances 0.000 description 8
• 238000004587 chromatography analysis Methods 0.000 description 8
• 239000012230 colorless oil Substances 0.000 description 8
• 238000001914 filtration Methods 0.000 description 8
• 235000019253 formic acid Nutrition 0.000 description 8
• 230000007062 hydrolysis Effects 0.000 description 8
• 239000000543 intermediate Substances 0.000 description 8
• 229920006395 saturated elastomer Polymers 0.000 description 8
• 239000000126 substance Substances 0.000 description 8
• 238000001665 trituration Methods 0.000 description 8
• 238000005406 washing Methods 0.000 description 8
• 238000003556 assay Methods 0.000 description 7
• 239000000872 buffer Substances 0.000 description 7
• 239000003153 chemical reaction reagent Substances 0.000 description 7
• 239000000460 chlorine Substances 0.000 description 7
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 7
• NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 7
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 7
• 239000000463 material Substances 0.000 description 7
• 229910052720 vanadium Inorganic materials 0.000 description 7
• YEDUAINPPJYDJZ-UHFFFAOYSA-N 2-hydroxybenzothiazole Chemical compound C1=CC=C2SC(O)=NC2=C1 YEDUAINPPJYDJZ-UHFFFAOYSA-N 0.000 description 6
• PZDIVDDFLGKWID-UHFFFAOYSA-N 5-chloro-6-propan-2-yloxypyridine-3-carboxylic acid Chemical compound CC(C)OC1=NC=C(C(O)=O)C=C1Cl PZDIVDDFLGKWID-UHFFFAOYSA-N 0.000 description 6
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
• SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 6
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
• 229960000583 acetic acid Drugs 0.000 description 6
• 238000004458 analytical method Methods 0.000 description 6
• XBPOBCXHALHJFP-UHFFFAOYSA-N ethyl 4-bromobutanoate Chemical compound CCOC(=O)CCCBr XBPOBCXHALHJFP-UHFFFAOYSA-N 0.000 description 6
• FMKOJHQHASLBPH-UHFFFAOYSA-N isopropyl iodide Chemical compound CC(C)I FMKOJHQHASLBPH-UHFFFAOYSA-N 0.000 description 6
• 210000004698 lymphocyte Anatomy 0.000 description 6
• GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical group [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 description 6
• 239000003960 organic solvent Substances 0.000 description 6
• 239000007858 starting material Substances 0.000 description 6
• CEUFGDDOMXCXFW-UHFFFAOYSA-N 1h-indole-4-carbonitrile Chemical compound N#CC1=CC=CC2=C1C=CN2 CEUFGDDOMXCXFW-UHFFFAOYSA-N 0.000 description 5
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 5
• DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 5
• JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 5
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical group [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 5
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 5
• 238000005903 acid hydrolysis reaction Methods 0.000 description 5
• 239000008346 aqueous phase Substances 0.000 description 5
• 239000003125 aqueous solvent Substances 0.000 description 5
• 230000015572 biosynthetic process Effects 0.000 description 5
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 5
• 229910052794 bromium Inorganic materials 0.000 description 5
• 208000035475 disorder Diseases 0.000 description 5
• 238000001035 drying Methods 0.000 description 5
• 150000002148 esters Chemical class 0.000 description 5
• 238000002347 injection Methods 0.000 description 5
• 239000007924 injection Substances 0.000 description 5
• 229910052740 iodine Inorganic materials 0.000 description 5
• KFZMGEQAYNKOFK-UHFFFAOYSA-N isopropyl alcohol Natural products CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 5
• 239000007788 liquid Substances 0.000 description 5
• 238000000746 purification Methods 0.000 description 5
• 229910052708 sodium Inorganic materials 0.000 description 5
• 238000003756 stirring Methods 0.000 description 5
• 239000003826 tablet Substances 0.000 description 5
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
• YHYLDEVWYOFIJK-UHFFFAOYSA-N 1h-indole-5-carbonitrile Chemical compound N#CC1=CC=C2NC=CC2=C1 YHYLDEVWYOFIJK-UHFFFAOYSA-N 0.000 description 4
• AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 4
• FQGLEMDXDTZJMJ-UHFFFAOYSA-N 3-cyano-4-propan-2-yloxybenzoic acid Chemical compound CC(C)OC1=CC=C(C(O)=O)C=C1C#N FQGLEMDXDTZJMJ-UHFFFAOYSA-N 0.000 description 4
• KPVYJUNQUVKVFE-UHFFFAOYSA-N 3-ethyl-4-piperidin-1-ylbenzonitrile Chemical compound CCC1=CC(C#N)=CC=C1N1CCCCC1 KPVYJUNQUVKVFE-UHFFFAOYSA-N 0.000 description 4
• RGROENIAPQNTQC-UHFFFAOYSA-N 4-(cyclohexen-1-yl)-3-ethylbenzoic acid Chemical compound CCC1=CC(C(O)=O)=CC=C1C1=CCCCC1 RGROENIAPQNTQC-UHFFFAOYSA-N 0.000 description 4
• HQSCAILVLDFMPX-UHFFFAOYSA-N 4-(cyclohexen-1-yl)-3-ethylbenzonitrile Chemical compound CCC1=CC(C#N)=CC=C1C1=CCCCC1 HQSCAILVLDFMPX-UHFFFAOYSA-N 0.000 description 4
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
• 230000005526 G1 to G0 transition Effects 0.000 description 4
• 241001465754 Metazoa Species 0.000 description 4
• 235000019502 Orange oil Nutrition 0.000 description 4
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
• WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
• ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 4
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 4
• 230000036471 bradycardia Effects 0.000 description 4
• 208000006218 bradycardia Diseases 0.000 description 4
• 239000006071 cream Substances 0.000 description 4
• LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 4
• RZRPUEZALDQXOO-UHFFFAOYSA-N ethyl 3-[3-chloro-5-(n'-hydroxycarbamimidoyl)indol-1-yl]propanoate Chemical compound ONC(=N)C1=CC=C2N(CCC(=O)OCC)C=C(Cl)C2=C1 RZRPUEZALDQXOO-UHFFFAOYSA-N 0.000 description 4
• YVYQIPRDFHZKFJ-UHFFFAOYSA-N ethyl 3-[3-chloro-5-[5-(3-chloro-4-hydroxyphenyl)-1,2,4-oxadiazol-3-yl]indol-1-yl]propanoate Chemical compound C=1C=C2N(CCC(=O)OCC)C=C(Cl)C2=CC=1C(N=1)=NOC=1C1=CC=C(O)C(Cl)=C1 YVYQIPRDFHZKFJ-UHFFFAOYSA-N 0.000 description 4
• GJAUZUDZGRTZGC-UHFFFAOYSA-N ethyl 3-[5-(n'-hydroxycarbamimidoyl)indol-1-yl]propanoate Chemical compound ONC(=N)C1=CC=C2N(CCC(=O)OCC)C=CC2=C1 GJAUZUDZGRTZGC-UHFFFAOYSA-N 0.000 description 4
• 238000003818 flash chromatography Methods 0.000 description 4
• 125000000593 indol-1-yl group Chemical group [H]C1=C([H])C([H])=C2N([*])C([H])=C([H])C2=C1[H] 0.000 description 4
• 210000001165 lymph node Anatomy 0.000 description 4
• FVWVARXYHBRFPN-UHFFFAOYSA-N methyl 3-cyano-4-(trifluoromethylsulfonyloxy)benzoate Chemical compound COC(=O)C1=CC=C(OS(=O)(=O)C(F)(F)F)C(C#N)=C1 FVWVARXYHBRFPN-UHFFFAOYSA-N 0.000 description 4
• DUWWHGPELOTTOE-UHFFFAOYSA-N n-(5-chloro-2,4-dimethoxyphenyl)-3-oxobutanamide Chemical compound COC1=CC(OC)=C(NC(=O)CC(C)=O)C=C1Cl DUWWHGPELOTTOE-UHFFFAOYSA-N 0.000 description 4
• 239000010502 orange oil Substances 0.000 description 4
• NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 4
• 239000002245 particle Substances 0.000 description 4
• 239000002953 phosphate buffered saline Substances 0.000 description 4
• NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 description 4
• 239000000843 powder Substances 0.000 description 4
• 239000003755 preservative agent Substances 0.000 description 4
• 235000019260 propionic acid Nutrition 0.000 description 4
• 125000001424 substituent group Chemical group 0.000 description 4
• 239000000375 suspending agent Substances 0.000 description 4
• GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 4
• 239000003981 vehicle Substances 0.000 description 4
• QXSPLPLQLJAPSM-UHFFFAOYSA-N 3-chloro-4-propan-2-yloxybenzoic acid Chemical compound CC(C)OC1=CC=C(C(O)=O)C=C1Cl QXSPLPLQLJAPSM-UHFFFAOYSA-N 0.000 description 3
• KSXUIQQDHHFSRN-UHFFFAOYSA-N 4-bromo-3-(trifluoromethyl)benzonitrile Chemical compound FC(F)(F)C1=CC(C#N)=CC=C1Br KSXUIQQDHHFSRN-UHFFFAOYSA-N 0.000 description 3
• QHGFTWWODIJZFN-UHFFFAOYSA-N 4-cyclohexyl-3-(trifluoromethyl)benzamide Chemical compound FC(F)(F)C1=CC(C(=O)N)=CC=C1C1CCCCC1 QHGFTWWODIJZFN-UHFFFAOYSA-N 0.000 description 3
• XIWQGDFYIINJLV-UHFFFAOYSA-N 4-cyclohexyl-3-(trifluoromethyl)benzoic acid Chemical compound FC(F)(F)C1=CC(C(=O)O)=CC=C1C1CCCCC1 XIWQGDFYIINJLV-UHFFFAOYSA-N 0.000 description 3
• TYJVZKADZOHYAB-UHFFFAOYSA-N 4-phenyl-3-(trifluoromethyl)benzoic acid Chemical compound FC(F)(F)C1=CC(C(=O)O)=CC=C1C1=CC=CC=C1 TYJVZKADZOHYAB-UHFFFAOYSA-N 0.000 description 3
• FMRZLMJTOCTKPU-UHFFFAOYSA-N 4-propan-2-yloxy-3-(trifluoromethyl)benzoic acid Chemical compound CC(C)OC1=CC=C(C(O)=O)C=C1C(F)(F)F FMRZLMJTOCTKPU-UHFFFAOYSA-N 0.000 description 3
• HHPNPKXRNMRKDX-UHFFFAOYSA-N 5-(3-chloro-4-propan-2-yloxyphenyl)-3-(1h-indol-5-yl)-1,2,4-oxadiazole Chemical compound C1=C(Cl)C(OC(C)C)=CC=C1C1=NC(C=2C=C3C=CNC3=CC=2)=NO1 HHPNPKXRNMRKDX-UHFFFAOYSA-N 0.000 description 3
• WDYVUKGVKRZQNM-UHFFFAOYSA-N 6-phosphonohexylphosphonic acid Chemical compound OP(O)(=O)CCCCCCP(O)(O)=O WDYVUKGVKRZQNM-UHFFFAOYSA-N 0.000 description 3
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 3
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 3
• 208000016557 Acute basophilic leukemia Diseases 0.000 description 3
• 229910017976 MgO 4 Inorganic materials 0.000 description 3
• FIWILGQIZHDAQG-UHFFFAOYSA-N NC1=C(C(=O)NCC2=CC=C(C=C2)OCC(F)(F)F)C=C(C(=N1)N)N1N=C(N=C1)C1(CC1)C(F)(F)F Chemical compound NC1=C(C(=O)NCC2=CC=C(C=C2)OCC(F)(F)F)C=C(C(=N1)N)N1N=C(N=C1)C1(CC1)C(F)(F)F FIWILGQIZHDAQG-UHFFFAOYSA-N 0.000 description 3
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
• 239000012300 argon atmosphere Substances 0.000 description 3
• 125000004429 atom Chemical group 0.000 description 3
• 229910052799 carbon Inorganic materials 0.000 description 3
• 229910052801 chlorine Inorganic materials 0.000 description 3
• 238000010790 dilution Methods 0.000 description 3
• 239000012895 dilution Substances 0.000 description 3
• 239000002270 dispersing agent Substances 0.000 description 3
• 239000002552 dosage form Substances 0.000 description 3
• 239000000839 emulsion Substances 0.000 description 3
• 230000003511 endothelial effect Effects 0.000 description 3
• DHUWFXXVYZCJNF-UHFFFAOYSA-N ethyl 5-chloro-6-pyrrolidin-1-ylpyridine-3-carboxylate Chemical compound ClC1=CC(C(=O)OCC)=CN=C1N1CCCC1 DHUWFXXVYZCJNF-UHFFFAOYSA-N 0.000 description 3
• 238000002474 experimental method Methods 0.000 description 3
• 238000000605 extraction Methods 0.000 description 3
• 238000009472 formulation Methods 0.000 description 3
• 125000001072 heteroaryl group Chemical group 0.000 description 3
• PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 3
• RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 3
• 239000011630 iodine Substances 0.000 description 3
• 230000014759 maintenance of location Effects 0.000 description 3
• 238000004949 mass spectrometry Methods 0.000 description 3
• ZSBIMTDWIGWJPW-UHFFFAOYSA-N methyl 3-chloro-4-hydroxybenzoate Chemical compound COC(=O)C1=CC=C(O)C(Cl)=C1 ZSBIMTDWIGWJPW-UHFFFAOYSA-N 0.000 description 3
• GNMSHHJOPAWPFS-UHFFFAOYSA-N methyl 3-cyano-4-(2-methylpropyl)benzoate Chemical compound COC(=O)C1=CC=C(CC(C)C)C(C#N)=C1 GNMSHHJOPAWPFS-UHFFFAOYSA-N 0.000 description 3
• 239000002674 ointment Substances 0.000 description 3
• 150000007530 organic bases Chemical class 0.000 description 3
• 239000003208 petroleum Substances 0.000 description 3
• NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
• FPEXJKLHIIXYGD-UHFFFAOYSA-N propan-2-yl 3-bromo-4-propan-2-yloxybenzoate Chemical compound CC(C)OC(=O)C1=CC=C(OC(C)C)C(Br)=C1 FPEXJKLHIIXYGD-UHFFFAOYSA-N 0.000 description 3
• MMTIPKFZXCSGDA-UHFFFAOYSA-N propan-2-yl 4-propan-2-yloxy-3-(trifluoromethyl)benzoate Chemical compound CC(C)OC(=O)C1=CC=C(OC(C)C)C(C(F)(F)F)=C1 MMTIPKFZXCSGDA-UHFFFAOYSA-N 0.000 description 3
• 239000001397 quillaja saponaria molina bark Substances 0.000 description 3
• 238000004366 reverse phase liquid chromatography Methods 0.000 description 3
• 229930182490 saponin Natural products 0.000 description 3
• 150000007949 saponins Chemical class 0.000 description 3
• 238000013207 serial dilution Methods 0.000 description 3
• CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 3
• DUYSYHSSBDVJSM-KRWOKUGFSA-N sphingosine 1-phosphate Chemical compound CCCCCCCCCCCCC\C=C\[C@@H](O)[C@@H](N)COP(O)(O)=O DUYSYHSSBDVJSM-KRWOKUGFSA-N 0.000 description 3
• 239000003381 stabilizer Substances 0.000 description 3
• 238000010561 standard procedure Methods 0.000 description 3
• 239000006228 supernatant Substances 0.000 description 3
• 238000003786 synthesis reaction Methods 0.000 description 3
• 238000002604 ultrasonography Methods 0.000 description 3
• HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
• BTANRVKWQNVYAZ-UHFFFAOYSA-N 2-butanol Substances CCC(C)O BTANRVKWQNVYAZ-UHFFFAOYSA-N 0.000 description 2
• MOFRJTLODZILCR-UHFFFAOYSA-N 2-fluoro-5-formylbenzonitrile Chemical compound FC1=CC=C(C=O)C=C1C#N MOFRJTLODZILCR-UHFFFAOYSA-N 0.000 description 2
• HEVDXQCKNZVCSD-UHFFFAOYSA-N 3-(1h-indol-5-yl)-5-[4-phenyl-5-(trifluoromethyl)thiophen-2-yl]-1,2,4-oxadiazole Chemical compound FC(F)(F)C=1SC(C=2ON=C(N=2)C=2C=C3C=CNC3=CC=2)=CC=1C1=CC=CC=C1 HEVDXQCKNZVCSD-UHFFFAOYSA-N 0.000 description 2
• JQTAQZSGHTYHAQ-UHFFFAOYSA-N 3-(3-bromo-1h-indol-5-yl)-5-(3-chloro-4-propan-2-yloxyphenyl)-1,2,4-oxadiazole Chemical compound C1=C(Cl)C(OC(C)C)=CC=C1C1=NC(C=2C=C3C(Br)=CNC3=CC=2)=NO1 JQTAQZSGHTYHAQ-UHFFFAOYSA-N 0.000 description 2
• RVYKHFGOJJKVNB-UHFFFAOYSA-N 3-amino-4-(trifluoromethyl)benzoic acid Chemical compound NC1=CC(C(O)=O)=CC=C1C(F)(F)F RVYKHFGOJJKVNB-UHFFFAOYSA-N 0.000 description 2
• XMEQDAIDOBVHEK-UHFFFAOYSA-N 3-bromo-4-hydroxybenzoic acid Chemical compound OC(=O)C1=CC=C(O)C(Br)=C1 XMEQDAIDOBVHEK-UHFFFAOYSA-N 0.000 description 2
• NRSJYUSYBNFGAK-UHFFFAOYSA-N 3-bromo-4-propan-2-yloxybenzoic acid Chemical compound CC(C)OC1=CC=C(C(O)=O)C=C1Br NRSJYUSYBNFGAK-UHFFFAOYSA-N 0.000 description 2
• GVSMQKKMAYLKMM-UHFFFAOYSA-N 3-chloro-1h-indole Chemical compound C1=CC=C2C(Cl)=CNC2=C1 GVSMQKKMAYLKMM-UHFFFAOYSA-N 0.000 description 2
• FFWYOXSEMHRRRB-UHFFFAOYSA-N 3-chloro-1h-indole-5-carbonitrile Chemical compound C1=C(C#N)C=C2C(Cl)=CNC2=C1 FFWYOXSEMHRRRB-UHFFFAOYSA-N 0.000 description 2
• QGVQWEOEEXGRSD-UHFFFAOYSA-N 3-chloro-4-(trifluoromethoxy)benzoic acid Chemical compound OC(=O)C1=CC=C(OC(F)(F)F)C(Cl)=C1 QGVQWEOEEXGRSD-UHFFFAOYSA-N 0.000 description 2
• QGNLHMKIGMZKJX-UHFFFAOYSA-N 3-chloro-4-hydroxybenzoic acid Chemical compound OC(=O)C1=CC=C(O)C(Cl)=C1 QGNLHMKIGMZKJX-UHFFFAOYSA-N 0.000 description 2
• WOBLCPMGDGMEBX-UHFFFAOYSA-N 3-chloro-4-propoxybenzoic acid Chemical compound CCCOC1=CC=C(C(O)=O)C=C1Cl WOBLCPMGDGMEBX-UHFFFAOYSA-N 0.000 description 2
• BTTODLVUYZDUNK-UHFFFAOYSA-N 3-ethyl-4-iodobenzonitrile Chemical compound CCC1=CC(C#N)=CC=C1I BTTODLVUYZDUNK-UHFFFAOYSA-N 0.000 description 2
• RFWAPFNVNGVNIG-UHFFFAOYSA-N 3-ethyl-4-piperidin-1-ylbenzoic acid Chemical compound CCC1=CC(C(O)=O)=CC=C1N1CCCCC1 RFWAPFNVNGVNIG-UHFFFAOYSA-N 0.000 description 2
• IVKIPJWZBNYCBV-UHFFFAOYSA-N 4-(2-methylpropyl)-3-(trifluoromethyl)benzamide Chemical compound CC(C)CC1=CC=C(C(N)=O)C=C1C(F)(F)F IVKIPJWZBNYCBV-UHFFFAOYSA-N 0.000 description 2
• KXMVACOQTVWZDY-UHFFFAOYSA-N 4-(cyclohexen-1-yl)-3-(trifluoromethyl)benzamide Chemical compound FC(F)(F)C1=CC(C(=O)N)=CC=C1C1=CCCCC1 KXMVACOQTVWZDY-UHFFFAOYSA-N 0.000 description 2
• YOHLABDNVQLZIA-UHFFFAOYSA-N 4-amino-3-ethylbenzonitrile Chemical compound CCC1=CC(C#N)=CC=C1N YOHLABDNVQLZIA-UHFFFAOYSA-N 0.000 description 2
• PPHHAZOVVZBSCM-UHFFFAOYSA-N 4-chloro-3-(trifluoromethyl)benzoic acid Chemical compound OC(=O)C1=CC=C(Cl)C(C(F)(F)F)=C1 PPHHAZOVVZBSCM-UHFFFAOYSA-N 0.000 description 2
• PAPAAXDBCHBFDH-UHFFFAOYSA-N 4-cyclohexyl-3-ethylbenzoic acid Chemical compound CCC1=CC(C(O)=O)=CC=C1C1CCCCC1 PAPAAXDBCHBFDH-UHFFFAOYSA-N 0.000 description 2
• YUVFOOJGEBCBAI-UHFFFAOYSA-N 4-phenyl-3-(trifluoromethyl)benzamide Chemical compound FC(F)(F)C1=CC(C(=O)N)=CC=C1C1=CC=CC=C1 YUVFOOJGEBCBAI-UHFFFAOYSA-N 0.000 description 2
• KCKNUMCDUNSFDO-UHFFFAOYSA-N 5-[3-(1h-indol-4-yl)-1,2,4-oxadiazol-5-yl]-2-propan-2-yloxybenzonitrile Chemical compound C1=C(C#N)C(OC(C)C)=CC=C1C1=NC(C=2C=3C=CNC=3C=CC=2)=NO1 KCKNUMCDUNSFDO-UHFFFAOYSA-N 0.000 description 2
• HDCDDGUJIBDWJF-UHFFFAOYSA-N 5-chloro-6-pyrrolidin-1-ylpyridine-3-carboxylic acid Chemical compound ClC1=CC(C(=O)O)=CN=C1N1CCCC1 HDCDDGUJIBDWJF-UHFFFAOYSA-N 0.000 description 2
• GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 2
• 229930024421 Adenine Natural products 0.000 description 2
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
• 239000005711 Benzoic acid Substances 0.000 description 2
• COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 2
• 125000001433 C-terminal amino-acid group Chemical group 0.000 description 2
• DRSHXJFUUPIBHX-UHFFFAOYSA-N COc1ccc(cc1)N1N=CC2C=NC(Nc3cc(OC)c(OC)c(OCCCN4CCN(C)CC4)c3)=NC12 Chemical compound COc1ccc(cc1)N1N=CC2C=NC(Nc3cc(OC)c(OC)c(OCCCN4CCN(C)CC4)c3)=NC12 DRSHXJFUUPIBHX-UHFFFAOYSA-N 0.000 description 2
• 101100428016 Caenorhabditis elegans upp-1 gene Proteins 0.000 description 2
• 101100365736 Candida albicans (strain SC5314 / ATCC MYA-2876) SEP7 gene Proteins 0.000 description 2
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
• RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 2
• 102000004127 Cytokines Human genes 0.000 description 2
• 108090000695 Cytokines Proteins 0.000 description 2
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
• 241000282412 Homo Species 0.000 description 2
• XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
• ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 2
• QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 2
• ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 2
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
• 241000699670 Mus sp. Species 0.000 description 2
• OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
• GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
• 239000004743 Polypropylene Substances 0.000 description 2
• 101150105385 SHS1 gene Proteins 0.000 description 2
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
• 210000001744 T-lymphocyte Anatomy 0.000 description 2
• QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 2
• 150000007513 acids Chemical class 0.000 description 2
• 239000004480 active ingredient Substances 0.000 description 2
• 229960000643 adenine Drugs 0.000 description 2
• 239000002168 alkylating agent Substances 0.000 description 2
• 229940100198 alkylating agent Drugs 0.000 description 2
• 150000001412 amines Chemical class 0.000 description 2
• 229910021529 ammonia Inorganic materials 0.000 description 2
• 238000010171 animal model Methods 0.000 description 2
• 229910052786 argon Inorganic materials 0.000 description 2
• 235000010233 benzoic acid Nutrition 0.000 description 2
• 230000033228 biological regulation Effects 0.000 description 2
• 210000004556 brain Anatomy 0.000 description 2
• 150000001649 bromium compounds Chemical class 0.000 description 2
• RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 2
• 239000002775 capsule Substances 0.000 description 2
• 125000004432 carbon atom Chemical group C* 0.000 description 2
• 239000003054 catalyst Substances 0.000 description 2
• 238000004440 column chromatography Methods 0.000 description 2
• 238000006880 cross-coupling reaction Methods 0.000 description 2
• XZWQKJXJNKYMAP-UHFFFAOYSA-N cyclohexen-1-ylboronic acid Chemical compound OB(O)C1=CCCCC1 XZWQKJXJNKYMAP-UHFFFAOYSA-N 0.000 description 2
• NXQGGXCHGDYOHB-UHFFFAOYSA-L cyclopenta-1,4-dien-1-yl(diphenyl)phosphane;dichloropalladium;iron(2+) Chemical compound [Fe+2].Cl[Pd]Cl.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 NXQGGXCHGDYOHB-UHFFFAOYSA-L 0.000 description 2
• LCSNDSFWVKMJCT-UHFFFAOYSA-N dicyclohexyl-(2-phenylphenyl)phosphane Chemical group C1CCCCC1P(C=1C(=CC=CC=1)C=1C=CC=CC=1)C1CCCCC1 LCSNDSFWVKMJCT-UHFFFAOYSA-N 0.000 description 2
• 230000004069 differentiation Effects 0.000 description 2
• 201000010099 disease Diseases 0.000 description 2
• 239000006185 dispersion Substances 0.000 description 2
• 238000004090 dissolution Methods 0.000 description 2
• 231100000673 dose–response relationship Toxicity 0.000 description 2
• 239000003995 emulsifying agent Substances 0.000 description 2
• 210000002889 endothelial cell Anatomy 0.000 description 2
• 238000011067 equilibration Methods 0.000 description 2
• NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 description 2
• ARFLASKVLJTEJD-UHFFFAOYSA-N ethyl 2-bromopropanoate Chemical compound CCOC(=O)C(C)Br ARFLASKVLJTEJD-UHFFFAOYSA-N 0.000 description 2
• PVGBDEYIVVTULK-UHFFFAOYSA-N ethyl 3-(3-chloro-5-cyanoindol-1-yl)propanoate Chemical compound N#CC1=CC=C2N(CCC(=O)OCC)C=C(Cl)C2=C1 PVGBDEYIVVTULK-UHFFFAOYSA-N 0.000 description 2
• PDVUUKUUESEFRP-UHFFFAOYSA-N ethyl 3-(4-cyanoindol-1-yl)propanoate Chemical compound C1=CC=C2N(CCC(=O)OCC)C=CC2=C1C#N PDVUUKUUESEFRP-UHFFFAOYSA-N 0.000 description 2
• VXLUONSACJUBNV-UHFFFAOYSA-N ethyl 3-(5-cyanoindol-1-yl)propanoate Chemical compound N#CC1=CC=C2N(CCC(=O)OCC)C=CC2=C1 VXLUONSACJUBNV-UHFFFAOYSA-N 0.000 description 2
• FULYVGSKWSLUOX-UHFFFAOYSA-N ethyl 3-[3-chloro-5-[5-(3-chloro-4-propan-2-yloxyphenyl)-1,2,4-oxadiazol-3-yl]indol-1-yl]propanoate Chemical compound C=1C=C2N(CCC(=O)OCC)C=C(Cl)C2=CC=1C(N=1)=NOC=1C1=CC=C(OC(C)C)C(Cl)=C1 FULYVGSKWSLUOX-UHFFFAOYSA-N 0.000 description 2
• WQHXRHBUWKMZTH-UHFFFAOYSA-N ethyl 3-[3-chloro-5-[5-[3-chloro-4-(trifluoromethoxy)phenyl]-1,2,4-oxadiazol-3-yl]indol-1-yl]propanoate Chemical compound C=1C=C2N(CCC(=O)OCC)C=C(Cl)C2=CC=1C(N=1)=NOC=1C1=CC=C(OC(F)(F)F)C(Cl)=C1 WQHXRHBUWKMZTH-UHFFFAOYSA-N 0.000 description 2
• WTNISFYPYZQLHW-UHFFFAOYSA-N ethyl 3-[4-[5-(3-cyano-4-propan-2-yloxyphenyl)-1,2,4-oxadiazol-3-yl]indol-1-yl]propanoate Chemical compound C1=CC=C2N(CCC(=O)OCC)C=CC2=C1C(N=1)=NOC=1C1=CC=C(OC(C)C)C(C#N)=C1 WTNISFYPYZQLHW-UHFFFAOYSA-N 0.000 description 2
• NYUFZJZUTWEXEK-UHFFFAOYSA-N ethyl 3-[4-[5-(5-chloro-6-propan-2-yloxypyridin-3-yl)-1,2,4-oxadiazol-3-yl]indol-1-yl]propanoate Chemical compound C1=CC=C2N(CCC(=O)OCC)C=CC2=C1C(N=1)=NOC=1C1=CN=C(OC(C)C)C(Cl)=C1 NYUFZJZUTWEXEK-UHFFFAOYSA-N 0.000 description 2
• GWVDMBXIDDOILH-UHFFFAOYSA-N ethyl 3-[4-[5-[4-phenyl-3-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-3-yl]indol-1-yl]propanoate Chemical compound C1=CC=C2N(CCC(=O)OCC)C=CC2=C1C(N=1)=NOC=1C(C=C1C(F)(F)F)=CC=C1C1=CC=CC=C1 GWVDMBXIDDOILH-UHFFFAOYSA-N 0.000 description 2
• CUZSVAKRUBUWRB-UHFFFAOYSA-N ethyl 3-[4-[5-[4-propan-2-yloxy-3-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-3-yl]indol-1-yl]propanoate Chemical compound C1=CC=C2N(CCC(=O)OCC)C=CC2=C1C(N=1)=NOC=1C1=CC=C(OC(C)C)C(C(F)(F)F)=C1 CUZSVAKRUBUWRB-UHFFFAOYSA-N 0.000 description 2
• AKCOOYLDEHSOPS-UHFFFAOYSA-N ethyl 3-[5-[5-(3-bromo-4-methoxyphenyl)-1,2,4-oxadiazol-3-yl]-3-chloroindol-1-yl]propanoate Chemical compound C=1C=C2N(CCC(=O)OCC)C=C(Cl)C2=CC=1C(N=1)=NOC=1C1=CC=C(OC)C(Br)=C1 AKCOOYLDEHSOPS-UHFFFAOYSA-N 0.000 description 2
• AXLXXJZVBUGTLC-UHFFFAOYSA-N ethyl 3-[5-[5-(3-cyano-4-propan-2-yloxyphenyl)-1,2,4-oxadiazol-3-yl]indol-1-yl]propanoate Chemical compound C=1C=C2N(CCC(=O)OCC)C=CC2=CC=1C(N=1)=NOC=1C1=CC=C(OC(C)C)C(C#N)=C1 AXLXXJZVBUGTLC-UHFFFAOYSA-N 0.000 description 2
• YZHIVMSMTNAZAV-UHFFFAOYSA-N ethyl 3-[5-[5-[4-phenyl-5-(trifluoromethyl)thiophen-2-yl]-1,2,4-oxadiazol-3-yl]indol-1-yl]propanoate Chemical compound C=1C=C2N(CCC(=O)OCC)C=CC2=CC=1C(N=1)=NOC=1C(SC=1C(F)(F)F)=CC=1C1=CC=CC=C1 YZHIVMSMTNAZAV-UHFFFAOYSA-N 0.000 description 2
• OKSCUZSVZULTMP-UHFFFAOYSA-N ethyl 3-bromo-2,2-dimethylpropanoate Chemical compound CCOC(=O)C(C)(C)CBr OKSCUZSVZULTMP-UHFFFAOYSA-N 0.000 description 2
• YEIALQDAVPMDOI-UHFFFAOYSA-N ethyl 3-chloro-4-(2-methylpropyl)benzoate Chemical compound CCOC(=O)C1=CC=C(CC(C)C)C(Cl)=C1 YEIALQDAVPMDOI-UHFFFAOYSA-N 0.000 description 2
• MGWBIXKGXKBGCG-UHFFFAOYSA-N ethyl 4-(4-cyanoindol-1-yl)butanoate Chemical compound C1=CC=C2N(CCCC(=O)OCC)C=CC2=C1C#N MGWBIXKGXKBGCG-UHFFFAOYSA-N 0.000 description 2
• NODUNTNHUABUAK-UHFFFAOYSA-N ethyl 4-[4-(n'-hydroxycarbamimidoyl)indol-1-yl]butanoate Chemical compound C1=CC=C2N(CCCC(=O)OCC)C=CC2=C1C(=N)NO NODUNTNHUABUAK-UHFFFAOYSA-N 0.000 description 2
• MFEKZEDRMMGDFI-UHFFFAOYSA-N ethyl 4-bromo-3-chlorobenzoate Chemical compound CCOC(=O)C1=CC=C(Br)C(Cl)=C1 MFEKZEDRMMGDFI-UHFFFAOYSA-N 0.000 description 2
• JGRYXJCSMVVDHR-UHFFFAOYSA-N ethyl 4-chloro-3-(trifluoromethyl)benzoate Chemical compound CCOC(=O)C1=CC=C(Cl)C(C(F)(F)F)=C1 JGRYXJCSMVVDHR-UHFFFAOYSA-N 0.000 description 2
• 239000011737 fluorine Substances 0.000 description 2
• 229910052731 fluorine Inorganic materials 0.000 description 2
• 239000012362 glacial acetic acid Substances 0.000 description 2
• 229940093915 gynecological organic acid Drugs 0.000 description 2
• 230000003394 haemopoietic effect Effects 0.000 description 2
• 206010073071 hepatocellular carcinoma Diseases 0.000 description 2
• 125000005842 heteroatom Chemical group 0.000 description 2
• 239000003906 humectant Substances 0.000 description 2
• 208000026278 immune system disease Diseases 0.000 description 2
• 150000007529 inorganic bases Chemical class 0.000 description 2
• OKJPEAGHQZHRQV-UHFFFAOYSA-N iodoform Chemical compound IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 2
• 239000003456 ion exchange resin Substances 0.000 description 2
• 229920003303 ion-exchange polymer Polymers 0.000 description 2
• 238000004811 liquid chromatography Methods 0.000 description 2
• 239000006210 lotion Substances 0.000 description 2
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
• LLSAHMRBKPHTGK-UHFFFAOYSA-N methyl 3-chloro-4-propoxybenzoate Chemical compound CCCOC1=CC=C(C(=O)OC)C=C1Cl LLSAHMRBKPHTGK-UHFFFAOYSA-N 0.000 description 2
• GMRUPGLQTLIYMN-UHFFFAOYSA-N methyl 3-cyano-4-phenylbenzoate Chemical compound N#CC1=CC(C(=O)OC)=CC=C1C1=CC=CC=C1 GMRUPGLQTLIYMN-UHFFFAOYSA-N 0.000 description 2
• DWTWOQDUQXDGIM-UHFFFAOYSA-N methyl 4-methoxy-3-phenylbenzoate Chemical compound COC(=O)C1=CC=C(OC)C(C=2C=CC=CC=2)=C1 DWTWOQDUQXDGIM-UHFFFAOYSA-N 0.000 description 2
• 239000004005 microsphere Substances 0.000 description 2
• 230000005012 migration Effects 0.000 description 2
• 238000013508 migration Methods 0.000 description 2
• 239000002480 mineral oil Substances 0.000 description 2
• 235000010446 mineral oil Nutrition 0.000 description 2
• 150000007522 mineralic acids Chemical class 0.000 description 2
• 229910052757 nitrogen Inorganic materials 0.000 description 2
• 125000004433 nitrogen atom Chemical group N* 0.000 description 2
• 150000007524 organic acids Chemical class 0.000 description 2
• 235000005985 organic acids Nutrition 0.000 description 2
• 150000004866 oxadiazoles Chemical class 0.000 description 2
• 229910052760 oxygen Inorganic materials 0.000 description 2
• YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 2
• QJPQVXSHYBGQGM-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 QJPQVXSHYBGQGM-UHFFFAOYSA-N 0.000 description 2
• 239000008188 pellet Substances 0.000 description 2
• 108010091212 pepstatin Proteins 0.000 description 2
• FAXGPCHRFPCXOO-LXTPJMTPSA-N pepstatin A Chemical compound OC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C(C)C)NC(=O)[C@H](C(C)C)NC(=O)CC(C)C FAXGPCHRFPCXOO-LXTPJMTPSA-N 0.000 description 2
• 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 2
• 229920001155 polypropylene Polymers 0.000 description 2
• 238000002600 positron emission tomography Methods 0.000 description 2
• 229910052700 potassium Inorganic materials 0.000 description 2
• 239000011698 potassium fluoride Substances 0.000 description 2
• 235000003270 potassium fluoride Nutrition 0.000 description 2
• 230000002335 preservative effect Effects 0.000 description 2
• DZGWJMMDFNFBBH-UHFFFAOYSA-N propan-2-yl 5-chloro-6-propan-2-yloxypyridine-3-carboxylate Chemical compound CC(C)OC(=O)C1=CN=C(OC(C)C)C(Cl)=C1 DZGWJMMDFNFBBH-UHFFFAOYSA-N 0.000 description 2
• 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 2
• 108090000623 proteins and genes Proteins 0.000 description 2
• 239000002287 radioligand Substances 0.000 description 2
• 230000002441 reversible effect Effects 0.000 description 2
• 210000005212 secondary lymphoid organ Anatomy 0.000 description 2
• MFBOGIVSZKQAPD-UHFFFAOYSA-M sodium butyrate Chemical compound [Na+].CCCC([O-])=O MFBOGIVSZKQAPD-UHFFFAOYSA-M 0.000 description 2
• 239000011780 sodium chloride Substances 0.000 description 2
• QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 2
• 239000012312 sodium hydride Substances 0.000 description 2
• 229910000104 sodium hydride Inorganic materials 0.000 description 2
• LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
• 239000012418 sodium perborate tetrahydrate Substances 0.000 description 2
• IBDSNZLUHYKHQP-UHFFFAOYSA-N sodium;3-oxidodioxaborirane;tetrahydrate Chemical compound O.O.O.O.[Na+].[O-]B1OO1 IBDSNZLUHYKHQP-UHFFFAOYSA-N 0.000 description 2
• 238000000638 solvent extraction Methods 0.000 description 2
• 108010035597 sphingosine kinase Proteins 0.000 description 2
• 230000000638 stimulation Effects 0.000 description 2
• 239000000829 suppository Substances 0.000 description 2
• YAPQBXQYLJRXSA-UHFFFAOYSA-N theobromine Chemical compound CN1C(=O)NC(=O)C2=C1N=CN2C YAPQBXQYLJRXSA-UHFFFAOYSA-N 0.000 description 2
• 239000002562 thickening agent Substances 0.000 description 2
• 210000001519 tissue Anatomy 0.000 description 2
• 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 description 2
• 229960004799 tryptophan Drugs 0.000 description 2
• 229940035893 uracil Drugs 0.000 description 2
• DSDCDMKASWVZHI-UHFFFAOYSA-M zinc;2-methanidylpropane;bromide Chemical compound Br[Zn+].CC(C)[CH2-] DSDCDMKASWVZHI-UHFFFAOYSA-M 0.000 description 2
• WWUZIQQURGPMPG-UHFFFAOYSA-N (-)-D-erythro-Sphingosine Natural products CCCCCCCCCCCCCC=CC(O)C(N)CO WWUZIQQURGPMPG-UHFFFAOYSA-N 0.000 description 1
• QCSLIRFWJPOENV-UHFFFAOYSA-N (2-fluorophenyl)boronic acid Chemical compound OB(O)C1=CC=CC=C1F QCSLIRFWJPOENV-UHFFFAOYSA-N 0.000 description 1
• 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 description 1
• ZXSQEZNORDWBGZ-UHFFFAOYSA-N 1,3-dihydropyrrolo[2,3-b]pyridin-2-one Chemical compound C1=CN=C2NC(=O)CC2=C1 ZXSQEZNORDWBGZ-UHFFFAOYSA-N 0.000 description 1
• IBODDUNKEPPBKW-UHFFFAOYSA-N 1,5-dibromopentane Chemical compound BrCCCCCBr IBODDUNKEPPBKW-UHFFFAOYSA-N 0.000 description 1
• PRIGFEJKMMRJSF-UHFFFAOYSA-M 1-fluoro-2,4,6-trimethylpyridin-1-ium;trifluoromethanesulfonate Chemical compound [O-]S(=O)(=O)C(F)(F)F.CC1=CC(C)=[N+](F)C(C)=C1 PRIGFEJKMMRJSF-UHFFFAOYSA-M 0.000 description 1
• IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
• 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
• NRZNTGUFHSJBTD-HKOYGPOVSA-N 2-[2-(2-methoxyethoxy)ethoxy]ethyl (e)-2-cyano-3-(6-piperidin-1-ylnaphthalen-2-yl)prop-2-enoate Chemical compound C1=CC2=CC(/C=C(C(=O)OCCOCCOCCOC)\C#N)=CC=C2C=C1N1CCCCC1 NRZNTGUFHSJBTD-HKOYGPOVSA-N 0.000 description 1
• GRWKNBPOGBTZMN-UHFFFAOYSA-N 2-benzyl-3-phenylpropane-1,2-diamine Chemical compound C=1C=CC=CC=1CC(N)(CN)CC1=CC=CC=C1 GRWKNBPOGBTZMN-UHFFFAOYSA-N 0.000 description 1
• NAMYKGVDVNBCFQ-UHFFFAOYSA-N 2-bromopropane Chemical compound CC(C)Br NAMYKGVDVNBCFQ-UHFFFAOYSA-N 0.000 description 1
• BFSVOASYOCHEOV-UHFFFAOYSA-N 2-diethylaminoethanol Chemical compound CCN(CC)CCO BFSVOASYOCHEOV-UHFFFAOYSA-N 0.000 description 1
• 229940013085 2-diethylaminoethanol Drugs 0.000 description 1
• 125000003006 2-dimethylaminoethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
• NTIGNJOEVBTPJJ-UHFFFAOYSA-N 3,3-dibromopentane Chemical compound CCC(Br)(Br)CC NTIGNJOEVBTPJJ-UHFFFAOYSA-N 0.000 description 1
• QFSWXGPHYUWRPU-UHFFFAOYSA-N 3-(1h-indol-4-yl)-5-[4-phenyl-5-(trifluoromethyl)thiophen-2-yl]-1,2,4-oxadiazole Chemical compound FC(F)(F)C=1SC(C=2ON=C(N=2)C=2C=3C=CNC=3C=CC=2)=CC=1C1=CC=CC=C1 QFSWXGPHYUWRPU-UHFFFAOYSA-N 0.000 description 1
• KKXCZECAMJDFGO-UHFFFAOYSA-N 3-(3-chloro-1h-indol-4-yl)-5-[4-phenyl-5-(trifluoromethyl)thiophen-2-yl]-1,2,4-oxadiazole Chemical compound FC(F)(F)C=1SC(C=2ON=C(N=2)C=2C=3C(Cl)=CNC=3C=CC=2)=CC=1C1=CC=CC=C1 KKXCZECAMJDFGO-UHFFFAOYSA-N 0.000 description 1
• RIUSLZHPIWRGKY-UHFFFAOYSA-N 3-(3-chloro-1h-indol-5-yl)-5-(3-chloro-4-propan-2-yloxyphenyl)-1,2,4-oxadiazole Chemical compound C1=C(Cl)C(OC(C)C)=CC=C1C1=NC(C=2C=C3C(Cl)=CNC3=CC=2)=NO1 RIUSLZHPIWRGKY-UHFFFAOYSA-N 0.000 description 1
• PLYDHEXYEHADNP-UHFFFAOYSA-N 3-(3-chloro-1h-indol-5-yl)-5-[4-phenyl-5-(trifluoromethyl)thiophen-2-yl]-1,2,4-oxadiazole Chemical compound FC(F)(F)C=1SC(C=2ON=C(N=2)C=2C=C3C(Cl)=CNC3=CC=2)=CC=1C1=CC=CC=C1 PLYDHEXYEHADNP-UHFFFAOYSA-N 0.000 description 1
• BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
• PPQMRWFTOFYPQO-UHFFFAOYSA-N 3-bromo-2,2,3-trifluoropropanoic acid Chemical compound OC(=O)C(F)(F)C(F)Br PPQMRWFTOFYPQO-UHFFFAOYSA-N 0.000 description 1
• FYHBVTYDATZUEE-UHFFFAOYSA-N 3-bromo-2,2-dimethylpropanoic acid Chemical compound BrCC(C)(C)C(O)=O FYHBVTYDATZUEE-UHFFFAOYSA-N 0.000 description 1
• BBPZABXVRBFWGD-UHFFFAOYSA-N 3-bromo-4-methoxybenzoic acid Chemical compound COC1=CC=C(C(O)=O)C=C1Br BBPZABXVRBFWGD-UHFFFAOYSA-N 0.000 description 1
• DHXNZYCXMFBMHE-UHFFFAOYSA-M 3-bromopropanoate Chemical compound [O-]C(=O)CCBr DHXNZYCXMFBMHE-UHFFFAOYSA-M 0.000 description 1
• KDKJMZBICNRQQU-UHFFFAOYSA-N 3-chloro-4-(2-methylpropyl)benzoic acid Chemical compound CC(C)CC1=CC=C(C(O)=O)C=C1Cl KDKJMZBICNRQQU-UHFFFAOYSA-N 0.000 description 1
• PPRFRHNRCGDZIV-UHFFFAOYSA-N 3-cyano-4-(2-methylpropyl)benzoic acid Chemical compound CC(C)CC1=CC=C(C(O)=O)C=C1C#N PPRFRHNRCGDZIV-UHFFFAOYSA-N 0.000 description 1
• GQMIIRNVWXBQTI-UHFFFAOYSA-N 3-cyano-4-phenylbenzoic acid Chemical compound N#CC1=CC(C(=O)O)=CC=C1C1=CC=CC=C1 GQMIIRNVWXBQTI-UHFFFAOYSA-N 0.000 description 1
• VASNKPRZBWHYFN-UHFFFAOYSA-N 4-(2-fluorophenyl)-3-(trifluoromethyl)benzoic acid Chemical compound FC(F)(F)C1=CC(C(=O)O)=CC=C1C1=CC=CC=C1F VASNKPRZBWHYFN-UHFFFAOYSA-N 0.000 description 1
• KMBQTDRIDOTLSX-UHFFFAOYSA-N 4-(2-methylpropyl)-3-(trifluoromethyl)benzoic acid Chemical compound CC(C)CC1=CC=C(C(O)=O)C=C1C(F)(F)F KMBQTDRIDOTLSX-UHFFFAOYSA-N 0.000 description 1
• PSKJIHDVFDVNBU-UHFFFAOYSA-N 4-bromo-3-chlorobenzoic acid Chemical compound OC(=O)C1=CC=C(Br)C(Cl)=C1 PSKJIHDVFDVNBU-UHFFFAOYSA-N 0.000 description 1
• DPVRVZQEDJVWLS-UHFFFAOYSA-N 4-hydroxy-3-(trifluoromethyl)benzoic acid Chemical compound OC(=O)C1=CC=C(O)C(C(F)(F)F)=C1 DPVRVZQEDJVWLS-UHFFFAOYSA-N 0.000 description 1
• COWRCHINGJTIKJ-UHFFFAOYSA-N 4-methoxy-3-phenylbenzoic acid Chemical compound COC1=CC=C(C(O)=O)C=C1C1=CC=CC=C1 COWRCHINGJTIKJ-UHFFFAOYSA-N 0.000 description 1
• GIUAGKGTDDIMHB-UHFFFAOYSA-N 4-phenyl-5-(trifluoromethyl)thiophene-2-carboxylic acid Chemical compound S1C(C(=O)O)=CC(C=2C=CC=CC=2)=C1C(F)(F)F GIUAGKGTDDIMHB-UHFFFAOYSA-N 0.000 description 1
• OLTRUTPHSBQWAZ-UHFFFAOYSA-N 5-chloro-6-oxo-1h-pyridine-3-carboxylic acid Chemical compound OC(=O)C1=CNC(=O)C(Cl)=C1 OLTRUTPHSBQWAZ-UHFFFAOYSA-N 0.000 description 1
• HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
• 101710186708 Agglutinin Proteins 0.000 description 1
• 235000019489 Almond oil Nutrition 0.000 description 1
• KLSJWNVTNUYHDU-UHFFFAOYSA-N Amitrole Chemical compound NC1=NC=NN1 KLSJWNVTNUYHDU-UHFFFAOYSA-N 0.000 description 1
• QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
• USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 1
• 239000005695 Ammonium acetate Substances 0.000 description 1
• 244000144725 Amygdalus communis Species 0.000 description 1
• 235000011437 Amygdalus communis Nutrition 0.000 description 1
• 101100500467 Arabidopsis thaliana EAAC gene Proteins 0.000 description 1
• 239000004475 Arginine Substances 0.000 description 1
• 208000032116 Autoimmune Experimental Encephalomyelitis Diseases 0.000 description 1
• 108010001478 Bacitracin Proteins 0.000 description 1
• KWIUHFFTVRNATP-UHFFFAOYSA-N Betaine Natural products C[N+](C)(C)CC([O-])=O KWIUHFFTVRNATP-UHFFFAOYSA-N 0.000 description 1
• JQJPBYFTQAANLE-UHFFFAOYSA-N Butyl nitrite Chemical compound CCCCON=O JQJPBYFTQAANLE-UHFFFAOYSA-N 0.000 description 1
• CYVNUGNTRBROHF-UHFFFAOYSA-N C(C(C)C)[Zn].[Br] Chemical compound C(C(C)C)[Zn].[Br] CYVNUGNTRBROHF-UHFFFAOYSA-N 0.000 description 1
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
• OKTJSMMVPCPJKN-NJFSPNSNSA-N Carbon-14 Chemical compound [14C] OKTJSMMVPCPJKN-NJFSPNSNSA-N 0.000 description 1
• 229920002261 Corn starch Polymers 0.000 description 1
• 229930105110 Cyclosporin A Natural products 0.000 description 1
• PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 description 1
• 108010036949 Cyclosporine Proteins 0.000 description 1
• YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 1
• 241000792859 Enema Species 0.000 description 1
• 108090000790 Enzymes Proteins 0.000 description 1
• 102000004190 Enzymes Human genes 0.000 description 1
• IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 1
• PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
• 101710112457 Exoglucanase Proteins 0.000 description 1
• CWYNVVGOOAEACU-UHFFFAOYSA-N Fe2+ Chemical compound [Fe+2] CWYNVVGOOAEACU-UHFFFAOYSA-N 0.000 description 1
• XPDWGBQVDMORPB-UHFFFAOYSA-N Fluoroform Chemical class FC(F)F XPDWGBQVDMORPB-UHFFFAOYSA-N 0.000 description 1
• 229920000084 Gum arabic Polymers 0.000 description 1
• 101000888425 Homo sapiens Putative uncharacterized protein C11orf40 Proteins 0.000 description 1
• 101710146024 Horcolin Proteins 0.000 description 1
• HCUARRIEZVDMPT-UHFFFAOYSA-N Indole-2-carboxylic acid Chemical class C1=CC=C2NC(C(=O)O)=CC2=C1 HCUARRIEZVDMPT-UHFFFAOYSA-N 0.000 description 1
• 206010061218 Inflammation Diseases 0.000 description 1
• LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 description 1
• ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
• HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
• KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
• FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 1
• GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
• 101710189395 Lectin Proteins 0.000 description 1
• GDBQQVLCIARPGH-UHFFFAOYSA-N Leupeptin Natural products CC(C)CC(NC(C)=O)C(=O)NC(CC(C)C)C(=O)NC(C=O)CCCN=C(N)N GDBQQVLCIARPGH-UHFFFAOYSA-N 0.000 description 1
• WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
• 206010025327 Lymphopenia Diseases 0.000 description 1
• KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
• 239000004472 Lysine Substances 0.000 description 1
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
• 101710179758 Mannose-specific lectin Proteins 0.000 description 1
• 101710150763 Mannose-specific lectin 1 Proteins 0.000 description 1
• 101710150745 Mannose-specific lectin 2 Proteins 0.000 description 1
• 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
• HSHXDCVZWHOWCS-UHFFFAOYSA-N N'-hexadecylthiophene-2-carbohydrazide Chemical compound CCCCCCCCCCCCCCCCNNC(=O)c1cccs1 HSHXDCVZWHOWCS-UHFFFAOYSA-N 0.000 description 1
• KWIUHFFTVRNATP-UHFFFAOYSA-O N,N,N-trimethylglycinium Chemical compound C[N+](C)(C)CC(O)=O KWIUHFFTVRNATP-UHFFFAOYSA-O 0.000 description 1
• MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
• GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
• 108091028043 Nucleic acid sequence Proteins 0.000 description 1
• OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
• 240000006711 Pistacia vera Species 0.000 description 1
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
• 102100039548 Putative uncharacterized protein C11orf40 Human genes 0.000 description 1
• 241000144290 Sigmodon hispidus Species 0.000 description 1
• UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
• DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
• 241000209140 Triticum Species 0.000 description 1
• 235000021307 Triticum Nutrition 0.000 description 1
• YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 1
• HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
• 239000000205 acacia gum Substances 0.000 description 1
• 235000010489 acacia gum Nutrition 0.000 description 1
• 230000003044 adaptive effect Effects 0.000 description 1
• 239000000654 additive Substances 0.000 description 1
• 239000000443 aerosol Substances 0.000 description 1
• 239000000910 agglutinin Substances 0.000 description 1
• 230000008484 agonism Effects 0.000 description 1
• 239000003905 agrochemical Substances 0.000 description 1
• 150000001350 alkyl halides Chemical class 0.000 description 1
• 230000029936 alkylation Effects 0.000 description 1
• 238000005804 alkylation reaction Methods 0.000 description 1
• 235000020224 almond Nutrition 0.000 description 1
• 239000008168 almond oil Substances 0.000 description 1
• XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
• 229910052782 aluminium Inorganic materials 0.000 description 1
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
• 150000001408 amides Chemical class 0.000 description 1
• 235000019257 ammonium acetate Nutrition 0.000 description 1
• 229940043376 ammonium acetate Drugs 0.000 description 1
• 239000003708 ampul Substances 0.000 description 1
• 239000005557 antagonist Substances 0.000 description 1
• 230000001556 anti-picornavirus Effects 0.000 description 1
• 239000006286 aqueous extract Substances 0.000 description 1
• 239000008135 aqueous vehicle Substances 0.000 description 1
• ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
• 229960003121 arginine Drugs 0.000 description 1
• 238000011914 asymmetric synthesis Methods 0.000 description 1
• 239000012298 atmosphere Substances 0.000 description 1
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
• 230000001363 autoimmune Effects 0.000 description 1
• 239000012752 auxiliary agent Substances 0.000 description 1
• 229960003071 bacitracin Drugs 0.000 description 1
• 229930184125 bacitracin Natural products 0.000 description 1
• CLKOFPXJLQSYAH-ABRJDSQDSA-N bacitracin A Chemical compound C1SC([C@@H](N)[C@@H](C)CC)=N[C@@H]1C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]1C(=O)N[C@H](CCCN)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2N=CNC=2)C(=O)N[C@H](CC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)NCCCC1 CLKOFPXJLQSYAH-ABRJDSQDSA-N 0.000 description 1
• 239000011324 bead Substances 0.000 description 1
• 230000008901 benefit Effects 0.000 description 1
• 229960003237 betaine Drugs 0.000 description 1
• 239000011230 binding agent Substances 0.000 description 1
• 230000000975 bioactive effect Effects 0.000 description 1
• 230000004071 biological effect Effects 0.000 description 1
• 210000004369 blood Anatomy 0.000 description 1
• 239000008280 blood Substances 0.000 description 1
• 230000037396 body weight Effects 0.000 description 1
• 239000006172 buffering agent Substances 0.000 description 1
• PIJXRNNCIJAUOX-UHFFFAOYSA-N butanoic acid;hydrochloride Chemical compound Cl.CCCC(O)=O PIJXRNNCIJAUOX-UHFFFAOYSA-N 0.000 description 1
• 125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
• 229960001948 caffeine Drugs 0.000 description 1
• VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 description 1
• 239000011575 calcium Substances 0.000 description 1
• 229910052791 calcium Inorganic materials 0.000 description 1
• FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 description 1
• 150000001733 carboxylic acid esters Chemical class 0.000 description 1
• 230000015556 catabolic process Effects 0.000 description 1
• 230000020411 cell activation Effects 0.000 description 1
• 230000010261 cell growth Effects 0.000 description 1
• 230000009087 cell motility Effects 0.000 description 1
• 239000001913 cellulose Substances 0.000 description 1
• 235000010980 cellulose Nutrition 0.000 description 1
• 229920002678 cellulose Polymers 0.000 description 1
• 238000005119 centrifugation Methods 0.000 description 1
• 230000008859 change Effects 0.000 description 1
• 239000007810 chemical reaction solvent Substances 0.000 description 1
• 239000003795 chemical substances by application Substances 0.000 description 1
• 125000001309 chloro group Chemical group Cl* 0.000 description 1
• OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
• 229960001231 choline Drugs 0.000 description 1
• 238000011097 chromatography purification Methods 0.000 description 1
• 210000000349 chromosome Anatomy 0.000 description 1
• 229960001265 ciclosporin Drugs 0.000 description 1
• 238000004140 cleaning Methods 0.000 description 1
• 229940110456 cocoa butter Drugs 0.000 description 1
• 235000019868 cocoa butter Nutrition 0.000 description 1
• 239000003086 colorant Substances 0.000 description 1
• 238000004040 coloring Methods 0.000 description 1
• 238000009833 condensation Methods 0.000 description 1
• 230000005494 condensation Effects 0.000 description 1
• 239000007859 condensation product Substances 0.000 description 1
• 238000006482 condensation reaction Methods 0.000 description 1
• 238000013270 controlled release Methods 0.000 description 1
• 238000007796 conventional method Methods 0.000 description 1
• 229910052802 copper Inorganic materials 0.000 description 1
• 239000010949 copper Substances 0.000 description 1
• 239000008120 corn starch Substances 0.000 description 1
• 239000006184 cosolvent Substances 0.000 description 1
• 125000000000 cycloalkoxy group Chemical group 0.000 description 1
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• 125000001352 cyclobutyloxy group Chemical group C1(CCC1)O* 0.000 description 1
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
• 125000002933 cyclohexyloxy group Chemical group C1(CCCCC1)O* 0.000 description 1
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• 125000001887 cyclopentyloxy group Chemical group C1(CCCC1)O* 0.000 description 1
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
• 125000000131 cyclopropyloxy group Chemical group C1(CC1)O* 0.000 description 1
• 230000002950 deficient Effects 0.000 description 1
• 239000003405 delayed action preparation Substances 0.000 description 1
• 238000012217 deletion Methods 0.000 description 1
• 230000037430 deletion Effects 0.000 description 1
• 238000001514 detection method Methods 0.000 description 1
• OKKJLVBELUTLKV-MZCSYVLQSA-N deuterated methanol Substances [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 1
• 229910052805 deuterium Inorganic materials 0.000 description 1
• 235000019700 dicalcium phosphate Nutrition 0.000 description 1
• HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
• 239000007884 disintegrant Substances 0.000 description 1
• CETRZFQIITUQQL-UHFFFAOYSA-N dmso dimethylsulfoxide Chemical compound CS(C)=O.CS(C)=O CETRZFQIITUQQL-UHFFFAOYSA-N 0.000 description 1
• 238000009513 drug distribution Methods 0.000 description 1
• 210000005069 ears Anatomy 0.000 description 1
• 230000005684 electric field Effects 0.000 description 1
• 201000002491 encephalomyelitis Diseases 0.000 description 1
• 239000007920 enema Substances 0.000 description 1
• 229940079360 enema for constipation Drugs 0.000 description 1
• BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
• 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
• VTYGPWKAOGTHBB-UHFFFAOYSA-N ethyl 3-[3-chloro-5-[5-(3-chloro-4-ethoxyphenyl)-1,2,4-oxadiazol-3-yl]indol-1-yl]propanoate Chemical compound C=1C=C2N(CCC(=O)OCC)C=C(Cl)C2=CC=1C(N=1)=NOC=1C1=CC=C(OCC)C(Cl)=C1 VTYGPWKAOGTHBB-UHFFFAOYSA-N 0.000 description 1
• RFBWJMQCZQAIHR-UHFFFAOYSA-N ethyl 3-[3-chloro-5-[5-(3-chloro-4-propoxyphenyl)-1,2,4-oxadiazol-3-yl]indol-1-yl]propanoate Chemical compound C1=C(Cl)C(OCCC)=CC=C1C1=NC(C=2C=C3C(Cl)=CN(CCC(=O)OCC)C3=CC=2)=NO1 RFBWJMQCZQAIHR-UHFFFAOYSA-N 0.000 description 1
• ISIYSZFSLGIMBP-UHFFFAOYSA-N ethyl 3-[3-chloro-5-[5-(4-methoxy-3-phenylphenyl)-1,2,4-oxadiazol-3-yl]indol-1-yl]propanoate Chemical compound C=1C=C2N(CCC(=O)OCC)C=C(Cl)C2=CC=1C(N=1)=NOC=1C(C=1)=CC=C(OC)C=1C1=CC=CC=C1 ISIYSZFSLGIMBP-UHFFFAOYSA-N 0.000 description 1
• KZCIDOGWEOMKSB-UHFFFAOYSA-N ethyl 3-[5-[5-(3-chloro-4-propan-2-yloxyphenyl)-1,2,4-oxadiazol-3-yl]indol-1-yl]propanoate Chemical compound C=1C=C2N(CCC(=O)OCC)C=CC2=CC=1C(N=1)=NOC=1C1=CC=C(OC(C)C)C(Cl)=C1 KZCIDOGWEOMKSB-UHFFFAOYSA-N 0.000 description 1
• CJNFKLLEODJXCH-UHFFFAOYSA-N ethyl 3-[5-[5-[3-phenyl-4-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-3-yl]indol-1-yl]propanoate Chemical compound C=1C=C2N(CCC(=O)OCC)C=CC2=CC=1C(N=1)=NOC=1C(C=1)=CC=C(C(F)(F)F)C=1C1=CC=CC=C1 CJNFKLLEODJXCH-UHFFFAOYSA-N 0.000 description 1
• XYPUVGVJGYCVPK-UHFFFAOYSA-N ethyl 4-[4-[5-(3-cyano-4-propan-2-yloxyphenyl)-1,2,4-oxadiazol-3-yl]indol-1-yl]butanoate Chemical compound C1=CC=C2N(CCCC(=O)OCC)C=CC2=C1C(N=1)=NOC=1C1=CC=C(OC(C)C)C(C#N)=C1 XYPUVGVJGYCVPK-UHFFFAOYSA-N 0.000 description 1
• 230000005284 excitation Effects 0.000 description 1
• 208000012997 experimental autoimmune encephalomyelitis Diseases 0.000 description 1
• 239000003925 fat Substances 0.000 description 1
• 235000019197 fats Nutrition 0.000 description 1
• KTWOOEGAPBSYNW-UHFFFAOYSA-N ferrocene Chemical compound [Fe+2].C=1C=C[CH-]C=1.C=1C=C[CH-]C=1 KTWOOEGAPBSYNW-UHFFFAOYSA-N 0.000 description 1
• 239000000945 filler Substances 0.000 description 1
• 238000011049 filling Methods 0.000 description 1
• GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 1
• 238000011010 flushing procedure Methods 0.000 description 1
• 239000006260 foam Substances 0.000 description 1
• 235000013305 food Nutrition 0.000 description 1
• 235000003599 food sweetener Nutrition 0.000 description 1
• 239000000417 fungicide Substances 0.000 description 1
• 125000003838 furazanyl group Chemical group 0.000 description 1
• 125000002541 furyl group Chemical group 0.000 description 1
• 229940083124 ganglion-blocking antiadrenergic secondary and tertiary amines Drugs 0.000 description 1
• 239000000499 gel Substances 0.000 description 1
• 239000003349 gelling agent Substances 0.000 description 1
• 239000011521 glass Substances 0.000 description 1
• 125000005456 glyceride group Chemical group 0.000 description 1
• 239000008187 granular material Substances 0.000 description 1
• 210000003630 histaminocyte Anatomy 0.000 description 1
• HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
• 229960002885 histidine Drugs 0.000 description 1
• 239000012456 homogeneous solution Substances 0.000 description 1
• XGIHQYAWBCFNPY-AZOCGYLKSA-N hydrabamine Chemical compound C([C@@H]12)CC3=CC(C(C)C)=CC=C3[C@@]2(C)CCC[C@@]1(C)CNCCNC[C@@]1(C)[C@@H]2CCC3=CC(C(C)C)=CC=C3[C@@]2(C)CCC1 XGIHQYAWBCFNPY-AZOCGYLKSA-N 0.000 description 1
• 150000004677 hydrates Chemical class 0.000 description 1
• 150000002431 hydrogen Chemical class 0.000 description 1
• 230000002209 hydrophobic effect Effects 0.000 description 1
• XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
• 125000002768 hydroxyalkyl group Chemical group 0.000 description 1
• 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
• 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
• 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
• 125000002883 imidazolyl group Chemical group 0.000 description 1
• 210000002865 immune cell Anatomy 0.000 description 1
• 239000002955 immunomodulating agent Substances 0.000 description 1
• 229940121354 immunomodulator Drugs 0.000 description 1
• 230000001506 immunosuppresive effect Effects 0.000 description 1
• 238000002513 implantation Methods 0.000 description 1
• 239000012535 impurity Substances 0.000 description 1
• 238000011534 incubation Methods 0.000 description 1
• 125000001041 indolyl group Chemical group 0.000 description 1
• 230000006698 induction Effects 0.000 description 1
• 230000002757 inflammatory effect Effects 0.000 description 1
• 230000004054 inflammatory process Effects 0.000 description 1
• 239000003978 infusion fluid Substances 0.000 description 1
• 239000003112 inhibitor Substances 0.000 description 1
• 229910003480 inorganic solid Inorganic materials 0.000 description 1
• 238000010255 intramuscular injection Methods 0.000 description 1
• 239000007927 intramuscular injection Substances 0.000 description 1
• OCVXZQOKBHXGRU-UHFFFAOYSA-N iodine(1+) Chemical compound [I+] OCVXZQOKBHXGRU-UHFFFAOYSA-N 0.000 description 1
• HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 1
• 229910052742 iron Inorganic materials 0.000 description 1
• 125000002510 isobutoxy group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])O* 0.000 description 1
• 125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 description 1
• JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 1
• 125000001786 isothiazolyl group Chemical group 0.000 description 1
• 125000000842 isoxazolyl group Chemical group 0.000 description 1
• 239000008101 lactose Substances 0.000 description 1
• 239000000787 lecithin Substances 0.000 description 1
• 235000010445 lecithin Nutrition 0.000 description 1
• 229940067606 lecithin Drugs 0.000 description 1
• 229960003136 leucine Drugs 0.000 description 1
• 102000003835 leukotriene receptors Human genes 0.000 description 1
• 108090000146 leukotriene receptors Proteins 0.000 description 1
• GDBQQVLCIARPGH-ULQDDVLXSA-N leupeptin Chemical compound CC(C)C[C@H](NC(C)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C=O)CCCN=C(N)N GDBQQVLCIARPGH-ULQDDVLXSA-N 0.000 description 1
• 108010052968 leupeptin Proteins 0.000 description 1
• 150000002632 lipids Chemical class 0.000 description 1
• 229910052744 lithium Inorganic materials 0.000 description 1
• 239000003589 local anesthetic agent Substances 0.000 description 1
• 229960005015 local anesthetics Drugs 0.000 description 1
• 239000007937 lozenge Substances 0.000 description 1
• 210000002751 lymph Anatomy 0.000 description 1
• 230000001926 lymphatic effect Effects 0.000 description 1
• 231100001023 lymphopenia Toxicity 0.000 description 1
• 239000011777 magnesium Substances 0.000 description 1
• 229910052749 magnesium Inorganic materials 0.000 description 1
• 235000019359 magnesium stearate Nutrition 0.000 description 1
• 210000001161 mammalian embryo Anatomy 0.000 description 1
• WPBNNNQJVZRUHP-UHFFFAOYSA-L manganese(2+);methyl n-[[2-(methoxycarbonylcarbamothioylamino)phenyl]carbamothioyl]carbamate;n-[2-(sulfidocarbothioylamino)ethyl]carbamodithioate Chemical compound [Mn+2].[S-]C(=S)NCCNC([S-])=S.COC(=O)NC(=S)NC1=CC=CC=C1NC(=S)NC(=O)OC WPBNNNQJVZRUHP-UHFFFAOYSA-L 0.000 description 1
• COTNUBDHGSIOTA-UHFFFAOYSA-N meoh methanol Chemical compound OC.OC COTNUBDHGSIOTA-UHFFFAOYSA-N 0.000 description 1
• 108020004999 messenger RNA Proteins 0.000 description 1
• 230000002503 metabolic effect Effects 0.000 description 1
• 239000002207 metabolite Substances 0.000 description 1
• UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 1
• 229960000485 methotrexate Drugs 0.000 description 1
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
• QTKAQJWFVXPIFV-YFKPBYRVSA-N methyl (2r)-2-acetamido-3-sulfanylpropanoate Chemical compound COC(=O)[C@H](CS)NC(C)=O QTKAQJWFVXPIFV-YFKPBYRVSA-N 0.000 description 1
• ZREVPFANJBZHEU-UHFFFAOYSA-N methyl 3-bromo-4-methoxybenzoate Chemical compound COC(=O)C1=CC=C(OC)C(Br)=C1 ZREVPFANJBZHEU-UHFFFAOYSA-N 0.000 description 1
• AHPCEMBOTQXADD-UHFFFAOYSA-N methyl 3-cyano-4-hydroxybenzoate Chemical compound COC(=O)C1=CC=C(O)C(C#N)=C1 AHPCEMBOTQXADD-UHFFFAOYSA-N 0.000 description 1
• RDMSDMSSVFMCKQ-UHFFFAOYSA-N methyl 4-phenyl-5-(trifluoromethyl)thiophene-2-carboxylate Chemical compound S1C(C(=O)OC)=CC(C=2C=CC=CC=2)=C1C(F)(F)F RDMSDMSSVFMCKQ-UHFFFAOYSA-N 0.000 description 1
• 150000004702 methyl esters Chemical class 0.000 description 1
• 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
• 239000011325 microbead Substances 0.000 description 1
• 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
• 239000008108 microcrystalline cellulose Substances 0.000 description 1
• 229940016286 microcrystalline cellulose Drugs 0.000 description 1
• 238000002156 mixing Methods 0.000 description 1
• 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• PVWOIHVRPOBWPI-UHFFFAOYSA-N n-propyl iodide Chemical compound CCCI PVWOIHVRPOBWPI-UHFFFAOYSA-N 0.000 description 1
• PSZYNBSKGUBXEH-UHFFFAOYSA-N naphthalene-1-sulfonic acid Chemical compound C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1 PSZYNBSKGUBXEH-UHFFFAOYSA-N 0.000 description 1
• 229910017604 nitric acid Inorganic materials 0.000 description 1
• 239000012299 nitrogen atmosphere Substances 0.000 description 1
• 230000003287 optical effect Effects 0.000 description 1
• 125000001715 oxadiazolyl group Chemical group 0.000 description 1
• 125000002971 oxazolyl group Chemical group 0.000 description 1
• KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 1
• 239000001301 oxygen Substances 0.000 description 1
• 229910052763 palladium Inorganic materials 0.000 description 1
• PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 1
• 238000007911 parenteral administration Methods 0.000 description 1
• 239000002304 perfume Substances 0.000 description 1
• 230000002093 peripheral effect Effects 0.000 description 1
• 239000000575 pesticide Substances 0.000 description 1
• 230000000144 pharmacologic effect Effects 0.000 description 1
• 238000005191 phase separation Methods 0.000 description 1
• 229910052698 phosphorus Inorganic materials 0.000 description 1
• 239000011574 phosphorus Substances 0.000 description 1
• 230000026731 phosphorylation Effects 0.000 description 1
• 238000006366 phosphorylation reaction Methods 0.000 description 1
• 239000002798 polar solvent Substances 0.000 description 1
• 229920000768 polyamine Polymers 0.000 description 1
• 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
• 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
• 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
• 239000011591 potassium Substances 0.000 description 1
• 229920001592 potato starch Polymers 0.000 description 1
• 239000002243 precursor Substances 0.000 description 1
• 238000002953 preparative HPLC Methods 0.000 description 1
• 238000004262 preparative liquid chromatography Methods 0.000 description 1
• 150000003141 primary amines Chemical class 0.000 description 1
• MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
• 229960004919 procaine Drugs 0.000 description 1
• 238000012545 processing Methods 0.000 description 1
• 239000000651 prodrug Substances 0.000 description 1
• 229940002612 prodrug Drugs 0.000 description 1
• 230000035755 proliferation Effects 0.000 description 1
• 238000011321 prophylaxis Methods 0.000 description 1
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
• QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical class CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 1
• 102000004169 proteins and genes Human genes 0.000 description 1
• 239000012264 purified product Substances 0.000 description 1
• 150000003212 purines Chemical class 0.000 description 1
• 125000003226 pyrazolyl group Chemical group 0.000 description 1
• 125000000168 pyrrolyl group Chemical group 0.000 description 1
• 230000002285 radioactive effect Effects 0.000 description 1
• ZAHRKKWIAAJSAO-UHFFFAOYSA-N rapamycin Natural products COCC(O)C(=C/C(C)C(=O)CC(OC(=O)C1CCCCN1C(=O)C(=O)C2(O)OC(CC(OC)C(=CC=CC=CC(C)CC(C)C(=O)C)C)CCC2C)C(C)CC3CCC(O)C(C3)OC)C ZAHRKKWIAAJSAO-UHFFFAOYSA-N 0.000 description 1
• 238000001953 recrystallisation Methods 0.000 description 1
• 230000000306 recurrent effect Effects 0.000 description 1
• 239000011347 resin Substances 0.000 description 1
• 229920005989 resin Polymers 0.000 description 1
• 230000004044 response Effects 0.000 description 1
• 238000002821 scintillation proximity assay Methods 0.000 description 1
• 125000005920 sec-butoxy group Chemical group 0.000 description 1
• 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
• 238000000926 separation method Methods 0.000 description 1
• 230000009919 sequestration Effects 0.000 description 1
• 229910001958 silver carbonate Inorganic materials 0.000 description 1
• LKZMBDSASOBTPN-UHFFFAOYSA-L silver carbonate Substances [Ag].[O-]C([O-])=O LKZMBDSASOBTPN-UHFFFAOYSA-L 0.000 description 1
• 238000002603 single-photon emission computed tomography Methods 0.000 description 1
• QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 description 1
• 229960002930 sirolimus Drugs 0.000 description 1
• 239000010802 sludge Substances 0.000 description 1
• 229910000029 sodium carbonate Inorganic materials 0.000 description 1
• 235000011182 sodium carbonates Nutrition 0.000 description 1
• 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
• 235000010288 sodium nitrite Nutrition 0.000 description 1
• 239000001488 sodium phosphate Substances 0.000 description 1
• 229910000162 sodium phosphate Inorganic materials 0.000 description 1
• 159000000000 sodium salts Chemical class 0.000 description 1
• 229940079832 sodium starch glycolate Drugs 0.000 description 1
• 239000008109 sodium starch glycolate Substances 0.000 description 1
• 229920003109 sodium starch glycolate Polymers 0.000 description 1
• 239000012453 solvate Substances 0.000 description 1
• 235000010199 sorbic acid Nutrition 0.000 description 1
• 239000004334 sorbic acid Substances 0.000 description 1
• 229940075582 sorbic acid Drugs 0.000 description 1
• 239000000600 sorbitol Substances 0.000 description 1
• 235000010356 sorbitol Nutrition 0.000 description 1
• 230000003595 spectral effect Effects 0.000 description 1
• WWUZIQQURGPMPG-KRWOKUGFSA-N sphingosine Chemical compound CCCCCCCCCCCCC\C=C\[C@@H](O)[C@@H](N)CO WWUZIQQURGPMPG-KRWOKUGFSA-N 0.000 description 1
• 210000000952 spleen Anatomy 0.000 description 1
• 239000007921 spray Substances 0.000 description 1
• 230000000087 stabilizing effect Effects 0.000 description 1
• 230000000707 stereoselective effect Effects 0.000 description 1
• 230000001954 sterilising effect Effects 0.000 description 1
• 238000004659 sterilization and disinfection Methods 0.000 description 1
• 150000003431 steroids Chemical class 0.000 description 1
• 239000011550 stock solution Substances 0.000 description 1
• 239000002511 suppository base Substances 0.000 description 1
• 230000001629 suppression Effects 0.000 description 1
• 239000004094 surface-active agent Substances 0.000 description 1
• 239000003765 sweetening agent Substances 0.000 description 1
• 208000024891 symptom Diseases 0.000 description 1
• 239000006188 syrup Substances 0.000 description 1
• 235000020357 syrup Nutrition 0.000 description 1
• 239000002278 tabletting lubricant Substances 0.000 description 1
• 239000000454 talc Substances 0.000 description 1
• 229910052623 talc Inorganic materials 0.000 description 1
• 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
• WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
• 125000003831 tetrazolyl group Chemical group 0.000 description 1
• 229960004559 theobromine Drugs 0.000 description 1
• 230000001225 therapeutic effect Effects 0.000 description 1
• 238000002560 therapeutic procedure Methods 0.000 description 1
• 125000001113 thiadiazolyl group Chemical group 0.000 description 1
• 125000000335 thiazolyl group Chemical group 0.000 description 1
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
• 238000011200 topical administration Methods 0.000 description 1
• 230000000699 topical effect Effects 0.000 description 1
• 238000012546 transfer Methods 0.000 description 1
• 125000001425 triazolyl group Chemical group 0.000 description 1
• YFTHZRPMJXBUME-UHFFFAOYSA-N tripropylamine Chemical compound CCCN(CCC)CCC YFTHZRPMJXBUME-UHFFFAOYSA-N 0.000 description 1
• LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
• RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
• 229910052722 tritium Inorganic materials 0.000 description 1
• 238000009827 uniform distribution Methods 0.000 description 1
• NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
• 235000015112 vegetable and seed oil Nutrition 0.000 description 1
• 239000008158 vegetable oil Substances 0.000 description 1
• 210000005253 yeast cell Anatomy 0.000 description 1
• 239000011701 zinc Substances 0.000 description 1
• 229910052725 zinc Inorganic materials 0.000 description 1