ES2321028T3 - Derivados de tiazol condensados que tienen afinidad por el receptor h3 de histamina. - Google Patents

Info

Publication number

ES2321028T3

ES2321028T3 ES06710058T ES06710058T ES2321028T3 ES 2321028 T3 ES2321028 T3 ES 2321028T3 ES 06710058 T ES06710058 T ES 06710058T ES 06710058 T ES06710058 T ES 06710058T ES 2321028 T3 ES2321028 T3 ES 2321028T3

Authority

ES

Spain

Prior art keywords

tetrahydro

thiazolo

cyclobutyl

azepin

alkyl

Prior art date

2005-03-14

Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)

Active

Links

• Espacenet
• Global Dossier
• Discuss

• NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 title description 38
• 229960001340 histamine Drugs 0.000 title description 19
• 238000000034 method Methods 0.000 claims abstract description 118
• 230000008569 process Effects 0.000 claims abstract description 56
• 238000011282 treatment Methods 0.000 claims abstract description 18
• 238000002360 preparation method Methods 0.000 claims abstract description 16
• 208000012902 Nervous system disease Diseases 0.000 claims abstract description 6
• 208000025966 Neurological disease Diseases 0.000 claims abstract description 6
• 125000000217 alkyl group Chemical group 0.000 claims description 118
• 150000001875 compounds Chemical class 0.000 claims description 104
• 125000001072 heteroaryl group Chemical group 0.000 claims description 73
• 125000003118 aryl group Chemical group 0.000 claims description 72
• -1 hydroxy, cyano, amino Chemical group 0.000 claims description 70
• 125000000623 heterocyclic group Chemical group 0.000 claims description 62
• 229910052736 halogen Inorganic materials 0.000 claims description 50
• 229910052739 hydrogen Inorganic materials 0.000 claims description 50
• 150000002367 halogens Chemical group 0.000 claims description 48
• 239000001257 hydrogen Substances 0.000 claims description 44
• 125000001424 substituent group Chemical group 0.000 claims description 36
• 125000004321 azepin-2-yl group Chemical group [H]N1C([H])=C([H])C([H])=C([H])C([H])=C1* 0.000 claims description 35
• VFHJFPGGWIXTMI-UHFFFAOYSA-N 6-cyclobutyl-2-piperidin-4-yl-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepine Chemical compound C1CCC1N1CCC(SC(=N2)C3CCNCC3)=C2CC1 VFHJFPGGWIXTMI-UHFFFAOYSA-N 0.000 claims description 31
• 150000003839 salts Chemical class 0.000 claims description 31
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 29
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 28
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 26
• 239000012453 solvate Substances 0.000 claims description 26
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 24
• XYOVOXDWRFGKEX-UHFFFAOYSA-N azepine Chemical compound N1C=CC=CC=C1 XYOVOXDWRFGKEX-UHFFFAOYSA-N 0.000 claims description 23
• WUFMUYFEWPBICZ-UHFFFAOYSA-N 5-[3-(6-cyclobutyl-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepin-2-yl)pyrrolidin-1-yl]pyridine-2-carbonitrile Chemical compound C1=NC(C#N)=CC=C1N1CC(C=2SC=3CCN(CCC=3N=2)C2CCC2)CC1 WUFMUYFEWPBICZ-UHFFFAOYSA-N 0.000 claims description 18
• 229910002091 carbon monoxide Inorganic materials 0.000 claims description 17
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 17
• 150000002431 hydrogen Chemical group 0.000 claims description 16
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 14
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 14
• 239000003814 drug Substances 0.000 claims description 13
• 229910052760 oxygen Inorganic materials 0.000 claims description 13
• YXCBMVKTMYRQHH-UHFFFAOYSA-N 2-(4-bromophenyl)-6-cyclobutyl-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepine Chemical compound C1=CC(Br)=CC=C1C(S1)=NC2=C1CCN(C1CCC1)CC2 YXCBMVKTMYRQHH-UHFFFAOYSA-N 0.000 claims description 12
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 12
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 12
• 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 11
• SOSZRSSOEUVNSJ-UHFFFAOYSA-N 2-(6-chloropyridin-3-yl)-6-cyclobutyl-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepine Chemical compound C1=NC(Cl)=CC=C1C(S1)=NC2=C1CCN(C1CCC1)CC2 SOSZRSSOEUVNSJ-UHFFFAOYSA-N 0.000 claims description 11
• NQULAAUVWPUYMT-UHFFFAOYSA-N 6-cyclobutyl-2-pyrrolidin-3-yl-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepine Chemical compound C1CCC1N1CCC(SC(=N2)C3CNCC3)=C2CC1 NQULAAUVWPUYMT-UHFFFAOYSA-N 0.000 claims description 11
• 125000003545 alkoxy group Chemical group 0.000 claims description 11
• JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 claims description 11
• LOMSQGIKFZLYTD-UHFFFAOYSA-N 5-(6-cyclobutyl-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepin-2-yl)pyridine-2-carboxylic acid Chemical compound C1=NC(C(=O)O)=CC=C1C(S1)=NC2=C1CCN(C1CCC1)CC2 LOMSQGIKFZLYTD-UHFFFAOYSA-N 0.000 claims description 8
• DXAMKIWWMUKGFJ-UHFFFAOYSA-N 5-[4-(6-cyclobutyl-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepin-2-yl)piperidin-1-yl]pyridine-2-carbonitrile Chemical compound C1=NC(C#N)=CC=C1N1CCC(C=2SC=3CCN(CCC=3N=2)C2CCC2)CC1 DXAMKIWWMUKGFJ-UHFFFAOYSA-N 0.000 claims description 8
• 229910052757 nitrogen Inorganic materials 0.000 claims description 8
• NWISRHCDYAIVGL-UHFFFAOYSA-N 4-(6-cyclobutyl-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepin-2-yl)benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1C(S1)=NC2=C1CCN(C1CCC1)CC2 NWISRHCDYAIVGL-UHFFFAOYSA-N 0.000 claims description 7
• 229910052799 carbon Inorganic materials 0.000 claims description 7
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 7
• 125000001188 haloalkyl group Chemical group 0.000 claims description 7
• SSXWYPXUESEVTG-UHFFFAOYSA-N 5-(6-cyclobutyl-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepin-2-yl)pyridine-2-carbonitrile Chemical compound C1=NC(C#N)=CC=C1C(S1)=NC2=C1CCN(C1CCC1)CC2 SSXWYPXUESEVTG-UHFFFAOYSA-N 0.000 claims description 6
• AVGWDAZNMDHRLW-UHFFFAOYSA-N 5-[4-(6-cyclobutyl-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepin-2-yl)piperidin-1-yl]-n,n-dimethylpyridine-2-carboxamide Chemical compound C1=NC(C(=O)N(C)C)=CC=C1N1CCC(C=2SC=3CCN(CCC=3N=2)C2CCC2)CC1 AVGWDAZNMDHRLW-UHFFFAOYSA-N 0.000 claims description 6
• MXNROENSEHWVOE-UHFFFAOYSA-N [4-(6-cyclobutyl-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepin-2-yl)piperidin-1-yl]-(5-methylpyridin-3-yl)methanone Chemical compound CC1=CN=CC(C(=O)N2CCC(CC2)C=2SC=3CCN(CCC=3N=2)C2CCC2)=C1 MXNROENSEHWVOE-UHFFFAOYSA-N 0.000 claims description 6
• FTVIUIXLKVOCFD-UHFFFAOYSA-N [4-(6-cyclobutyl-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepin-2-yl)piperidin-1-yl]-(6-methylpyridin-2-yl)methanone Chemical compound CC1=CC=CC(C(=O)N2CCC(CC2)C=2SC=3CCN(CCC=3N=2)C2CCC2)=N1 FTVIUIXLKVOCFD-UHFFFAOYSA-N 0.000 claims description 6
• 125000005119 alkyl cycloalkyl group Chemical group 0.000 claims description 6
• 239000008194 pharmaceutical composition Substances 0.000 claims description 6
• GVFNIRHEMHBGKK-UHFFFAOYSA-N 1-[4-(6-cyclobutyl-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepin-2-yl)phenyl]-3-methylimidazolidin-2-one Chemical compound O=C1N(C)CCN1C1=CC=C(C=2SC=3CCN(CCC=3N=2)C2CCC2)C=C1 GVFNIRHEMHBGKK-UHFFFAOYSA-N 0.000 claims description 5
• KNTSKCCSKLRVDW-UHFFFAOYSA-N 1-[5-(6-cyclobutyl-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepin-2-yl)pyridin-2-yl]-3-methylimidazolidin-2-one Chemical compound O=C1N(C)CCN1C1=CC=C(C=2SC=3CCN(CCC=3N=2)C2CCC2)C=N1 KNTSKCCSKLRVDW-UHFFFAOYSA-N 0.000 claims description 5
• FCKBSFHPXHYQIF-UHFFFAOYSA-N 1-[5-(6-cyclobutyl-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepin-2-yl)pyridin-2-yl]pyrrolidin-2-one Chemical compound O=C1CCCN1C1=CC=C(C=2SC=3CCN(CCC=3N=2)C2CCC2)C=N1 FCKBSFHPXHYQIF-UHFFFAOYSA-N 0.000 claims description 5
• NGNYCAXHGYNGLH-UHFFFAOYSA-N 2-(2-chloropyrimidin-5-yl)-6-cyclobutyl-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepine Chemical compound C1=NC(Cl)=NC=C1C(S1)=NC2=C1CCN(C1CCC1)CC2 NGNYCAXHGYNGLH-UHFFFAOYSA-N 0.000 claims description 5
• INCVZKRMUFWNJO-UHFFFAOYSA-N 5-(6-cyclobutyl-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepin-2-yl)-1H-pyrimidin-2-one Chemical compound N1C(=O)N=CC(C=2SC=3CCN(CCC=3N=2)C2CCC2)=C1 INCVZKRMUFWNJO-UHFFFAOYSA-N 0.000 claims description 5
• ITTSBLBFNODHJE-UHFFFAOYSA-N 5-[3-(6-cyclobutyl-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepin-2-yl)pyrrolidin-1-yl]pyridine-3-carbonitrile Chemical compound N#CC1=CN=CC(N2CC(CC2)C=2SC=3CCN(CCC=3N=2)C2CCC2)=C1 ITTSBLBFNODHJE-UHFFFAOYSA-N 0.000 claims description 5
• DGLSFKHHVVNPBJ-UHFFFAOYSA-N 5-[4-(6-cyclobutyl-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepin-2-yl)piperidin-1-yl]pyridine-2-carboxylic acid Chemical compound C1=NC(C(=O)O)=CC=C1N1CCC(C=2SC=3CCN(CCC=3N=2)C2CCC2)CC1 DGLSFKHHVVNPBJ-UHFFFAOYSA-N 0.000 claims description 5
• YBMAQOPLYKMTRY-UHFFFAOYSA-N 6-(6-cyclobutyl-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepin-2-yl)pyridine-3-carboxylic acid Chemical compound N1=CC(C(=O)O)=CC=C1C(S1)=NC2=C1CCN(C1CCC1)CC2 YBMAQOPLYKMTRY-UHFFFAOYSA-N 0.000 claims description 5
• ARVIAZSNBGBVQQ-UHFFFAOYSA-N 6-cyclobutyl-2-[6-(trifluoromethyl)pyridin-3-yl]-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepine Chemical compound C1=NC(C(F)(F)F)=CC=C1C(S1)=NC2=C1CCN(C1CCC1)CC2 ARVIAZSNBGBVQQ-UHFFFAOYSA-N 0.000 claims description 5
• 208000024827 Alzheimer disease Diseases 0.000 claims description 5
• GMTABOUGVASQOI-UHFFFAOYSA-N [4-(6-cyclobutyl-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepin-2-yl)piperidin-1-yl]-(thiadiazol-4-yl)methanone Chemical compound C=1SN=NC=1C(=O)N(CC1)CCC1C(SC=1CC2)=NC=1CCN2C1CCC1 GMTABOUGVASQOI-UHFFFAOYSA-N 0.000 claims description 5
• IHVIWVIMGNJRJG-UHFFFAOYSA-N [4-(6-cyclobutyl-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepin-2-yl)piperidin-1-yl]-pyrrolidin-1-ylmethanone Chemical compound C1CC(C=2SC=3CCN(CCC=3N=2)C2CCC2)CCN1C(=O)N1CCCC1 IHVIWVIMGNJRJG-UHFFFAOYSA-N 0.000 claims description 5
• NPHYKULDZXXDSA-UHFFFAOYSA-N [5-[4-(6-cyclobutyl-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepin-2-yl)piperidin-1-yl]pyridin-2-yl]-imidazol-1-ylmethanone Chemical compound C1=CN=CN1C(=O)C(N=C1)=CC=C1N(CC1)CCC1C(SC=1CC2)=NC=1CCN2C1CCC1 NPHYKULDZXXDSA-UHFFFAOYSA-N 0.000 claims description 5
• 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 5
• 229910052717 sulfur Inorganic materials 0.000 claims description 5
• RVMLJMMOHPMSBM-UHFFFAOYSA-N 1-[4-(6-cyclobutyl-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepin-2-yl)phenyl]imidazolidin-2-one Chemical compound O=C1NCCN1C1=CC=C(C=2SC=3CCN(CCC=3N=2)C2CCC2)C=C1 RVMLJMMOHPMSBM-UHFFFAOYSA-N 0.000 claims description 4
• VZWORUHCRUFYEY-UHFFFAOYSA-N 1-[4-(6-cyclobutyl-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepin-2-yl)phenyl]pyrrolidin-2-one Chemical compound O=C1CCCN1C1=CC=C(C=2SC=3CCN(CCC=3N=2)C2CCC2)C=C1 VZWORUHCRUFYEY-UHFFFAOYSA-N 0.000 claims description 4
• ZSVDVQPHRFNSMG-UHFFFAOYSA-N 1-[4-(6-ethyl-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepin-2-yl)phenyl]-3-methylimidazolidin-2-one Chemical compound S1C=2CCN(CC)CCC=2N=C1C(C=C1)=CC=C1N1CCN(C)C1=O ZSVDVQPHRFNSMG-UHFFFAOYSA-N 0.000 claims description 4
• APJQLFKODBWPDL-UHFFFAOYSA-N 4-(6-cyclobutyl-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepin-2-yl)-n-ethylbenzamide Chemical compound C1=CC(C(=O)NCC)=CC=C1C(S1)=NC2=C1CCN(C1CCC1)CC2 APJQLFKODBWPDL-UHFFFAOYSA-N 0.000 claims description 4
• RDFKBDPHVJMWFC-UHFFFAOYSA-N 4-(6-cyclobutyl-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepin-2-yl)-n-methylbenzamide Chemical compound C1=CC(C(=O)NC)=CC=C1C(S1)=NC2=C1CCN(C1CCC1)CC2 RDFKBDPHVJMWFC-UHFFFAOYSA-N 0.000 claims description 4
• OGZGDVSJDJSXRL-UHFFFAOYSA-N 4-(6-cyclobutyl-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepin-2-yl)-n-methylpiperidine-1-carboxamide Chemical compound C1CN(C(=O)NC)CCC1C(S1)=NC2=C1CCN(C1CCC1)CC2 OGZGDVSJDJSXRL-UHFFFAOYSA-N 0.000 claims description 4
• ABTJPHUBNMVYRC-UHFFFAOYSA-N 4-(6-cyclobutyl-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepin-2-yl)benzamide Chemical compound C1=CC(C(=O)N)=CC=C1C(S1)=NC2=C1CCN(C1CCC1)CC2 ABTJPHUBNMVYRC-UHFFFAOYSA-N 0.000 claims description 4
• OAJQEKCJHNEGFM-UHFFFAOYSA-N 4-(6-cyclobutyl-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepin-2-yl)benzonitrile Chemical compound C1=CC(C#N)=CC=C1C(S1)=NC2=C1CCN(C1CCC1)CC2 OAJQEKCJHNEGFM-UHFFFAOYSA-N 0.000 claims description 4
• ZVFZYFSORBEUBH-UHFFFAOYSA-N 5-(6-cyclobutyl-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepin-2-yl)-n-methylpyridine-2-carboxamide Chemical compound C1=NC(C(=O)NC)=CC=C1C(S1)=NC2=C1CCN(C1CCC1)CC2 ZVFZYFSORBEUBH-UHFFFAOYSA-N 0.000 claims description 4
• AVGKKMYFTPYADB-UHFFFAOYSA-N 5-(6-cyclobutyl-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepin-2-yl)pyrimidine-2-carbonitrile Chemical compound C1=NC(C#N)=NC=C1C(S1)=NC2=C1CCN(C1CCC1)CC2 AVGKKMYFTPYADB-UHFFFAOYSA-N 0.000 claims description 4
• BDKLWAUFRJERTL-UHFFFAOYSA-N 5-[4-(6-cyclobutyl-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepin-2-yl)piperidin-1-yl]pyridine-2-carboxamide Chemical compound C1=NC(C(=O)N)=CC=C1N1CCC(C=2SC=3CCN(CCC=3N=2)C2CCC2)CC1 BDKLWAUFRJERTL-UHFFFAOYSA-N 0.000 claims description 4
• WWPVRQKZMFSHRJ-UHFFFAOYSA-N 5-[4-(6-cyclobutyl-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepin-2-yl)piperidin-1-yl]pyridine-3-carbonitrile Chemical compound N#CC1=CN=CC(N2CCC(CC2)C=2SC=3CCN(CCC=3N=2)C2CCC2)=C1 WWPVRQKZMFSHRJ-UHFFFAOYSA-N 0.000 claims description 4
• HIRZXBANJRNRGX-UHFFFAOYSA-N 6-(6-cyclobutyl-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepin-2-yl)-n-methylpyridine-3-carboxamide Chemical compound N1=CC(C(=O)NC)=CC=C1C(S1)=NC2=C1CCN(C1CCC1)CC2 HIRZXBANJRNRGX-UHFFFAOYSA-N 0.000 claims description 4
• COVWKBKVYSUUTK-UHFFFAOYSA-N 6-(6-cyclobutyl-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepin-2-yl)pyridine-3-carbonitrile Chemical compound N1=CC(C#N)=CC=C1C(S1)=NC2=C1CCN(C1CCC1)CC2 COVWKBKVYSUUTK-UHFFFAOYSA-N 0.000 claims description 4
• DYBCSSJJWNWADI-UHFFFAOYSA-N 6-cyclobutyl-2-(2-methoxypyrimidin-5-yl)-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepine Chemical compound C1=NC(OC)=NC=C1C(S1)=NC2=C1CCN(C1CCC1)CC2 DYBCSSJJWNWADI-UHFFFAOYSA-N 0.000 claims description 4
• WZFDNRHSPIWFGF-UHFFFAOYSA-N 6-cyclobutyl-2-(2-piperidin-1-ylpyrimidin-5-yl)-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepine Chemical compound C1CCC1N1CCC(SC(=N2)C=3C=NC(=NC=3)N3CCCCC3)=C2CC1 WZFDNRHSPIWFGF-UHFFFAOYSA-N 0.000 claims description 4
• WYIASRRSAYDLAP-UHFFFAOYSA-N 6-cyclobutyl-2-(6-piperidin-1-ylpyridin-3-yl)-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepine Chemical compound C1CCC1N1CCC(SC(=N2)C=3C=NC(=CC=3)N3CCCCC3)=C2CC1 WYIASRRSAYDLAP-UHFFFAOYSA-N 0.000 claims description 4
• CIWXEZHAIHMTFD-UHFFFAOYSA-N 6-cyclobutyl-2-[1-(6-methylpyridin-3-yl)piperidin-4-yl]-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepine Chemical compound C1=NC(C)=CC=C1N1CCC(C=2SC=3CCN(CCC=3N=2)C2CCC2)CC1 CIWXEZHAIHMTFD-UHFFFAOYSA-N 0.000 claims description 4
• ACMAJZRVPSPJKG-UHFFFAOYSA-N 6-cyclobutyl-2-[4-(thiadiazol-4-yl)phenyl]-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepine Chemical compound C1CCC1N1CCC(SC(=N2)C=3C=CC(=CC=3)C=3N=NSC=3)=C2CC1 ACMAJZRVPSPJKG-UHFFFAOYSA-N 0.000 claims description 4
• NKXWJIQQHXTQEG-UHFFFAOYSA-N 6-cyclobutyl-2-[4-(trifluoromethyl)phenyl]-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepine Chemical compound C1=CC(C(F)(F)F)=CC=C1C(S1)=NC2=C1CCN(C1CCC1)CC2 NKXWJIQQHXTQEG-UHFFFAOYSA-N 0.000 claims description 4
• XFXFJCRNRYSIPV-UHFFFAOYSA-N 6-cyclobutyl-2-phenyl-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepine Chemical compound C1CCC1N1CCC(SC(=N2)C=3C=CC=CC=3)=C2CC1 XFXFJCRNRYSIPV-UHFFFAOYSA-N 0.000 claims description 4
• LVMRXGWJRPUFLC-UHFFFAOYSA-N 6-cyclobutyl-2-pyrimidin-5-yl-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepine Chemical compound C1CCC1N1CCC(SC(=N2)C=3C=NC=NC=3)=C2CC1 LVMRXGWJRPUFLC-UHFFFAOYSA-N 0.000 claims description 4
• YYFHICBSQKCHMO-UHFFFAOYSA-N [3-(6-cyclobutyl-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepin-2-yl)pyrrolidin-1-yl]-(6-methylpyridin-3-yl)methanone Chemical compound C1=NC(C)=CC=C1C(=O)N1CC(C=2SC=3CCN(CCC=3N=2)C2CCC2)CC1 YYFHICBSQKCHMO-UHFFFAOYSA-N 0.000 claims description 4
• OMCDUIFVZLNNKH-UHFFFAOYSA-N [4-(6-cyclobutyl-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepin-2-yl)phenyl]-pyrrolidin-1-ylmethanone Chemical compound C=1C=C(C=2SC=3CCN(CCC=3N=2)C2CCC2)C=CC=1C(=O)N1CCCC1 OMCDUIFVZLNNKH-UHFFFAOYSA-N 0.000 claims description 4
• DUMAQEXHTRTIPK-UHFFFAOYSA-N [4-(6-cyclobutyl-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepin-2-yl)piperidin-1-yl]-(3-methyl-1,2-oxazol-5-yl)methanone Chemical compound O1N=C(C)C=C1C(=O)N1CCC(C=2SC=3CCN(CCC=3N=2)C2CCC2)CC1 DUMAQEXHTRTIPK-UHFFFAOYSA-N 0.000 claims description 4
• DMEWXAWXKCSFEE-UHFFFAOYSA-N [4-(6-cyclobutyl-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepin-2-yl)piperidin-1-yl]-(5-methyl-1,2-oxazol-3-yl)methanone Chemical compound O1C(C)=CC(C(=O)N2CCC(CC2)C=2SC=3CCN(CCC=3N=2)C2CCC2)=N1 DMEWXAWXKCSFEE-UHFFFAOYSA-N 0.000 claims description 4
• JTEQSKLWBKWBIG-UHFFFAOYSA-N [4-(6-cyclobutyl-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepin-2-yl)piperidin-1-yl]-(5-methylpyrazin-2-yl)methanone Chemical compound C1=NC(C)=CN=C1C(=O)N1CCC(C=2SC=3CCN(CCC=3N=2)C2CCC2)CC1 JTEQSKLWBKWBIG-UHFFFAOYSA-N 0.000 claims description 4
• YRYSNAMJGFNGDC-UHFFFAOYSA-N [4-(6-cyclobutyl-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepin-2-yl)piperidin-1-yl]-(6-methylpyridin-3-yl)methanone Chemical compound C1=NC(C)=CC=C1C(=O)N1CCC(C=2SC=3CCN(CCC=3N=2)C2CCC2)CC1 YRYSNAMJGFNGDC-UHFFFAOYSA-N 0.000 claims description 4
• LNDSGYUJTANTEK-UHFFFAOYSA-N [4-(6-cyclobutyl-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepin-2-yl)piperidin-1-yl]-morpholin-4-ylmethanone Chemical compound C1CC(C=2SC=3CCN(CCC=3N=2)C2CCC2)CCN1C(=O)N1CCOCC1 LNDSGYUJTANTEK-UHFFFAOYSA-N 0.000 claims description 4
• LYSZRXZCMVFRKX-UHFFFAOYSA-N [4-(6-cyclobutyl-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepin-2-yl)piperidin-1-yl]-pyridin-4-ylmethanone Chemical compound C=1C=NC=CC=1C(=O)N(CC1)CCC1C(SC=1CC2)=NC=1CCN2C1CCC1 LYSZRXZCMVFRKX-UHFFFAOYSA-N 0.000 claims description 4
• 125000004429 atom Chemical group 0.000 claims description 4
• 230000006735 deficit Effects 0.000 claims description 4
• YLVZOKZFPLFDOV-UHFFFAOYSA-N 1-[4-(6-cyclopentyl-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepin-2-yl)phenyl]-3-methylimidazolidin-2-one Chemical compound O=C1N(C)CCN1C1=CC=C(C=2SC=3CCN(CCC=3N=2)C2CCCC2)C=C1 YLVZOKZFPLFDOV-UHFFFAOYSA-N 0.000 claims description 3
• JSIBKAHJYBHGFF-UHFFFAOYSA-N 1-[4-[6-(cyclohexylmethyl)-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepin-2-yl]phenyl]-3-methylimidazolidin-2-one Chemical compound O=C1N(C)CCN1C1=CC=C(C=2SC=3CCN(CC4CCCCC4)CCC=3N=2)C=C1 JSIBKAHJYBHGFF-UHFFFAOYSA-N 0.000 claims description 3
• SPGRSHYTPNOOMK-UHFFFAOYSA-N 3-(6-cyclobutyl-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepin-2-yl)benzonitrile Chemical compound N#CC1=CC=CC(C=2SC=3CCN(CCC=3N=2)C2CCC2)=C1 SPGRSHYTPNOOMK-UHFFFAOYSA-N 0.000 claims description 3
• AOTYOKVTTWNHCA-UHFFFAOYSA-N 3-[4-(6-cyclobutyl-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepin-2-yl)phenyl]-1,3-oxazolidin-2-one Chemical compound O=C1OCCN1C1=CC=C(C=2SC=3CCN(CCC=3N=2)C2CCC2)C=C1 AOTYOKVTTWNHCA-UHFFFAOYSA-N 0.000 claims description 3
• NMAJUNHZWKZQLX-UHFFFAOYSA-N 4-[4-(6-cyclobutyl-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepin-2-yl)piperidin-1-yl]benzonitrile Chemical compound C1=CC(C#N)=CC=C1N1CCC(C=2SC=3CCN(CCC=3N=2)C2CCC2)CC1 NMAJUNHZWKZQLX-UHFFFAOYSA-N 0.000 claims description 3
• NUJUIGFVMNONIJ-UHFFFAOYSA-N 5-[4-(6-cyclobutyl-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepin-2-yl)piperidine-1-carbonyl]pyridine-2-carbonitrile Chemical compound C=1C=C(C#N)N=CC=1C(=O)N(CC1)CCC1C(SC=1CC2)=NC=1CCN2C1CCC1 NUJUIGFVMNONIJ-UHFFFAOYSA-N 0.000 claims description 3
• LXDYIVJGTBVLND-UHFFFAOYSA-N 6-(6-cyclopentyl-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepin-2-yl)pyridine-3-carbonitrile Chemical compound N1=CC(C#N)=CC=C1C(S1)=NC2=C1CCN(C1CCCC1)CC2 LXDYIVJGTBVLND-UHFFFAOYSA-N 0.000 claims description 3
• 235000007119 Ananas comosus Nutrition 0.000 claims description 3
• HTARIVNCVQUOOW-UHFFFAOYSA-N [3-(6-cyclobutyl-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepin-2-yl)pyrrolidin-1-yl]-(6-methylpyridin-2-yl)methanone Chemical compound CC1=CC=CC(C(=O)N2CC(CC2)C=2SC=3CCN(CCC=3N=2)C2CCC2)=N1 HTARIVNCVQUOOW-UHFFFAOYSA-N 0.000 claims description 3
• JGVUKKZQWKHHQZ-UHFFFAOYSA-N [4-(6-cyclobutyl-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepin-2-yl)piperidin-1-yl]-(4-methylphenyl)methanone Chemical compound C1=CC(C)=CC=C1C(=O)N1CCC(C=2SC=3CCN(CCC=3N=2)C2CCC2)CC1 JGVUKKZQWKHHQZ-UHFFFAOYSA-N 0.000 claims description 3
• WYVXEACMFLHOHV-UHFFFAOYSA-N [5-(6-cyclobutyl-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepin-2-yl)pyridin-2-yl]-pyrrolidin-1-ylmethanone Chemical compound C=1C=C(C=2SC=3CCN(CCC=3N=2)C2CCC2)C=NC=1C(=O)N1CCCC1 WYVXEACMFLHOHV-UHFFFAOYSA-N 0.000 claims description 3
• 125000005843 halogen group Chemical group 0.000 claims description 3
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
• 238000011321 prophylaxis Methods 0.000 claims description 3
• 238000002560 therapeutic procedure Methods 0.000 claims description 3
• 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 2
• GKWWOSUNLNILHL-UHFFFAOYSA-N 1-[5-(6-cyclobutyl-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepin-2-yl)pyridin-2-yl]imidazolidin-2-one Chemical compound O=C1NCCN1C1=CC=C(C=2SC=3CCN(CCC=3N=2)C2CCC2)C=N1 GKWWOSUNLNILHL-UHFFFAOYSA-N 0.000 claims description 2
• AHWJFRMVTYDAFH-UHFFFAOYSA-N 4-[3-(6-cyclobutyl-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepin-2-yl)pyrrolidine-1-carbonyl]benzonitrile Chemical compound C=1C=C(C#N)C=CC=1C(=O)N(C1)CCC1C(SC=1CC2)=NC=1CCN2C1CCC1 AHWJFRMVTYDAFH-UHFFFAOYSA-N 0.000 claims description 2
• HYUJTDMDPUQHJI-UHFFFAOYSA-N 4-[4-(6-cyclobutyl-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepin-2-yl)phenyl]morpholine Chemical compound C1CCC1N1CCC(SC(=N2)C=3C=CC(=CC=3)N3CCOCC3)=C2CC1 HYUJTDMDPUQHJI-UHFFFAOYSA-N 0.000 claims description 2
• XGJNVHKCNGYJST-UHFFFAOYSA-N 4-[4-(6-cyclobutyl-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepin-2-yl)piperidine-1-carbonyl]benzonitrile Chemical compound C=1C=C(C#N)C=CC=1C(=O)N(CC1)CCC1C(SC=1CC2)=NC=1CCN2C1CCC1 XGJNVHKCNGYJST-UHFFFAOYSA-N 0.000 claims description 2
• RBQKBTJTROCBND-UHFFFAOYSA-N 4-[5-(6-cyclobutyl-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepin-2-yl)pyridin-2-yl]morpholine Chemical compound C1CCC1N1CCC(SC(=N2)C=3C=NC(=CC=3)N3CCOCC3)=C2CC1 RBQKBTJTROCBND-UHFFFAOYSA-N 0.000 claims description 2
• TWVFVZDAGLYQKN-UHFFFAOYSA-N 5-(6-cyclobutyl-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepin-2-yl)-n-methylpyrazine-2-carboxamide Chemical compound C1=NC(C(=O)NC)=CN=C1C(S1)=NC2=C1CCN(C1CCC1)CC2 TWVFVZDAGLYQKN-UHFFFAOYSA-N 0.000 claims description 2
• BWKSPZHVGXFVPD-UHFFFAOYSA-N 5-(6-cyclobutyl-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepin-2-yl)pyridine-2-carboxamide Chemical compound C1=NC(C(=O)N)=CC=C1C(S1)=NC2=C1CCN(C1CCC1)CC2 BWKSPZHVGXFVPD-UHFFFAOYSA-N 0.000 claims description 2
• HWMACOXIHLFZBK-UHFFFAOYSA-N 5-[5-(6-cyclobutyl-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepin-2-yl)pyridin-2-yl]-3-methyl-1,2,4-oxadiazole Chemical compound CC1=NOC(C=2N=CC(=CC=2)C=2SC=3CCN(CCC=3N=2)C2CCC2)=N1 HWMACOXIHLFZBK-UHFFFAOYSA-N 0.000 claims description 2
• CZTPSHHGWFFMLC-UHFFFAOYSA-N 6-cyclobutyl-2-(6-pyrrolidin-1-ylpyridin-3-yl)-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepine Chemical compound C1CCC1N1CCC(SC(=N2)C=3C=NC(=CC=3)N3CCCC3)=C2CC1 CZTPSHHGWFFMLC-UHFFFAOYSA-N 0.000 claims description 2
• 230000001149 cognitive effect Effects 0.000 claims description 2
• 229940079593 drug Drugs 0.000 claims description 2
• FQEWDKXICTYDND-UHFFFAOYSA-N methyl 4-(6-cyclobutyl-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepin-2-yl)benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1C(S1)=NC2=C1CCN(C1CCC1)CC2 FQEWDKXICTYDND-UHFFFAOYSA-N 0.000 claims description 2
• 239000000126 substance Substances 0.000 claims description 2
• UDNYAWMBFZKZSW-UHFFFAOYSA-N tert-butyl 3-(6-cyclobutyl-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepin-2-yl)pyrrolidine-1-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCC1C(S1)=NC2=C1CCN(C1CCC1)CC2 UDNYAWMBFZKZSW-UHFFFAOYSA-N 0.000 claims description 2
• YLFLQWWDDQBOFO-UHFFFAOYSA-N tert-butyl 4-(6-cyclobutyl-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepin-2-yl)piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1C(S1)=NC2=C1CCN(C1CCC1)CC2 YLFLQWWDDQBOFO-UHFFFAOYSA-N 0.000 claims description 2
• 230000001225 therapeutic effect Effects 0.000 claims description 2
• 241000234671 Ananas Species 0.000 claims 2
• JJESDBWWAOIYRI-UHFFFAOYSA-N (3-chlorophenyl)-[4-(6-cyclobutyl-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepin-2-yl)piperidin-1-yl]methanone Chemical compound ClC1=CC=CC(C(=O)N2CCC(CC2)C=2SC=3CCN(CCC=3N=2)C2CCC2)=C1 JJESDBWWAOIYRI-UHFFFAOYSA-N 0.000 claims 1
• PYQRZFDCHITHKJ-UHFFFAOYSA-N (4-chlorophenyl)-[4-(6-cyclobutyl-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepin-2-yl)piperidin-1-yl]methanone Chemical compound C1=CC(Cl)=CC=C1C(=O)N1CCC(C=2SC=3CCN(CCC=3N=2)C2CCC2)CC1 PYQRZFDCHITHKJ-UHFFFAOYSA-N 0.000 claims 1
• YGHXJMJGWRFTPW-UHFFFAOYSA-N 1-[4-(6-cyclohexyl-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepin-2-yl)phenyl]-3-methylimidazolidin-2-one Chemical compound O=C1N(C)CCN1C1=CC=C(C=2SC=3CCN(CCC=3N=2)C2CCCCC2)C=C1 YGHXJMJGWRFTPW-UHFFFAOYSA-N 0.000 claims 1
• FDQDCCGVWABUQA-UHFFFAOYSA-N 1-[4-[6-(cyclopropylmethyl)-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepin-2-yl]phenyl]-3-methylimidazolidin-2-one Chemical compound O=C1N(C)CCN1C1=CC=C(C=2SC=3CCN(CC4CC4)CCC=3N=2)C=C1 FDQDCCGVWABUQA-UHFFFAOYSA-N 0.000 claims 1
• DIDIOZDWRNVRNP-UHFFFAOYSA-N 1-methyl-3-[4-(6-propan-2-yl-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepin-2-yl)phenyl]imidazolidin-2-one Chemical compound S1C=2CCN(C(C)C)CCC=2N=C1C(C=C1)=CC=C1N1CCN(C)C1=O DIDIOZDWRNVRNP-UHFFFAOYSA-N 0.000 claims 1
• ZLIWIVSLGCGFLS-UHFFFAOYSA-N 1-methyl-3-[4-[6-(2-methylpropyl)-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepin-2-yl]phenyl]imidazolidin-2-one Chemical compound S1C=2CCN(CC(C)C)CCC=2N=C1C(C=C1)=CC=C1N1CCN(C)C1=O ZLIWIVSLGCGFLS-UHFFFAOYSA-N 0.000 claims 1
• ZVMZJBNUSFSMBE-UHFFFAOYSA-N 6-cyclobutyl-2-[1-(6-methylpyridin-2-yl)pyrrolidin-3-yl]-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepine Chemical compound CC1=CC=CC(N2CC(CC2)C=2SC=3CCN(CCC=3N=2)C2CCC2)=N1 ZVMZJBNUSFSMBE-UHFFFAOYSA-N 0.000 claims 1
• LZCVMFHNCFEQBN-UHFFFAOYSA-N [4-(6-cyclobutyl-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepin-2-yl)piperidin-1-yl]-(1,4-dimethylpyrazol-3-yl)methanone Chemical compound CC1=CN(C)N=C1C(=O)N1CCC(C=2SC=3CCN(CCC=3N=2)C2CCC2)CC1 LZCVMFHNCFEQBN-UHFFFAOYSA-N 0.000 claims 1
• ZCWOVBSKYOXYHB-UHFFFAOYSA-N [4-(6-cyclobutyl-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepin-2-yl)piperidin-1-yl]-(1,5-dimethylpyrazol-3-yl)methanone Chemical compound CN1C(C)=CC(C(=O)N2CCC(CC2)C=2SC=3CCN(CCC=3N=2)C2CCC2)=N1 ZCWOVBSKYOXYHB-UHFFFAOYSA-N 0.000 claims 1
• DOXIGROKACQQGX-UHFFFAOYSA-N [4-(6-cyclobutyl-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepin-2-yl)piperidin-1-yl]-(1-methylimidazol-4-yl)methanone Chemical compound CN1C=NC(C(=O)N2CCC(CC2)C=2SC=3CCN(CCC=3N=2)C2CCC2)=C1 DOXIGROKACQQGX-UHFFFAOYSA-N 0.000 claims 1
• GOVZCKWJXLMLSQ-UHFFFAOYSA-N [4-(6-cyclobutyl-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepin-2-yl)piperidin-1-yl]-(1h-pyrazol-5-yl)methanone Chemical compound C1=CNN=C1C(=O)N(CC1)CCC1C(SC=1CC2)=NC=1CCN2C1CCC1 GOVZCKWJXLMLSQ-UHFFFAOYSA-N 0.000 claims 1
• RKKSFIDZQDMJLF-UHFFFAOYSA-N [4-(6-cyclobutyl-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepin-2-yl)piperidin-1-yl]-(2-methylpyridin-4-yl)methanone Chemical compound C1=NC(C)=CC(C(=O)N2CCC(CC2)C=2SC=3CCN(CCC=3N=2)C2CCC2)=C1 RKKSFIDZQDMJLF-UHFFFAOYSA-N 0.000 claims 1
• MYDSTCPPPATBQE-UHFFFAOYSA-N [4-(6-cyclobutyl-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepin-2-yl)piperidin-1-yl]-(3-methylimidazol-4-yl)methanone Chemical compound CN1C=NC=C1C(=O)N1CCC(C=2SC=3CCN(CCC=3N=2)C2CCC2)CC1 MYDSTCPPPATBQE-UHFFFAOYSA-N 0.000 claims 1
• CDUYWKKLUPBBFP-UHFFFAOYSA-N [4-(6-cyclobutyl-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepin-2-yl)piperidin-1-yl]-(3-methylphenyl)methanone Chemical compound CC1=CC=CC(C(=O)N2CCC(CC2)C=2SC=3CCN(CCC=3N=2)C2CCC2)=C1 CDUYWKKLUPBBFP-UHFFFAOYSA-N 0.000 claims 1
• AVXCJVCPWJBIHR-UHFFFAOYSA-N [4-(6-cyclobutyl-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepin-2-yl)piperidin-1-yl]-(3-methylpyridin-2-yl)methanone Chemical compound CC1=CC=CN=C1C(=O)N1CCC(C=2SC=3CCN(CCC=3N=2)C2CCC2)CC1 AVXCJVCPWJBIHR-UHFFFAOYSA-N 0.000 claims 1
• HBBSCJIDJBODNX-UHFFFAOYSA-N [4-(6-cyclobutyl-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepin-2-yl)piperidin-1-yl]-(6-methylpyrazin-2-yl)methanone Chemical compound CC1=CN=CC(C(=O)N2CCC(CC2)C=2SC=3CCN(CCC=3N=2)C2CCC2)=N1 HBBSCJIDJBODNX-UHFFFAOYSA-N 0.000 claims 1
• KBFMATOGLCSFDM-UHFFFAOYSA-N [4-(6-cyclobutyl-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepin-2-yl)piperidin-1-yl]-pyridin-2-ylmethanone Chemical compound C=1C=CC=NC=1C(=O)N(CC1)CCC1C(SC=1CC2)=NC=1CCN2C1CCC1 KBFMATOGLCSFDM-UHFFFAOYSA-N 0.000 claims 1
• DGBQZUQJMLUSLR-UHFFFAOYSA-N [4-(6-cyclobutyl-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepin-2-yl)piperidin-1-yl]-pyridin-3-ylmethanone Chemical compound C=1C=CN=CC=1C(=O)N(CC1)CCC1C(SC=1CC2)=NC=1CCN2C1CCC1 DGBQZUQJMLUSLR-UHFFFAOYSA-N 0.000 claims 1
• 239000003937 drug carrier Substances 0.000 claims 1
• 230000000626 neurodegenerative effect Effects 0.000 claims 1
• 239000000203 mixture Substances 0.000 abstract description 263
• 150000007979 thiazole derivatives Chemical class 0.000 abstract description 4
• 230000000144 pharmacologic effect Effects 0.000 abstract description 3
• 208000020016 psychiatric disease Diseases 0.000 abstract description 3
• 230000000926 neurological effect Effects 0.000 abstract description 2
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 675
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 279
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 218
• 239000000243 solution Substances 0.000 description 135
• 239000000047 product Substances 0.000 description 113
• 229910021529 ammonia Inorganic materials 0.000 description 109
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 90
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 84
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 78
• 238000012799 strong cation exchange Methods 0.000 description 75
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 72
• 238000010992 reflux Methods 0.000 description 69
• 238000005342 ion exchange Methods 0.000 description 66
• 239000012300 argon atmosphere Substances 0.000 description 56
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 48
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 48
• 230000002829 reductive effect Effects 0.000 description 41
• 239000002904 solvent Substances 0.000 description 39
• 238000006243 chemical reaction Methods 0.000 description 37
• 239000011541 reaction mixture Substances 0.000 description 35
• 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 33
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 33
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 32
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 31
• 238000004440 column chromatography Methods 0.000 description 30
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 27
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 26
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 24
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
• 210000004027 cell Anatomy 0.000 description 23
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 22
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 22
• 239000002253 acid Substances 0.000 description 22
• 238000010898 silica gel chromatography Methods 0.000 description 21
• PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 20
• 238000003756 stirring Methods 0.000 description 20
• OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 19
• 239000000741 silica gel Substances 0.000 description 19
• 229910002027 silica gel Inorganic materials 0.000 description 19
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 18
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 18
• 238000004587 chromatography analysis Methods 0.000 description 18
• 239000000725 suspension Substances 0.000 description 18
• 229910000027 potassium carbonate Inorganic materials 0.000 description 16
• CXNIUSPIQKWYAI-UHFFFAOYSA-N xantphos Chemical compound C=12OC3=C(P(C=4C=CC=CC=4)C=4C=CC=CC=4)C=CC=C3C(C)(C)C2=CC=CC=1P(C=1C=CC=CC=1)C1=CC=CC=C1 CXNIUSPIQKWYAI-UHFFFAOYSA-N 0.000 description 16
• NGKHTLLTBXIGQX-UHFFFAOYSA-N 1-[2-(6-chloropyridin-3-yl)-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepin-6-yl]-2,2,2-trifluoroethanone Chemical compound S1C=2CCN(C(=O)C(F)(F)F)CCC=2N=C1C1=CC=C(Cl)N=C1 NGKHTLLTBXIGQX-UHFFFAOYSA-N 0.000 description 15
• SHQSVMDWKBRBGB-UHFFFAOYSA-N cyclobutanone Chemical compound O=C1CCC1 SHQSVMDWKBRBGB-UHFFFAOYSA-N 0.000 description 15
• 239000012321 sodium triacetoxyborohydride Substances 0.000 description 15
• VLTPTYUTFLPHFK-UHFFFAOYSA-N 2,2,2-trifluoro-1-(2-iodo-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepin-6-yl)ethanone Chemical compound C1CN(C(=O)C(F)(F)F)CCC2=C1SC(I)=N2 VLTPTYUTFLPHFK-UHFFFAOYSA-N 0.000 description 14
• BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 14
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 14
• 229910052794 bromium Inorganic materials 0.000 description 14
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 13
• IMNFDUFMRHMDMM-UHFFFAOYSA-N anhydrous n-heptane Natural products CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 13
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 13
• 235000019341 magnesium sulphate Nutrition 0.000 description 13
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 12
• 239000005557 antagonist Substances 0.000 description 12
• YNHIGQDRGKUECZ-UHFFFAOYSA-N dichloropalladium;triphenylphosphanium Chemical compound Cl[Pd]Cl.C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-N 0.000 description 12
• 239000004793 Polystyrene Substances 0.000 description 11
• 239000012298 atmosphere Substances 0.000 description 11
• XHOGXAKOVBDTCY-UHFFFAOYSA-N 1-cyclobutylazepan-4-one Chemical compound C1CC(=O)CCCN1C1CCC1 XHOGXAKOVBDTCY-UHFFFAOYSA-N 0.000 description 10
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 10
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 10
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 10
• 229920002223 polystyrene Polymers 0.000 description 10
• 229910000029 sodium carbonate Inorganic materials 0.000 description 10
• ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 9
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 9
• 239000007983 Tris buffer Substances 0.000 description 9
• 229910052786 argon Inorganic materials 0.000 description 9
• YNHIGQDRGKUECZ-UHFFFAOYSA-L bis(triphenylphosphine)palladium(ii) dichloride Chemical compound [Cl-].[Cl-].[Pd+2].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 YNHIGQDRGKUECZ-UHFFFAOYSA-L 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
• WMKGGPCROCCUDY-PHEQNACWSA-N dibenzylideneacetone Chemical compound C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 WMKGGPCROCCUDY-PHEQNACWSA-N 0.000 description 9
• 239000002609 medium Substances 0.000 description 9
• PBMIETCUUSQZCG-UHFFFAOYSA-N n'-cyclohexylmethanediimine Chemical compound N=C=NC1CCCCC1 PBMIETCUUSQZCG-UHFFFAOYSA-N 0.000 description 9
• 239000007787 solid Substances 0.000 description 9
• 239000003981 vehicle Substances 0.000 description 9
• GYBIVLSDYIABQH-UHFFFAOYSA-N (6-chloropyridin-3-yl)-trimethylstannane Chemical compound C[Sn](C)(C)C1=CC=C(Cl)N=C1 GYBIVLSDYIABQH-UHFFFAOYSA-N 0.000 description 8
• BSEBWOQMJFGBDM-UHFFFAOYSA-N 2-(6-chloropyridin-3-yl)-5,6,7,8-tetrahydro-4h-[1,3]thiazolo[4,5-d]azepine Chemical compound C1=NC(Cl)=CC=C1C(S1)=NC2=C1CCNCC2 BSEBWOQMJFGBDM-UHFFFAOYSA-N 0.000 description 8
• DSLIOSJHXFXKLW-UHFFFAOYSA-N 5-bromo-1-cyclobutylazepan-4-one Chemical compound C1CC(=O)C(Br)CCN1C1CCC1 DSLIOSJHXFXKLW-UHFFFAOYSA-N 0.000 description 8
• 239000012043 crude product Substances 0.000 description 8
• BGTOWKSIORTVQH-UHFFFAOYSA-N cyclopentanone Chemical compound O=C1CCCC1 BGTOWKSIORTVQH-UHFFFAOYSA-N 0.000 description 8
• 208000035475 disorder Diseases 0.000 description 8
• 125000002950 monocyclic group Chemical group 0.000 description 8
• 238000004366 reverse phase liquid chromatography Methods 0.000 description 8
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 8
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N DMSO Substances CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 7
• 102000004384 Histamine H3 receptors Human genes 0.000 description 7
• 108090000981 Histamine H3 receptors Proteins 0.000 description 7
• 125000002619 bicyclic group Chemical group 0.000 description 7
• IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 7
• 229910000041 hydrogen chloride Inorganic materials 0.000 description 7
• 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 description 7
• ZARMWDJPQZIACM-UHFFFAOYSA-N 6-(5,6,7,8-tetrahydro-4h-[1,3]thiazolo[4,5-d]azepin-2-yl)pyridine-3-carbonitrile Chemical compound N1=CC(C#N)=CC=C1C(S1)=NC2=C1CCNCC2 ZARMWDJPQZIACM-UHFFFAOYSA-N 0.000 description 6
• 102000003834 Histamine H1 Receptors Human genes 0.000 description 6
• 108090000110 Histamine H1 Receptors Proteins 0.000 description 6
• TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 6
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 6
• 238000003556 assay Methods 0.000 description 6
• 239000002585 base Substances 0.000 description 6
• MUALRAIOVNYAIW-UHFFFAOYSA-N binap Chemical compound C1=CC=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 MUALRAIOVNYAIW-UHFFFAOYSA-N 0.000 description 6
• 150000003840 hydrochlorides Chemical class 0.000 description 6
• 239000012528 membrane Substances 0.000 description 6
• QPJVMBTYPHYUOC-UHFFFAOYSA-N methyl benzoate Chemical compound COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 description 6
• NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 6
• 239000000377 silicon dioxide Substances 0.000 description 6
• MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 6
• 229940124597 therapeutic agent Drugs 0.000 description 6
• HYTTVKRGUYTJLN-UHFFFAOYSA-N tributyl-(6-chloropyridin-3-yl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C1=CC=C(Cl)N=C1 HYTTVKRGUYTJLN-UHFFFAOYSA-N 0.000 description 6
• YNFHSHYLEKIMGJ-UHFFFAOYSA-N 1-(2,2,2-trifluoroacetyl)azepan-4-one Chemical compound FC(F)(F)C(=O)N1CCCC(=O)CC1 YNFHSHYLEKIMGJ-UHFFFAOYSA-N 0.000 description 5
• BUTQEKSJGNPVFJ-UHFFFAOYSA-N 1-methyl-3-[4-(5,6,7,8-tetrahydro-4h-[1,3]thiazolo[4,5-d]azepin-2-yl)phenyl]imidazolidin-2-one Chemical compound O=C1N(C)CCN1C1=CC=C(C=2SC=3CCNCCC=3N=2)C=C1 BUTQEKSJGNPVFJ-UHFFFAOYSA-N 0.000 description 5
• BZWZPAWYSLUFGH-UHFFFAOYSA-N 3-(5,6,7,8-tetrahydro-4h-[1,3]thiazolo[4,5-d]azepin-2-yl)benzonitrile Chemical compound N#CC1=CC=CC(C=2SC=3CCNCCC=3N=2)=C1 BZWZPAWYSLUFGH-UHFFFAOYSA-N 0.000 description 5
• 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 5
• QQABDGFUYZJHPN-UHFFFAOYSA-N 5-trimethylstannylpyridine-2-carbonitrile Chemical compound C[Sn](C)(C)C1=CC=C(C#N)N=C1 QQABDGFUYZJHPN-UHFFFAOYSA-N 0.000 description 5
• PAWPHUONZMRSEA-UHFFFAOYSA-N 6-[6-(2,2,2-trifluoroacetyl)-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepin-2-yl]pyridine-3-carbonitrile Chemical compound S1C=2CCN(C(=O)C(F)(F)F)CCC=2N=C1C1=CC=C(C#N)C=N1 PAWPHUONZMRSEA-UHFFFAOYSA-N 0.000 description 5
• 239000004229 Alkannin Substances 0.000 description 5
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 5
• UXRDAJMOOGEIAQ-CKOZHMEPSA-N [(8r,9s,10r,13s,14s,17r)-17-acetyl-10,13-dimethyl-16-methylidene-3-oxo-1,2,8,9,11,12,14,15-octahydrocyclopenta[a]phenanthren-17-yl] acetate Chemical compound C1=CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC(=C)[C@](OC(=O)C)(C(C)=O)[C@@]1(C)CC2 UXRDAJMOOGEIAQ-CKOZHMEPSA-N 0.000 description 5
• 238000005859 coupling reaction Methods 0.000 description 5
• 239000013058 crude material Substances 0.000 description 5
• 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 5
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 5
• 201000010099 disease Diseases 0.000 description 5
• 239000000706 filtrate Substances 0.000 description 5
• 235000019253 formic acid Nutrition 0.000 description 5
• 229910052763 palladium Inorganic materials 0.000 description 5
• MUJIDPITZJWBSW-UHFFFAOYSA-N palladium(2+) Chemical compound [Pd+2] MUJIDPITZJWBSW-UHFFFAOYSA-N 0.000 description 5
• 239000013612 plasmid Substances 0.000 description 5
• 125000006239 protecting group Chemical group 0.000 description 5
• 102000005962 receptors Human genes 0.000 description 5
• 108020003175 receptors Proteins 0.000 description 5
• 239000004173 sunset yellow FCF Substances 0.000 description 5
• 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 5
• JUDXOKKZTISQDJ-UHFFFAOYSA-N triphenylphosphane;hydrochloride Chemical compound Cl.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 JUDXOKKZTISQDJ-UHFFFAOYSA-N 0.000 description 5
• CXRDZSYYRXWCQE-UHFFFAOYSA-N 1-(2-amino-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepin-6-yl)-2,2,2-trifluoroethanone Chemical compound C1CN(C(=O)C(F)(F)F)CCC2=C1N=C(N)S2 CXRDZSYYRXWCQE-UHFFFAOYSA-N 0.000 description 4
• KUUXEMFCTRODSD-UHFFFAOYSA-N 1-[5-(5,6,7,8-tetrahydro-4h-[1,3]thiazolo[4,5-d]azepin-2-yl)pyridin-2-yl]pyrrolidin-2-one Chemical compound O=C1CCCN1C1=CC=C(C=2SC=3CCNCCC=3N=2)C=N1 KUUXEMFCTRODSD-UHFFFAOYSA-N 0.000 description 4
• YQPDUEMFYVFHFF-UHFFFAOYSA-N 1-methyl-3-[5-(5,6,7,8-tetrahydro-4h-[1,3]thiazolo[4,5-d]azepin-2-yl)pyridin-2-yl]imidazolidin-2-one Chemical compound O=C1N(C)CCN1C1=CC=C(C=2SC=3CCNCCC=3N=2)C=N1 YQPDUEMFYVFHFF-UHFFFAOYSA-N 0.000 description 4
• MYCDLLAVPSEMGA-UHFFFAOYSA-N 2-methylpyrimidine-4-carbonitrile Chemical compound CC1=NC=CC(C#N)=N1 MYCDLLAVPSEMGA-UHFFFAOYSA-N 0.000 description 4
• CDBDBWCUGHXFTN-UHFFFAOYSA-N 2-methylpyrimidine-4-carboxylic acid Chemical compound CC1=NC=CC(C(O)=O)=N1 CDBDBWCUGHXFTN-UHFFFAOYSA-N 0.000 description 4
• NMGIXZFBQPETOK-UHFFFAOYSA-N 2-methylpyrimidine-5-carboxylic acid Chemical compound CC1=NC=C(C(O)=O)C=N1 NMGIXZFBQPETOK-UHFFFAOYSA-N 0.000 description 4
• 125000004575 3-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 4
• MOXYNXUPGSPCKJ-UHFFFAOYSA-N 4-(5,6,7,8-tetrahydro-4h-[1,3]thiazolo[4,5-d]azepin-2-yl)benzonitrile Chemical compound C1=CC(C#N)=CC=C1C(S1)=NC2=C1CCNCC2 MOXYNXUPGSPCKJ-UHFFFAOYSA-N 0.000 description 4
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 4
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
• KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 4
• MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
• DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 4
• PJXWMZUNTLHCNG-UHFFFAOYSA-N [4-(6-cyclobutyl-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepin-2-yl)piperidin-1-yl]-(1-methylpyrazol-3-yl)methanone Chemical compound CN1C=CC(C(=O)N2CCC(CC2)C=2SC=3CCN(CCC=3N=2)C2CCC2)=N1 PJXWMZUNTLHCNG-UHFFFAOYSA-N 0.000 description 4
• 239000000556 agonist Substances 0.000 description 4
• ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 4
• 239000003795 chemical substances by application Substances 0.000 description 4
• 239000000284 extract Substances 0.000 description 4
• 238000001914 filtration Methods 0.000 description 4
• 239000011630 iodine Substances 0.000 description 4
• 229910052740 iodine Inorganic materials 0.000 description 4
• OUBSYFKIZZHQKH-UHFFFAOYSA-N n,n-dimethyl-4-(5,6,7,8-tetrahydro-4h-[1,3]thiazolo[4,5-d]azepin-2-yl)aniline Chemical compound C1=CC(N(C)C)=CC=C1C(S1)=NC2=C1CCNCC2 OUBSYFKIZZHQKH-UHFFFAOYSA-N 0.000 description 4
• DBABZHXKTCFAPX-UHFFFAOYSA-N probenecid Chemical compound CCCN(CCC)S(=O)(=O)C1=CC=C(C(O)=O)C=C1 DBABZHXKTCFAPX-UHFFFAOYSA-N 0.000 description 4
• 229960003081 probenecid Drugs 0.000 description 4
• AAWSTBOGMLZUEQ-UHFFFAOYSA-N pyridin-4-yl-[4-(5,6,7,8-tetrahydro-4h-[1,3]thiazolo[4,5-d]azepin-2-yl)piperidin-1-yl]methanone Chemical compound C1CC(C=2SC=3CCNCCC=3N=2)CCN1C(=O)C1=CC=NC=C1 AAWSTBOGMLZUEQ-UHFFFAOYSA-N 0.000 description 4
• LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 4
• UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 4
• QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 4
• 125000004512 1,2,3-thiadiazol-4-yl group Chemical group S1N=NC(=C1)* 0.000 description 3
• MSGNPERVJMAARG-UHFFFAOYSA-N 1-[2-(4-bromophenyl)-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepin-6-yl]-2,2,2-trifluoroethanone Chemical compound S1C=2CCN(C(=O)C(F)(F)F)CCC=2N=C1C1=CC=C(Br)C=C1 MSGNPERVJMAARG-UHFFFAOYSA-N 0.000 description 3
• AUSYMLVRROPQLG-UHFFFAOYSA-N 1-methyl-3-[5-[6-(2,2,2-trifluoroacetyl)-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepin-2-yl]pyridin-2-yl]imidazolidin-2-one Chemical compound O=C1N(C)CCN1C1=CC=C(C=2SC=3CCN(CCC=3N=2)C(=O)C(F)(F)F)C=N1 AUSYMLVRROPQLG-UHFFFAOYSA-N 0.000 description 3
• JTPZTKBRUCILQD-UHFFFAOYSA-N 1-methylimidazolidin-2-one Chemical compound CN1CCNC1=O JTPZTKBRUCILQD-UHFFFAOYSA-N 0.000 description 3
• GVBFDWHTLUBZCF-UHFFFAOYSA-N 2,2,2-trifluoro-1-(2-piperidin-4-yl-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepin-6-yl)ethanone Chemical compound S1C=2CCN(C(=O)C(F)(F)F)CCC=2N=C1C1CCNCC1 GVBFDWHTLUBZCF-UHFFFAOYSA-N 0.000 description 3
• JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 3
• PMDHIMMPXRSDML-UHFFFAOYSA-N 2-methylpyridine-4-carboxylic acid Chemical compound CC1=CC(C(O)=O)=CC=N1 PMDHIMMPXRSDML-UHFFFAOYSA-N 0.000 description 3
• QMBBZFQXLXNVEX-UHFFFAOYSA-N 5-[4-(6-cyclobutyl-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepin-2-yl)piperidin-1-yl]-n-methylpyridine-2-carboxamide Chemical compound C1=NC(C(=O)NC)=CC=C1N1CCC(C=2SC=3CCN(CCC=3N=2)C2CCC2)CC1 QMBBZFQXLXNVEX-UHFFFAOYSA-N 0.000 description 3
• DMSHUVBQFSNBBL-UHFFFAOYSA-N 5-bromopyridine-2-carbonitrile Chemical compound BrC1=CC=C(C#N)N=C1 DMSHUVBQFSNBBL-UHFFFAOYSA-N 0.000 description 3
• MQEVKGXAHHFTOC-UHFFFAOYSA-N 6-cyclobutyl-2-iodo-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepine Chemical compound C1CC=2SC(I)=NC=2CCN1C1CCC1 MQEVKGXAHHFTOC-UHFFFAOYSA-N 0.000 description 3
• YDSUJIRXXROKQG-UHFFFAOYSA-N 6-methylpyrazine-2-carboxylic acid Chemical compound CC1=CN=CC(C(O)=O)=N1 YDSUJIRXXROKQG-UHFFFAOYSA-N 0.000 description 3
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
• 208000028698 Cognitive impairment Diseases 0.000 description 3
• 239000004230 Fast Yellow AB Substances 0.000 description 3
• QGWNDRXFNXRZMB-UUOKFMHZSA-K GDP(3-) Chemical compound C1=NC=2C(=O)NC(N)=NC=2N1[C@@H]1O[C@H](COP([O-])(=O)OP([O-])([O-])=O)[C@@H](O)[C@H]1O QGWNDRXFNXRZMB-UUOKFMHZSA-K 0.000 description 3
• 239000007995 HEPES buffer Substances 0.000 description 3
• 239000004231 Riboflavin-5-Sodium Phosphate Substances 0.000 description 3
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
• 239000004234 Yellow 2G Substances 0.000 description 3
• 108010084455 Zeocin Proteins 0.000 description 3
• RDJCDKVNQVXCKX-UHFFFAOYSA-N [4-(6-cyclobutyl-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepin-2-yl)piperidin-1-yl]-(2-methylpyridin-3-yl)methanone Chemical compound CC1=NC=CC=C1C(=O)N1CCC(C=2SC=3CCN(CCC=3N=2)C2CCC2)CC1 RDJCDKVNQVXCKX-UHFFFAOYSA-N 0.000 description 3
• WTPKWZYOWAJOHQ-UHFFFAOYSA-N [4-(6-cyclobutyl-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepin-2-yl)piperidin-1-yl]-(2-methylpyrimidin-4-yl)methanone Chemical compound CC1=NC=CC(C(=O)N2CCC(CC2)C=2SC=3CCN(CCC=3N=2)C2CCC2)=N1 WTPKWZYOWAJOHQ-UHFFFAOYSA-N 0.000 description 3
• OFWLDAJCMZVWGE-UHFFFAOYSA-N [4-(6-cyclobutyl-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepin-2-yl)piperidin-1-yl]-(2-methylpyrimidin-5-yl)methanone Chemical compound C1=NC(C)=NC=C1C(=O)N1CCC(C=2SC=3CCN(CCC=3N=2)C2CCC2)CC1 OFWLDAJCMZVWGE-UHFFFAOYSA-N 0.000 description 3
• KWHSUWNOBPGPBU-UHFFFAOYSA-N [4-(6-cyclobutyl-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepin-2-yl)piperidin-1-yl]-(6-methylpyridazin-3-yl)methanone Chemical compound N1=NC(C)=CC=C1C(=O)N1CCC(C=2SC=3CCN(CCC=3N=2)C2CCC2)CC1 KWHSUWNOBPGPBU-UHFFFAOYSA-N 0.000 description 3
• 150000001412 amines Chemical class 0.000 description 3
• 238000004458 analytical method Methods 0.000 description 3
• 150000001502 aryl halides Chemical class 0.000 description 3
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
• 239000000872 buffer Substances 0.000 description 3
• 239000000460 chlorine Substances 0.000 description 3
• 229910052801 chlorine Inorganic materials 0.000 description 3
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
• 208000010877 cognitive disease Diseases 0.000 description 3
• 239000004148 curcumin Substances 0.000 description 3
• 239000012039 electrophile Substances 0.000 description 3
• 238000001704 evaporation Methods 0.000 description 3
• 230000008020 evaporation Effects 0.000 description 3
• QGWNDRXFNXRZMB-UHFFFAOYSA-N guanidine diphosphate Natural products C1=2NC(N)=NC(=O)C=2N=CN1C1OC(COP(O)(=O)OP(O)(O)=O)C(O)C1O QGWNDRXFNXRZMB-UHFFFAOYSA-N 0.000 description 3
• 150000002430 hydrocarbons Chemical class 0.000 description 3
• 230000007062 hydrolysis Effects 0.000 description 3
• 238000006460 hydrolysis reaction Methods 0.000 description 3
• 230000005764 inhibitory process Effects 0.000 description 3
• HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 3
• 239000007788 liquid Substances 0.000 description 3
• 229910001629 magnesium chloride Inorganic materials 0.000 description 3
• 230000001404 mediated effect Effects 0.000 description 3
• FWQVHCUKDCCJSJ-UHFFFAOYSA-N methyl 4-carbamothioylbenzoate Chemical compound COC(=O)C1=CC=C(C(N)=S)C=C1 FWQVHCUKDCCJSJ-UHFFFAOYSA-N 0.000 description 3
• 239000003921 oil Substances 0.000 description 3
• YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 3
• 239000011049 pearl Substances 0.000 description 3
• 239000012071 phase Substances 0.000 description 3
• CWCMIVBLVUHDHK-ZSNHEYEWSA-N phleomycin D1 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC[C@@H](N=1)C=1SC=C(N=1)C(=O)NCCCCNC(N)=N)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C CWCMIVBLVUHDHK-ZSNHEYEWSA-N 0.000 description 3
• 125000003386 piperidinyl group Chemical group 0.000 description 3
• BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 3
• 238000000746 purification Methods 0.000 description 3
• 125000000719 pyrrolidinyl group Chemical group 0.000 description 3
• 229920006395 saturated elastomer Polymers 0.000 description 3
• 238000000926 separation method Methods 0.000 description 3
• 229910052938 sodium sulfate Inorganic materials 0.000 description 3
• 235000011152 sodium sulphate Nutrition 0.000 description 3
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
• 238000001890 transfection Methods 0.000 description 3
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 3
• QBLFZIBJXUQVRF-UHFFFAOYSA-N (4-bromophenyl)boronic acid Chemical compound OB(O)C1=CC=C(Br)C=C1 QBLFZIBJXUQVRF-UHFFFAOYSA-N 0.000 description 2
• 125000004505 1,2,4-oxadiazol-5-yl group Chemical group O1N=CN=C1* 0.000 description 2
• NQYULMAXFMZNGV-UHFFFAOYSA-N 1-methyl-3-[4-[6-(2,2,2-trifluoroacetyl)-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepin-2-yl]phenyl]imidazolidin-2-one Chemical compound O=C1N(C)CCN1C1=CC=C(C=2SC=3CCN(CCC=3N=2)C(=O)C(F)(F)F)C=C1 NQYULMAXFMZNGV-UHFFFAOYSA-N 0.000 description 2
• HJFZAYHYIWGLNL-UHFFFAOYSA-N 2,6-Dimethylpyrazine Chemical compound CC1=CN=CC(C)=N1 HJFZAYHYIWGLNL-UHFFFAOYSA-N 0.000 description 2
• LNJMHEJAYSYZKK-UHFFFAOYSA-N 2-methylpyrimidine Chemical compound CC1=NC=CC=N1 LNJMHEJAYSYZKK-UHFFFAOYSA-N 0.000 description 2
• JJYPMNFTHPTTDI-UHFFFAOYSA-N 3-methylaniline Chemical compound CC1=CC=CC(N)=C1 JJYPMNFTHPTTDI-UHFFFAOYSA-N 0.000 description 2
• ADCUEPOHPCPMCE-UHFFFAOYSA-N 4-cyanobenzoic acid Chemical compound OC(=O)C1=CC=C(C#N)C=C1 ADCUEPOHPCPMCE-UHFFFAOYSA-N 0.000 description 2
• OFKWIQJLYCKDNY-UHFFFAOYSA-N 5-bromo-2-methylpyridine Chemical compound CC1=CC=C(Br)C=N1 OFKWIQJLYCKDNY-UHFFFAOYSA-N 0.000 description 2
• FTFFHWWIPOQCBC-UHFFFAOYSA-N 5-bromopyridine-3-carbonitrile Chemical compound BrC1=CN=CC(C#N)=C1 FTFFHWWIPOQCBC-UHFFFAOYSA-N 0.000 description 2
• LTUUGSGSUZRPRV-UHFFFAOYSA-N 6-methylpyridine-2-carboxylic acid Chemical compound CC1=CC=CC(C(O)=O)=N1 LTUUGSGSUZRPRV-UHFFFAOYSA-N 0.000 description 2
• RZOKQIPOABEQAM-UHFFFAOYSA-N 6-methylpyridine-3-carboxylic acid Chemical compound CC1=CC=C(C(O)=O)C=N1 RZOKQIPOABEQAM-UHFFFAOYSA-N 0.000 description 2
• 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 2
• 208000008035 Back Pain Diseases 0.000 description 2
• 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
• RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 2
• 206010012289 Dementia Diseases 0.000 description 2
• ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
• 108090000790 Enzymes Proteins 0.000 description 2
• 102000004190 Enzymes Human genes 0.000 description 2
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
• 102000000543 Histamine Receptors Human genes 0.000 description 2
• 108010002059 Histamine Receptors Proteins 0.000 description 2
• 206010065390 Inflammatory pain Diseases 0.000 description 2
• ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 2
• 229930182816 L-glutamine Natural products 0.000 description 2
• 241000124008 Mammalia Species 0.000 description 2
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
• 239000004235 Orange GGN Substances 0.000 description 2
• 208000002193 Pain Diseases 0.000 description 2
• XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 2
• WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
• 208000006011 Stroke Diseases 0.000 description 2
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
• XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
• 230000004913 activation Effects 0.000 description 2
• 238000001994 activation Methods 0.000 description 2
• 238000007112 amidation reaction Methods 0.000 description 2
• 150000001408 amides Chemical class 0.000 description 2
• 239000007864 aqueous solution Substances 0.000 description 2
• 239000012131 assay buffer Substances 0.000 description 2
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
• WFTRLIZPJMFJER-UHFFFAOYSA-N azepan-1-ium-4-one;chloride Chemical compound Cl.O=C1CCCNCC1 WFTRLIZPJMFJER-UHFFFAOYSA-N 0.000 description 2
• 150000001538 azepines Chemical class 0.000 description 2
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
• 125000004622 benzoxazinyl group Chemical group O1NC(=CC2=C1C=CC=C2)* 0.000 description 2
• 230000015572 biosynthetic process Effects 0.000 description 2
• 210000004556 brain Anatomy 0.000 description 2
• 238000005893 bromination reaction Methods 0.000 description 2
• 239000002775 capsule Substances 0.000 description 2
• 125000004432 carbon atom Chemical group C* 0.000 description 2
• 210000003169 central nervous system Anatomy 0.000 description 2
• 239000003153 chemical reaction reagent Substances 0.000 description 2
• 239000003638 chemical reducing agent Substances 0.000 description 2
• 238000004296 chiral HPLC Methods 0.000 description 2
• 229910052802 copper Inorganic materials 0.000 description 2
• 239000010949 copper Substances 0.000 description 2
• KVFDZFBHBWTVID-UHFFFAOYSA-N cyclohexanecarbaldehyde Chemical compound O=CC1CCCCC1 KVFDZFBHBWTVID-UHFFFAOYSA-N 0.000 description 2
• 239000002552 dosage form Substances 0.000 description 2
• 239000000975 dye Substances 0.000 description 2
• 230000000694 effects Effects 0.000 description 2
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
• 238000002474 experimental method Methods 0.000 description 2
• 239000011737 fluorine Substances 0.000 description 2
• 229910052731 fluorine Inorganic materials 0.000 description 2
• 238000009472 formulation Methods 0.000 description 2
• 238000005227 gel permeation chromatography Methods 0.000 description 2
• 125000005842 heteroatom Chemical group 0.000 description 2
• FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid group Chemical group C(CCCCC)(=O)O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 2
• 239000011539 homogenization buffer Substances 0.000 description 2
• YAMHXTCMCPHKLN-UHFFFAOYSA-N imidazolidin-2-one Chemical compound O=C1NCCN1 YAMHXTCMCPHKLN-UHFFFAOYSA-N 0.000 description 2
• 238000000338 in vitro Methods 0.000 description 2
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
• NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 2
• GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 description 2
• 238000002156 mixing Methods 0.000 description 2
• 125000002757 morpholinyl group Chemical group 0.000 description 2
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
• 210000005036 nerve Anatomy 0.000 description 2
• 208000015122 neurodegenerative disease Diseases 0.000 description 2
• 125000004433 nitrogen atom Chemical group N* 0.000 description 2
• 239000012038 nucleophile Substances 0.000 description 2
• RNVCVTLRINQCPJ-UHFFFAOYSA-N o-toluidine Chemical compound CC1=CC=CC=C1N RNVCVTLRINQCPJ-UHFFFAOYSA-N 0.000 description 2
• 125000001715 oxadiazolyl group Chemical group 0.000 description 2
• 125000000160 oxazolidinyl group Chemical group 0.000 description 2
• 239000001301 oxygen Substances 0.000 description 2
• LPNBBFKOUUSUDB-UHFFFAOYSA-N p-toluic acid Chemical compound CC1=CC=C(C(O)=O)C=C1 LPNBBFKOUUSUDB-UHFFFAOYSA-N 0.000 description 2
• RZXMPPFPUUCRFN-UHFFFAOYSA-N p-toluidine Chemical compound CC1=CC=C(N)C=C1 RZXMPPFPUUCRFN-UHFFFAOYSA-N 0.000 description 2
• 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 2
• JLTDJTHDQAWBAV-UHFFFAOYSA-N phenyldimethylamine Natural products CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 2
• XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
• 239000000843 powder Substances 0.000 description 2
• 238000002953 preparative HPLC Methods 0.000 description 2
• 239000003755 preservative agent Substances 0.000 description 2
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
• 108090000623 proteins and genes Proteins 0.000 description 2
• 125000003373 pyrazinyl group Chemical group 0.000 description 2
• 125000004076 pyridyl group Chemical group 0.000 description 2
• 125000000714 pyrimidinyl group Chemical group 0.000 description 2
• HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 2
• 239000004172 quinoline yellow Substances 0.000 description 2
• 239000011347 resin Substances 0.000 description 2
• 229920005989 resin Polymers 0.000 description 2
• 239000002151 riboflavin Substances 0.000 description 2
• 238000007363 ring formation reaction Methods 0.000 description 2
• 239000012047 saturated solution Substances 0.000 description 2
• 201000000980 schizophrenia Diseases 0.000 description 2
• 239000013049 sediment Substances 0.000 description 2
• 235000017557 sodium bicarbonate Nutrition 0.000 description 2
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
• 239000011780 sodium chloride Substances 0.000 description 2
• 235000010288 sodium nitrite Nutrition 0.000 description 2
• 239000011593 sulfur Chemical group 0.000 description 2
• 238000003786 synthesis reaction Methods 0.000 description 2
• 239000004149 tartrazine Substances 0.000 description 2
• DPKBAXPHAYBPRL-UHFFFAOYSA-M tetrabutylazanium;iodide Chemical compound [I-].CCCC[N+](CCCC)(CCCC)CCCC DPKBAXPHAYBPRL-UHFFFAOYSA-M 0.000 description 2
• 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 2
• VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
• 229910052723 transition metal Inorganic materials 0.000 description 2
• 150000003624 transition metals Chemical class 0.000 description 2
• 239000013598 vector Substances 0.000 description 2
• 239000003039 volatile agent Substances 0.000 description 2
• VCGRFBXVSFAGGA-UHFFFAOYSA-N (1,1-dioxo-1,4-thiazinan-4-yl)-[6-[[3-(4-fluorophenyl)-5-methyl-1,2-oxazol-4-yl]methoxy]pyridin-3-yl]methanone Chemical compound CC=1ON=C(C=2C=CC(F)=CC=2)C=1COC(N=C1)=CC=C1C(=O)N1CCS(=O)(=O)CC1 VCGRFBXVSFAGGA-UHFFFAOYSA-N 0.000 description 1
• DIIFZCPZIRQDIJ-UHFFFAOYSA-N (3,5-dimethyl-1,2-oxazol-4-yl)boronic acid Chemical compound CC1=NOC(C)=C1B(O)O DIIFZCPZIRQDIJ-UHFFFAOYSA-N 0.000 description 1
• XDBHWPLGGBLUHH-UHFFFAOYSA-N (3-cyanophenyl)boronic acid Chemical compound OB(O)C1=CC=CC(C#N)=C1 XDBHWPLGGBLUHH-UHFFFAOYSA-N 0.000 description 1
• CEBAHYWORUOILU-UHFFFAOYSA-N (4-cyanophenyl)boronic acid Chemical compound OB(O)C1=CC=C(C#N)C=C1 CEBAHYWORUOILU-UHFFFAOYSA-N 0.000 description 1
• 125000006273 (C1-C3) alkyl group Chemical group 0.000 description 1
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 description 1
• QIQWRCNAPQJQLL-COALEZEGSA-N (z)-but-2-enedioic acid;5-[(1r,2r)-2-(5,5-dimethylhex-1-ynyl)cyclopropyl]-1h-imidazole Chemical compound OC(=O)\C=C/C(O)=O.CC(C)(C)CCC#C[C@@H]1C[C@H]1C1=CN=CN1 QIQWRCNAPQJQLL-COALEZEGSA-N 0.000 description 1
• CYSGHNMQYZDMIA-UHFFFAOYSA-N 1,3-Dimethyl-2-imidazolidinon Chemical compound CN1CCN(C)C1=O CYSGHNMQYZDMIA-UHFFFAOYSA-N 0.000 description 1
• FZTLLUYFWAOGGB-UHFFFAOYSA-N 1,4-dioxane dioxane Chemical compound C1COCCO1.C1COCCO1 FZTLLUYFWAOGGB-UHFFFAOYSA-N 0.000 description 1
• YTDXNYIWTGSVSE-UHFFFAOYSA-N 1-[5-[6-(2,2,2-trifluoroacetyl)-4,5,7,8-tetrahydro-[1,3]thiazolo[4,5-d]azepin-2-yl]pyridin-2-yl]pyrrolidin-2-one Chemical compound S1C=2CCN(C(=O)C(F)(F)F)CCC=2N=C1C(C=N1)=CC=C1N1CCCC1=O YTDXNYIWTGSVSE-UHFFFAOYSA-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
• MWVMYAWMFTVYED-UHFFFAOYSA-N 2,3,4,5-tetrahydro-1h-3-benzazepine Chemical compound C1CNCCC2=CC=CC=C21 MWVMYAWMFTVYED-UHFFFAOYSA-N 0.000 description 1
• 239000001934 2,5-dimethylpyrazine Substances 0.000 description 1
• BZFGKBQHQJVAHS-UHFFFAOYSA-N 2-(trifluoromethyl)pyridine-4-carboxylic acid Chemical compound OC(=O)C1=CC=NC(C(F)(F)F)=C1 BZFGKBQHQJVAHS-UHFFFAOYSA-N 0.000 description 1
• IZXIZTKNFFYFOF-UHFFFAOYSA-N 2-Oxazolidone Chemical compound O=C1NCCO1 IZXIZTKNFFYFOF-UHFFFAOYSA-N 0.000 description 1
• SOHDPICLICFSOP-UHFFFAOYSA-N 2-bromo-6-methylpyridine Chemical compound CC1=CC=CC(Br)=N1 SOHDPICLICFSOP-UHFFFAOYSA-N 0.000 description 1
• QWLGCWXSNYKKDO-UHFFFAOYSA-N 2-chloro-5-iodopyridine Chemical compound ClC1=CC=C(I)C=N1 QWLGCWXSNYKKDO-UHFFFAOYSA-N 0.000 description 1
• ZGZMEKHQIZSZOH-UHFFFAOYSA-N 2-chloro-6-methylpyridine-4-carboxylic acid Chemical compound CC1=CC(C(O)=O)=CC(Cl)=N1 ZGZMEKHQIZSZOH-UHFFFAOYSA-N 0.000 description 1
• ZSPHQFZPSFCXIX-UHFFFAOYSA-N 2-iodo-5,6,7,8-tetrahydro-4h-[1,3]thiazolo[4,5-d]azepine Chemical compound C1CNCCC2=C1N=C(I)S2 ZSPHQFZPSFCXIX-UHFFFAOYSA-N 0.000 description 1
• HNTZKNJGAFJMHQ-UHFFFAOYSA-N 2-methylpyridine-3-carboxylic acid Chemical compound CC1=NC=CC=C1C(O)=O HNTZKNJGAFJMHQ-UHFFFAOYSA-N 0.000 description 1
• 229940080296 2-naphthalenesulfonate Drugs 0.000 description 1
• 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
• 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 1
• QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
• KVCQTKNUUQOELD-UHFFFAOYSA-N 4-amino-n-[1-(3-chloro-2-fluoroanilino)-6-methylisoquinolin-5-yl]thieno[3,2-d]pyrimidine-7-carboxamide Chemical compound N=1C=CC2=C(NC(=O)C=3C4=NC=NC(N)=C4SC=3)C(C)=CC=C2C=1NC1=CC=CC(Cl)=C1F KVCQTKNUUQOELD-UHFFFAOYSA-N 0.000 description 1
• HQSCPPCMBMFJJN-UHFFFAOYSA-N 4-bromobenzonitrile Chemical compound BrC1=CC=C(C#N)C=C1 HQSCPPCMBMFJJN-UHFFFAOYSA-N 0.000 description 1
• HSIBRQJIZHDEBI-UHFFFAOYSA-N 4-carbamothioyl-n-methylbenzamide Chemical compound CNC(=O)C1=CC=C(C(N)=S)C=C1 HSIBRQJIZHDEBI-UHFFFAOYSA-N 0.000 description 1
• QRAOZQGIUIDZQZ-UHFFFAOYSA-N 4-methyl-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-dihydro-1,4-benzoxazine Chemical compound C=1C=C2N(C)CCOC2=CC=1B1OC(C)(C)C(C)(C)O1 QRAOZQGIUIDZQZ-UHFFFAOYSA-N 0.000 description 1
• 229940124801 5-HT6 antagonist Drugs 0.000 description 1
• PEAOEIWYQVXZMB-UHFFFAOYSA-N 5-bromo-2-chloropyridine Chemical compound ClC1=CC=C(Br)C=N1 PEAOEIWYQVXZMB-UHFFFAOYSA-N 0.000 description 1
• FXJOTWLLDJYKAG-UHFFFAOYSA-N 5-chloropyrazine-2-carboxylic acid Chemical compound OC(=O)C1=CN=C(Cl)C=N1 FXJOTWLLDJYKAG-UHFFFAOYSA-N 0.000 description 1
• RBYJWCRKFLGNDB-UHFFFAOYSA-N 5-methylpyrazine-2-carboxylic acid Chemical compound CC1=CN=C(C(O)=O)C=N1 RBYJWCRKFLGNDB-UHFFFAOYSA-N 0.000 description 1
• DJDHHXDFKSLEQY-UHFFFAOYSA-N 5-methylpyridine-3-carboxylic acid Chemical compound CC1=CN=CC(C(O)=O)=C1 DJDHHXDFKSLEQY-UHFFFAOYSA-N 0.000 description 1
• XOVRJGNBQGFTDV-UHFFFAOYSA-N 5-trimethylstannylpyrimidine-2-carbonitrile Chemical compound C[Sn](C)(C)C1=CN=C(C#N)N=C1 XOVRJGNBQGFTDV-UHFFFAOYSA-N 0.000 description 1
• JNYLMODTPLSLIF-UHFFFAOYSA-N 6-(trifluoromethyl)pyridine-3-carboxylic acid Chemical compound OC(=O)C1=CC=C(C(F)(F)F)N=C1 JNYLMODTPLSLIF-UHFFFAOYSA-N 0.000 description 1
• ORIQLMBUPMABDV-UHFFFAOYSA-N 6-chloropyridine-3-carbonitrile Chemical compound ClC1=CC=C(C#N)C=N1 ORIQLMBUPMABDV-UHFFFAOYSA-N 0.000 description 1
• WMHSQCDPPJRWIL-UHFFFAOYSA-N 6-cyanopyridine-3-carboxylic acid Chemical compound OC(=O)C1=CC=C(C#N)N=C1 WMHSQCDPPJRWIL-UHFFFAOYSA-N 0.000 description 1
• SJWGLCDFBFCHNV-UHFFFAOYSA-N 6-methylpyridazine-3-carboxylic acid Chemical compound CC1=CC=C(C(O)=O)N=N1 SJWGLCDFBFCHNV-UHFFFAOYSA-N 0.000 description 1
• IOOWXRIGAUNUOW-UHFFFAOYSA-N 6-tributylstannylpyridine-3-carbonitrile Chemical compound CCCC[Sn](CCCC)(CCCC)C1=CC=C(C#N)C=N1 IOOWXRIGAUNUOW-UHFFFAOYSA-N 0.000 description 1
• CYJRNFFLTBEQSQ-UHFFFAOYSA-N 8-(3-methyl-1-benzothiophen-5-yl)-N-(4-methylsulfonylpyridin-3-yl)quinoxalin-6-amine Chemical compound CS(=O)(=O)C1=C(C=NC=C1)NC=1C=C2N=CC=NC2=C(C=1)C=1C=CC2=C(C(=CS2)C)C=1 CYJRNFFLTBEQSQ-UHFFFAOYSA-N 0.000 description 1
• OQLZINXFSUDMHM-UHFFFAOYSA-N Acetamidine Chemical compound CC(N)=N OQLZINXFSUDMHM-UHFFFAOYSA-N 0.000 description 1
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
• 229920001817 Agar Polymers 0.000 description 1
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
• VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
• 244000099147 Ananas comosus Species 0.000 description 1
• 208000019901 Anxiety disease Diseases 0.000 description 1
• 206010003178 Arterial thrombosis Diseases 0.000 description 1
• 108010001478 Bacitracin Proteins 0.000 description 1
• 241000894006 Bacteria Species 0.000 description 1
• COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
• UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
• 241000283707 Capra Species 0.000 description 1
• 239000004215 Carbon black (E152) Substances 0.000 description 1
• KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
• 206010012335 Dependence Diseases 0.000 description 1
• FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
• YQYJSBFKSSDGFO-UHFFFAOYSA-N Epihygromycin Natural products OC1C(O)C(C(=O)C)OC1OC(C(=C1)O)=CC=C1C=C(C)C(=O)NC1C(O)C(O)C2OCOC2C1O YQYJSBFKSSDGFO-UHFFFAOYSA-N 0.000 description 1
• 241000620209 Escherichia coli DH5[alpha] Species 0.000 description 1
• 108090000371 Esterases Proteins 0.000 description 1
• IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 1
• OUVXYXNWSVIOSJ-UHFFFAOYSA-N Fluo-4 Chemical compound CC1=CC=C(N(CC(O)=O)CC(O)=O)C(OCCOC=2C(=CC=C(C=2)C2=C3C=C(F)C(=O)C=C3OC3=CC(O)=C(F)C=C32)N(CC(O)=O)CC(O)=O)=C1 OUVXYXNWSVIOSJ-UHFFFAOYSA-N 0.000 description 1
• KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 1
• BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
• VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
• 230000005526 G1 to G0 transition Effects 0.000 description 1
• 208000018522 Gastrointestinal disease Diseases 0.000 description 1
• WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
• 241000282412 Homo Species 0.000 description 1
• 101001016833 Homo sapiens Histamine H3 receptor Proteins 0.000 description 1
• CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical class Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
• AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 1
• 208000031226 Hyperlipidaemia Diseases 0.000 description 1
• CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
• WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
• JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 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
• 239000006137 Luria-Bertani broth Substances 0.000 description 1
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
• 208000019695 Migraine disease Diseases 0.000 description 1
• 239000004909 Moisturizer Substances 0.000 description 1
• 208000016285 Movement disease Diseases 0.000 description 1
• 229940121948 Muscarinic receptor antagonist Drugs 0.000 description 1
• QKDDJDBFONZGBW-UHFFFAOYSA-N N-Cyclohexy-4-(imidazol-4-yl)-1-piperidinecarbothioamide Chemical compound C1CC(C=2NC=NC=2)CCN1C(=S)NC1CCCCC1 QKDDJDBFONZGBW-UHFFFAOYSA-N 0.000 description 1
• AYCPARAPKDAOEN-LJQANCHMSA-N N-[(1S)-2-(dimethylamino)-1-phenylethyl]-6,6-dimethyl-3-[(2-methyl-4-thieno[3,2-d]pyrimidinyl)amino]-1,4-dihydropyrrolo[3,4-c]pyrazole-5-carboxamide Chemical compound C1([C@H](NC(=O)N2C(C=3NN=C(NC=4C=5SC=CC=5N=C(C)N=4)C=3C2)(C)C)CN(C)C)=CC=CC=C1 AYCPARAPKDAOEN-LJQANCHMSA-N 0.000 description 1
• 229910002651 NO3 Inorganic materials 0.000 description 1
• 239000007832 Na2SO4 Substances 0.000 description 1
• 206010029240 Neuritis Diseases 0.000 description 1
• NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
• 208000008589 Obesity Diseases 0.000 description 1
• 241000283973 Oryctolagus cuniculus Species 0.000 description 1
• 229910019142 PO4 Inorganic materials 0.000 description 1
• 208000018737 Parkinson disease Diseases 0.000 description 1
• BELBBZDIHDAJOR-UHFFFAOYSA-N Phenolsulfonephthalein Chemical compound C1=CC(O)=CC=C1C1(C=2C=CC(O)=CC=2)C2=CC=CC=C2S(=O)(=O)O1 BELBBZDIHDAJOR-UHFFFAOYSA-N 0.000 description 1
• YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 1
• 239000004743 Polypropylene Substances 0.000 description 1
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
• QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
• 238000006069 Suzuki reaction reaction Methods 0.000 description 1
• 201000004810 Vascular dementia Diseases 0.000 description 1
• 206010047249 Venous thrombosis Diseases 0.000 description 1
• 108010046516 Wheat Germ Agglutinins Proteins 0.000 description 1
• HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
• RIIPFHVHLXPMHQ-UHFFFAOYSA-N [4-(dimethylamino)phenyl]boronic acid Chemical compound CN(C)C1=CC=C(B(O)O)C=C1 RIIPFHVHLXPMHQ-UHFFFAOYSA-N 0.000 description 1
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
• OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 1
• 229960004373 acetylcholine Drugs 0.000 description 1
• 238000005903 acid hydrolysis reaction Methods 0.000 description 1
• 150000007513 acids Chemical class 0.000 description 1
• 239000011149 active material Substances 0.000 description 1
• 230000001154 acute effect Effects 0.000 description 1
• 208000005298 acute pain Diseases 0.000 description 1
• 125000002252 acyl group Chemical group 0.000 description 1
• 239000000654 additive Substances 0.000 description 1
• 239000002671 adjuvant Substances 0.000 description 1
• 239000008272 agar Substances 0.000 description 1
• 230000002776 aggregation Effects 0.000 description 1
• 238000004220 aggregation Methods 0.000 description 1
• 230000029936 alkylation Effects 0.000 description 1
• 238000005804 alkylation reaction Methods 0.000 description 1
• 238000005576 amination reaction Methods 0.000 description 1
• 235000011114 ammonium hydroxide Nutrition 0.000 description 1
• 230000008485 antagonism Effects 0.000 description 1
• 239000003242 anti bacterial agent Substances 0.000 description 1
• 230000036506 anxiety Effects 0.000 description 1
• 239000008346 aqueous phase Substances 0.000 description 1
• 125000003710 aryl alkyl group Chemical group 0.000 description 1
• 229940009098 aspartate Drugs 0.000 description 1
• 238000011888 autopsy Methods 0.000 description 1
• 125000005334 azaindolyl group Chemical group N1N=C(C2=CC=CC=C12)* 0.000 description 1
• GMHPWGYTSXHHPI-UHFFFAOYSA-N azepan-4-one Chemical compound O=C1CCCNCC1 GMHPWGYTSXHHPI-UHFFFAOYSA-N 0.000 description 1
• 125000003725 azepanyl group Chemical group 0.000 description 1
• 125000002393 azetidinyl group Chemical group 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
• 230000001580 bacterial effect Effects 0.000 description 1
• SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
• 229940077388 benzenesulfonate Drugs 0.000 description 1
• 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
• 125000004619 benzopyranyl group Chemical group O1C(C=CC2=C1C=CC=C2)* 0.000 description 1
• 125000005874 benzothiadiazolyl group Chemical group 0.000 description 1
• 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
• 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
• 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
• 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
• WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
• 239000011230 binding agent Substances 0.000 description 1
• 230000003115 biocidal effect Effects 0.000 description 1
• 230000004071 biological effect Effects 0.000 description 1
• 125000005620 boronic acid group Chemical class 0.000 description 1
• 239000012267 brine Substances 0.000 description 1
• 239000006172 buffering agent Substances 0.000 description 1
• 239000001110 calcium chloride Substances 0.000 description 1
• 235000011148 calcium chloride Nutrition 0.000 description 1
• 229910001628 calcium chloride Inorganic materials 0.000 description 1
• 230000028956 calcium-mediated signaling Effects 0.000 description 1
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 1
• 150000001728 carbonyl compounds Chemical class 0.000 description 1
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
• 239000003054 catalyst Substances 0.000 description 1
• 238000006555 catalytic reaction Methods 0.000 description 1
• 210000003710 cerebral cortex Anatomy 0.000 description 1
• 210000004978 chinese hamster ovary cell Anatomy 0.000 description 1
• 210000002932 cholinergic neuron Anatomy 0.000 description 1
• 125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 description 1
• UCAIEVHKDLMIFL-UHFFFAOYSA-N clobenpropit Chemical compound C1=CC(Cl)=CC=C1CNC(=N)SCCCC1=CNC=N1 UCAIEVHKDLMIFL-UHFFFAOYSA-N 0.000 description 1
• 230000019771 cognition Effects 0.000 description 1
• 230000007278 cognition impairment Effects 0.000 description 1
• 239000002299 complementary DNA Substances 0.000 description 1
• 238000001816 cooling Methods 0.000 description 1
• 230000008878 coupling Effects 0.000 description 1
• 238000010168 coupling process Methods 0.000 description 1
• 238000002425 crystallisation Methods 0.000 description 1
• 230000008025 crystallization Effects 0.000 description 1
• 210000004748 cultured cell Anatomy 0.000 description 1
• 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
• 125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
• 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
• ACQBHJXEAYTHCY-UHFFFAOYSA-N cyclopropyl-[4-[3-(1H-imidazol-5-yl)propoxy]phenyl]methanone Chemical compound C=1C=C(OCCCC=2NC=NC=2)C=CC=1C(=O)C1CC1 ACQBHJXEAYTHCY-UHFFFAOYSA-N 0.000 description 1
• 238000006114 decarboxylation reaction Methods 0.000 description 1
• 125000005959 diazepanyl group Chemical group 0.000 description 1
• 239000002027 dichloromethane extract Substances 0.000 description 1
• 230000029087 digestion Effects 0.000 description 1
• 125000005043 dihydropyranyl group Chemical group O1C(CCC=C1)* 0.000 description 1
• 238000007865 diluting Methods 0.000 description 1
• 125000000532 dioxanyl group Chemical group 0.000 description 1
• 125000005879 dioxolanyl group Chemical group 0.000 description 1
• 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 1
• 239000007884 disintegrant Substances 0.000 description 1
• 238000010494 dissociation reaction Methods 0.000 description 1
• 230000005593 dissociations Effects 0.000 description 1
• 238000004821 distillation Methods 0.000 description 1
• 125000005883 dithianyl group Chemical group 0.000 description 1
• 238000007345 electrophilic aromatic substitution reaction Methods 0.000 description 1
• 239000003995 emulsifying agent Substances 0.000 description 1
• 239000000839 emulsion Substances 0.000 description 1
• 238000005516 engineering process Methods 0.000 description 1
• 206010015037 epilepsy Diseases 0.000 description 1
• 238000006345 epimerization reaction Methods 0.000 description 1
• 238000010931 ester hydrolysis Methods 0.000 description 1
• XWBDWHCCBGMXKG-UHFFFAOYSA-N ethanamine;hydron;chloride Chemical compound Cl.CCN XWBDWHCCBGMXKG-UHFFFAOYSA-N 0.000 description 1
• CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
• 239000013604 expression vector Substances 0.000 description 1
• 239000012091 fetal bovine serum Substances 0.000 description 1
• 239000012894 fetal calf serum Substances 0.000 description 1
• 239000000945 filler Substances 0.000 description 1
• 239000012530 fluid Substances 0.000 description 1
• 238000001943 fluorescence-activated cell sorting Methods 0.000 description 1
• 125000003784 fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 description 1
• WBJINCZRORDGAQ-UHFFFAOYSA-N formic acid ethyl ester Natural products CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 description 1
• 239000012458 free base Substances 0.000 description 1
• 125000003838 furazanyl group Chemical group 0.000 description 1
• 125000004612 furopyridinyl group Chemical group O1C(=CC2=C1C=CC=N2)* 0.000 description 1
• 125000002541 furyl group Chemical group 0.000 description 1
• 210000001035 gastrointestinal tract Anatomy 0.000 description 1
• 239000011521 glass Substances 0.000 description 1
• 229930195712 glutamate Natural products 0.000 description 1
• 239000008187 granular material Substances 0.000 description 1
• 238000010438 heat treatment Methods 0.000 description 1
• 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000003707 hexyloxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 1
• 238000004128 high performance liquid chromatography Methods 0.000 description 1
• 210000001320 hippocampus Anatomy 0.000 description 1
• 230000000742 histaminergic effect Effects 0.000 description 1
• 150000004677 hydrates Chemical class 0.000 description 1
• 229930195733 hydrocarbon Natural products 0.000 description 1
• 238000007327 hydrogenolysis reaction Methods 0.000 description 1
• 208000013403 hyperactivity Diseases 0.000 description 1
• 239000005457 ice water Substances 0.000 description 1
• 125000002632 imidazolidinyl group Chemical group 0.000 description 1
• 125000002883 imidazolyl group Chemical group 0.000 description 1
• 238000001727 in vivo Methods 0.000 description 1
• 238000011534 incubation Methods 0.000 description 1
• 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
• 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 description 1
• 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 description 1
• 125000001041 indolyl group Chemical group 0.000 description 1
• 230000006698 induction Effects 0.000 description 1
• 230000001939 inductive effect Effects 0.000 description 1
• 239000003112 inhibitor Substances 0.000 description 1
• 238000002347 injection Methods 0.000 description 1
• 239000007924 injection Substances 0.000 description 1
• PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
• 125000001977 isobenzofuranyl group Chemical group C=1(OC=C2C=CC=CC12)* 0.000 description 1
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
• 125000004594 isoindolinyl group Chemical group C1(NCC2=CC=CC=C12)* 0.000 description 1
• 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 1
• TWBYWOBDOCUKOW-UHFFFAOYSA-N isonicotinic acid Natural products OC(=O)C1=CC=NC=C1 TWBYWOBDOCUKOW-UHFFFAOYSA-N 0.000 description 1
• 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
• JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 1
• 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
• 125000001786 isothiazolyl group Chemical group 0.000 description 1
• 125000000842 isoxazolyl group Chemical group 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
• 210000004558 lewy body Anatomy 0.000 description 1
• 239000003446 ligand Substances 0.000 description 1
• 125000005647 linker group Chemical group 0.000 description 1
• 238000011068 loading method Methods 0.000 description 1
• 239000003589 local anesthetic agent Substances 0.000 description 1
• 229960005015 local anesthetics Drugs 0.000 description 1
• 239000000314 lubricant Substances 0.000 description 1
• VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
• 210000004962 mammalian cell Anatomy 0.000 description 1
• 239000003550 marker Substances 0.000 description 1
• 239000000463 material Substances 0.000 description 1
• 230000007074 memory dysfunction Effects 0.000 description 1
• 239000002032 methanolic fraction Substances 0.000 description 1
• SMCVPMKCDDNUCQ-UHFFFAOYSA-N methyl 3,3-dimethoxypropanoate Chemical compound COC(OC)CC(=O)OC SMCVPMKCDDNUCQ-UHFFFAOYSA-N 0.000 description 1
• 229940095102 methyl benzoate Drugs 0.000 description 1
• 229960003248 mifepristone Drugs 0.000 description 1
• VKHAHZOOUSRJNA-GCNJZUOMSA-N mifepristone Chemical compound C1([C@@H]2C3=C4CCC(=O)C=C4CC[C@H]3[C@@H]3CC[C@@]([C@]3(C2)C)(O)C#CC)=CC=C(N(C)C)C=C1 VKHAHZOOUSRJNA-GCNJZUOMSA-N 0.000 description 1
• 150000007522 mineralic acids Chemical class 0.000 description 1
• 239000007758 minimum essential medium Substances 0.000 description 1
• 239000003607 modifier Substances 0.000 description 1
• 230000001333 moisturizer Effects 0.000 description 1
• 239000003068 molecular probe Substances 0.000 description 1
• 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 1
• XMWFMEYDRNJSOO-UHFFFAOYSA-N morpholine-4-carbonyl chloride Chemical compound ClC(=O)N1CCOCC1 XMWFMEYDRNJSOO-UHFFFAOYSA-N 0.000 description 1
• 201000006417 multiple sclerosis Diseases 0.000 description 1
• 239000003149 muscarinic antagonist Substances 0.000 description 1
• 230000003551 muscarinic effect Effects 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
• 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• PSZYNBSKGUBXEH-UHFFFAOYSA-M naphthalene-1-sulfonate Chemical compound C1=CC=C2C(S(=O)(=O)[O-])=CC=CC2=C1 PSZYNBSKGUBXEH-UHFFFAOYSA-M 0.000 description 1
• KVBGVZZKJNLNJU-UHFFFAOYSA-M naphthalene-2-sulfonate Chemical compound C1=CC=CC2=CC(S(=O)(=O)[O-])=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-M 0.000 description 1
• 125000001624 naphthyl group Chemical group 0.000 description 1
• 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 description 1
• 201000003631 narcolepsy Diseases 0.000 description 1
• 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• 208000004296 neuralgia Diseases 0.000 description 1
• 230000002981 neuropathic effect Effects 0.000 description 1
• 239000002858 neurotransmitter agent Substances 0.000 description 1
• 230000003957 neurotransmitter release Effects 0.000 description 1
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
• 239000002687 nonaqueous vehicle Substances 0.000 description 1
• 238000007339 nucleophilic aromatic substitution reaction Methods 0.000 description 1
• 230000000269 nucleophilic effect Effects 0.000 description 1
• 238000010534 nucleophilic substitution reaction Methods 0.000 description 1
• 235000020824 obesity Nutrition 0.000 description 1
• 230000003287 optical effect Effects 0.000 description 1
• 150000007524 organic acids Chemical class 0.000 description 1
• 239000003960 organic solvent Substances 0.000 description 1
• 150000002902 organometallic compounds Chemical class 0.000 description 1
• 125000002524 organometallic group Chemical group 0.000 description 1
• 201000008482 osteoarthritis Diseases 0.000 description 1
• 125000005880 oxathiolanyl group Chemical group 0.000 description 1
• 125000002971 oxazolyl group Chemical group 0.000 description 1
• 125000003566 oxetanyl group Chemical group 0.000 description 1
• 230000003647 oxidation Effects 0.000 description 1
• 238000007254 oxidation reaction Methods 0.000 description 1
• 125000000466 oxiranyl group Chemical group 0.000 description 1
• 238000007911 parenteral administration Methods 0.000 description 1
• 239000002245 particle Substances 0.000 description 1
• 230000001575 pathological effect Effects 0.000 description 1
• 239000008188 pellet Substances 0.000 description 1
• 230000002093 peripheral effect Effects 0.000 description 1
• 150000002978 peroxides Chemical class 0.000 description 1
• 150000002989 phenols Chemical class 0.000 description 1
• 229960003531 phenolsulfonphthalein Drugs 0.000 description 1
• UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
• 239000010452 phosphate Substances 0.000 description 1
• 239000002953 phosphate buffered saline Substances 0.000 description 1
• 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
• 239000006187 pill Substances 0.000 description 1
• 125000004193 piperazinyl group Chemical group 0.000 description 1
• 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 1
• 229920001155 polypropylene Polymers 0.000 description 1
• 239000012286 potassium permanganate Substances 0.000 description 1
• 230000001012 protector Effects 0.000 description 1
• 102000004169 proteins and genes Human genes 0.000 description 1
• 125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 0.000 description 1
• 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
• 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
• 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 description 1
• 125000003072 pyrazolidinyl group Chemical group 0.000 description 1
• 125000003226 pyrazolyl group Chemical group 0.000 description 1
• 125000002098 pyridazinyl group Chemical group 0.000 description 1
• 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 description 1
• XACWJIQLDLUFSR-UHFFFAOYSA-N pyrrolidine-1-carbonyl chloride Chemical compound ClC(=O)N1CCCC1 XACWJIQLDLUFSR-UHFFFAOYSA-N 0.000 description 1
• 125000000168 pyrrolyl group Chemical group 0.000 description 1
• 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
• 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
• 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
• 125000004621 quinuclidinyl group Chemical group N12C(CC(CC1)CC2)* 0.000 description 1
• 239000002994 raw material Substances 0.000 description 1
• 238000012950 reanalysis Methods 0.000 description 1
• 230000009467 reduction Effects 0.000 description 1
• 238000006722 reduction reaction Methods 0.000 description 1
• 230000001105 regulatory effect Effects 0.000 description 1
• 108091008146 restriction endonucleases Proteins 0.000 description 1
• 238000004007 reversed phase HPLC Methods 0.000 description 1
• 206010039073 rheumatoid arthritis Diseases 0.000 description 1
• 238000011808 rodent model Methods 0.000 description 1
• YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
• 229960001860 salicylate Drugs 0.000 description 1
• 229930195734 saturated hydrocarbon Natural products 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
• 239000000198 serotonin 5-HT3 receptor agonist Substances 0.000 description 1
• XGVXKJKTISMIOW-ZDUSSCGKSA-N simurosertib Chemical compound N1N=CC(C=2SC=3C(=O)NC(=NC=3C=2)[C@H]2N3CCC(CC3)C2)=C1C XGVXKJKTISMIOW-ZDUSSCGKSA-N 0.000 description 1
• 208000019116 sleep disease Diseases 0.000 description 1
• QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
• 239000012312 sodium hydride Substances 0.000 description 1
• 229910000104 sodium hydride Inorganic materials 0.000 description 1
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
• 239000007790 solid phase Substances 0.000 description 1
• 238000010186 staining Methods 0.000 description 1
• 230000001954 sterilising effect Effects 0.000 description 1
• 238000004659 sterilization and disinfection Methods 0.000 description 1
• 208000023516 stroke disease Diseases 0.000 description 1
• KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
• 239000006228 supernatant Substances 0.000 description 1
• 239000000829 suppository Substances 0.000 description 1
• 230000001629 suppression Effects 0.000 description 1
• 239000004094 surface-active agent Substances 0.000 description 1
• 239000000375 suspending agent Substances 0.000 description 1
• 230000002889 sympathetic effect Effects 0.000 description 1
• 238000002636 symptomatic treatment Methods 0.000 description 1
• 230000016978 synaptic transmission, cholinergic Effects 0.000 description 1
• 239000006188 syrup Substances 0.000 description 1
• 235000020357 syrup Nutrition 0.000 description 1
• 229940095064 tartrate Drugs 0.000 description 1
• FKLPAGOTHFVRLL-UHFFFAOYSA-N tert-butyl 3-carbamothioylpyrrolidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(C(N)=S)C1 FKLPAGOTHFVRLL-UHFFFAOYSA-N 0.000 description 1
• SCGQNJHAAYUQOO-UHFFFAOYSA-N tert-butyl 4-carbamothioylpiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(C(N)=S)CC1 SCGQNJHAAYUQOO-UHFFFAOYSA-N 0.000 description 1
• 125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 description 1
• 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
• 125000004853 tetrahydropyridinyl group Chemical group N1(CCCC=C1)* 0.000 description 1
• 125000003507 tetrahydrothiofenyl group Chemical group 0.000 description 1
• 125000004632 tetrahydrothiopyranyl group Chemical group S1C(CCCC1)* 0.000 description 1
• 125000005247 tetrazinyl group Chemical group N1=NN=NC(=C1)* 0.000 description 1
• 125000003831 tetrazolyl group Chemical group 0.000 description 1
• HJZYBDPHAHGHAZ-UHFFFAOYSA-N thiadiazole-4-carboxylic acid Chemical compound OC(=O)C1=CSN=N1 HJZYBDPHAHGHAZ-UHFFFAOYSA-N 0.000 description 1
• 125000001113 thiadiazolyl group Chemical group 0.000 description 1
• 125000001984 thiazolidinyl group Chemical group 0.000 description 1
• 125000000335 thiazolyl group Chemical group 0.000 description 1
• 125000001544 thienyl group Chemical group 0.000 description 1
• 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
• 150000003606 tin compounds Chemical class 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
• 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
• 238000012250 transgenic expression Methods 0.000 description 1
• 125000004306 triazinyl group Chemical group 0.000 description 1
• 125000001425 triazolyl group Chemical group 0.000 description 1
• 125000004205 trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
• LEIMLDGFXIOXMT-UHFFFAOYSA-N trimethylsilyl cyanide Chemical compound C[Si](C)(C)C#N LEIMLDGFXIOXMT-UHFFFAOYSA-N 0.000 description 1
• 238000009827 uniform distribution Methods 0.000 description 1
• 238000005406 washing Methods 0.000 description 1
• 239000000080 wetting agent Substances 0.000 description 1
• 229910052725 zinc Inorganic materials 0.000 description 1
• 239000011701 zinc Substances 0.000 description 1