JP5848251B2 - オレキシン受容体調節因子としての縮合複素環式化合物 - Google Patents

Info

Publication number

JP5848251B2

JP5848251B2 JP2012535386A JP2012535386A JP5848251B2 JP 5848251 B2 JP5848251 B2 JP 5848251B2 JP 2012535386 A JP2012535386 A JP 2012535386A JP 2012535386 A JP2012535386 A JP 2012535386A JP 5848251 B2 JP5848251 B2 JP 5848251B2

Authority

JP

Japan

Prior art keywords

phenyl

diazabicyclo

triazol

fluoro

octane

Prior art date

2009-10-23

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.)

Expired - Fee Related

Links

• Espacenet
• Global Dossier
• Discuss

• 108050000742 Orexin Receptor Proteins 0.000 title description 21
• 102000008834 Orexin receptor Human genes 0.000 title description 20
• 150000002391 heterocyclic compounds Chemical class 0.000 title 1
• 150000001875 compounds Chemical class 0.000 claims description 383
• -1 1H-pyrazol-1-yl Chemical group 0.000 claims description 265
• 150000003839 salts Chemical class 0.000 claims description 53
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 33
• 125000000217 alkyl group Chemical group 0.000 claims description 32
• 125000001424 substituent group Chemical group 0.000 claims description 28
• 239000000126 substance Substances 0.000 claims description 21
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 14
• SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims description 12
• 125000003545 alkoxy group Chemical group 0.000 claims description 12
• 229910052799 carbon Inorganic materials 0.000 claims description 12
• QWENRTYMTSOGBR-UHFFFAOYSA-N 1H-1,2,3-Triazole Chemical compound C=1C=NNN=1 QWENRTYMTSOGBR-UHFFFAOYSA-N 0.000 claims description 11
• WSFSSNUMVMOOMR-BJUDXGSMSA-N methanone Chemical compound O=[11CH2] WSFSSNUMVMOOMR-BJUDXGSMSA-N 0.000 claims description 11
• 125000001072 heteroaryl group Chemical group 0.000 claims description 10
• 125000001607 1,2,3-triazol-1-yl group Chemical group [*]N1N=NC([H])=C1[H] 0.000 claims description 9
• 230000027455 binding Effects 0.000 claims description 9
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 9
• SMUQFGGVLNAIOZ-UHFFFAOYSA-N quinaldine Chemical compound C1=CC=CC2=NC(C)=CC=C21 SMUQFGGVLNAIOZ-UHFFFAOYSA-N 0.000 claims description 8
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 7
• 125000004262 quinoxalin-2-yl group Chemical group [H]C1=NC2=C([H])C([H])=C([H])C([H])=C2N=C1* 0.000 claims description 7
• XSCHRSMBECNVNS-UHFFFAOYSA-N quinoxaline Chemical compound N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 claims description 6
• GKVDLTTVBNOGNJ-UHFFFAOYSA-N 2-methylpyrimidin-4-amine Chemical compound CC1=NC=CC(N)=N1 GKVDLTTVBNOGNJ-UHFFFAOYSA-N 0.000 claims description 4
• 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 4
• 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 4
• JJOOKXUUVWIARB-UHFFFAOYSA-N 6-chloro-1,3-benzoxazole Chemical compound ClC1=CC=C2N=COC2=C1 JJOOKXUUVWIARB-UHFFFAOYSA-N 0.000 claims description 4
• RZWKLEHRXNOKGT-UHFFFAOYSA-N CC=1C(=C(C=CC1)C=O)C1=CC=NN1 Chemical compound CC=1C(=C(C=CC1)C=O)C1=CC=NN1 RZWKLEHRXNOKGT-UHFFFAOYSA-N 0.000 claims description 4
• KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 claims description 4
• KDUWWQCGLSYDIY-UHFFFAOYSA-N n,n,2-trimethylpyrimidin-4-amine Chemical compound CN(C)C1=CC=NC(C)=N1 KDUWWQCGLSYDIY-UHFFFAOYSA-N 0.000 claims description 4
• LAURYIYOSYVBIZ-UHFFFAOYSA-N n,n,4-trimethylpyrimidin-2-amine Chemical compound CN(C)C1=NC=CC(C)=N1 LAURYIYOSYVBIZ-UHFFFAOYSA-N 0.000 claims description 4
• MSXIOWULDXZJLX-UHFFFAOYSA-N n,n-dimethylpyrimidin-4-amine Chemical compound CN(C)C1=CC=NC=N1 MSXIOWULDXZJLX-UHFFFAOYSA-N 0.000 claims description 4
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
• USOABOIEIQKGGQ-UHFFFAOYSA-N (2-bromophenyl)-[3-(4,6-dimethylpyrimidin-2-yl)-3,6-diazabicyclo[3.2.0]heptan-6-yl]methanone Chemical compound CC1=CC(C)=NC(N2CC3N(CC3C2)C(=O)C=2C(=CC=CC=2)Br)=N1 USOABOIEIQKGGQ-UHFFFAOYSA-N 0.000 claims description 3
• 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 3
• HBAPRWLCCBZDNA-UHFFFAOYSA-N 4-methyl-6,7-dihydro-5h-cyclopenta[d]pyrimidine Chemical compound CC1=NC=NC2=C1CCC2 HBAPRWLCCBZDNA-UHFFFAOYSA-N 0.000 claims description 3
• PGEXEBHDXNLTIE-UHFFFAOYSA-N FC=1C(=C(C=CC1)C=O)C1=CC(=NO1)C Chemical compound FC=1C(=C(C=CC1)C=O)C1=CC(=NO1)C PGEXEBHDXNLTIE-UHFFFAOYSA-N 0.000 claims description 3
• STLYQTNIULBKGY-UHFFFAOYSA-N FC=1C(=C(C=CC1)C=O)C1=CC=NO1 Chemical compound FC=1C(=C(C=CC1)C=O)C1=CC=NO1 STLYQTNIULBKGY-UHFFFAOYSA-N 0.000 claims description 3
• CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 3
• OFXUUYPFMNNTIU-UHFFFAOYSA-N [3-(4,6-dimethylpyrimidin-2-yl)-3,6-diazabicyclo[3.2.0]heptan-6-yl]-(2-phenylphenyl)methanone Chemical compound CC1=CC(C)=NC(N2CC3N(CC3C2)C(=O)C=2C(=CC=CC=2)C=2C=CC=CC=2)=N1 OFXUUYPFMNNTIU-UHFFFAOYSA-N 0.000 claims description 3
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 3
• 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims description 3
• ZERSCKSOBJMLBC-UHFFFAOYSA-N (2,6-dimethoxyphenyl)-(4-quinoxalin-6-yl-4,7-diazabicyclo[4.2.0]octan-7-yl)methanone Chemical compound COC1=CC=CC(OC)=C1C(=O)N1C2CN(C=3C=C4N=CC=NC4=CC=3)CCC2C1 ZERSCKSOBJMLBC-UHFFFAOYSA-N 0.000 claims description 2
• MERAYSGZQADQGE-UHFFFAOYSA-N (2,6-dimethoxyphenyl)-[4-(4-phenylpyrimidin-2-yl)-4,7-diazabicyclo[4.2.0]octan-7-yl]methanone Chemical compound COC1=CC=CC(OC)=C1C(=O)N1C2CN(C=3N=C(C=CN=3)C=3C=CC=CC=3)CCC2C1 MERAYSGZQADQGE-UHFFFAOYSA-N 0.000 claims description 2
• GXDONUFNDCCJQI-UHFFFAOYSA-N (2-bromophenyl)-[3-(4-methylpyrimidin-2-yl)-3,6-diazabicyclo[3.2.0]heptan-6-yl]methanone Chemical compound CC1=CC=NC(N2CC3N(CC3C2)C(=O)C=2C(=CC=CC=2)Br)=N1 GXDONUFNDCCJQI-UHFFFAOYSA-N 0.000 claims description 2
• JXXXJWSNTPQUSL-UHFFFAOYSA-N (2-phenylphenyl)-(3-quinoxalin-2-yl-3,6-diazabicyclo[3.2.0]heptan-6-yl)methanone Chemical compound C1C2CN(C=3N=C4C=CC=CC4=NC=3)CC2N1C(=O)C1=CC=CC=C1C1=CC=CC=C1 JXXXJWSNTPQUSL-UHFFFAOYSA-N 0.000 claims description 2
• NCRSYKPNXDTNQA-UHFFFAOYSA-N (2-phenylphenyl)-(4-quinoxalin-2-yl-4,7-diazabicyclo[4.2.0]octan-7-yl)methanone Chemical compound C1C2CCN(C=3N=C4C=CC=CC4=NC=3)CC2N1C(=O)C1=CC=CC=C1C1=CC=CC=C1 NCRSYKPNXDTNQA-UHFFFAOYSA-N 0.000 claims description 2
• WWHREMBTHQBQAA-UHFFFAOYSA-N (2-phenylphenyl)-[3-(4-phenylpyrimidin-2-yl)-3,6-diazabicyclo[3.2.0]heptan-6-yl]methanone Chemical compound C=1C=CC=C(C=2C=CC=CC=2)C=1C(=O)N(C1C2)CC1CN2C(N=1)=NC=CC=1C1=CC=CC=C1 WWHREMBTHQBQAA-UHFFFAOYSA-N 0.000 claims description 2
• FCAOJQYTXNQTOI-UHFFFAOYSA-N (2-phenylphenyl)-[4-(4-phenylpyrimidin-2-yl)-4,7-diazabicyclo[4.2.0]octan-7-yl]methanone Chemical compound C=1C=CC=C(C=2C=CC=CC=2)C=1C(=O)N(C1C2)CC1CCN2C(N=1)=NC=CC=1C1=CC=CC=C1 FCAOJQYTXNQTOI-UHFFFAOYSA-N 0.000 claims description 2
• KLIDCXVFHGNTTM-UHFFFAOYSA-N 2,6-dimethoxyphenol Chemical group COC1=CC=CC(OC)=C1O KLIDCXVFHGNTTM-UHFFFAOYSA-N 0.000 claims description 2
• YHUWINJRLYIHCD-UHFFFAOYSA-N 2-[7-(2,5-dimethylphenyl)sulfonyl-4,7-diazabicyclo[4.2.0]octan-4-yl]quinoxaline Chemical compound CC1=CC=C(C)C(S(=O)(=O)N2C3CN(CCC3C2)C=2N=C3C=CC=CC3=NC=2)=C1 YHUWINJRLYIHCD-UHFFFAOYSA-N 0.000 claims description 2
• 125000006276 2-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C(*)C([H])=C1[H] 0.000 claims description 2
• YESCPKTWTUCNTK-UHFFFAOYSA-N 2-fluoro-6-(triazol-2-yl)benzaldehyde Chemical compound FC1=C(C(=CC=C1)N1N=CC=N1)C=O YESCPKTWTUCNTK-UHFFFAOYSA-N 0.000 claims description 2
• VZWOXDYRBDIHMA-UHFFFAOYSA-N 2-methyl-1,3-thiazole Chemical group CC1=NC=CS1 VZWOXDYRBDIHMA-UHFFFAOYSA-N 0.000 claims description 2
• 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
• AGFPGULYIMKQGT-UHFFFAOYSA-N 3-fluoro-2-(1H-pyrazol-5-yl)benzaldehyde Chemical compound FC=1C(=C(C=CC=1)C=O)C=1NN=CC=1 AGFPGULYIMKQGT-UHFFFAOYSA-N 0.000 claims description 2
• QSYWKQLZNHTFCV-UHFFFAOYSA-N 3-fluoro-2-(triazol-2-yl)benzaldehyde Chemical compound FC1=CC=CC(C=O)=C1N1N=CC=N1 QSYWKQLZNHTFCV-UHFFFAOYSA-N 0.000 claims description 2
• OBFNEMXIPDVHRI-UHFFFAOYSA-N 4-fluoro-2-pyrimidin-2-ylbenzaldehyde Chemical compound FC1=CC(=C(C=C1)C=O)C1=NC=CC=N1 OBFNEMXIPDVHRI-UHFFFAOYSA-N 0.000 claims description 2
• ZJTUYXLOPPDBGH-UHFFFAOYSA-N 4-methoxy-2-(triazol-2-yl)benzaldehyde Chemical compound COC1=CC=C(C=O)C(N2N=CC=N2)=C1 ZJTUYXLOPPDBGH-UHFFFAOYSA-N 0.000 claims description 2
• PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 claims description 2
• ZFZULBCQSGGOHR-DNVCBOLYSA-N [(1r,6s)-4-(4,5-dimethylpyrimidin-2-yl)-4,7-diazabicyclo[4.2.0]octan-7-yl]-[5-fluoro-2-(triazol-2-yl)phenyl]methanone Chemical compound N1=C(C)C(C)=CN=C1N1C[C@H]2N(C(=O)C=3C(=CC=C(F)C=3)N3N=CC=N3)C[C@H]2CC1 ZFZULBCQSGGOHR-DNVCBOLYSA-N 0.000 claims description 2
• DBODIMKUPBUYBB-SJLPKXTDSA-N [(1r,6s)-4-(4,5-dimethylpyrimidin-2-yl)-4,7-diazabicyclo[4.2.0]octan-7-yl]-[6-methyl-2-(triazol-1-yl)pyridin-3-yl]methanone Chemical compound C([C@@H]1CN([C@@H]1C1)C(=O)C2=CC=C(N=C2N2N=NC=C2)C)CN1C1=NC=C(C)C(C)=N1 DBODIMKUPBUYBB-SJLPKXTDSA-N 0.000 claims description 2
• VNNKBQGOFHYHOZ-VQIMIIECSA-N [(1r,6s)-4-(4,6-dimethylpyridin-2-yl)-4,7-diazabicyclo[4.2.0]octan-7-yl]-[2-fluoro-6-(triazol-2-yl)phenyl]methanone Chemical compound CC1=CC(C)=NC(N2C[C@H]3N(C[C@H]3CC2)C(=O)C=2C(=CC=CC=2F)N2N=CC=N2)=C1 VNNKBQGOFHYHOZ-VQIMIIECSA-N 0.000 claims description 2
• ARCNMXAESGIZJJ-VQIMIIECSA-N [(1r,6s)-4-(4,6-dimethylpyrimidin-2-yl)-4,7-diazabicyclo[4.2.0]octan-7-yl]-(3-fluoro-2-pyrazol-1-ylphenyl)methanone Chemical compound CC1=CC(C)=NC(N2C[C@H]3N(C[C@H]3CC2)C(=O)C=2C(=C(F)C=CC=2)N2N=CC=C2)=N1 ARCNMXAESGIZJJ-VQIMIIECSA-N 0.000 claims description 2
• RAWRQCGINRXFGJ-VQIMIIECSA-N [(1r,6s)-4-(4,6-dimethylpyrimidin-2-yl)-4,7-diazabicyclo[4.2.0]octan-7-yl]-(3-fluoro-2-pyrimidin-2-ylphenyl)methanone Chemical compound CC1=CC(C)=NC(N2C[C@H]3N(C[C@H]3CC2)C(=O)C=2C(=C(F)C=CC=2)C=2N=CC=CN=2)=N1 RAWRQCGINRXFGJ-VQIMIIECSA-N 0.000 claims description 2
• RNPBAIRMGAFCTD-UYAOXDASSA-N [(1r,6s)-4-(4,6-dimethylpyrimidin-2-yl)-4,7-diazabicyclo[4.2.0]octan-7-yl]-(3-methyl-2-pyrazol-1-ylphenyl)methanone Chemical compound CC1=CC(C)=NC(N2C[C@H]3N(C[C@H]3CC2)C(=O)C=2C(=C(C)C=CC=2)N2N=CC=C2)=N1 RNPBAIRMGAFCTD-UYAOXDASSA-N 0.000 claims description 2
• NFHNWNGGAXTAHB-VQIMIIECSA-N [(1r,6s)-4-(4,6-dimethylpyrimidin-2-yl)-4,7-diazabicyclo[4.2.0]octan-7-yl]-[2-(3-methyl-1,2,4-oxadiazol-5-yl)phenyl]methanone Chemical compound CC1=NOC(C=2C(=CC=CC=2)C(=O)N2[C@@H]3CN(CC[C@@H]3C2)C=2N=C(C)C=C(C)N=2)=N1 NFHNWNGGAXTAHB-VQIMIIECSA-N 0.000 claims description 2
• QMUHLWWRQXORGR-CRAIPNDOSA-N [(1r,6s)-4-(4,6-dimethylpyrimidin-2-yl)-4,7-diazabicyclo[4.2.0]octan-7-yl]-[2-fluoro-6-(3-methyl-1,2,4-oxadiazol-5-yl)phenyl]methanone Chemical compound CC1=NOC(C=2C(=C(F)C=CC=2)C(=O)N2[C@@H]3CN(CC[C@@H]3C2)C=2N=C(C)C=C(C)N=2)=N1 QMUHLWWRQXORGR-CRAIPNDOSA-N 0.000 claims description 2
• GDIQDZVRMKTDML-CRAIPNDOSA-N [(1r,6s)-4-(4,6-dimethylpyrimidin-2-yl)-4,7-diazabicyclo[4.2.0]octan-7-yl]-[2-fluoro-6-(triazol-2-yl)phenyl]methanone Chemical compound CC1=CC(C)=NC(N2C[C@H]3N(C[C@H]3CC2)C(=O)C=2C(=CC=CC=2F)N2N=CC=N2)=N1 GDIQDZVRMKTDML-CRAIPNDOSA-N 0.000 claims description 2
• VQLZITAIIORYNU-DNVCBOLYSA-N [(1r,6s)-4-(4,6-dimethylpyrimidin-2-yl)-4,7-diazabicyclo[4.2.0]octan-7-yl]-[3-fluoro-2-(1h-pyrazol-5-yl)phenyl]methanone Chemical compound CC1=CC(C)=NC(N2C[C@H]3N(C[C@H]3CC2)C(=O)C=2C(=C(F)C=CC=2)C=2NN=CC=2)=N1 VQLZITAIIORYNU-DNVCBOLYSA-N 0.000 claims description 2
• CNVDHNKVDSWDHK-CRAIPNDOSA-N [(1r,6s)-4-(4,6-dimethylpyrimidin-2-yl)-4,7-diazabicyclo[4.2.0]octan-7-yl]-[3-fluoro-2-(triazol-1-yl)phenyl]methanone Chemical compound CC1=CC(C)=NC(N2C[C@H]3N(C[C@H]3CC2)C(=O)C=2C(=C(F)C=CC=2)N2N=NC=C2)=N1 CNVDHNKVDSWDHK-CRAIPNDOSA-N 0.000 claims description 2
• KPLJXBDVXNWNGI-CRAIPNDOSA-N [(1r,6s)-4-(4,6-dimethylpyrimidin-2-yl)-4,7-diazabicyclo[4.2.0]octan-7-yl]-[3-fluoro-2-(triazol-2-yl)phenyl]methanone Chemical compound CC1=CC(C)=NC(N2C[C@H]3N(C[C@H]3CC2)C(=O)C=2C(=C(F)C=CC=2)N2N=CC=N2)=N1 KPLJXBDVXNWNGI-CRAIPNDOSA-N 0.000 claims description 2
• MUKSCISAZPPELV-SJLPKXTDSA-N [(1r,6s)-4-(4,6-dimethylpyrimidin-2-yl)-4,7-diazabicyclo[4.2.0]octan-7-yl]-[3-methoxy-2-(triazol-1-yl)phenyl]methanone Chemical compound C([C@@H]1CN([C@@H]1C1)C(=O)C=2C=CC=C(C=2N2N=NC=C2)OC)CN1C1=NC(C)=CC(C)=N1 MUKSCISAZPPELV-SJLPKXTDSA-N 0.000 claims description 2
• RHJBVNFMVXMMQA-SJLPKXTDSA-N [(1r,6s)-4-(4,6-dimethylpyrimidin-2-yl)-4,7-diazabicyclo[4.2.0]octan-7-yl]-[3-methoxy-2-(triazol-2-yl)phenyl]methanone Chemical compound C([C@@H]1CN([C@@H]1C1)C(=O)C=2C=CC=C(C=2N2N=CC=N2)OC)CN1C1=NC(C)=CC(C)=N1 RHJBVNFMVXMMQA-SJLPKXTDSA-N 0.000 claims description 2
• KALRYPOHHCRTNN-IEBWSBKVSA-N [(1r,6s)-4-(4,6-dimethylpyrimidin-2-yl)-4,7-diazabicyclo[4.2.0]octan-7-yl]-[3-methyl-2-(triazol-1-yl)phenyl]methanone Chemical compound CC1=CC(C)=NC(N2C[C@H]3N(C[C@H]3CC2)C(=O)C=2C(=C(C)C=CC=2)N2N=NC=C2)=N1 KALRYPOHHCRTNN-IEBWSBKVSA-N 0.000 claims description 2
• IPKRWZKTQZLMOQ-OXQOHEQNSA-N [(1r,6s)-4-(4,6-dimethylpyrimidin-2-yl)-4,7-diazabicyclo[4.2.0]octan-7-yl]-[4-methoxy-2-(triazol-2-yl)phenyl]methanone Chemical compound C([C@@H]1CN([C@@H]1C1)C(=O)C2=CC=C(C=C2N2N=CC=N2)OC)CN1C1=NC(C)=CC(C)=N1 IPKRWZKTQZLMOQ-OXQOHEQNSA-N 0.000 claims description 2
• FLWWBLDVCVQTRI-DNVCBOLYSA-N [(1r,6s)-4-(4,6-dimethylpyrimidin-2-yl)-4,7-diazabicyclo[4.2.0]octan-7-yl]-[5-fluoro-2-(triazol-2-yl)phenyl]methanone Chemical compound CC1=CC(C)=NC(N2C[C@H]3N(C[C@H]3CC2)C(=O)C=2C(=CC=C(F)C=2)N2N=CC=N2)=N1 FLWWBLDVCVQTRI-DNVCBOLYSA-N 0.000 claims description 2
• XTBUKDIQTIIDEW-OXQOHEQNSA-N [(1r,6s)-4-(4,6-dimethylpyrimidin-2-yl)-4,7-diazabicyclo[4.2.0]octan-7-yl]-[5-methoxy-2-(triazol-2-yl)phenyl]methanone Chemical compound C([C@@H]1CN([C@@H]1C1)C(=O)C=2C(=CC=C(C=2)OC)N2N=CC=N2)CN1C1=NC(C)=CC(C)=N1 XTBUKDIQTIIDEW-OXQOHEQNSA-N 0.000 claims description 2
• MTLHNBTZPPYZMD-SJLPKXTDSA-N [(1r,6s)-4-(4,6-dimethylpyrimidin-2-yl)-4,7-diazabicyclo[4.2.0]octan-7-yl]-[6-methyl-2-(triazol-1-yl)pyridin-3-yl]methanone Chemical compound C([C@@H]1CN([C@@H]1C1)C(=O)C2=CC=C(N=C2N2N=NC=C2)C)CN1C1=NC(C)=CC(C)=N1 MTLHNBTZPPYZMD-SJLPKXTDSA-N 0.000 claims description 2
• DHGNKEKRMDXCQR-CXAGYDPISA-N [(1r,6s)-4-(4-aminopyrimidin-2-yl)-4,7-diazabicyclo[4.2.0]octan-7-yl]-[5-methoxy-2-(triazol-2-yl)phenyl]methanone Chemical compound C([C@@H]1CN([C@@H]1C1)C(=O)C=2C(=CC=C(C=2)OC)N2N=CC=N2)CN1C1=NC=CC(N)=N1 DHGNKEKRMDXCQR-CXAGYDPISA-N 0.000 claims description 2
• MBJQSBKKTPPLFW-SJLPKXTDSA-N [(1r,6s)-4-(4-methylpyridin-2-yl)-4,7-diazabicyclo[4.2.0]octan-7-yl]-[6-methyl-2-(triazol-1-yl)pyridin-3-yl]methanone Chemical compound CC1=CC=NC(N2C[C@H]3N(C[C@H]3CC2)C(=O)C=2C(=NC(C)=CC=2)N2N=NC=C2)=C1 MBJQSBKKTPPLFW-SJLPKXTDSA-N 0.000 claims description 2
• SCAZJSXMMAEAFL-CRAIPNDOSA-N [(1r,6s)-4-(5-chloro-4,6-dimethylpyrimidin-2-yl)-4,7-diazabicyclo[4.2.0]octan-7-yl]-[2-(3-methyl-1,2,4-oxadiazol-5-yl)phenyl]methanone Chemical compound CC1=NOC(C=2C(=CC=CC=2)C(=O)N2[C@@H]3CN(CC[C@@H]3C2)C=2N=C(C)C(Cl)=C(C)N=2)=N1 SCAZJSXMMAEAFL-CRAIPNDOSA-N 0.000 claims description 2
• ZNRGINVDUKPUGG-RDTXWAMCSA-N [(1r,6s)-4-(5-chloro-4-methylpyrimidin-2-yl)-4,7-diazabicyclo[4.2.0]octan-7-yl]-[2-(3-methyl-1,2,4-oxadiazol-5-yl)phenyl]methanone Chemical compound CC1=NOC(C=2C(=CC=CC=2)C(=O)N2[C@@H]3CN(CC[C@@H]3C2)C=2N=C(C)C(Cl)=CN=2)=N1 ZNRGINVDUKPUGG-RDTXWAMCSA-N 0.000 claims description 2
• FTJRZQDAPUBTRL-CRAIPNDOSA-N [(1r,6s)-4-(5-fluoro-4,6-dimethylpyrimidin-2-yl)-4,7-diazabicyclo[4.2.0]octan-7-yl]-[2-(3-methyl-1,2,4-oxadiazol-5-yl)phenyl]methanone Chemical compound CC1=NOC(C=2C(=CC=CC=2)C(=O)N2[C@@H]3CN(CC[C@@H]3C2)C=2N=C(C)C(F)=C(C)N=2)=N1 FTJRZQDAPUBTRL-CRAIPNDOSA-N 0.000 claims description 2
• QAWGVYWAZNEIQG-RHSMWYFYSA-N [(1r,6s)-4-(5-fluoro-4,6-dimethylpyrimidin-2-yl)-4,7-diazabicyclo[4.2.0]octan-7-yl]-[3-fluoro-2-(1,2-oxazol-5-yl)phenyl]methanone Chemical compound CC1=C(F)C(C)=NC(N2C[C@H]3N(C[C@H]3CC2)C(=O)C=2C(=C(F)C=CC=2)C=2ON=CC=2)=N1 QAWGVYWAZNEIQG-RHSMWYFYSA-N 0.000 claims description 2
• GZVFQNVGXNUCDW-RDTXWAMCSA-N [(1r,6s)-4-(5-fluoro-4,6-dimethylpyrimidin-2-yl)-4,7-diazabicyclo[4.2.0]octan-7-yl]-[3-fluoro-2-(1h-pyrazol-5-yl)phenyl]methanone Chemical compound CC1=C(F)C(C)=NC(N2C[C@H]3N(C[C@H]3CC2)C(=O)C=2C(=C(F)C=CC=2)C=2NN=CC=2)=N1 GZVFQNVGXNUCDW-RDTXWAMCSA-N 0.000 claims description 2
• GJJBYNIKRYEDKK-CRAIPNDOSA-N [(1r,6s)-4-(5-fluoro-4,6-dimethylpyrimidin-2-yl)-4,7-diazabicyclo[4.2.0]octan-7-yl]-[3-fluoro-2-(3-methyl-1,2-oxazol-5-yl)phenyl]methanone Chemical compound O1N=C(C)C=C1C1=C(F)C=CC=C1C(=O)N1[C@@H]2CN(C=3N=C(C)C(F)=C(C)N=3)CC[C@@H]2C1 GJJBYNIKRYEDKK-CRAIPNDOSA-N 0.000 claims description 2
• MTPLZRJKIYAGIP-CXAGYDPISA-N [(1r,6s)-4-(5-fluoro-4-methylpyrimidin-2-yl)-4,7-diazabicyclo[4.2.0]octan-7-yl]-[3-fluoro-2-(triazol-2-yl)phenyl]methanone Chemical compound C1=C(F)C(C)=NC(N2C[C@H]3N(C[C@H]3CC2)C(=O)C=2C(=C(F)C=CC=2)N2N=CC=N2)=N1 MTPLZRJKIYAGIP-CXAGYDPISA-N 0.000 claims description 2
• MGMPEAOCKQATPX-AUUYWEPGSA-N [(1r,6s)-4-(5-fluoro-4-methylpyrimidin-2-yl)-4,7-diazabicyclo[4.2.0]octan-7-yl]-[5-methoxy-2-(triazol-2-yl)phenyl]methanone Chemical compound C([C@@H]1CN([C@@H]1C1)C(=O)C=2C(=CC=C(C=2)OC)N2N=CC=N2)CN1C1=NC=C(F)C(C)=N1 MGMPEAOCKQATPX-AUUYWEPGSA-N 0.000 claims description 2
• PXPUTKAXBSAKFK-RHSMWYFYSA-N [(1r,6s)-4-(5-fluoro-4-methylpyrimidin-2-yl)-4,7-diazabicyclo[4.2.0]octan-7-yl]-[6-methyl-2-(triazol-1-yl)pyridin-3-yl]methanone Chemical compound C([C@@H]1CN([C@@H]1C1)C(=O)C2=CC=C(N=C2N2N=NC=C2)C)CN1C1=NC=C(F)C(C)=N1 PXPUTKAXBSAKFK-RHSMWYFYSA-N 0.000 claims description 2
• YQBCCVKQJDKKLH-RDTXWAMCSA-N [(1r,6s)-4-(6-chloro-1,3-benzoxazol-2-yl)-4,7-diazabicyclo[4.2.0]octan-7-yl]-[6-methyl-2-(triazol-1-yl)pyridin-3-yl]methanone Chemical compound N=1C(C)=CC=C(C(=O)N2[C@@H]3CN(CC[C@@H]3C2)C=2OC3=CC(Cl)=CC=C3N=2)C=1N1C=CN=N1 YQBCCVKQJDKKLH-RDTXWAMCSA-N 0.000 claims description 2
• BWZPGVXWIPAXHT-OXQOHEQNSA-N [(1r,6s)-4-[2-(dimethylamino)-6-methylpyrimidin-4-yl]-4,7-diazabicyclo[4.2.0]octan-7-yl]-[4-methoxy-2-(triazol-2-yl)phenyl]methanone Chemical compound C([C@@H]1CN([C@@H]1C1)C(=O)C2=CC=C(C=C2N2N=CC=N2)OC)CN1C1=CC(C)=NC(N(C)C)=N1 BWZPGVXWIPAXHT-OXQOHEQNSA-N 0.000 claims description 2
• XYDFOQGVMNVZED-OXQOHEQNSA-N [(1r,6s)-4-[2-(dimethylamino)-6-methylpyrimidin-4-yl]-4,7-diazabicyclo[4.2.0]octan-7-yl]-[5-methoxy-2-(triazol-2-yl)phenyl]methanone Chemical compound C([C@@H]1CN([C@@H]1C1)C(=O)C=2C(=CC=C(C=2)OC)N2N=CC=N2)CN1C1=CC(C)=NC(N(C)C)=N1 XYDFOQGVMNVZED-OXQOHEQNSA-N 0.000 claims description 2
• JZNNDXCXDLORRN-OXQOHEQNSA-N [(1r,6s)-4-[6-(dimethylamino)-2-methylpyrimidin-4-yl]-4,7-diazabicyclo[4.2.0]octan-7-yl]-[4-methoxy-2-(triazol-2-yl)phenyl]methanone Chemical compound C([C@@H]1CN([C@@H]1C1)C(=O)C2=CC=C(C=C2N2N=CC=N2)OC)CN1C1=CC(N(C)C)=NC(C)=N1 JZNNDXCXDLORRN-OXQOHEQNSA-N 0.000 claims description 2
• WZEYQMOJZMWFRR-OXQOHEQNSA-N [(1r,6s)-4-[6-(dimethylamino)-2-methylpyrimidin-4-yl]-4,7-diazabicyclo[4.2.0]octan-7-yl]-[5-methoxy-2-(triazol-2-yl)phenyl]methanone Chemical compound C([C@@H]1CN([C@@H]1C1)C(=O)C=2C(=CC=C(C=2)OC)N2N=CC=N2)CN1C1=CC(N(C)C)=NC(C)=N1 WZEYQMOJZMWFRR-OXQOHEQNSA-N 0.000 claims description 2
• MQKFUBZBDXWABR-CRAIPNDOSA-N [(1r,6s)-4-[6-(dimethylamino)pyrimidin-4-yl]-4,7-diazabicyclo[4.2.0]octan-7-yl]-[2-(3-methyl-1,2,4-oxadiazol-5-yl)phenyl]methanone Chemical compound C1=NC(N(C)C)=CC(N2C[C@H]3N(C[C@H]3CC2)C(=O)C=2C(=CC=CC=2)C=2ON=C(C)N=2)=N1 MQKFUBZBDXWABR-CRAIPNDOSA-N 0.000 claims description 2
• MXTVTJUCDQIPFH-CRAIPNDOSA-N [(1r,6s)-4-[6-(dimethylamino)pyrimidin-4-yl]-4,7-diazabicyclo[4.2.0]octan-7-yl]-[2-(triazol-2-yl)phenyl]methanone Chemical compound C1=NC(N(C)C)=CC(N2C[C@H]3N(C[C@H]3CC2)C(=O)C=2C(=CC=CC=2)N2N=CC=N2)=N1 MXTVTJUCDQIPFH-CRAIPNDOSA-N 0.000 claims description 2
• WPXGIWSOQDTKFO-DNVCBOLYSA-N [(1r,6s)-4-[6-(dimethylamino)pyrimidin-4-yl]-4,7-diazabicyclo[4.2.0]octan-7-yl]-[4-methoxy-2-(triazol-2-yl)phenyl]methanone Chemical compound C([C@@H]1CN([C@@H]1C1)C(=O)C2=CC=C(C=C2N2N=CC=N2)OC)CN1C1=CC(N(C)C)=NC=N1 WPXGIWSOQDTKFO-DNVCBOLYSA-N 0.000 claims description 2
• FSRQWMZGEOOPHT-DNVCBOLYSA-N [(1r,6s)-4-[6-(dimethylamino)pyrimidin-4-yl]-4,7-diazabicyclo[4.2.0]octan-7-yl]-[5-methoxy-2-(triazol-2-yl)phenyl]methanone Chemical compound C([C@@H]1CN([C@@H]1C1)C(=O)C=2C(=CC=C(C=2)OC)N2N=CC=N2)CN1C1=CC(N(C)C)=NC=N1 FSRQWMZGEOOPHT-DNVCBOLYSA-N 0.000 claims description 2
• UJSDQRUUAHJSND-PXNSSMCTSA-N [(1s,6r)-4-(4,6-dimethylpyrimidin-2-yl)-4,7-diazabicyclo[4.2.0]octan-7-yl]-(2-thiophen-2-ylphenyl)methanone Chemical compound CC1=CC(C)=NC(N2C[C@@H]3N(C[C@@H]3CC2)C(=O)C=2C(=CC=CC=2)C=2SC=CC=2)=N1 UJSDQRUUAHJSND-PXNSSMCTSA-N 0.000 claims description 2
• GDIQDZVRMKTDML-YJBOKZPZSA-N [(1s,6r)-4-(4,6-dimethylpyrimidin-2-yl)-4,7-diazabicyclo[4.2.0]octan-7-yl]-[2-fluoro-6-(triazol-2-yl)phenyl]methanone Chemical compound CC1=CC(C)=NC(N2C[C@@H]3N(C[C@@H]3CC2)C(=O)C=2C(=CC=CC=2F)N2N=CC=N2)=N1 GDIQDZVRMKTDML-YJBOKZPZSA-N 0.000 claims description 2
• KNERPANAKIIIDU-YLJYHZDGSA-N [2-(3-methyl-1,2,4-oxadiazol-5-yl)phenyl]-[(1r,6s)-4-(4,5,6-trimethylpyrimidin-2-yl)-4,7-diazabicyclo[4.2.0]octan-7-yl]methanone Chemical compound CC1=NOC(C=2C(=CC=CC=2)C(=O)N2[C@@H]3CN(CC[C@@H]3C2)C=2N=C(C)C(C)=C(C)N=2)=N1 KNERPANAKIIIDU-YLJYHZDGSA-N 0.000 claims description 2
• SZKASESVFVXQAK-UZUQRXQVSA-N [2-fluoro-6-(triazol-2-yl)phenyl]-[(1r,6s)-4-(2-methylquinolin-4-yl)-4,7-diazabicyclo[4.2.0]octan-7-yl]methanone Chemical compound C([C@H]1CCN(C[C@H]11)C=2C=C(N=C3C=CC=CC3=2)C)N1C(=O)C1=C(F)C=CC=C1N1N=CC=N1 SZKASESVFVXQAK-UZUQRXQVSA-N 0.000 claims description 2
• ZDIDFEWWLZIXGF-VQIMIIECSA-N [2-fluoro-6-(triazol-2-yl)phenyl]-[(1r,6s)-4-(4,5,6-trimethylpyrimidin-2-yl)-4,7-diazabicyclo[4.2.0]octan-7-yl]methanone Chemical compound CC1=C(C)C(C)=NC(N2C[C@H]3N(C[C@H]3CC2)C(=O)C=2C(=CC=CC=2F)N2N=CC=N2)=N1 ZDIDFEWWLZIXGF-VQIMIIECSA-N 0.000 claims description 2
• NPXVZFRHSSBVEF-IUODEOHRSA-N [2-fluoro-6-(triazol-2-yl)phenyl]-[(1r,6s)-4-[4-(trifluoromethyl)pyrimidin-2-yl]-4,7-diazabicyclo[4.2.0]octan-7-yl]methanone Chemical compound C([C@@H]1CN([C@@H]1C1)C(=O)C2=C(C=CC=C2F)N2N=CC=N2)CN1C1=NC=CC(C(F)(F)F)=N1 NPXVZFRHSSBVEF-IUODEOHRSA-N 0.000 claims description 2
• VPFCLKHXIUNDJX-OPAMFIHVSA-N [2-fluoro-6-(triazol-2-yl)phenyl]-[(1r,6s)-4-quinolin-4-yl-4,7-diazabicyclo[4.2.0]octan-7-yl]methanone Chemical compound N1([C@@H]2CN(CC[C@@H]2C1)C=1C2=CC=CC=C2N=CC=1)C(=O)C=1C(F)=CC=CC=1N1N=CC=N1 VPFCLKHXIUNDJX-OPAMFIHVSA-N 0.000 claims description 2
• NPXVZFRHSSBVEF-WFASDCNBSA-N [2-fluoro-6-(triazol-2-yl)phenyl]-[(1s,6r)-4-[4-(trifluoromethyl)pyrimidin-2-yl]-4,7-diazabicyclo[4.2.0]octan-7-yl]methanone Chemical compound C([C@H]1CN([C@H]1C1)C(=O)C2=C(C=CC=C2F)N2N=CC=N2)CN1C1=NC=CC(C(F)(F)F)=N1 NPXVZFRHSSBVEF-WFASDCNBSA-N 0.000 claims description 2
• DUZGNMGVQFOPMO-UHFFFAOYSA-N [2-fluoro-6-(triazol-2-yl)phenyl]-[3-[4-methyl-6-(trifluoromethyl)pyrimidin-2-yl]-3,6-diazabicyclo[3.2.0]heptan-6-yl]methanone Chemical compound CC1=CC(C(F)(F)F)=NC(N2CC3N(CC3C2)C(=O)C=2C(=CC=CC=2F)N2N=CC=N2)=N1 DUZGNMGVQFOPMO-UHFFFAOYSA-N 0.000 claims description 2
• NAQKCUDYBFCCNK-UHFFFAOYSA-N [3-(3,6-dimethylpyrazin-2-yl)-3,6-diazabicyclo[3.2.0]heptan-6-yl]-[2-fluoro-6-(triazol-2-yl)phenyl]methanone Chemical compound CC1=CN=C(C)C(N2CC3N(CC3C2)C(=O)C=2C(=CC=CC=2F)N2N=CC=N2)=N1 NAQKCUDYBFCCNK-UHFFFAOYSA-N 0.000 claims description 2
• VFIAMRFRWFFWTA-UHFFFAOYSA-N [3-(4,6-dimethoxypyrimidin-2-yl)-3,6-diazabicyclo[3.2.0]heptan-6-yl]-[2-fluoro-6-(triazol-2-yl)phenyl]methanone Chemical compound COC1=CC(OC)=NC(N2CC3N(CC3C2)C(=O)C=2C(=CC=CC=2F)N2N=CC=N2)=N1 VFIAMRFRWFFWTA-UHFFFAOYSA-N 0.000 claims description 2
• RUUBWSXPUVGENA-UHFFFAOYSA-N [3-(4,6-dimethylpyrimidin-2-yl)-3,6-diazabicyclo[3.2.0]heptan-6-yl]-(2-thiophen-2-ylphenyl)methanone Chemical compound CC1=CC(C)=NC(N2CC3N(CC3C2)C(=O)C=2C(=CC=CC=2)C=2SC=CC=2)=N1 RUUBWSXPUVGENA-UHFFFAOYSA-N 0.000 claims description 2
• GWVNNSNIAOPTHK-UHFFFAOYSA-N [3-(4,6-dimethylpyrimidin-2-yl)-3,6-diazabicyclo[3.2.0]heptan-6-yl]-(5-fluoro-2-pyrimidin-2-ylphenyl)methanone Chemical compound CC1=CC(C)=NC(N2CC3N(CC3C2)C(=O)C=2C(=CC=C(F)C=2)C=2N=CC=CN=2)=N1 GWVNNSNIAOPTHK-UHFFFAOYSA-N 0.000 claims description 2
• HXQRNACRFYBQKE-UHFFFAOYSA-N [3-(4,6-dimethylpyrimidin-2-yl)-3,6-diazabicyclo[3.2.0]heptan-6-yl]-[2-(triazol-2-yl)phenyl]methanone Chemical compound CC1=CC(C)=NC(N2CC3N(CC3C2)C(=O)C=2C(=CC=CC=2)N2N=CC=N2)=N1 HXQRNACRFYBQKE-UHFFFAOYSA-N 0.000 claims description 2
• XZELEIIAULBWNR-UHFFFAOYSA-N [3-(4,6-dimethylpyrimidin-2-yl)-3,6-diazabicyclo[3.2.0]heptan-6-yl]-[2-fluoro-6-(triazol-2-yl)phenyl]methanone Chemical compound CC1=CC(C)=NC(N2CC3N(CC3C2)C(=O)C=2C(=CC=CC=2F)N2N=CC=N2)=N1 XZELEIIAULBWNR-UHFFFAOYSA-N 0.000 claims description 2
• UDXTYHKJPIAMNH-UHFFFAOYSA-N [3-(4,6-dimethylpyrimidin-2-yl)-3,6-diazabicyclo[3.2.0]heptan-6-yl]-[3-fluoro-2-(triazol-2-yl)phenyl]methanone Chemical compound CC1=CC(C)=NC(N2CC3N(CC3C2)C(=O)C=2C(=C(F)C=CC=2)N2N=CC=N2)=N1 UDXTYHKJPIAMNH-UHFFFAOYSA-N 0.000 claims description 2
• VHRBCQYXYFTSKC-UHFFFAOYSA-N [3-(4-methylpyrimidin-2-yl)-3,6-diazabicyclo[3.2.0]heptan-6-yl]-(2-phenylphenyl)methanone Chemical compound CC1=CC=NC(N2CC3N(CC3C2)C(=O)C=2C(=CC=CC=2)C=2C=CC=CC=2)=N1 VHRBCQYXYFTSKC-UHFFFAOYSA-N 0.000 claims description 2
• ULIIXYYYZPFWOG-UHFFFAOYSA-N [3-(4-methylpyrimidin-2-yl)-3,6-diazabicyclo[3.2.0]heptan-6-yl]-(2-thiophen-2-ylphenyl)methanone Chemical compound CC1=CC=NC(N2CC3N(CC3C2)C(=O)C=2C(=CC=CC=2)C=2SC=CC=2)=N1 ULIIXYYYZPFWOG-UHFFFAOYSA-N 0.000 claims description 2
• KLPFRSAEGIGZFZ-VQIMIIECSA-N [3-fluoro-2-(1,2-oxazol-5-yl)phenyl]-[(1r,6s)-4-(4,5,6-trimethylpyrimidin-2-yl)-4,7-diazabicyclo[4.2.0]octan-7-yl]methanone Chemical compound CC1=C(C)C(C)=NC(N2C[C@H]3N(C[C@H]3CC2)C(=O)C=2C(=C(F)C=CC=2)C=2ON=CC=2)=N1 KLPFRSAEGIGZFZ-VQIMIIECSA-N 0.000 claims description 2
• LLRGSYGXXWURGI-CXAGYDPISA-N [3-fluoro-2-(triazol-2-yl)phenyl]-[(1r,6s)-4-[4-(trifluoromethyl)pyridin-2-yl]-4,7-diazabicyclo[4.2.0]octan-7-yl]methanone Chemical compound C([C@@H]1CN([C@@H]1C1)C(=O)C=2C=CC=C(C=2N2N=CC=N2)F)CN1C1=CC(C(F)(F)F)=CC=N1 LLRGSYGXXWURGI-CXAGYDPISA-N 0.000 claims description 2
• DAYJKGFFLDEOFR-CZUORRHYSA-N [3-fluoro-2-(triazol-2-yl)phenyl]-[(1r,6s)-4-[6-(trifluoromethyl)pyridin-2-yl]-4,7-diazabicyclo[4.2.0]octan-7-yl]methanone Chemical compound C([C@@H]1CN([C@@H]1C1)C(=O)C=2C=CC=C(C=2N2N=CC=N2)F)CN1C1=CC=CC(C(F)(F)F)=N1 DAYJKGFFLDEOFR-CZUORRHYSA-N 0.000 claims description 2
• XOSYGJTXILGMNE-IUODEOHRSA-N [3-fluoro-2-(triazol-2-yl)phenyl]-[(1r,6s)-4-[6-(trifluoromethyl)pyrimidin-4-yl]-4,7-diazabicyclo[4.2.0]octan-7-yl]methanone Chemical compound C([C@@H]1CN([C@@H]1C1)C(=O)C=2C=CC=C(C=2N2N=CC=N2)F)CN1C1=CC(C(F)(F)F)=NC=N1 XOSYGJTXILGMNE-IUODEOHRSA-N 0.000 claims description 2
• JCWXAQBOQLLUDY-UHFFFAOYSA-N [4-(1,3-benzoxazol-2-yl)-4,7-diazabicyclo[4.2.0]octan-7-yl]-(2,6-dimethoxyphenyl)methanone Chemical compound COC1=CC=CC(OC)=C1C(=O)N1C2CN(C=3OC4=CC=CC=C4N=3)CCC2C1 JCWXAQBOQLLUDY-UHFFFAOYSA-N 0.000 claims description 2
• NFDWZLRKHQEVLP-UHFFFAOYSA-N [4-(1,3-benzoxazol-2-yl)-4,7-diazabicyclo[4.2.0]octan-7-yl]-(2-phenylphenyl)methanone Chemical compound C1C2CCN(C=3OC4=CC=CC=C4N=3)CC2N1C(=O)C1=CC=CC=C1C1=CC=CC=C1 NFDWZLRKHQEVLP-UHFFFAOYSA-N 0.000 claims description 2
• RHAQHUQDCKSIOL-DYESRHJHSA-N [4-methoxy-2-(triazol-2-yl)phenyl]-[(1r,6s)-4-(4,5,6-trimethylpyrimidin-2-yl)-4,7-diazabicyclo[4.2.0]octan-7-yl]methanone Chemical compound C([C@@H]1CN([C@@H]1C1)C(=O)C2=CC=C(C=C2N2N=CC=N2)OC)CN1C1=NC(C)=C(C)C(C)=N1 RHAQHUQDCKSIOL-DYESRHJHSA-N 0.000 claims description 2
• ZMSRLKXGHBGSKN-AUUYWEPGSA-N [4-methoxy-2-(triazol-2-yl)phenyl]-[(1r,6s)-4-[4-(trifluoromethyl)pyridin-2-yl]-4,7-diazabicyclo[4.2.0]octan-7-yl]methanone Chemical compound C([C@@H]1CN([C@@H]1C1)C(=O)C2=CC=C(C=C2N2N=CC=N2)OC)CN1C1=CC(C(F)(F)F)=CC=N1 ZMSRLKXGHBGSKN-AUUYWEPGSA-N 0.000 claims description 2
• PVMSLIIKRSPXBQ-CXAGYDPISA-N [4-methoxy-2-(triazol-2-yl)phenyl]-[(1r,6s)-4-[4-(trifluoromethyl)pyrimidin-2-yl]-4,7-diazabicyclo[4.2.0]octan-7-yl]methanone Chemical compound C([C@@H]1CN([C@@H]1C1)C(=O)C2=CC=C(C=C2N2N=CC=N2)OC)CN1C1=NC=CC(C(F)(F)F)=N1 PVMSLIIKRSPXBQ-CXAGYDPISA-N 0.000 claims description 2
• JWRRTEMALCSEPJ-OXQOHEQNSA-N [5-fluoro-2-(triazol-2-yl)phenyl]-[(1r,6s)-4-(4,5,6-trimethylpyrimidin-2-yl)-4,7-diazabicyclo[4.2.0]octan-7-yl]methanone Chemical compound CC1=C(C)C(C)=NC(N2C[C@H]3N(C[C@H]3CC2)C(=O)C=2C(=CC=C(F)C=2)N2N=CC=N2)=N1 JWRRTEMALCSEPJ-OXQOHEQNSA-N 0.000 claims description 2
• RHFDARLFDIHFTH-RDTXWAMCSA-N [5-fluoro-2-(triazol-2-yl)phenyl]-[(1r,6s)-4-(4-methylpyrimidin-2-yl)-4,7-diazabicyclo[4.2.0]octan-7-yl]methanone Chemical compound CC1=CC=NC(N2C[C@H]3N(C[C@H]3CC2)C(=O)C=2C(=CC=C(F)C=2)N2N=CC=N2)=N1 RHFDARLFDIHFTH-RDTXWAMCSA-N 0.000 claims description 2
• BJJXKASZDJGHDW-FZKQIMNGSA-N [5-fluoro-2-(triazol-2-yl)phenyl]-[(1r,6s)-4-[4-(trifluoromethyl)pyridin-2-yl]-4,7-diazabicyclo[4.2.0]octan-7-yl]methanone Chemical compound C([C@@H]1CN([C@@H]1C1)C(=O)C=2C(=CC=C(C=2)F)N2N=CC=N2)CN1C1=CC(C(F)(F)F)=CC=N1 BJJXKASZDJGHDW-FZKQIMNGSA-N 0.000 claims description 2
• CWIQEEQAULWTRE-MLGOLLRUSA-N [5-fluoro-2-(triazol-2-yl)phenyl]-[(1r,6s)-4-[4-(trifluoromethyl)pyrimidin-2-yl]-4,7-diazabicyclo[4.2.0]octan-7-yl]methanone Chemical compound C([C@@H]1CN([C@@H]1C1)C(=O)C=2C(=CC=C(C=2)F)N2N=CC=N2)CN1C1=NC=CC(C(F)(F)F)=N1 CWIQEEQAULWTRE-MLGOLLRUSA-N 0.000 claims description 2
• ZDZQWBZVNPMBHS-CXAGYDPISA-N [5-fluoro-2-(triazol-2-yl)phenyl]-[(1r,6s)-4-[6-(trifluoromethyl)pyridin-2-yl]-4,7-diazabicyclo[4.2.0]octan-7-yl]methanone Chemical compound C([C@@H]1CN([C@@H]1C1)C(=O)C=2C(=CC=C(C=2)F)N2N=CC=N2)CN1C1=CC=CC(C(F)(F)F)=N1 ZDZQWBZVNPMBHS-CXAGYDPISA-N 0.000 claims description 2
• URQSGYXCJATHTI-MLGOLLRUSA-N [5-fluoro-2-(triazol-2-yl)phenyl]-[(1r,6s)-4-[6-(trifluoromethyl)pyrimidin-4-yl]-4,7-diazabicyclo[4.2.0]octan-7-yl]methanone Chemical compound C([C@@H]1CN([C@@H]1C1)C(=O)C=2C(=CC=C(C=2)F)N2N=CC=N2)CN1C1=CC(C(F)(F)F)=NC=N1 URQSGYXCJATHTI-MLGOLLRUSA-N 0.000 claims description 2
• YRYYISJZOFBAKI-DYESRHJHSA-N [5-methoxy-2-(triazol-2-yl)phenyl]-[(1r,6s)-4-(4,5,6-trimethylpyrimidin-2-yl)-4,7-diazabicyclo[4.2.0]octan-7-yl]methanone Chemical compound C([C@@H]1CN([C@@H]1C1)C(=O)C=2C(=CC=C(C=2)OC)N2N=CC=N2)CN1C1=NC(C)=C(C)C(C)=N1 YRYYISJZOFBAKI-DYESRHJHSA-N 0.000 claims description 2
• BTDMODRYHJWHFY-OPAMFIHVSA-N [5-methoxy-2-(triazol-2-yl)phenyl]-[(1r,6s)-4-(4-methyl-6,7-dihydro-5h-cyclopenta[d]pyrimidin-2-yl)-4,7-diazabicyclo[4.2.0]octan-7-yl]methanone Chemical compound N1([C@@H]2CN(CC[C@@H]2C1)C=1N=C(C)C=2CCCC=2N=1)C(=O)C1=CC(OC)=CC=C1N1N=CC=N1 BTDMODRYHJWHFY-OPAMFIHVSA-N 0.000 claims description 2
• OGYTURZSQDMGIH-CXAGYDPISA-N [5-methoxy-2-(triazol-2-yl)phenyl]-[(1r,6s)-4-[4-(trifluoromethyl)pyrimidin-2-yl]-4,7-diazabicyclo[4.2.0]octan-7-yl]methanone Chemical compound C([C@@H]1CN([C@@H]1C1)C(=O)C=2C(=CC=C(C=2)OC)N2N=CC=N2)CN1C1=NC=CC(C(F)(F)F)=N1 OGYTURZSQDMGIH-CXAGYDPISA-N 0.000 claims description 2
• 125000006269 biphenyl-2-yl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C1=C(*)C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
• SSJXIUAHEKJCMH-WDSKDSINSA-N (1s,2s)-cyclohexane-1,2-diamine Chemical compound N[C@H]1CCCC[C@@H]1N SSJXIUAHEKJCMH-WDSKDSINSA-N 0.000 claims 5
• 125000001475 halogen functional group Chemical group 0.000 claims 4
• 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 claims 2
• NUZBBIHTIXZDDY-UHFFFAOYSA-N 7-(2,5-dimethylphenyl)sulfonyl-4-(4-phenylpyrimidin-2-yl)-4,7-diazabicyclo[4.2.0]octane Chemical compound CC1=CC=C(C)C(S(=O)(=O)N2C3CN(CCC3C2)C=2N=C(C=CN=2)C=2C=CC=CC=2)=C1 NUZBBIHTIXZDDY-UHFFFAOYSA-N 0.000 claims 1
• YJDODUFNQDTQKZ-REWPJTCUSA-N [(1s,6r)-4-(4,6-dimethylpyrimidin-2-yl)-4,7-diazabicyclo[4.2.0]octan-7-yl]-(2-phenylphenyl)methanone Chemical compound CC1=CC(C)=NC(N2C[C@@H]3N(C[C@@H]3CC2)C(=O)C=2C(=CC=CC=2)C=2C=CC=CC=2)=N1 YJDODUFNQDTQKZ-REWPJTCUSA-N 0.000 claims 1
• VEYPYYVAYRDHBG-UHFFFAOYSA-N [5-(2-fluorophenyl)-2-methyl-1,3-thiazol-4-yl]-(4-quinoxalin-6-yl-4,7-diazabicyclo[4.2.0]octan-7-yl)methanone Chemical compound S1C(C)=NC(C(=O)N2C3CN(CCC3C2)C=2C=C3N=CC=NC3=CC=2)=C1C1=CC=CC=C1F VEYPYYVAYRDHBG-UHFFFAOYSA-N 0.000 claims 1
• HNYOPLTXPVRDBG-UHFFFAOYSA-N barbituric acid Chemical compound O=C1CC(=O)NC(=O)N1 HNYOPLTXPVRDBG-UHFFFAOYSA-N 0.000 claims 1
• CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 claims 1
• 238000001819 mass spectrum Methods 0.000 description 164
• 238000000132 electrospray ionisation Methods 0.000 description 162
• 238000005481 NMR spectroscopy Methods 0.000 description 125
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 115
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 113
• 239000000203 mixture Substances 0.000 description 106
• 239000000243 solution Substances 0.000 description 90
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 84
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 82
• 239000002904 solvent Substances 0.000 description 70
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 63
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical group CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 60
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 60
• 238000006243 chemical reaction Methods 0.000 description 57
• 239000010410 layer Substances 0.000 description 54
• 230000002829 reductive effect Effects 0.000 description 54
• 239000011541 reaction mixture Substances 0.000 description 53
• 239000011734 sodium Substances 0.000 description 51
• RZVPFDOTMFYQHR-UHFFFAOYSA-N 2-chloro-4,6-dimethylpyrimidine Chemical compound CC1=CC(C)=NC(Cl)=N1 RZVPFDOTMFYQHR-UHFFFAOYSA-N 0.000 description 50
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 50
• 235000019439 ethyl acetate Nutrition 0.000 description 48
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 47
• 102000002512 Orexin Human genes 0.000 description 46
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 45
• 108060005714 orexin Proteins 0.000 description 45
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 44
• 238000011282 treatment Methods 0.000 description 38
• 238000000034 method Methods 0.000 description 37
• 239000007787 solid Substances 0.000 description 37
• 239000000460 chlorine Substances 0.000 description 36
• 239000000047 product Substances 0.000 description 36
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 35
• 239000012044 organic layer Substances 0.000 description 30
• 239000002585 base Substances 0.000 description 29
• IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 28
• KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 28
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 27
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 27
• 235000019441 ethanol Nutrition 0.000 description 27
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 25
• 239000000651 prodrug Substances 0.000 description 25
• 229940002612 prodrug Drugs 0.000 description 25
• 102000005962 receptors Human genes 0.000 description 25
• 108020003175 receptors Proteins 0.000 description 25
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 25
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 23
• 239000002253 acid Substances 0.000 description 23
• 238000000746 purification Methods 0.000 description 23
• 238000010992 reflux Methods 0.000 description 22
• 210000004027 cell Anatomy 0.000 description 21
• 238000003818 flash chromatography Methods 0.000 description 21
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 20
• IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 20
• 229910052757 nitrogen Inorganic materials 0.000 description 20
• 238000005160 1H NMR spectroscopy Methods 0.000 description 17
• 230000000694 effects Effects 0.000 description 17
• 239000003921 oil Substances 0.000 description 17
• 235000019198 oils Nutrition 0.000 description 17
• RGEZZAHULVFHET-UHFFFAOYSA-N 2-chloro-4,5,6-trimethylpyrimidine Chemical compound CC1=NC(Cl)=NC(C)=C1C RGEZZAHULVFHET-UHFFFAOYSA-N 0.000 description 16
• 208000035475 disorder Diseases 0.000 description 16
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 14
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 14
• 239000000463 material Substances 0.000 description 14
• CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 14
• 239000012267 brine Substances 0.000 description 13
• 239000003054 catalyst Substances 0.000 description 13
• 239000012043 crude product Substances 0.000 description 13
• 230000001404 mediated effect Effects 0.000 description 13
• 239000002609 medium Substances 0.000 description 13
• 239000008194 pharmaceutical composition Substances 0.000 description 13
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 13
• XPFMQYOPTHMSJJ-UHFFFAOYSA-N 5-fluoro-2-iodobenzoic acid Chemical compound OC(=O)C1=CC(F)=CC=C1I XPFMQYOPTHMSJJ-UHFFFAOYSA-N 0.000 description 12
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
• 239000003814 drug Substances 0.000 description 12
• 238000010438 heat treatment Methods 0.000 description 12
• 238000004128 high performance liquid chromatography Methods 0.000 description 12
• 239000000556 agonist Substances 0.000 description 11
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 11
• 201000010099 disease Diseases 0.000 description 11
• 229940079593 drug Drugs 0.000 description 11
• 150000002148 esters Chemical class 0.000 description 11
• DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 11
• GWMKAAUPDKIVQV-UHFFFAOYSA-N 4,7-diazabicyclo[4.2.0]octan-7-yl-(2-phenylphenyl)methanone Chemical compound C1C2CCNCC2N1C(=O)C1=CC=CC=C1C1=CC=CC=C1 GWMKAAUPDKIVQV-UHFFFAOYSA-N 0.000 description 10
• 101000598921 Homo sapiens Orexin Proteins 0.000 description 10
• 239000013543 active substance Substances 0.000 description 10
• 150000001412 amines Chemical class 0.000 description 10
• 238000004587 chromatography analysis Methods 0.000 description 10
• 239000007789 gas Substances 0.000 description 10
• 239000007788 liquid Substances 0.000 description 10
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 10
• 235000019341 magnesium sulphate Nutrition 0.000 description 10
• 229920006395 saturated elastomer Polymers 0.000 description 10
• 238000003756 stirring Methods 0.000 description 10
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 9
• BYHVGQHIAFURIL-UHFFFAOYSA-N 2-chloroquinoxaline Chemical compound C1=CC=CC2=NC(Cl)=CN=C21 BYHVGQHIAFURIL-UHFFFAOYSA-N 0.000 description 9
• 229910004298 SiO 2 Inorganic materials 0.000 description 9
• 230000015572 biosynthetic process Effects 0.000 description 9
• 239000000706 filtrate Substances 0.000 description 9
• 239000000546 pharmaceutical excipient Substances 0.000 description 9
• 239000002002 slurry Substances 0.000 description 9
• 241000894007 species Species 0.000 description 9
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 8
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 8
• AMQJEAYHLZJPGS-UHFFFAOYSA-N N-Pentanol Chemical compound CCCCCO AMQJEAYHLZJPGS-UHFFFAOYSA-N 0.000 description 8
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
• DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 8
• 210000004556 brain Anatomy 0.000 description 8
• 125000005843 halogen group Chemical group 0.000 description 8
• 239000002207 metabolite Substances 0.000 description 8
• 229910052763 palladium Inorganic materials 0.000 description 8
• 239000000843 powder Substances 0.000 description 8
• 208000024891 symptom Diseases 0.000 description 8
• 229940086542 triethylamine Drugs 0.000 description 8
• JWUJQDFVADABEY-UHFFFAOYSA-N 2-methyltetrahydrofuran Chemical compound CC1CCCO1 JWUJQDFVADABEY-UHFFFAOYSA-N 0.000 description 7
• UWURZZHFZYZWTJ-UHFFFAOYSA-N 3-fluoro-2-(3-methyl-1,2,4-oxadiazol-5-yl)benzoic acid Chemical compound CC1=NOC(C=2C(=CC=CC=2F)C(O)=O)=N1 UWURZZHFZYZWTJ-UHFFFAOYSA-N 0.000 description 7
• 239000005711 Benzoic acid Substances 0.000 description 7
• 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 7
• 150000001408 amides Chemical class 0.000 description 7
• 235000010233 benzoic acid Nutrition 0.000 description 7
• 238000001914 filtration Methods 0.000 description 7
• 229910052739 hydrogen Inorganic materials 0.000 description 7
• 239000001257 hydrogen Substances 0.000 description 7
• 239000003446 ligand Substances 0.000 description 7
• 210000002569 neuron Anatomy 0.000 description 7
• 230000004044 response Effects 0.000 description 7
• FZRBTBCCMVNZBD-UHFFFAOYSA-N 2-chloro-4-(trifluoromethyl)pyrimidine Chemical compound FC(F)(F)C1=CC=NC(Cl)=N1 FZRBTBCCMVNZBD-UHFFFAOYSA-N 0.000 description 6
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 6
• DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 6
• IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 6
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
• DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 6
• 229960000583 acetic acid Drugs 0.000 description 6
• YRKCREAYFQTBPV-UHFFFAOYSA-N acetylacetone Chemical compound CC(=O)CC(C)=O YRKCREAYFQTBPV-UHFFFAOYSA-N 0.000 description 6
• 235000001014 amino acid Nutrition 0.000 description 6
• 125000003118 aryl group Chemical group 0.000 description 6
• 239000011575 calcium Substances 0.000 description 6
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
• 239000012230 colorless oil Substances 0.000 description 6
• 150000007529 inorganic bases Chemical class 0.000 description 6
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 6
• 150000007530 organic bases Chemical class 0.000 description 6
• 238000002360 preparation method Methods 0.000 description 6
• 239000002287 radioligand Substances 0.000 description 6
• 125000006413 ring segment Chemical group 0.000 description 6
• CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
• 239000003826 tablet Substances 0.000 description 6
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 6
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 6
• JRHPOFJADXHYBR-HTQZYQBOSA-N (1r,2r)-1-n,2-n-dimethylcyclohexane-1,2-diamine Chemical compound CN[C@@H]1CCCC[C@H]1NC JRHPOFJADXHYBR-HTQZYQBOSA-N 0.000 description 5
• 0 *N(CCC1C2)CC1N2S(*)(=O)=O Chemical compound *N(CCC1C2)CC1N2S(*)(=O)=O 0.000 description 5
• NWDXVJNAXAQTFY-UHFFFAOYSA-N 3-fluoro-2-pyrimidin-2-ylbenzoic acid Chemical compound OC(=O)C1=CC=CC(F)=C1C1=NC=CC=N1 NWDXVJNAXAQTFY-UHFFFAOYSA-N 0.000 description 5
• 102000013455 Amyloid beta-Peptides Human genes 0.000 description 5
• 108010090849 Amyloid beta-Peptides Proteins 0.000 description 5
• 229910021595 Copper(I) iodide Inorganic materials 0.000 description 5
• BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 5
• 208000012902 Nervous system disease Diseases 0.000 description 5
• 208000025966 Neurological disease Diseases 0.000 description 5
• 229940123730 Orexin receptor antagonist Drugs 0.000 description 5
• 241000283984 Rodentia Species 0.000 description 5
• VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 5
• 239000004480 active ingredient Substances 0.000 description 5
• 230000003042 antagnostic effect Effects 0.000 description 5
• 230000037007 arousal Effects 0.000 description 5
• 230000008901 benefit Effects 0.000 description 5
• WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 5
• 125000001309 chloro group Chemical group Cl* 0.000 description 5
• 239000000284 extract Substances 0.000 description 5
• 239000006260 foam Substances 0.000 description 5
• 230000014509 gene expression Effects 0.000 description 5
• 230000007062 hydrolysis Effects 0.000 description 5
• 238000006460 hydrolysis reaction Methods 0.000 description 5
• 230000003993 interaction Effects 0.000 description 5
• 230000004060 metabolic process Effects 0.000 description 5
• 208000019116 sleep disease Diseases 0.000 description 5
• 239000007858 starting material Substances 0.000 description 5
• 238000003786 synthesis reaction Methods 0.000 description 5
• VGJOEEIXDPWTAZ-RKDXNWHRSA-N tert-butyl (1r,6s)-4,7-diazabicyclo[4.2.0]octane-4-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CC[C@@H]2CN[C@@H]21 VGJOEEIXDPWTAZ-RKDXNWHRSA-N 0.000 description 5
• 230000001225 therapeutic effect Effects 0.000 description 5
• VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 5
• JHLHKCWPDVKWNS-UHFFFAOYSA-N 2-(3-methyl-1,2,4-oxadiazol-5-yl)benzoic acid Chemical compound CC1=NOC(C=2C(=CC=CC=2)C(O)=O)=N1 JHLHKCWPDVKWNS-UHFFFAOYSA-N 0.000 description 4
• GBNPVXZNWBWNEN-UHFFFAOYSA-N 2-chloro-4-(trifluoromethyl)pyridine Chemical compound FC(F)(F)C1=CC=NC(Cl)=C1 GBNPVXZNWBWNEN-UHFFFAOYSA-N 0.000 description 4
• AAZYJKNISGEWEV-UHFFFAOYSA-N 2-chloro-4-phenylpyrimidine Chemical compound ClC1=NC=CC(C=2C=CC=CC=2)=N1 AAZYJKNISGEWEV-UHFFFAOYSA-N 0.000 description 4
• ITAJKPNAPXHDDZ-UHFFFAOYSA-N 2-chloro-5-fluoro-4-methylpyrimidine Chemical compound CC1=NC(Cl)=NC=C1F ITAJKPNAPXHDDZ-UHFFFAOYSA-N 0.000 description 4
• UNCQVRBWJWWJBF-UHFFFAOYSA-N 2-chloropyrimidine Chemical compound ClC1=NC=CC=N1 UNCQVRBWJWWJBF-UHFFFAOYSA-N 0.000 description 4
• CYCXAPWOBWWNRK-UHFFFAOYSA-N 2-fluoro-6-iodobenzoic acid Chemical compound OC(=O)C1=C(F)C=CC=C1I CYCXAPWOBWWNRK-UHFFFAOYSA-N 0.000 description 4
• MPJOJCZVGBOVOV-UHFFFAOYSA-N 2-phenylbenzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1C1=CC=CC=C1 MPJOJCZVGBOVOV-UHFFFAOYSA-N 0.000 description 4
• JGBSDYQSGSBVTP-UHFFFAOYSA-N 3-fluoro-2-pyrimidin-2-ylbenzonitrile Chemical compound FC1=CC=CC(C#N)=C1C1=NC=CC=N1 JGBSDYQSGSBVTP-UHFFFAOYSA-N 0.000 description 4
• QCOCOZHFOVXTJL-UHFFFAOYSA-N 6-methyl-2-(triazol-1-yl)pyridine-3-carboxylic acid Chemical compound CC1=CC=C(C(O)=O)C(N2N=NC=C2)=N1 QCOCOZHFOVXTJL-UHFFFAOYSA-N 0.000 description 4
• VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 4
• 208000019888 Circadian rhythm sleep disease Diseases 0.000 description 4
• 239000007821 HATU Substances 0.000 description 4
• WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 4
• JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 4
• 206010033307 Overweight Diseases 0.000 description 4
• 229910019142 PO4 Inorganic materials 0.000 description 4
• XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 4
• 206010062519 Poor quality sleep Diseases 0.000 description 4
• OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 4
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
• 229920002472 Starch Polymers 0.000 description 4
• 239000005557 antagonist Substances 0.000 description 4
• 239000007864 aqueous solution Substances 0.000 description 4
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 4
• 230000005587 bubbling Effects 0.000 description 4
• 125000004432 carbon atom Chemical group C* 0.000 description 4
• 229910002091 carbon monoxide Inorganic materials 0.000 description 4
• 150000001732 carboxylic acid derivatives Chemical group 0.000 description 4
• 238000005660 chlorination reaction Methods 0.000 description 4
• 238000001816 cooling Methods 0.000 description 4
• 150000000117 diazepanes Chemical class 0.000 description 4
• 238000009472 formulation Methods 0.000 description 4
• 230000027119 gastric acid secretion Effects 0.000 description 4
• 239000008241 heterogeneous mixture Substances 0.000 description 4
• 238000003384 imaging method Methods 0.000 description 4
• 238000000338 in vitro Methods 0.000 description 4
• 238000002347 injection Methods 0.000 description 4
• 239000007924 injection Substances 0.000 description 4
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
• 230000002503 metabolic effect Effects 0.000 description 4
• QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 4
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
• 238000002156 mixing Methods 0.000 description 4
• 125000002950 monocyclic group Chemical group 0.000 description 4
• 229910052760 oxygen Inorganic materials 0.000 description 4
• 239000001301 oxygen Substances 0.000 description 4
• 239000008188 pellet Substances 0.000 description 4
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 4
• 239000010452 phosphate Substances 0.000 description 4
• RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 description 4
• 239000000523 sample Substances 0.000 description 4
• 229910052708 sodium Inorganic materials 0.000 description 4
• 235000017281 sodium acetate Nutrition 0.000 description 4
• 239000012453 solvate Substances 0.000 description 4
• 229940032147 starch Drugs 0.000 description 4
• 239000008107 starch Substances 0.000 description 4
• 235000019698 starch Nutrition 0.000 description 4
• VGJOEEIXDPWTAZ-UHFFFAOYSA-N tert-butyl 4,7-diazabicyclo[4.2.0]octane-4-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCC2CNC21 VGJOEEIXDPWTAZ-UHFFFAOYSA-N 0.000 description 4
• FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
• COIOYMYWGDAQPM-UHFFFAOYSA-N tris(2-methylphenyl)phosphane Chemical group CC1=CC=CC=C1P(C=1C(=CC=CC=1)C)C1=CC=CC=C1C COIOYMYWGDAQPM-UHFFFAOYSA-N 0.000 description 4
• 208000001072 type 2 diabetes mellitus Diseases 0.000 description 4
• KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 3
• LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 3
• HBAONQJODJLDTG-UHFFFAOYSA-N 2-(triazol-1-yl)benzoic acid Chemical compound OC(=O)C1=CC=CC=C1N1N=NC=C1 HBAONQJODJLDTG-UHFFFAOYSA-N 0.000 description 3
• NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 3
• DBQFXQNGQUPVER-UHFFFAOYSA-N 2-chloro-4,5-dimethylpyrimidine Chemical compound CC1=CN=C(Cl)N=C1C DBQFXQNGQUPVER-UHFFFAOYSA-N 0.000 description 3
• ACQXHCHKMFYDPM-UHFFFAOYSA-N 2-chloro-6-methylpyridine-3-carboxylic acid Chemical compound CC1=CC=C(C(O)=O)C(Cl)=N1 ACQXHCHKMFYDPM-UHFFFAOYSA-N 0.000 description 3
• CXPLPVNWMLRKTO-UHFFFAOYSA-N 3-fluoro-2-iodobenzoic acid Chemical compound OC(=O)C1=CC=CC(F)=C1I CXPLPVNWMLRKTO-UHFFFAOYSA-N 0.000 description 3
• ZABRUMFAJKMYDU-UHFFFAOYSA-N 3-methyl-2-(triazol-2-yl)benzonitrile Chemical compound CC1=CC=CC(C#N)=C1N1N=CC=N1 ZABRUMFAJKMYDU-UHFFFAOYSA-N 0.000 description 3
• AOHVRTKHQDBFDT-UHFFFAOYSA-N 4,7-diazabicyclo[4.2.0]octan-7-yl-[4-(2-fluorophenyl)-2-methyl-1,3-thiazol-5-yl]methanone Chemical compound C1C2CCNCC2N1C(=O)C=1SC(C)=NC=1C1=CC=CC=C1F AOHVRTKHQDBFDT-UHFFFAOYSA-N 0.000 description 3
• 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 3
• XQZQSDBOJMYFIR-UHFFFAOYSA-N 5-(2-fluoro-6-iodophenyl)-3-methyl-1,2,4-oxadiazole Chemical compound CC1=NOC(C=2C(=CC=CC=2F)I)=N1 XQZQSDBOJMYFIR-UHFFFAOYSA-N 0.000 description 3
• RJCPGIDCCOBOPD-UHFFFAOYSA-N 5-fluoro-6-hydroxy-1h-pyrimidine-2,4-dione Chemical compound OC=1NC(=O)NC(=O)C=1F RJCPGIDCCOBOPD-UHFFFAOYSA-N 0.000 description 3
• HDALTFQFPQOGQO-UHFFFAOYSA-N 7-(2,4-dimethylphenyl)sulfonyl-4,7-diazabicyclo[4.2.0]octane Chemical compound CC1=CC(C)=CC=C1S(=O)(=O)N1C2CNCCC2C1 HDALTFQFPQOGQO-UHFFFAOYSA-N 0.000 description 3
• 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 3
• OQLZINXFSUDMHM-UHFFFAOYSA-N Acetamidine Chemical compound CC(N)=N OQLZINXFSUDMHM-UHFFFAOYSA-N 0.000 description 3
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
• 208000024827 Alzheimer disease Diseases 0.000 description 3
• 206010002383 Angina Pectoris Diseases 0.000 description 3
• GSNUFIFRDBKVIE-UHFFFAOYSA-N DMF Natural products CC1=CC=C(C)O1 GSNUFIFRDBKVIE-UHFFFAOYSA-N 0.000 description 3
• VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 3
• 108010010803 Gelatin Proteins 0.000 description 3
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
• 206010020772 Hypertension Diseases 0.000 description 3
• DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
• 239000012359 Methanesulfonyl chloride Substances 0.000 description 3
• 208000008589 Obesity Diseases 0.000 description 3
• MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
• 101150003085 Pdcl gene Proteins 0.000 description 3
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 3
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 3
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 3
• 208000001871 Tachycardia Diseases 0.000 description 3
• DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 3
• XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 3
• 150000007513 acids Chemical class 0.000 description 3
• 239000012190 activator Substances 0.000 description 3
• 150000001413 amino acids Chemical class 0.000 description 3
• 229910021529 ammonia Inorganic materials 0.000 description 3
• 238000003556 assay Methods 0.000 description 3
• JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 3
• 239000000872 buffer Substances 0.000 description 3
• FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 3
• 229910000024 caesium carbonate Inorganic materials 0.000 description 3
• 239000002775 capsule Substances 0.000 description 3
• 230000003197 catalytic effect Effects 0.000 description 3
• 210000003169 central nervous system Anatomy 0.000 description 3
• 210000004978 chinese hamster ovary cell Anatomy 0.000 description 3
• 239000012320 chlorinating reagent Substances 0.000 description 3
• GBRBMTNGQBKBQE-UHFFFAOYSA-L copper;diiodide Chemical compound I[Cu]I GBRBMTNGQBKBQE-UHFFFAOYSA-L 0.000 description 3
• 125000000753 cycloalkyl group Chemical group 0.000 description 3
• 238000013461 design Methods 0.000 description 3
• 238000010494 dissociation reaction Methods 0.000 description 3
• 230000005593 dissociations Effects 0.000 description 3
• 238000004453 electron probe microanalysis Methods 0.000 description 3
• VFRSADQPWYCXDG-LEUCUCNGSA-N ethyl (2s,5s)-5-methylpyrrolidine-2-carboxylate;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.CCOC(=O)[C@@H]1CC[C@H](C)N1 VFRSADQPWYCXDG-LEUCUCNGSA-N 0.000 description 3
• 210000003722 extracellular fluid Anatomy 0.000 description 3
• 235000019253 formic acid Nutrition 0.000 description 3
• 230000006870 function Effects 0.000 description 3
• 239000008273 gelatin Substances 0.000 description 3
• 229920000159 gelatin Polymers 0.000 description 3
• 239000007903 gelatin capsule Substances 0.000 description 3
• 235000019322 gelatine Nutrition 0.000 description 3
• 235000011852 gelatine desserts Nutrition 0.000 description 3
• 229940093915 gynecological organic acid Drugs 0.000 description 3
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 3
• 230000036512 infertility Effects 0.000 description 3
• 231100000535 infertility Toxicity 0.000 description 3
• 239000003112 inhibitor Substances 0.000 description 3
• LZKLAOYSENRNKR-LNTINUHCSA-N iron;(z)-4-oxoniumylidenepent-2-en-2-olate Chemical compound [Fe].C\C(O)=C\C(C)=O.C\C(O)=C\C(C)=O.C\C(O)=C\C(C)=O LZKLAOYSENRNKR-LNTINUHCSA-N 0.000 description 3
• VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 3
• 150000004702 methyl esters Chemical class 0.000 description 3
• 150000007522 mineralic acids Chemical class 0.000 description 3
• 201000003631 narcolepsy Diseases 0.000 description 3
• 210000005036 nerve Anatomy 0.000 description 3
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 3
• 231100000252 nontoxic Toxicity 0.000 description 3
• 230000003000 nontoxic effect Effects 0.000 description 3
• 235000020824 obesity Nutrition 0.000 description 3
• OFNHNCAUVYOTPM-IIIOAANCSA-N orexin-a Chemical compound C([C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)CNC(=O)[C@H](C)NC(=O)CNC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H]1NC(=O)[C@H](CO)NC(=O)[C@@H]2CSSC[C@@H](C(=O)N[C@H](C(N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N2)[C@@H](C)O)=O)CSSC1)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC(C)C)NC(=O)[C@H]1N(CCC1)C(=O)[C@H]1NC(=O)CC1)C1=CNC=N1 OFNHNCAUVYOTPM-IIIOAANCSA-N 0.000 description 3
• 230000000446 orexinergic effect Effects 0.000 description 3
• 150000007524 organic acids Chemical class 0.000 description 3
• 235000005985 organic acids Nutrition 0.000 description 3
• 230000000069 prophylactic effect Effects 0.000 description 3
• VTGOHKSTWXHQJK-UHFFFAOYSA-N pyrimidin-2-ol Chemical compound OC1=NC=CC=N1 VTGOHKSTWXHQJK-UHFFFAOYSA-N 0.000 description 3
• 238000001953 recrystallisation Methods 0.000 description 3
• 238000004007 reversed phase HPLC Methods 0.000 description 3
• 239000000741 silica gel Substances 0.000 description 3
• 229910002027 silica gel Inorganic materials 0.000 description 3
• 229910000029 sodium carbonate Inorganic materials 0.000 description 3
• 230000006794 tachycardia Effects 0.000 description 3
• 210000001519 tissue Anatomy 0.000 description 3
• 230000009466 transformation Effects 0.000 description 3
• 238000000844 transformation Methods 0.000 description 3
• 150000003852 triazoles Chemical group 0.000 description 3
• 210000001186 vagus nerve Anatomy 0.000 description 3
• LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 2
• JTARFZSNUAGHRB-UHFFFAOYSA-N 1-(6,8-difluoro-2-methyl-4-quinolinyl)-3-[4-(dimethylamino)phenyl]urea Chemical compound C1=CC(N(C)C)=CC=C1NC(=O)NC1=CC(C)=NC2=C(F)C=C(F)C=C12 JTARFZSNUAGHRB-UHFFFAOYSA-N 0.000 description 2
• VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
• QSFOZEQAJZUCJM-UHFFFAOYSA-N 2,3-dimethoxy-6-(triazol-1-yl)benzoic acid Chemical compound OC(=O)C1=C(OC)C(OC)=CC=C1N1N=NC=C1 QSFOZEQAJZUCJM-UHFFFAOYSA-N 0.000 description 2
• CUEJKXDENXDWNU-UHFFFAOYSA-N 2,3-dimethoxy-6-(triazol-2-yl)benzoic acid Chemical compound OC(=O)C1=C(OC)C(OC)=CC=C1N1N=CC=N1 CUEJKXDENXDWNU-UHFFFAOYSA-N 0.000 description 2
• XXBZSPPWTVRISV-UHFFFAOYSA-N 2,4,6-trichloro-5-fluoropyrimidine Chemical compound FC1=C(Cl)N=C(Cl)N=C1Cl XXBZSPPWTVRISV-UHFFFAOYSA-N 0.000 description 2
• WHPFEQUEHBULBW-UHFFFAOYSA-N 2,4-dichloro-5-fluoropyrimidine Chemical compound FC1=CN=C(Cl)N=C1Cl WHPFEQUEHBULBW-UHFFFAOYSA-N 0.000 description 2
• BDKLKNJTMLIAFE-UHFFFAOYSA-N 2-(3-fluorophenyl)-1,3-oxazole-4-carbaldehyde Chemical compound FC1=CC=CC(C=2OC=C(C=O)N=2)=C1 BDKLKNJTMLIAFE-UHFFFAOYSA-N 0.000 description 2
• BBVQDWDBTWSGHQ-UHFFFAOYSA-N 2-chloro-1,3-benzoxazole Chemical compound C1=CC=C2OC(Cl)=NC2=C1 BBVQDWDBTWSGHQ-UHFFFAOYSA-N 0.000 description 2
• BHAKRVSCGILCEW-UHFFFAOYSA-N 2-chloro-4-methylpyrimidine Chemical compound CC1=CC=NC(Cl)=N1 BHAKRVSCGILCEW-UHFFFAOYSA-N 0.000 description 2
• ADVQMCQMDHBTHJ-UHFFFAOYSA-N 2-chloro-6-(trifluoromethyl)pyridine Chemical compound FC(F)(F)C1=CC=CC(Cl)=N1 ADVQMCQMDHBTHJ-UHFFFAOYSA-N 0.000 description 2
• ZFISALWGLDMIKD-UHFFFAOYSA-N 2-ethyl-5-methylhexanedioic acid Chemical compound CCC(C(O)=O)CCC(C)C(O)=O ZFISALWGLDMIKD-UHFFFAOYSA-N 0.000 description 2
• PALKZAFODAZJLL-UHFFFAOYSA-N 2-fluoro-6-(3-methyl-1,2,4-oxadiazol-5-yl)benzoic acid Chemical compound CC1=NOC(C=2C(=C(F)C=CC=2)C(O)=O)=N1 PALKZAFODAZJLL-UHFFFAOYSA-N 0.000 description 2
• NTPOZDBAGMLNQA-UHFFFAOYSA-N 2-fluoro-6-(triazol-2-yl)benzoic acid Chemical compound OC(=O)C1=C(F)C=CC=C1N1N=CC=N1 NTPOZDBAGMLNQA-UHFFFAOYSA-N 0.000 description 2
• IZHVBANLECCAGF-UHFFFAOYSA-N 2-hydroxy-3-(octadecanoyloxy)propyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)COC(=O)CCCCCCCCCCCCCCCCC IZHVBANLECCAGF-UHFFFAOYSA-N 0.000 description 2
• IWZPIQDEFDUXKK-UHFFFAOYSA-N 2-o-[(e)-1-aminoethylideneamino] 1-o-methyl 3-fluorobenzene-1,2-dicarboxylate Chemical compound COC(=O)C1=CC=CC(F)=C1C(=O)O\N=C(\C)N IWZPIQDEFDUXKK-UHFFFAOYSA-N 0.000 description 2
• XKEYAOJRNJYJMM-UHFFFAOYSA-N 3,6-diazabicyclo[3.2.0]heptane Chemical class C1NCC2CNC21 XKEYAOJRNJYJMM-UHFFFAOYSA-N 0.000 description 2
• YDNKDTDNIBCYCV-UHFFFAOYSA-N 3-(4-phenylpyrimidin-2-yl)-3,6-diazabicyclo[3.2.0]heptane Chemical compound C1C2CNC2CN1C(N=1)=NC=CC=1C1=CC=CC=C1 YDNKDTDNIBCYCV-UHFFFAOYSA-N 0.000 description 2
• MIABSWOAWHSFMW-UHFFFAOYSA-N 3-fluoro-2-(triazol-1-yl)benzonitrile Chemical compound FC1=CC=CC(C#N)=C1N1N=NC=C1 MIABSWOAWHSFMW-UHFFFAOYSA-N 0.000 description 2
• ALACTBSPYZFNIK-UHFFFAOYSA-N 3-fluoro-2-(triazol-2-yl)benzoic acid Chemical compound OC(=O)C1=CC=CC(F)=C1N1N=CC=N1 ALACTBSPYZFNIK-UHFFFAOYSA-N 0.000 description 2
• XUBKFYZGWDCGBP-UHFFFAOYSA-N 3-fluoro-2-(triazol-2-yl)benzonitrile Chemical compound FC1=CC=CC(C#N)=C1N1N=CC=N1 XUBKFYZGWDCGBP-UHFFFAOYSA-N 0.000 description 2
• CUKPIEAMFVXIRK-UHFFFAOYSA-N 3-methoxy-2-(triazol-2-yl)benzoic acid Chemical compound COC1=CC=CC(C(O)=O)=C1N1N=CC=N1 CUKPIEAMFVXIRK-UHFFFAOYSA-N 0.000 description 2
• YXZWVSIXBFPESW-UHFFFAOYSA-N 3-methyl-2-pyrazol-1-ylbenzoic acid Chemical compound CC1=CC=CC(C(O)=O)=C1N1N=CC=C1 YXZWVSIXBFPESW-UHFFFAOYSA-N 0.000 description 2
• LZPWAYBEOJRFAX-UHFFFAOYSA-N 4,4,5,5-tetramethyl-1,3,2$l^{2}-dioxaborolane Chemical compound CC1(C)O[B]OC1(C)C LZPWAYBEOJRFAX-UHFFFAOYSA-N 0.000 description 2
• ZRQPOQRDNYJQNB-UHFFFAOYSA-N 4,5,6-trimethyl-1h-pyrimidin-2-one Chemical compound CC1=NC(=O)NC(C)=C1C ZRQPOQRDNYJQNB-UHFFFAOYSA-N 0.000 description 2
• CPGFQLIXICGYSN-UHFFFAOYSA-N 4,7-diazabicyclo[4.2.0]octane Chemical class C1NCCC2CNC21 CPGFQLIXICGYSN-UHFFFAOYSA-N 0.000 description 2
• TYSPDLZOMUDHQZ-UHFFFAOYSA-N 4-chloro-6-(trifluoromethyl)pyrimidine Chemical compound FC(F)(F)C1=CC(Cl)=NC=N1 TYSPDLZOMUDHQZ-UHFFFAOYSA-N 0.000 description 2
• PJCDNTVCCXJUAC-UHFFFAOYSA-N 4-chloro-6-methyl-2-propan-2-ylpyrimidine Chemical compound CC(C)C1=NC(C)=CC(Cl)=N1 PJCDNTVCCXJUAC-UHFFFAOYSA-N 0.000 description 2
• JDYDIHVYOFAERC-UHFFFAOYSA-N 4-chloro-n,n,6-trimethylpyrimidin-2-amine Chemical compound CN(C)C1=NC(C)=CC(Cl)=N1 JDYDIHVYOFAERC-UHFFFAOYSA-N 0.000 description 2
• YGGGBTQWZFFFBQ-UHFFFAOYSA-N 5-fluoro-2-(1h-pyrazol-5-yl)benzoic acid Chemical compound OC(=O)C1=CC(F)=CC=C1C1=CC=NN1 YGGGBTQWZFFFBQ-UHFFFAOYSA-N 0.000 description 2
• HCYLTPJADJTYPX-UHFFFAOYSA-N 5-fluoro-2-(triazol-2-yl)benzoic acid Chemical compound OC(=O)C1=CC(F)=CC=C1N1N=CC=N1 HCYLTPJADJTYPX-UHFFFAOYSA-N 0.000 description 2
• GWFSRJKDYXADOG-UHFFFAOYSA-N 5-fluoro-2-pyrimidin-2-ylbenzoic acid Chemical compound OC(=O)C1=CC(F)=CC=C1C1=NC=CC=N1 GWFSRJKDYXADOG-UHFFFAOYSA-N 0.000 description 2
• SRBAGFIYKNQXDV-UHFFFAOYSA-N 5-methyl-2-(triazol-2-yl)benzoic acid Chemical compound OC(=O)C1=CC(C)=CC=C1N1N=CC=N1 SRBAGFIYKNQXDV-UHFFFAOYSA-N 0.000 description 2
• MEFOLQWSRBDONE-UHFFFAOYSA-N 6-chloro-n,n,2-trimethylpyrimidin-4-amine Chemical compound CN(C)C1=CC(Cl)=NC(C)=N1 MEFOLQWSRBDONE-UHFFFAOYSA-N 0.000 description 2
• WAGVAZQFCOMORW-UHFFFAOYSA-N 6-chloro-n,n-dimethylpyrimidin-4-amine Chemical compound CN(C)C1=CC(Cl)=NC=N1 WAGVAZQFCOMORW-UHFFFAOYSA-N 0.000 description 2
• VNGUNPFSPAFWJG-UHFFFAOYSA-N 6-methyl-2-(triazol-2-yl)pyridine-3-carboxylic acid Chemical compound CC1=CC=C(C(O)=O)C(N2N=CC=N2)=N1 VNGUNPFSPAFWJG-UHFFFAOYSA-N 0.000 description 2
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
• 208000019901 Anxiety disease Diseases 0.000 description 2
• 208000006820 Arthralgia Diseases 0.000 description 2
• CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
• 208000008035 Back Pain Diseases 0.000 description 2
• 208000020925 Bipolar disease Diseases 0.000 description 2
• LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 2
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
• 235000008733 Citrus aurantifolia Nutrition 0.000 description 2
• FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
• FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 2
• 206010012218 Delirium Diseases 0.000 description 2
• 206010012289 Dementia Diseases 0.000 description 2
• 206010012735 Diarrhoea Diseases 0.000 description 2
• 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 2
• 208000001640 Fibromyalgia Diseases 0.000 description 2
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
• IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 description 2
• 201000004311 Gilles de la Tourette syndrome Diseases 0.000 description 2
• 239000004471 Glycine Substances 0.000 description 2
• AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
• 239000007818 Grignard reagent Substances 0.000 description 2
• 229910004373 HOAc Inorganic materials 0.000 description 2
• XLYOFNOQVPJJNP-ZSJDYOACSA-N Heavy water Chemical compound [2H]O[2H] XLYOFNOQVPJJNP-ZSJDYOACSA-N 0.000 description 2
• 241000282412 Homo Species 0.000 description 2
• WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 2
• 208000031226 Hyperlipidaemia Diseases 0.000 description 2
• 208000001953 Hypotension Diseases 0.000 description 2
• 206010022489 Insulin Resistance Diseases 0.000 description 2
• XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
• 208000001456 Jet Lag Syndrome Diseases 0.000 description 2
• 208000008930 Low Back Pain Diseases 0.000 description 2
• 241001465754 Metazoa Species 0.000 description 2
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
• 206010028980 Neoplasm Diseases 0.000 description 2
• 102100037757 Orexin Human genes 0.000 description 2
• 229940127340 Orexin Receptor Agonists Drugs 0.000 description 2
• 102100026450 POU domain, class 3, transcription factor 4 Human genes 0.000 description 2
• 101710133389 POU domain, class 3, transcription factor 4 Proteins 0.000 description 2
• 208000002193 Pain Diseases 0.000 description 2
• 208000018737 Parkinson disease Diseases 0.000 description 2
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
• GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
• 229920002873 Polyethylenimine Polymers 0.000 description 2
• 239000004743 Polypropylene Substances 0.000 description 2
• 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 2
• WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical group C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 2
• LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 2
• NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 2
• 241000700159 Rattus Species 0.000 description 2
• 208000005793 Restless legs syndrome Diseases 0.000 description 2
• 208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 description 2
• 208000022249 Sleep-Wake Transition disease Diseases 0.000 description 2
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
• 235000021355 Stearic acid Nutrition 0.000 description 2
• 235000011941 Tilia x europaea Nutrition 0.000 description 2
• 208000000323 Tourette Syndrome Diseases 0.000 description 2
• 208000016620 Tourette disease Diseases 0.000 description 2
• 208000025865 Ulcer Diseases 0.000 description 2
• UPTWLWSNUNUYEN-BXUZGUMPSA-N [(1r,6s)-4,7-diazabicyclo[4.2.0]octan-7-yl]-[2-(3-methyl-1,2,4-oxadiazol-5-yl)phenyl]methanone Chemical compound CC1=NOC(C=2C(=CC=CC=2)C(=O)N2[C@@H]3CNCC[C@@H]3C2)=N1 UPTWLWSNUNUYEN-BXUZGUMPSA-N 0.000 description 2
• SAJVSUWKFSROAQ-ZWNOBZJWSA-N [(1r,6s)-4,7-diazabicyclo[4.2.0]octan-7-yl]-[2-fluoro-6-(triazol-2-yl)phenyl]methanone Chemical compound N1([C@@H]2CNCC[C@@H]2C1)C(=O)C=1C(F)=CC=CC=1N1N=CC=N1 SAJVSUWKFSROAQ-ZWNOBZJWSA-N 0.000 description 2
• SYUUTJNLGFCAPO-ZWNOBZJWSA-N [(1r,6s)-4,7-diazabicyclo[4.2.0]octan-7-yl]-[3-fluoro-2-(triazol-2-yl)phenyl]methanone Chemical compound FC1=CC=CC(C(=O)N2[C@@H]3CNCC[C@@H]3C2)=C1N1N=CC=N1 SYUUTJNLGFCAPO-ZWNOBZJWSA-N 0.000 description 2
• VFWSBJTWRHUMEK-DGCLKSJQSA-N [(1r,6s)-4,7-diazabicyclo[4.2.0]octan-7-yl]-[6-methyl-2-(triazol-1-yl)pyridin-3-yl]methanone Chemical compound N=1C(C)=CC=C(C(=O)N2[C@@H]3CNCC[C@@H]3C2)C=1N1C=CN=N1 VFWSBJTWRHUMEK-DGCLKSJQSA-N 0.000 description 2
• SLIDICQEBXZUFC-WFASDCNBSA-N [(1s,6r)-4,7-diazabicyclo[4.2.0]octan-7-yl]-(2-thiophen-2-ylphenyl)methanone Chemical compound N1([C@H]2CNCC[C@H]2C1)C(=O)C1=CC=CC=C1C1=CC=CS1 SLIDICQEBXZUFC-WFASDCNBSA-N 0.000 description 2
• SAJVSUWKFSROAQ-GWCFXTLKSA-N [(1s,6r)-4,7-diazabicyclo[4.2.0]octan-7-yl]-[2-fluoro-6-(triazol-2-yl)phenyl]methanone Chemical compound N1([C@H]2CNCC[C@H]2C1)C(=O)C=1C(F)=CC=CC=1N1N=CC=N1 SAJVSUWKFSROAQ-GWCFXTLKSA-N 0.000 description 2
• DEWMJZBQGSHSAQ-OXQOHEQNSA-N [3-fluoro-2-(1h-pyrazol-5-yl)phenyl]-[(1r,6s)-4-(4,5,6-trimethylpyrimidin-2-yl)-4,7-diazabicyclo[4.2.0]octan-7-yl]methanone Chemical compound CC1=C(C)C(C)=NC(N2C[C@H]3N(C[C@H]3CC2)C(=O)C=2C(=C(F)C=CC=2)C=2NN=CC=2)=N1 DEWMJZBQGSHSAQ-OXQOHEQNSA-N 0.000 description 2
• PTPUOMXKXCCSEN-UHFFFAOYSA-N acetyloxymethyl 2-[2-[2-[5-[3-(acetyloxymethoxy)-2,7-dichloro-6-oxoxanthen-9-yl]-2-[bis[2-(acetyloxymethoxy)-2-oxoethyl]amino]phenoxy]ethoxy]-n-[2-(acetyloxymethoxy)-2-oxoethyl]-4-methylanilino]acetate Chemical compound CC(=O)OCOC(=O)CN(CC(=O)OCOC(C)=O)C1=CC=C(C)C=C1OCCOC1=CC(C2=C3C=C(Cl)C(=O)C=C3OC3=CC(OCOC(C)=O)=C(Cl)C=C32)=CC=C1N(CC(=O)OCOC(C)=O)CC(=O)OCOC(C)=O PTPUOMXKXCCSEN-UHFFFAOYSA-N 0.000 description 2
• 230000002378 acidificating effect Effects 0.000 description 2
• 125000002252 acyl group Chemical class 0.000 description 2
• 125000004423 acyloxy group Chemical group 0.000 description 2
• 125000005907 alkyl ester group Chemical group 0.000 description 2
• BHELZAPQIKSEDF-UHFFFAOYSA-N allyl bromide Chemical compound BrCC=C BHELZAPQIKSEDF-UHFFFAOYSA-N 0.000 description 2
• 125000000539 amino acid group Chemical group 0.000 description 2
• 102000001307 androgen receptors Human genes 0.000 description 2
• 108010080146 androgen receptors Proteins 0.000 description 2
• 230000036506 anxiety Effects 0.000 description 2
• 208000008784 apnea Diseases 0.000 description 2
• 230000036528 appetite Effects 0.000 description 2
• 235000019789 appetite Nutrition 0.000 description 2
• 239000012298 atmosphere Substances 0.000 description 2
• 125000004429 atom Chemical group 0.000 description 2
• YXCPNFNWSNFFFZ-UHFFFAOYSA-N benzyl 3-amino-4-(hydroxymethyl)pyrrolidine-1-carboxylate Chemical compound C1C(CO)C(N)CN1C(=O)OCC1=CC=CC=C1 YXCPNFNWSNFFFZ-UHFFFAOYSA-N 0.000 description 2
• JEGCOCKTVYVGSS-UHFFFAOYSA-N benzyl n-(2,2-dimethoxyethyl)-n-prop-2-enylcarbamate Chemical compound COC(OC)CN(CC=C)C(=O)OCC1=CC=CC=C1 JEGCOCKTVYVGSS-UHFFFAOYSA-N 0.000 description 2
• XUEMBLJTQGDMMM-UHFFFAOYSA-N benzyl n-(2-oxoethyl)-n-prop-2-enylcarbamate Chemical compound C=CCN(CC=O)C(=O)OCC1=CC=CC=C1 XUEMBLJTQGDMMM-UHFFFAOYSA-N 0.000 description 2
• HTZCNXWZYVXIMZ-UHFFFAOYSA-M benzyl(triethyl)azanium;chloride Chemical compound [Cl-].CC[N+](CC)(CC)CC1=CC=CC=C1 HTZCNXWZYVXIMZ-UHFFFAOYSA-M 0.000 description 2
• 239000011230 binding agent Substances 0.000 description 2
• 208000028683 bipolar I disease Diseases 0.000 description 2
• 230000037396 body weight Effects 0.000 description 2
• 230000036471 bradycardia Effects 0.000 description 2
• 208000006218 bradycardia Diseases 0.000 description 2
• 125000001246 bromo group Chemical group Br* 0.000 description 2
• 239000008366 buffered solution Substances 0.000 description 2
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
• 230000001275 ca(2+)-mobilization Effects 0.000 description 2
• 229910052791 calcium Inorganic materials 0.000 description 2
• 229910000019 calcium carbonate Inorganic materials 0.000 description 2
• 239000001506 calcium phosphate Substances 0.000 description 2
• 229910000389 calcium phosphate Inorganic materials 0.000 description 2
• 235000011010 calcium phosphates Nutrition 0.000 description 2
• 201000011510 cancer Diseases 0.000 description 2
• 239000004202 carbamide Substances 0.000 description 2
• 239000006285 cell suspension Substances 0.000 description 2
• 238000005119 centrifugation Methods 0.000 description 2
• 230000008859 change Effects 0.000 description 2
• PBAYDYUZOSNJGU-UHFFFAOYSA-N chelidonic acid Natural products OC(=O)C1=CC(=O)C=C(C(O)=O)O1 PBAYDYUZOSNJGU-UHFFFAOYSA-N 0.000 description 2
• 239000003638 chemical reducing agent Substances 0.000 description 2
• 229910052801 chlorine Inorganic materials 0.000 description 2
• 201000001883 cholelithiasis Diseases 0.000 description 2
• 238000003776 cleavage reaction Methods 0.000 description 2
• 239000003086 colorant Substances 0.000 description 2
• 229940125810 compound 20 Drugs 0.000 description 2
• 238000002591 computed tomography Methods 0.000 description 2
• 238000007796 conventional method Methods 0.000 description 2
• LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 2
• 238000012937 correction Methods 0.000 description 2
• 239000013078 crystal Substances 0.000 description 2
• 125000004093 cyano group Chemical group *C#N 0.000 description 2
• 239000012024 dehydrating agents‎ Substances 0.000 description 2
• 238000001212 derivatisation Methods 0.000 description 2
• 239000002274 desiccant Substances 0.000 description 2
• 238000001514 detection method Methods 0.000 description 2
• LFQSCWFLJHTTHZ-WFVSFCRTSA-N deuteriooxyethane Chemical compound [2H]OCC LFQSCWFLJHTTHZ-WFVSFCRTSA-N 0.000 description 2
• 238000011161 development Methods 0.000 description 2
• 239000003085 diluting agent Substances 0.000 description 2
• XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
• 239000007884 disintegrant Substances 0.000 description 2
• POULHZVOKOAJMA-UHFFFAOYSA-N dodecanoic acid Chemical compound CCCCCCCCCCCC(O)=O POULHZVOKOAJMA-UHFFFAOYSA-N 0.000 description 2
• VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 2
• 239000002552 dosage form Substances 0.000 description 2
• 231100000673 dose–response relationship Toxicity 0.000 description 2
• 230000035622 drinking Effects 0.000 description 2
• 239000003937 drug carrier Substances 0.000 description 2
• 238000012377 drug delivery Methods 0.000 description 2
• 239000000839 emulsion Substances 0.000 description 2
• 230000002255 enzymatic effect Effects 0.000 description 2
• LFQSCWFLJHTTHZ-LIDOUZCJSA-N ethanol-d6 Chemical compound [2H]OC([2H])([2H])C([2H])([2H])[2H] LFQSCWFLJHTTHZ-LIDOUZCJSA-N 0.000 description 2
• 238000002474 experimental method Methods 0.000 description 2
• 238000000605 extraction Methods 0.000 description 2
• 230000035611 feeding Effects 0.000 description 2
• 239000000796 flavoring agent Substances 0.000 description 2
• 239000012530 fluid Substances 0.000 description 2
• 239000011737 fluorine Chemical group 0.000 description 2
• 229910052731 fluorine Inorganic materials 0.000 description 2
• 239000012458 free base Substances 0.000 description 2
• 125000000524 functional group Chemical group 0.000 description 2
• 208000001130 gallstones Diseases 0.000 description 2
• BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 2
• 230000030135 gastric motility Effects 0.000 description 2
• 208000021302 gastroesophageal reflux disease Diseases 0.000 description 2
• JAXFJECJQZDFJS-XHEPKHHKSA-N gtpl8555 Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@@H]1C(=O)N[C@H](B1O[C@@]2(C)[C@H]3C[C@H](C3(C)C)C[C@H]2O1)CCC1=CC=C(F)C=C1 JAXFJECJQZDFJS-XHEPKHHKSA-N 0.000 description 2
• 125000005842 heteroatom Chemical group 0.000 description 2
• 125000000592 heterocycloalkyl group Chemical group 0.000 description 2
• IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 2
• NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 2
• 230000036543 hypotension Effects 0.000 description 2
• 230000002267 hypothalamic effect Effects 0.000 description 2
• 210000003016 hypothalamus Anatomy 0.000 description 2
• 238000001727 in vivo Methods 0.000 description 2
• 208000000509 infertility Diseases 0.000 description 2
• 238000001802 infusion Methods 0.000 description 2
• 206010022437 insomnia Diseases 0.000 description 2
• UEXQBEVWFZKHNB-UHFFFAOYSA-N intermediate 29 Natural products C1=CC(N)=CC=C1NC1=NC=CC=N1 UEXQBEVWFZKHNB-UHFFFAOYSA-N 0.000 description 2
• 210000000936 intestine Anatomy 0.000 description 2
• 238000000185 intracerebroventricular administration Methods 0.000 description 2
• 238000001990 intravenous administration Methods 0.000 description 2
• 239000011630 iodine Chemical group 0.000 description 2
• 229910052740 iodine Chemical group 0.000 description 2
• 208000002551 irritable bowel syndrome Diseases 0.000 description 2
• SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 2
• 208000033915 jet lag type circadian rhythm sleep disease Diseases 0.000 description 2
• JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
• 239000004571 lime Substances 0.000 description 2
• 230000000670 limiting effect Effects 0.000 description 2
• 239000000314 lubricant Substances 0.000 description 2
• 235000019359 magnesium stearate Nutrition 0.000 description 2
• NXPHGHWWQRMDIA-UHFFFAOYSA-M magnesium;carbanide;bromide Chemical compound [CH3-].[Mg+2].[Br-] NXPHGHWWQRMDIA-UHFFFAOYSA-M 0.000 description 2
• IUYHWZFSGMZEOG-UHFFFAOYSA-M magnesium;propane;chloride Chemical compound [Mg+2].[Cl-].C[CH-]C IUYHWZFSGMZEOG-UHFFFAOYSA-M 0.000 description 2
• 239000011976 maleic acid Substances 0.000 description 2
• 229940098895 maleic acid Drugs 0.000 description 2
• 238000004519 manufacturing process Methods 0.000 description 2
• 238000005259 measurement Methods 0.000 description 2
• 208000030159 metabolic disease Diseases 0.000 description 2
• NRZYJCOEMQDDFP-UHFFFAOYSA-N methyl 5-fluoro-2-(1h-pyrazol-5-yl)benzoate Chemical compound COC(=O)C1=CC(F)=CC=C1C1=CC=NN1 NRZYJCOEMQDDFP-UHFFFAOYSA-N 0.000 description 2
• BRUNIDAHRLZQOH-UHFFFAOYSA-N methyl 5-fluoro-2-iodobenzoate Chemical compound COC(=O)C1=CC(F)=CC=C1I BRUNIDAHRLZQOH-UHFFFAOYSA-N 0.000 description 2
• QPJVMBTYPHYUOC-UHFFFAOYSA-N methyl benzoate Chemical compound COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 description 2
• 229920000609 methyl cellulose Polymers 0.000 description 2
• 239000001923 methylcellulose Substances 0.000 description 2
• 235000010981 methylcellulose Nutrition 0.000 description 2
• 239000002808 molecular sieve Substances 0.000 description 2
• 239000001788 mono and diglycerides of fatty acids Substances 0.000 description 2
• BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 2
• 230000008450 motivation Effects 0.000 description 2
• AEXITZJSLGALNH-UHFFFAOYSA-N n'-hydroxyethanimidamide Chemical compound CC(N)=NO AEXITZJSLGALNH-UHFFFAOYSA-N 0.000 description 2
• KJPHTXTWFHVJIG-UHFFFAOYSA-N n-ethyl-2-[(6-methoxypyridin-3-yl)-(2-methylphenyl)sulfonylamino]-n-(pyridin-3-ylmethyl)acetamide Chemical compound C=1C=C(OC)N=CC=1N(S(=O)(=O)C=1C(=CC=CC=1)C)CC(=O)N(CC)CC1=CC=CN=C1 KJPHTXTWFHVJIG-UHFFFAOYSA-N 0.000 description 2
• XBXCNNQPRYLIDE-UHFFFAOYSA-M n-tert-butylcarbamate Chemical compound CC(C)(C)NC([O-])=O XBXCNNQPRYLIDE-UHFFFAOYSA-M 0.000 description 2
• 208000004296 neuralgia Diseases 0.000 description 2
• 208000021722 neuropathic pain Diseases 0.000 description 2
• 230000007935 neutral effect Effects 0.000 description 2
• 150000002825 nitriles Chemical class 0.000 description 2
• 230000009871 nonspecific binding Effects 0.000 description 2
• QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 2
• OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 2
• OHOWSYIKESXDMN-WMQZXSDYSA-N orexin-b Chemical compound C([C@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)CNC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@@H](N)CCSC)[C@@H](C)O)[C@@H](C)CC)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCN=C(N)N)C(=O)NCC(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CCCN=C(N)N)C(N)=O)C1=CNC=N1 OHOWSYIKESXDMN-WMQZXSDYSA-N 0.000 description 2
• 230000008520 organization Effects 0.000 description 2
• 201000008482 osteoarthritis Diseases 0.000 description 2
• 239000000137 peptide hydrolase inhibitor Substances 0.000 description 2
• 229910000073 phosphorus hydride Inorganic materials 0.000 description 2
• 230000035790 physiological processes and functions Effects 0.000 description 2
• IVDFJHOHABJVEH-UHFFFAOYSA-N pinacol Chemical compound CC(C)(O)C(C)(C)O IVDFJHOHABJVEH-UHFFFAOYSA-N 0.000 description 2
• 229920001155 polypropylene Polymers 0.000 description 2
• 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
• 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
• 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
• 238000002600 positron emission tomography Methods 0.000 description 2
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
• 239000002243 precursor Substances 0.000 description 2
• 239000003755 preservative agent Substances 0.000 description 2
• 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 2
• 229960003081 probenecid Drugs 0.000 description 2
• 108090000765 processed proteins & peptides Proteins 0.000 description 2
• 238000001959 radiotherapy Methods 0.000 description 2
• 239000000376 reactant Substances 0.000 description 2
• 230000009467 reduction Effects 0.000 description 2
• 230000033458 reproduction Effects 0.000 description 2
• 238000011160 research Methods 0.000 description 2
• 239000011347 resin Substances 0.000 description 2
• 229920005989 resin Polymers 0.000 description 2
• YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
• 230000007017 scission Effects 0.000 description 2
• 238000000926 separation method Methods 0.000 description 2
• 201000002859 sleep apnea Diseases 0.000 description 2
• 239000001632 sodium acetate Substances 0.000 description 2
• 229940087562 sodium acetate trihydrate Drugs 0.000 description 2
• URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 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
• QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 2
• 229910052938 sodium sulfate Inorganic materials 0.000 description 2
• 235000011152 sodium sulphate Nutrition 0.000 description 2
• 238000003797 solvolysis reaction Methods 0.000 description 2
• 239000000600 sorbitol Substances 0.000 description 2
• 235000010356 sorbitol Nutrition 0.000 description 2
• 230000009870 specific binding Effects 0.000 description 2
• 239000008117 stearic acid Substances 0.000 description 2
• 229960004274 stearic acid Drugs 0.000 description 2
• 230000000638 stimulation Effects 0.000 description 2
• 230000035882 stress Effects 0.000 description 2
• 238000006467 substitution reaction Methods 0.000 description 2
• 235000000346 sugar Nutrition 0.000 description 2
• 229910052717 sulfur Chemical group 0.000 description 2
• 239000011593 sulfur Chemical group 0.000 description 2
• 239000006228 supernatant Substances 0.000 description 2
• 239000000829 suppository Substances 0.000 description 2
• 239000000725 suspension Substances 0.000 description 2
• 208000011580 syndromic disease Diseases 0.000 description 2
• XVBALHWOBSWBAE-CZUORRHYSA-N tert-butyl (1r,6s)-7-[2-fluoro-6-(triazol-2-yl)benzoyl]-4,7-diazabicyclo[4.2.0]octane-4-carboxylate Chemical compound C([C@H]1CCN(C[C@H]11)C(=O)OC(C)(C)C)N1C(=O)C1=C(F)C=CC=C1N1N=CC=N1 XVBALHWOBSWBAE-CZUORRHYSA-N 0.000 description 2
• VGJOEEIXDPWTAZ-IUCAKERBSA-N tert-butyl (1s,6r)-4,7-diazabicyclo[4.2.0]octane-4-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CC[C@H]2CN[C@H]21 VGJOEEIXDPWTAZ-IUCAKERBSA-N 0.000 description 2
• ROVTUJRZGCDHDL-UHFFFAOYSA-N tert-butyl 2-ethylheptanoate Chemical compound CCCCCC(CC)C(=O)OC(C)(C)C ROVTUJRZGCDHDL-UHFFFAOYSA-N 0.000 description 2
• 150000003512 tertiary amines Chemical class 0.000 description 2
• 238000012360 testing method Methods 0.000 description 2
• 238000003354 tissue distribution assay Methods 0.000 description 2
• 238000004448 titration Methods 0.000 description 2
• 238000011200 topical administration Methods 0.000 description 2
• QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 2
• 231100000397 ulcer Toxicity 0.000 description 2
• NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 2
• 210000003462 vein Anatomy 0.000 description 2
• 239000003039 volatile agent Substances 0.000 description 2
• DYWSVUBJGFTOQC-UHFFFAOYSA-N xi-2-Ethylheptanoic acid Chemical compound CCCCCC(CC)C(O)=O DYWSVUBJGFTOQC-UHFFFAOYSA-N 0.000 description 2
• OGNSCSPNOLGXSM-UHFFFAOYSA-N (+/-)-DABA Natural products NCCC(N)C(O)=O OGNSCSPNOLGXSM-UHFFFAOYSA-N 0.000 description 1
• SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 description 1
• RQEUFEKYXDPUSK-SSDOTTSWSA-N (1R)-1-phenylethanamine Chemical compound C[C@@H](N)C1=CC=CC=C1 RQEUFEKYXDPUSK-SSDOTTSWSA-N 0.000 description 1
• RQEUFEKYXDPUSK-ZETCQYMHSA-N (1S)-1-phenylethanamine Chemical compound C[C@H](N)C1=CC=CC=C1 RQEUFEKYXDPUSK-ZETCQYMHSA-N 0.000 description 1
• VADHNGDGWZCCKD-GHMZBOCLSA-N (1r,6s)-4-(4,6-dimethylpyrimidin-2-yl)-4,7-diazabicyclo[4.2.0]octane Chemical compound CC1=CC(C)=NC(N2C[C@H]3NC[C@H]3CC2)=N1 VADHNGDGWZCCKD-GHMZBOCLSA-N 0.000 description 1
• QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
• 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 description 1
• 125000006582 (C5-C6) heterocycloalkyl group Chemical group 0.000 description 1
• 125000006705 (C5-C7) cycloalkyl group Chemical group 0.000 description 1
• WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
• KWTSXDURSIMDCE-QMMMGPOBSA-N (S)-amphetamine Chemical compound C[C@H](N)CC1=CC=CC=C1 KWTSXDURSIMDCE-QMMMGPOBSA-N 0.000 description 1
• UWYVPFMHMJIBHE-OWOJBTEDSA-N (e)-2-hydroxybut-2-enedioic acid Chemical compound OC(=O)\C=C(\O)C(O)=O UWYVPFMHMJIBHE-OWOJBTEDSA-N 0.000 description 1
• UKAUYVFTDYCKQA-UHFFFAOYSA-N -2-Amino-4-hydroxybutanoic acid Natural products OC(=O)C(N)CCO UKAUYVFTDYCKQA-UHFFFAOYSA-N 0.000 description 1
• WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
• PFKFTWBEEFSNDU-UHFFFAOYSA-N 1,1'-Carbonyldiimidazole Substances C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 1
• 150000000128 1,4-diazepanes Chemical class 0.000 description 1
• LDMOEFOXLIZJOW-UHFFFAOYSA-N 1-dodecanesulfonic acid Chemical compound CCCCCCCCCCCCS(O)(=O)=O LDMOEFOXLIZJOW-UHFFFAOYSA-N 0.000 description 1
• FPIRBHDGWMWJEP-UHFFFAOYSA-N 1-hydroxy-7-azabenzotriazole Chemical compound C1=CN=C2N(O)N=NC2=C1 FPIRBHDGWMWJEP-UHFFFAOYSA-N 0.000 description 1
• IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
• RTBFRGCFXZNCOE-UHFFFAOYSA-N 1-methylsulfonylpiperidin-4-one Chemical compound CS(=O)(=O)N1CCC(=O)CC1 RTBFRGCFXZNCOE-UHFFFAOYSA-N 0.000 description 1
• JRHPOFJADXHYBR-UHFFFAOYSA-N 1-n,2-n-dimethylcyclohexane-1,2-diamine Chemical compound CNC1CCCCC1NC JRHPOFJADXHYBR-UHFFFAOYSA-N 0.000 description 1
• LNETULKMXZVUST-UHFFFAOYSA-N 1-naphthoic acid Chemical compound C1=CC=C2C(C(=O)O)=CC=CC2=C1 LNETULKMXZVUST-UHFFFAOYSA-N 0.000 description 1
• AGHYPEFIMHYYTJ-UHFFFAOYSA-N 1-o-[(z)-1-aminoethylideneamino] 2-o-methyl 3-fluorobenzene-1,2-dicarboxylate Chemical compound COC(=O)C1=C(F)C=CC=C1C(=O)O\N=C(\C)N AGHYPEFIMHYYTJ-UHFFFAOYSA-N 0.000 description 1
• IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
• NEUWPDLMDVINSN-UHFFFAOYSA-N 1h-pyrazol-5-ylboronic acid Chemical compound OB(O)C=1C=CNN=1 NEUWPDLMDVINSN-UHFFFAOYSA-N 0.000 description 1
• DRGAZIDRYFYHIJ-UHFFFAOYSA-N 2,2':6',2''-terpyridine Chemical group N1=CC=CC=C1C1=CC=CC(C=2N=CC=CC=2)=N1 DRGAZIDRYFYHIJ-UHFFFAOYSA-N 0.000 description 1
• XFEKIQFBJSDMQB-UHFFFAOYSA-N 2,2,2-trichloroethylbenzene Chemical compound ClC(Cl)(Cl)CC1=CC=CC=C1 XFEKIQFBJSDMQB-UHFFFAOYSA-N 0.000 description 1
• QKWWDTYDYOFRJL-UHFFFAOYSA-N 2,2-dimethoxyethanamine Chemical compound COC(CN)OC QKWWDTYDYOFRJL-UHFFFAOYSA-N 0.000 description 1
• GKPHNZYMLJPYJJ-UHFFFAOYSA-N 2,3-difluorobenzonitrile Chemical compound FC1=CC=CC(C#N)=C1F GKPHNZYMLJPYJJ-UHFFFAOYSA-N 0.000 description 1
• HCSBTDBGTNZOAB-UHFFFAOYSA-N 2,3-dinitrobenzoic acid Chemical compound OC(=O)C1=CC=CC([N+]([O-])=O)=C1[N+]([O-])=O HCSBTDBGTNZOAB-UHFFFAOYSA-N 0.000 description 1
• GIKMWFAAEIACRF-UHFFFAOYSA-N 2,4,5-trichloropyrimidine Chemical compound ClC1=NC=C(Cl)C(Cl)=N1 GIKMWFAAEIACRF-UHFFFAOYSA-N 0.000 description 1
• DQXNTSXKIUZJJS-UHFFFAOYSA-N 2,4-dichloro-5-methylpyrimidine Chemical compound CC1=CN=C(Cl)N=C1Cl DQXNTSXKIUZJJS-UHFFFAOYSA-N 0.000 description 1
• FREOGXBZEAMJQN-UHFFFAOYSA-N 2,4-dimethylbenzenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C(C)=C1 FREOGXBZEAMJQN-UHFFFAOYSA-N 0.000 description 1
• RUQQKYAEQGBNCT-UHFFFAOYSA-N 2,5-dichloro-4,6-dimethylpyrimidine Chemical compound CC1=NC(Cl)=NC(C)=C1Cl RUQQKYAEQGBNCT-UHFFFAOYSA-N 0.000 description 1
• NQQBBTQLATUFBF-UHFFFAOYSA-N 2,5-dichloro-4-methylpyrimidine Chemical compound CC1=NC(Cl)=NC=C1Cl NQQBBTQLATUFBF-UHFFFAOYSA-N 0.000 description 1
• LVVQTPZQNHQLOM-UHFFFAOYSA-N 2,6-dichloro-1,3-benzoxazole Chemical compound C1=C(Cl)C=C2OC(Cl)=NC2=C1 LVVQTPZQNHQLOM-UHFFFAOYSA-N 0.000 description 1
• NDXRPDJVAUCBOH-UHFFFAOYSA-N 2,6-dimethoxybenzoyl chloride Chemical compound COC1=CC=CC(OC)=C1C(Cl)=O NDXRPDJVAUCBOH-UHFFFAOYSA-N 0.000 description 1
• XEMUQIZRJUCNOR-UHFFFAOYSA-N 2-(1,3-dihydrotriazol-2-yl)-3-fluorobenzoic acid Chemical compound OC(=O)C1=CC=CC(F)=C1N1NC=CN1 XEMUQIZRJUCNOR-UHFFFAOYSA-N 0.000 description 1
• JOLXIPMUKIGMEX-UHFFFAOYSA-N 2-(2-chlorophenyl)pyrimidine Chemical compound ClC1=CC=CC=C1C1=NC=CC=N1 JOLXIPMUKIGMEX-UHFFFAOYSA-N 0.000 description 1
• XFOODIIFLVKQBJ-UHFFFAOYSA-N 2-(3,6-diazabicyclo[3.2.0]heptan-3-yl)quinoxaline Chemical compound C1=CC=CC2=NC(N3CC4NCC4C3)=CN=C21 XFOODIIFLVKQBJ-UHFFFAOYSA-N 0.000 description 1
• PMMZKTPZYZVFAA-UHFFFAOYSA-N 2-(sulfonylamino)acetic acid Chemical class OC(=O)CN=S(=O)=O PMMZKTPZYZVFAA-UHFFFAOYSA-N 0.000 description 1
• BXMZXSVBWGMYMV-UHFFFAOYSA-N 2-(triazol-1-yl)benzonitrile Chemical compound N#CC1=CC=CC=C1N1N=NC=C1 BXMZXSVBWGMYMV-UHFFFAOYSA-N 0.000 description 1
• UTENUPFWBIFKPW-UHFFFAOYSA-N 2-(triazol-2-yl)benzoic acid Chemical compound OC(=O)C1=CC=CC=C1N1N=CC=N1 UTENUPFWBIFKPW-UHFFFAOYSA-N 0.000 description 1
• 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 1
• ZNOVTXRBGFNYRX-UHFFFAOYSA-N 2-[[4-[(2-amino-5-methyl-4-oxo-1,6,7,8-tetrahydropteridin-6-yl)methylamino]benzoyl]amino]pentanedioic acid Chemical compound C1NC=2NC(N)=NC(=O)C=2N(C)C1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 ZNOVTXRBGFNYRX-UHFFFAOYSA-N 0.000 description 1
• GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 description 1
• HWFCHCRFQWEFMU-UHFFFAOYSA-N 2-bromo-4,5-dimethoxybenzoic acid Chemical compound COC1=CC(Br)=C(C(O)=O)C=C1OC HWFCHCRFQWEFMU-UHFFFAOYSA-N 0.000 description 1
• SEJVMKLJNIKFAF-UHFFFAOYSA-N 2-bromo-4-methoxybenzoic acid Chemical compound COC1=CC=C(C(O)=O)C(Br)=C1 SEJVMKLJNIKFAF-UHFFFAOYSA-N 0.000 description 1
• QPKKBDSNZFSSOD-UHFFFAOYSA-N 2-bromo-5-iodobenzoic acid Chemical compound OC(=O)C1=CC(I)=CC=C1Br QPKKBDSNZFSSOD-UHFFFAOYSA-N 0.000 description 1
• NZCKTGCKFJDGFD-UHFFFAOYSA-N 2-bromobenzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1Br NZCKTGCKFJDGFD-UHFFFAOYSA-N 0.000 description 1
• COVGXNSRDOYAJD-UHFFFAOYSA-N 2-chloro-4,6-dimethylpyridine Chemical compound CC1=CC(C)=NC(Cl)=C1 COVGXNSRDOYAJD-UHFFFAOYSA-N 0.000 description 1
• NBDRJKOKVCELFL-UHFFFAOYSA-N 2-chloro-4-methyl-6,7-dihydro-5h-cyclopenta[d]pyrimidine Chemical compound CC1=NC(Cl)=NC2=C1CCC2 NBDRJKOKVCELFL-UHFFFAOYSA-N 0.000 description 1
• MZVSTDHRRYQFGI-UHFFFAOYSA-N 2-chloro-4-methylpyridine Chemical compound CC1=CC=NC(Cl)=C1 MZVSTDHRRYQFGI-UHFFFAOYSA-N 0.000 description 1
• HEVMLRSJVWFVGE-UHFFFAOYSA-N 2-chloro-5-ethyl-4,6-dimethylpyrimidine Chemical compound CCC1=C(C)N=C(Cl)N=C1C HEVMLRSJVWFVGE-UHFFFAOYSA-N 0.000 description 1
• DWRLBBUURVUIEY-UHFFFAOYSA-N 2-chloro-5-fluoro-4,6-dimethylpyrimidine Chemical compound CC1=NC(Cl)=NC(C)=C1F DWRLBBUURVUIEY-UHFFFAOYSA-N 0.000 description 1
• FBEIDYLEFVIOEY-UHFFFAOYSA-N 2-chloro-6-methylpyrimidin-4-amine Chemical compound CC1=CC(N)=NC(Cl)=N1 FBEIDYLEFVIOEY-UHFFFAOYSA-N 0.000 description 1
• LPBDZVNGCNTELM-UHFFFAOYSA-N 2-chloropyrimidin-4-amine Chemical compound NC1=CC=NC(Cl)=N1 LPBDZVNGCNTELM-UHFFFAOYSA-N 0.000 description 1
• WUDDSDIHJHPJRP-UHFFFAOYSA-N 2-ethyloctanedioic acid Chemical compound CCC(C(O)=O)CCCCCC(O)=O WUDDSDIHJHPJRP-UHFFFAOYSA-N 0.000 description 1
• KBFVSJVSSMGQJC-UHFFFAOYSA-N 2-fluoro-3-methylbenzonitrile Chemical compound CC1=CC=CC(C#N)=C1F KBFVSJVSSMGQJC-UHFFFAOYSA-N 0.000 description 1
• FUMYBRCKPBFKKB-UHFFFAOYSA-N 2-fluoro-6-methoxycarbonylbenzoic acid Chemical compound COC(=O)C1=CC=CC(F)=C1C(O)=O FUMYBRCKPBFKKB-UHFFFAOYSA-N 0.000 description 1
• NEWFEFODKLAVHC-UHFFFAOYSA-N 2-fluoro-6-pyrimidin-2-ylbenzoic acid Chemical compound OC(=O)C1=C(F)C=CC=C1C1=NC=CC=N1 NEWFEFODKLAVHC-UHFFFAOYSA-N 0.000 description 1
• TZGPACAKMCUCKX-UHFFFAOYSA-N 2-hydroxyacetamide Chemical compound NC(=O)CO TZGPACAKMCUCKX-UHFFFAOYSA-N 0.000 description 1
• PZUXUOZSSYKAMX-UHFFFAOYSA-N 2-iodo-3-methylbenzoic acid Chemical compound CC1=CC=CC(C(O)=O)=C1I PZUXUOZSSYKAMX-UHFFFAOYSA-N 0.000 description 1
• DASWULXFGZZRIC-UHFFFAOYSA-N 2-iodo-5-methoxybenzoic acid Chemical compound COC1=CC=C(I)C(C(O)=O)=C1 DASWULXFGZZRIC-UHFFFAOYSA-N 0.000 description 1
• INGWGCDYAJKXKP-UHFFFAOYSA-N 2-iodo-5-methylbenzoic acid Chemical compound CC1=CC=C(I)C(C(O)=O)=C1 INGWGCDYAJKXKP-UHFFFAOYSA-N 0.000 description 1
• LLVYMVJLXNNRND-UHFFFAOYSA-N 2-iodo-6-methylbenzoic acid Chemical compound CC1=CC=CC(I)=C1C(O)=O LLVYMVJLXNNRND-UHFFFAOYSA-N 0.000 description 1
• CJNZAXGUTKBIHP-UHFFFAOYSA-N 2-iodobenzoic acid Chemical compound OC(=O)C1=CC=CC=C1I CJNZAXGUTKBIHP-UHFFFAOYSA-N 0.000 description 1
• PPJSLPYLJSWLFA-UHFFFAOYSA-N 2-methyl-6-(triazol-2-yl)benzoic acid Chemical compound CC1=CC=CC(N2N=CC=N2)=C1C(O)=O PPJSLPYLJSWLFA-UHFFFAOYSA-N 0.000 description 1
• WLJVXDMOQOGPHL-PPJXEINESA-N 2-phenylacetic acid Chemical compound O[14C](=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-PPJXEINESA-N 0.000 description 1
• BCLGTIBYZQQFJW-UHFFFAOYSA-N 2-pyrimidin-2-ylbenzoic acid Chemical compound OC(=O)C1=CC=CC=C1C1=NC=CC=N1 BCLGTIBYZQQFJW-UHFFFAOYSA-N 0.000 description 1
• JVOVWZAGQKKACR-UHFFFAOYSA-N 2-thiophen-2-ylbenzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1C1=CC=CS1 JVOVWZAGQKKACR-UHFFFAOYSA-N 0.000 description 1
• LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
• KDQDSYOTILMWRZ-UHFFFAOYSA-N 3-(4,6-dimethylpyrimidin-2-yl)-3,6-diazabicyclo[3.2.0]heptane Chemical compound CC1=CC(C)=NC(N2CC3NCC3C2)=N1 KDQDSYOTILMWRZ-UHFFFAOYSA-N 0.000 description 1
• WSAWTEYIENWKIX-UHFFFAOYSA-N 3-(4-methylpyrimidin-2-yl)-3,6-diazabicyclo[3.2.0]heptane Chemical compound CC1=CC=NC(N2CC3NCC3C2)=N1 WSAWTEYIENWKIX-UHFFFAOYSA-N 0.000 description 1
• FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 1
• HJBTXZYRCCWERT-UHFFFAOYSA-N 3-(triazol-2-yl)pyridine-2-carboxylic acid Chemical compound OC(=O)C1=NC=CC=C1N1N=CC=N1 HJBTXZYRCCWERT-UHFFFAOYSA-N 0.000 description 1
• BRMWTNUJHUMWMS-UHFFFAOYSA-N 3-Methylhistidine Natural products CN1C=NC(CC(N)C(O)=O)=C1 BRMWTNUJHUMWMS-UHFFFAOYSA-N 0.000 description 1
• BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
• KBDIRPOTVAODSA-UHFFFAOYSA-N 3-bromopyridine-2-carboxylic acid Chemical compound OC(=O)C1=NC=CC=C1Br KBDIRPOTVAODSA-UHFFFAOYSA-N 0.000 description 1
• NNBALVIZMGWZHS-UHFFFAOYSA-N 3-chloro-2,5-dimethylpyrazine Chemical compound CC1=CN=C(C)C(Cl)=N1 NNBALVIZMGWZHS-UHFFFAOYSA-N 0.000 description 1
• GTIDPPSUQCIPHI-UHFFFAOYSA-N 3-fluoro-2-(1h-pyrazol-5-yl)benzoic acid Chemical compound OC(=O)C1=CC=CC(F)=C1C1=CC=NN1 GTIDPPSUQCIPHI-UHFFFAOYSA-N 0.000 description 1
• INEDXGLRNUFWEM-UHFFFAOYSA-N 3-fluoro-2-(triazol-1-yl)benzoic acid Chemical compound OC(=O)C1=CC=CC(F)=C1N1N=NC=C1 INEDXGLRNUFWEM-UHFFFAOYSA-N 0.000 description 1
• KDSIMLRAHNEPRX-UHFFFAOYSA-N 3-fluoro-2-methoxycarbonylbenzoic acid Chemical compound COC(=O)C1=C(F)C=CC=C1C(O)=O KDSIMLRAHNEPRX-UHFFFAOYSA-N 0.000 description 1
• WHPUSKHJEBOLKR-UHFFFAOYSA-N 3-fluoro-2-pyrazol-1-ylbenzoic acid Chemical compound OC(=O)C1=CC=CC(F)=C1N1N=CC=C1 WHPUSKHJEBOLKR-UHFFFAOYSA-N 0.000 description 1
• PCQPABMNCWPYDY-UHFFFAOYSA-N 3-methoxy-2-(triazol-1-yl)benzoic acid Chemical compound COC1=CC=CC(C(O)=O)=C1N1N=NC=C1 PCQPABMNCWPYDY-UHFFFAOYSA-N 0.000 description 1
• WRIGYACYMAKMLR-UHFFFAOYSA-N 3-methyl-2-(triazol-1-yl)benzoic acid Chemical compound CC1=CC=CC(C(O)=O)=C1N1N=NC=C1 WRIGYACYMAKMLR-UHFFFAOYSA-N 0.000 description 1
• BCXIJWNXWNOYIQ-UHFFFAOYSA-N 3-methyl-2-(triazol-1-yl)benzonitrile Chemical compound CC1=CC=CC(C#N)=C1N1N=NC=C1 BCXIJWNXWNOYIQ-UHFFFAOYSA-N 0.000 description 1
• IBQJAAIBLGSGSO-UHFFFAOYSA-N 3-methyl-2-(triazol-2-yl)benzoic acid Chemical compound CC1=CC=CC(C(O)=O)=C1N1N=CC=N1 IBQJAAIBLGSGSO-UHFFFAOYSA-N 0.000 description 1
• AKQPXKGNPMHWBZ-UHFFFAOYSA-N 3-methylcyclohexane-1,2-diamine Chemical compound CC1CCCC(N)C1N AKQPXKGNPMHWBZ-UHFFFAOYSA-N 0.000 description 1
• MRWWWZLJWNIEEJ-UHFFFAOYSA-N 4,4,5,5-tetramethyl-2-propan-2-yloxy-1,3,2-dioxaborolane Chemical compound CC(C)OB1OC(C)(C)C(C)(C)O1 MRWWWZLJWNIEEJ-UHFFFAOYSA-N 0.000 description 1
• LSBIUXKNVUBKRI-UHFFFAOYSA-N 4,6-dimethylpyrimidine Chemical compound CC1=CC(C)=NC=N1 LSBIUXKNVUBKRI-UHFFFAOYSA-N 0.000 description 1
• ZZTSZEJUDISCNW-UHFFFAOYSA-N 4,7-diazabicyclo[4.2.0]octan-7-yl-(2,6-dimethoxyphenyl)methanone Chemical compound COC1=CC=CC(OC)=C1C(=O)N1C2CNCCC2C1 ZZTSZEJUDISCNW-UHFFFAOYSA-N 0.000 description 1
• ZZHWFUDVZGOQSF-UHFFFAOYSA-N 4,9-diazabicyclo[4.2.1]nonane Chemical compound C1NCCC2CCC1N2 ZZHWFUDVZGOQSF-UHFFFAOYSA-N 0.000 description 1
• FOFVOUCGNPPVAM-UHFFFAOYSA-N 4-(2-fluorophenyl)-2-methyl-1,3-thiazole-5-carboxylic acid Chemical compound S1C(C)=NC(C=2C(=CC=CC=2)F)=C1C(O)=O FOFVOUCGNPPVAM-UHFFFAOYSA-N 0.000 description 1
• XNJZNRSBNFXQGC-UHFFFAOYSA-N 4-(triazol-1-yl)pyridine-3-carboxylic acid Chemical compound OC(=O)C1=CN=CC=C1N1N=NC=C1 XNJZNRSBNFXQGC-UHFFFAOYSA-N 0.000 description 1
• DANLZOIRUUHIIX-UHFFFAOYSA-N 4-[1-[2-chloro-6-(trifluoromethyl)benzoyl]indazol-3-yl]benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1C(C1=CC=CC=C11)=NN1C(=O)C1=C(Cl)C=CC=C1C(F)(F)F DANLZOIRUUHIIX-UHFFFAOYSA-N 0.000 description 1
• YHQPBHIIVRDWDL-UHFFFAOYSA-N 4-chloro-2-(triazol-2-yl)benzoic acid Chemical compound OC(=O)C1=CC=C(Cl)C=C1N1N=CC=N1 YHQPBHIIVRDWDL-UHFFFAOYSA-N 0.000 description 1
• LRRDANNSUCQNDU-UHFFFAOYSA-N 4-chloro-2-iodobenzoic acid Chemical compound OC(=O)C1=CC=C(Cl)C=C1I LRRDANNSUCQNDU-UHFFFAOYSA-N 0.000 description 1
• HQAIROMRVBVWSK-UHFFFAOYSA-N 4-chloro-2-methylquinoline Chemical compound C1=CC=CC2=NC(C)=CC(Cl)=C21 HQAIROMRVBVWSK-UHFFFAOYSA-N 0.000 description 1
• IMRGVWZLCZERSQ-UHFFFAOYSA-N 4-chloropyridine-3-carboxylic acid Chemical compound OC(=O)C1=CN=CC=C1Cl IMRGVWZLCZERSQ-UHFFFAOYSA-N 0.000 description 1
• KNDOFJFSHZCKGT-UHFFFAOYSA-N 4-chloroquinoline Chemical compound C1=CC=C2C(Cl)=CC=NC2=C1 KNDOFJFSHZCKGT-UHFFFAOYSA-N 0.000 description 1
• FLTYWCWXBMTXJZ-UHFFFAOYSA-N 4-fluoro-2-(triazol-2-yl)benzoic acid Chemical compound OC(=O)C1=CC=C(F)C=C1N1N=CC=N1 FLTYWCWXBMTXJZ-UHFFFAOYSA-N 0.000 description 1
• WWJAZKZLSDRAIV-UHFFFAOYSA-N 4-fluoro-2-benzofuran-1,3-dione Chemical compound FC1=CC=CC2=C1C(=O)OC2=O WWJAZKZLSDRAIV-UHFFFAOYSA-N 0.000 description 1
• DUKFTVLJAXWGPI-UHFFFAOYSA-N 4-fluoro-2-iodobenzoic acid Chemical compound OC(=O)C1=CC=C(F)C=C1I DUKFTVLJAXWGPI-UHFFFAOYSA-N 0.000 description 1
• RGCHISPSDYWBMX-UHFFFAOYSA-N 4-fluoro-2-iodobenzonitrile Chemical compound FC1=CC=C(C#N)C(I)=C1 RGCHISPSDYWBMX-UHFFFAOYSA-N 0.000 description 1
• MTEVFUQSWSTKTE-UHFFFAOYSA-N 4-fluoro-2-pyrimidin-2-ylbenzoic acid Chemical compound OC(=O)C1=CC=C(F)C=C1C1=NC=CC=N1 MTEVFUQSWSTKTE-UHFFFAOYSA-N 0.000 description 1
• SJZRECIVHVDYJC-UHFFFAOYSA-N 4-hydroxybutyric acid Chemical compound OCCCC(O)=O SJZRECIVHVDYJC-UHFFFAOYSA-N 0.000 description 1
• OGGPTEUIVTXSEX-UHFFFAOYSA-N 4-methoxy-2-(triazol-1-yl)benzoic acid Chemical compound COC1=CC=C(C(O)=O)C(N2N=NC=C2)=C1 OGGPTEUIVTXSEX-UHFFFAOYSA-N 0.000 description 1
• DVEXRWNAGAABJM-UHFFFAOYSA-N 4-methoxy-2-(triazol-2-yl)benzoic acid Chemical compound COC1=CC=C(C(O)=O)C(N2N=CC=N2)=C1 DVEXRWNAGAABJM-UHFFFAOYSA-N 0.000 description 1
• KSLVCSSYROYEDL-UHFFFAOYSA-N 4-methoxy-2-pyrimidin-2-ylbenzoic acid Chemical compound COC1=CC=C(C(O)=O)C(C=2N=CC=CN=2)=C1 KSLVCSSYROYEDL-UHFFFAOYSA-N 0.000 description 1
• ZEYHEAKUIGZSGI-UHFFFAOYSA-N 4-methoxybenzoic acid Chemical compound COC1=CC=C(C(O)=O)C=C1 ZEYHEAKUIGZSGI-UHFFFAOYSA-N 0.000 description 1
• SSDOPBMPVFZPFN-UHFFFAOYSA-N 5-chloro-2-(triazol-2-yl)benzoic acid Chemical compound OC(=O)C1=CC(Cl)=CC=C1N1N=CC=N1 SSDOPBMPVFZPFN-UHFFFAOYSA-N 0.000 description 1
• NRPQWTVTBCRPEL-UHFFFAOYSA-N 5-chloro-2-iodobenzoic acid Chemical compound OC(=O)C1=CC(Cl)=CC=C1I NRPQWTVTBCRPEL-UHFFFAOYSA-N 0.000 description 1
• HQNDPBJMXXODGK-UHFFFAOYSA-N 5-chloro-4,6-dimethyl-1h-pyrimidin-2-one Chemical compound CC1=NC(O)=NC(C)=C1Cl HQNDPBJMXXODGK-UHFFFAOYSA-N 0.000 description 1
• KAAMZHMDJBQVPQ-UHFFFAOYSA-N 5-ethyl-4,6-dimethyl-1h-pyrimidin-2-one Chemical compound CCC1=C(C)N=C(O)N=C1C KAAMZHMDJBQVPQ-UHFFFAOYSA-N 0.000 description 1
• FHIDNBAQOFJWCA-UAKXSSHOSA-N 5-fluorouridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(F)=C1 FHIDNBAQOFJWCA-UAKXSSHOSA-N 0.000 description 1
• INSCQDXCTFSRAN-UHFFFAOYSA-N 5-iodo-2-(triazol-2-yl)benzoic acid Chemical compound OC(=O)C1=CC(I)=CC=C1N1N=CC=N1 INSCQDXCTFSRAN-UHFFFAOYSA-N 0.000 description 1
• 125000006163 5-membered heteroaryl group Chemical group 0.000 description 1
• OFURCFFCWJMVKQ-UHFFFAOYSA-N 5-methoxy-2-(triazol-2-yl)benzoic acid Chemical compound OC(=O)C1=CC(OC)=CC=C1N1N=CC=N1 OFURCFFCWJMVKQ-UHFFFAOYSA-N 0.000 description 1
• SSAYHQQUDKQNAC-UHFFFAOYSA-N 6-chloro-2-methylpyrimidin-4-amine Chemical compound CC1=NC(N)=CC(Cl)=N1 SSAYHQQUDKQNAC-UHFFFAOYSA-N 0.000 description 1
• WGPJAQWJLFHECC-UHFFFAOYSA-N 7-(2,5-dimethylphenyl)sulfonyl-4-(2-phenylpyrimidin-4-yl)-4,7-diazabicyclo[4.2.0]octane Chemical compound CC1=CC=C(C)C(S(=O)(=O)N2C3CN(CCC3C2)C=2N=C(N=CC=2)C=2C=CC=CC=2)=C1 WGPJAQWJLFHECC-UHFFFAOYSA-N 0.000 description 1
• GBAMNSNKCDOBOO-HZPDHXFCSA-N 7-o-benzyl 4-o-tert-butyl (1r,6s)-4,7-diazabicyclo[4.2.0]octane-4,7-dicarboxylate Chemical compound C([C@H]1CCN(C[C@H]11)C(=O)OC(C)(C)C)N1C(=O)OCC1=CC=CC=C1 GBAMNSNKCDOBOO-HZPDHXFCSA-N 0.000 description 1
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-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
• QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
• NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 description 1
• 208000007848 Alcoholism Diseases 0.000 description 1
• 235000019489 Almond oil Nutrition 0.000 description 1
• DKMACHNQISHMDN-RPLLCQBOSA-N Almorexant Chemical compound C([C@H]1C2=CC(OC)=C(OC)C=C2CCN1[C@@H](C(=O)NC)C=1C=CC=CC=1)CC1=CC=C(C(F)(F)F)C=C1 DKMACHNQISHMDN-RPLLCQBOSA-N 0.000 description 1
• GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
• 201000000736 Amenorrhea Diseases 0.000 description 1
• 206010001928 Amenorrhoea Diseases 0.000 description 1
• 208000037259 Amyloid Plaque Diseases 0.000 description 1
• 239000004475 Arginine Substances 0.000 description 1
• BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
• 206010003591 Ataxia Diseases 0.000 description 1
• 229930003347 Atropine Natural products 0.000 description 1
• 208000023275 Autoimmune disease Diseases 0.000 description 1
• BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
• CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
• 208000032841 Bulimia Diseases 0.000 description 1
• 206010006550 Bulimia nervosa Diseases 0.000 description 1
• FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 1
• IZRVVXSZIBLPHA-UHFFFAOYSA-N C(C(=O)O)(=O)O.C(C#C)(=O)O Chemical compound C(C(=O)O)(=O)O.C(C#C)(=O)O IZRVVXSZIBLPHA-UHFFFAOYSA-N 0.000 description 1
• OWCGQNATGGRRCR-UHFFFAOYSA-N C(C)(C)(C)OC(=O)C1NN2CCC2CC1 Chemical compound C(C)(C)(C)OC(=O)C1NN2CCC2CC1 OWCGQNATGGRRCR-UHFFFAOYSA-N 0.000 description 1
• KGASQEOXAOJOJT-UHFFFAOYSA-N C(C)(C)(C)OC(=O)N1CC2(NCC2CC1)C(=O)C1=C(N=C(S1)C)C1=C(C=CC=C1)F Chemical compound C(C)(C)(C)OC(=O)N1CC2(NCC2CC1)C(=O)C1=C(N=C(S1)C)C1=C(C=CC=C1)F KGASQEOXAOJOJT-UHFFFAOYSA-N 0.000 description 1
• JVZHXPHAKLZZNF-UHFFFAOYSA-N C(C)(C)(C)OC(=O)N1CC2NCC2CC1.C(C)(C)(C)OC(=O)N1CC2N(CC2CC1)C(=O)C=1C(=CC=CC1)C1=CC=CC=C1 Chemical compound C(C)(C)(C)OC(=O)N1CC2NCC2CC1.C(C)(C)(C)OC(=O)N1CC2N(CC2CC1)C(=O)C=1C(=CC=CC1)C1=CC=CC=C1 JVZHXPHAKLZZNF-UHFFFAOYSA-N 0.000 description 1
• YLXJFJYNNOWJQZ-SATBOSKTSA-N C(C)(C)(C)OC(=O)N1CC2NCC2CC1.CC1=NOC(=N1)C1=C(C(=O)N2C[C@H]3CCN(C[C@@H]23)C(=O)OC(C)(C)C)C=CC=C1 Chemical compound C(C)(C)(C)OC(=O)N1CC2NCC2CC1.CC1=NOC(=N1)C1=C(C(=O)N2C[C@H]3CCN(C[C@@H]23)C(=O)OC(C)(C)C)C=CC=C1 YLXJFJYNNOWJQZ-SATBOSKTSA-N 0.000 description 1
• CHFMIBZXUASTRD-UHFFFAOYSA-N C(C)(C)(C)OC(=O)N1CCC(=C(C1)NCC1=CC=CC=C1)C(=O)O.C(C)OC(=O)C1C(CN(CC1)C(=O)OC(C)(C)C)NCC1=CC=CC=C1 Chemical compound C(C)(C)(C)OC(=O)N1CCC(=C(C1)NCC1=CC=CC=C1)C(=O)O.C(C)OC(=O)C1C(CN(CC1)C(=O)OC(C)(C)C)NCC1=CC=CC=C1 CHFMIBZXUASTRD-UHFFFAOYSA-N 0.000 description 1
• GZNMRSDNKPFTOG-UHFFFAOYSA-N C(C)OC(=O)C1C(CN(CC1)CC1=CC=CC=C1)=O.C(C)OC(=O)C1C(CN(CC1)C(=O)OC(C)(C)C)=O Chemical compound C(C)OC(=O)C1C(CN(CC1)CC1=CC=CC=C1)=O.C(C)OC(=O)C1C(CN(CC1)C(=O)OC(C)(C)C)=O GZNMRSDNKPFTOG-UHFFFAOYSA-N 0.000 description 1
• SKBHZIXKUJGGTN-UHFFFAOYSA-N C(C1=CC=CC=C1)N1CC2CCN(CC12)C(=O)O.C(C)(C)(C)OC(=O)N1CC2NCC2CC1 Chemical compound C(C1=CC=CC=C1)N1CC2CCN(CC12)C(=O)O.C(C)(C)(C)OC(=O)N1CC2NCC2CC1 SKBHZIXKUJGGTN-UHFFFAOYSA-N 0.000 description 1
• VWKFFNKOAZSYRP-UHFFFAOYSA-N C=1(C(=CC=CC1)C(=O)N1CC2CCN(CC12)C(=O)O)C1=CC=CC=C1 Chemical compound C=1(C(=CC=CC1)C(=O)N1CC2CCN(CC12)C(=O)O)C1=CC=CC=C1 VWKFFNKOAZSYRP-UHFFFAOYSA-N 0.000 description 1
• HRMKROQUATWXQW-UVTDQMKNSA-N CC(/N=C(/c1cccc(F)c1C(O)=O)\ON)=C Chemical compound CC(/N=C(/c1cccc(F)c1C(O)=O)\ON)=C HRMKROQUATWXQW-UVTDQMKNSA-N 0.000 description 1
• NCCFTFFKRMSQHC-SGZOKEPCSA-N CC(C1)([C@@H](C2)CCN1c1nc(C)cc(C)n1)N2C(c(c(-c1nc(C)n[o]1)ccc1)c1F)O Chemical compound CC(C1)([C@@H](C2)CCN1c1nc(C)cc(C)n1)N2C(c(c(-c1nc(C)n[o]1)ccc1)c1F)O NCCFTFFKRMSQHC-SGZOKEPCSA-N 0.000 description 1
• CMSMGYXRPYPLMB-UHFFFAOYSA-N CC1=CC(=NC=N1)C.ClC1=NC=C(C(=N1)Cl)Cl Chemical compound CC1=CC(=NC=N1)C.ClC1=NC=C(C(=N1)Cl)Cl CMSMGYXRPYPLMB-UHFFFAOYSA-N 0.000 description 1
• TTXWGILQQGNJEZ-FWLQFDHPSA-N CC1=NC(=NC(=C1)C)N1C[C@H]2N(C[C@H]2CC1)C(=O)OCC1=CC=CC=C1.[C@H]12CN(CC[C@@H]2CN1)C(=O)OC(C)(C)C Chemical compound CC1=NC(=NC(=C1)C)N1C[C@H]2N(C[C@H]2CC1)C(=O)OCC1=CC=CC=C1.[C@H]12CN(CC[C@@H]2CN1)C(=O)OC(C)(C)C TTXWGILQQGNJEZ-FWLQFDHPSA-N 0.000 description 1
• JGLMVXWAHNTPRF-CMDGGOBGSA-N CCN1N=C(C)C=C1C(=O)NC1=NC2=CC(=CC(OC)=C2N1C\C=C\CN1C(NC(=O)C2=CC(C)=NN2CC)=NC2=CC(=CC(OCCCN3CCOCC3)=C12)C(N)=O)C(N)=O Chemical compound CCN1N=C(C)C=C1C(=O)NC1=NC2=CC(=CC(OC)=C2N1C\C=C\CN1C(NC(=O)C2=CC(C)=NN2CC)=NC2=CC(=CC(OCCCN3CCOCC3)=C12)C(N)=O)C(N)=O JGLMVXWAHNTPRF-CMDGGOBGSA-N 0.000 description 1
• FYTFXWWMNZYJGQ-UHFFFAOYSA-N COC(C1=C(C=CC(=C1)F)C1=NC=CC=N1)=O.FC=1C=CC(=C(C(=O)O)C1)C1=NC=CC=N1 Chemical compound COC(C1=C(C=CC(=C1)F)C1=NC=CC=N1)=O.FC=1C=CC(=C(C(=O)O)C1)C1=NC=CC=N1 FYTFXWWMNZYJGQ-UHFFFAOYSA-N 0.000 description 1
• FSXSPJMTMWMOAU-UHFFFAOYSA-N COC(C1=C(C=CC=C1C1=NC=CC=N1)F)=O.FC1=C(C(=O)O)C(=CC=C1)C1=NC=CC=N1 Chemical compound COC(C1=C(C=CC=C1C1=NC=CC=N1)F)=O.FC1=C(C(=O)O)C(=CC=C1)C1=NC=CC=N1 FSXSPJMTMWMOAU-UHFFFAOYSA-N 0.000 description 1
• IJZWNILWCHKIPM-UHFFFAOYSA-N COc1cccc(OC)c1C(N(C1)C(C2)C1CCN2c1nc(cccc2)c2nc1)=O Chemical compound COc1cccc(OC)c1C(N(C1)C(C2)C1CCN2c1nc(cccc2)c2nc1)=O IJZWNILWCHKIPM-UHFFFAOYSA-N 0.000 description 1
• AVZINIYILGDSHF-UHFFFAOYSA-N COc1nc(N(CC2C3)CC2N3C(c(c(-[n]2nccn2)ccc2)c2F)=O)ncc1 Chemical compound COc1nc(N(CC2C3)CC2N3C(c(c(-[n]2nccn2)ccc2)c2F)=O)ncc1 AVZINIYILGDSHF-UHFFFAOYSA-N 0.000 description 1
• 241000282465 Canis Species 0.000 description 1
• 241000282472 Canis lupus familiaris Species 0.000 description 1
• CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 1
• BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
• 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
• CWPQYODFULFHRR-YAWCZAFZSA-N Cc(cc1)cc(C(NCC2CCNCC2)=O)c1N/N=C\C=N Chemical compound Cc(cc1)cc(C(NCC2CCNCC2)=O)c1N/N=C\C=N CWPQYODFULFHRR-YAWCZAFZSA-N 0.000 description 1
• YPAOCMMAEOHODS-MGMFDXOMSA-N Cc1n[o]c(-c2ccccc2C(N(C2)[C@H](C3)[C@@H]2CCN3C2N=C(C)C=C(C)N2)=O)n1 Chemical compound Cc1n[o]c(-c2ccccc2C(N(C2)[C@H](C3)[C@@H]2CCN3C2N=C(C)C=C(C)N2)=O)n1 YPAOCMMAEOHODS-MGMFDXOMSA-N 0.000 description 1
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
• WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-N 0.000 description 1
• 208000028698 Cognitive impairment Diseases 0.000 description 1
• 102100032373 Coiled-coil domain-containing protein 85B Human genes 0.000 description 1
• RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
• FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
• 206010012335 Dependence Diseases 0.000 description 1
• YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 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
• 229940121891 Dopamine receptor antagonist Drugs 0.000 description 1
• 206010013654 Drug abuse Diseases 0.000 description 1
• 208000030814 Eating disease Diseases 0.000 description 1
• JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 1
• PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical class NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
• AMBZBVRHQLFXTO-UHFFFAOYSA-N FC1=C(C(C(=O)OC(C2=C(C=CC=C2C(=O)OC)F)=O)=CC=C1)C(=O)O Chemical compound FC1=C(C(C(=O)OC(C2=C(C=CC=C2C(=O)OC)F)=O)=CC=C1)C(=O)O AMBZBVRHQLFXTO-UHFFFAOYSA-N 0.000 description 1
• NFJGDNURBZQMMR-UHFFFAOYSA-N FC=1C(=C(C#N)C=CC1)C1=NC=CC=N1.FC=1C(=C(C(=O)O)C=CC1)C1=NC=CC=N1 Chemical compound FC=1C(=C(C#N)C=CC1)C1=NC=CC=N1.FC=1C(=C(C(=O)O)C=CC1)C1=NC=CC=N1 NFJGDNURBZQMMR-UHFFFAOYSA-N 0.000 description 1
• BEJMMFWGNUEVBF-UHFFFAOYSA-N FC=1C(=C(C#N)C=CC1)N1N=CC=N1.FC=1C(=C(C(=O)O)C=CC1)N1N=CC=N1 Chemical compound FC=1C(=C(C#N)C=CC1)N1N=CC=N1.FC=1C(=C(C(=O)O)C=CC1)N1N=CC=N1 BEJMMFWGNUEVBF-UHFFFAOYSA-N 0.000 description 1
• OPAOMFVLASHPIC-OALZAMAHSA-N FC=1C(=C(C(=O)O)C=CC1)N1N=CC=N1.FC=1C(=C(C(=O)N2C[C@H]3CCN(C[C@@H]23)C(=O)OC(C)(C)C)C=CC1)N1N=CC=N1 Chemical compound FC=1C(=C(C(=O)O)C=CC1)N1N=CC=N1.FC=1C(=C(C(=O)N2C[C@H]3CCN(C[C@@H]23)C(=O)OC(C)(C)C)C=CC1)N1N=CC=N1 OPAOMFVLASHPIC-OALZAMAHSA-N 0.000 description 1
• 208000019454 Feeding and Eating disease Diseases 0.000 description 1
• BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 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
• WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
• AEMRFAOFKBGASW-UHFFFAOYSA-M Glycolate Chemical compound OCC([O-])=O AEMRFAOFKBGASW-UHFFFAOYSA-M 0.000 description 1
• 239000007995 HEPES buffer Substances 0.000 description 1
• 206010019280 Heart failures Diseases 0.000 description 1
• 102000003964 Histone deacetylase Human genes 0.000 description 1
• 108090000353 Histone deacetylase Proteins 0.000 description 1
• 101000868814 Homo sapiens Coiled-coil domain-containing protein 85B Proteins 0.000 description 1
• 239000004354 Hydroxyethyl cellulose Substances 0.000 description 1
• 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 1
• AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 1
• LCWXJXMHJVIJFK-UHFFFAOYSA-N Hydroxylysine Natural products NCC(O)CC(N)CC(O)=O LCWXJXMHJVIJFK-UHFFFAOYSA-N 0.000 description 1
• PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical compound O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 description 1
• RKUNBYITZUJHSG-UHFFFAOYSA-N Hyosciamin-hydrochlorid Natural products CN1C(C2)CCC1CC2OC(=O)C(CO)C1=CC=CC=C1 RKUNBYITZUJHSG-UHFFFAOYSA-N 0.000 description 1
• 206010020751 Hypersensitivity Diseases 0.000 description 1
• GISBWRBQTJNZDF-UHFFFAOYSA-N IC1=C(C#N)C=CC(=C1)F.FC=1C(=C(C#N)C=CC1)C1=NC=CC=N1 Chemical compound IC1=C(C#N)C=CC(=C1)F.FC=1C(=C(C#N)C=CC1)C1=NC=CC=N1 GISBWRBQTJNZDF-UHFFFAOYSA-N 0.000 description 1
• SNDPXSYFESPGGJ-BYPYZUCNSA-N L-2-aminopentanoic acid Chemical compound CCC[C@H](N)C(O)=O SNDPXSYFESPGGJ-BYPYZUCNSA-N 0.000 description 1
• AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 description 1
• QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
• ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
• CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
• RHGKLRLOHDJJDR-BYPYZUCNSA-N L-citrulline Chemical compound NC(=O)NCCC[C@H]([NH3+])C([O-])=O RHGKLRLOHDJJDR-BYPYZUCNSA-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
• FFFHZYDWPBMWHY-VKHMYHEASA-N L-homocysteine Chemical compound OC(=O)[C@@H](N)CCS FFFHZYDWPBMWHY-VKHMYHEASA-N 0.000 description 1
• UKAUYVFTDYCKQA-VKHMYHEASA-N L-homoserine Chemical compound OC(=O)[C@@H](N)CCO UKAUYVFTDYCKQA-VKHMYHEASA-N 0.000 description 1
• KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
• UCUNFLYVYCGDHP-BYPYZUCNSA-N L-methionine sulfone Chemical compound CS(=O)(=O)CC[C@H](N)C(O)=O UCUNFLYVYCGDHP-BYPYZUCNSA-N 0.000 description 1
• SNDPXSYFESPGGJ-UHFFFAOYSA-N L-norVal-OH Natural products CCCC(N)C(O)=O SNDPXSYFESPGGJ-UHFFFAOYSA-N 0.000 description 1
• JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
• GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
• 239000005639 Lauric acid Substances 0.000 description 1
• 229910010082 LiAlH Inorganic materials 0.000 description 1
• WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
• 239000004472 Lysine Substances 0.000 description 1
• KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
• OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 description 1
• 229930195725 Mannitol Natural products 0.000 description 1
• 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
• 241000699670 Mus sp. Species 0.000 description 1
• JDHILDINMRGULE-LURJTMIESA-N N(pros)-methyl-L-histidine Chemical compound CN1C=NC=C1C[C@H](N)C(O)=O JDHILDINMRGULE-LURJTMIESA-N 0.000 description 1
• MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
• RHGKLRLOHDJJDR-UHFFFAOYSA-N Ndelta-carbamoyl-DL-ornithine Natural products OC(=O)C(N)CCCNC(N)=O RHGKLRLOHDJJDR-UHFFFAOYSA-N 0.000 description 1
• GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
• COHUXBIXXAHHGZ-UHFFFAOYSA-N O=C1CN(CCC1C(=O)O)C(=O)O.C(C)OC(=O)C=1CCN(CC1NCC1=CC=CC=C1)C(=O)OC(C)(C)C Chemical compound O=C1CN(CCC1C(=O)O)C(=O)O.C(C)OC(=O)C=1CCN(CC1NCC1=CC=CC=C1)C(=O)OC(C)(C)C COHUXBIXXAHHGZ-UHFFFAOYSA-N 0.000 description 1
• 239000005642 Oleic acid Substances 0.000 description 1
• ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
• AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 description 1
• UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 description 1
• OTFNJMVDNAAYBZ-UHFFFAOYSA-N P(=O)(O)(O)O.C(CCC)(=O)OC1=CC=CC=C1 Chemical compound P(=O)(O)(O)O.C(CCC)(=O)OC1=CC=CC=C1 OTFNJMVDNAAYBZ-UHFFFAOYSA-N 0.000 description 1
• 235000021314 Palmitic acid Nutrition 0.000 description 1
• 235000019483 Peanut oil Nutrition 0.000 description 1
• NBIIXXVUZAFLBC-UHFFFAOYSA-L Phosphate ion(2-) Chemical compound OP([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-L 0.000 description 1
• OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
• 239000004698 Polyethylene Substances 0.000 description 1
• 239000002202 Polyethylene glycol Substances 0.000 description 1
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
• XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
• LCTONWCANYUPML-UHFFFAOYSA-M Pyruvate Chemical compound CC(=O)C([O-])=O LCTONWCANYUPML-UHFFFAOYSA-M 0.000 description 1
• IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
• 239000012980 RPMI-1640 medium Substances 0.000 description 1
• 208000010340 Sleep Deprivation Diseases 0.000 description 1
• KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
• QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
• LSNNMFCWUKXFEE-UHFFFAOYSA-N Sulfurous acid Chemical compound OS(O)=O LSNNMFCWUKXFEE-UHFFFAOYSA-N 0.000 description 1
• FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
• 208000037063 Thinness Diseases 0.000 description 1
• ZZXDRXVIRVJQBT-UHFFFAOYSA-M Xylenesulfonate Chemical compound CC1=CC=CC(S([O-])(=O)=O)=C1C ZZXDRXVIRVJQBT-UHFFFAOYSA-M 0.000 description 1
• HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
• LREBBXICQLAZFB-IAQYHMDHSA-N [(1r,6s)-4,7-diazabicyclo[4.2.0]octan-7-yl]-[4-methoxy-2-(triazol-2-yl)phenyl]methanone Chemical compound C=1C(OC)=CC=C(C(=O)N2[C@@H]3CNCC[C@@H]3C2)C=1N1N=CC=N1 LREBBXICQLAZFB-IAQYHMDHSA-N 0.000 description 1
• HLQWSXDZNSSEBI-QMTHXVAHSA-N [(1r,6s)-4,7-diazabicyclo[4.2.0]octan-7-yl]-[5-fluoro-2-(triazol-2-yl)phenyl]methanone Chemical compound N1([C@@H]2CNCC[C@@H]2C1)C(=O)C1=CC(F)=CC=C1N1N=CC=N1 HLQWSXDZNSSEBI-QMTHXVAHSA-N 0.000 description 1
• OITOYHBLQALWKO-IAQYHMDHSA-N [(1r,6s)-4,7-diazabicyclo[4.2.0]octan-7-yl]-[5-methoxy-2-(triazol-2-yl)phenyl]methanone Chemical compound N1([C@@H]2CNCC[C@@H]2C1)C(=O)C1=CC(OC)=CC=C1N1N=CC=N1 OITOYHBLQALWKO-IAQYHMDHSA-N 0.000 description 1
• SVCWGHGYYCQQNF-DNVCBOLYSA-N [(1r,6s)-4-(3,6-dimethylpyrazin-2-yl)-4,7-diazabicyclo[4.2.0]octan-7-yl]-[5-fluoro-2-(triazol-2-yl)phenyl]methanone Chemical compound CC1=CN=C(C)C(N2C[C@H]3N(C[C@H]3CC2)C(=O)C=2C(=CC=C(F)C=2)N2N=CC=N2)=N1 SVCWGHGYYCQQNF-DNVCBOLYSA-N 0.000 description 1
• OYCXSWTUVZIONC-RDTXWAMCSA-N [(1r,6s)-4-(6-amino-2-methylpyrimidin-4-yl)-4,7-diazabicyclo[4.2.0]octan-7-yl]-[5-methoxy-2-(triazol-2-yl)phenyl]methanone Chemical compound C([C@@H]1CN([C@@H]1C1)C(=O)C=2C(=CC=C(C=2)OC)N2N=CC=N2)CN1C1=CC(N)=NC(C)=N1 OYCXSWTUVZIONC-RDTXWAMCSA-N 0.000 description 1
• FKCMADOPPWWGNZ-YUMQZZPRSA-N [(2r)-1-[(2s)-2-amino-3-methylbutanoyl]pyrrolidin-2-yl]boronic acid Chemical class CC(C)[C@H](N)C(=O)N1CCC[C@H]1B(O)O FKCMADOPPWWGNZ-YUMQZZPRSA-N 0.000 description 1
• HYBZWVLPALMACV-JQGZANCBSA-N [(2s)-2-[[5-(2,6-ditritiophenyl)-1,3,4-oxadiazol-2-yl]methyl]pyrrolidin-1-yl]-[5-(2-fluorophenyl)-2-methyl-1,3-thiazol-4-yl]methanone Chemical compound [3H]C1=CC=CC([3H])=C1C(O1)=NN=C1C[C@H]1N(C(=O)C2=C(SC(C)=N2)C=2C(=CC=CC=2)F)CCC1 HYBZWVLPALMACV-JQGZANCBSA-N 0.000 description 1
• QCBKBBXQMFUWOV-UHFFFAOYSA-N [2-(4,6-dimethylpyrimidin-2-yl)-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-5-yl]-[3-methoxy-2-(triazol-1-yl)phenyl]methanone Chemical compound C1=CN=NN1C=1C(OC)=CC=CC=1C(=O)N(CC1C2)CC1CN2C1=NC(C)=CC(C)=N1 QCBKBBXQMFUWOV-UHFFFAOYSA-N 0.000 description 1
• DKYXHSFAXVCDFL-WIYYLYMNSA-N [3-methyl-2-(1h-pyrazol-5-yl)phenyl]-[(1r,6s)-4-(4,5,6-trimethylpyrimidin-2-yl)-4,7-diazabicyclo[4.2.0]octan-7-yl]methanone Chemical compound C([C@@H]1CN([C@@H]1C1)C(=O)C=2C=CC=C(C=2C=2NN=CC=2)C)CN1C1=NC(C)=C(C)C(C)=N1 DKYXHSFAXVCDFL-WIYYLYMNSA-N 0.000 description 1
• OIFJFTUWXXNBOJ-DYESRHJHSA-N [4-methoxy-2-(triazol-2-yl)phenyl]-[(1r,6s)-4-(6-methyl-2-propan-2-ylpyrimidin-4-yl)-4,7-diazabicyclo[4.2.0]octan-7-yl]methanone Chemical compound C([C@@H]1CN([C@@H]1C1)C(=O)C2=CC=C(C=C2N2N=CC=N2)OC)CN1C1=CC(C)=NC(C(C)C)=N1 OIFJFTUWXXNBOJ-DYESRHJHSA-N 0.000 description 1
• HYBZWVLPALMACV-KRWDZBQOSA-N [5-(2-fluorophenyl)-2-methyl-1,3-thiazol-4-yl]-[(2s)-2-[(5-phenyl-1,3,4-oxadiazol-2-yl)methyl]pyrrolidin-1-yl]methanone Chemical compound C([C@@H]1CCCN1C(=O)C=1N=C(SC=1C=1C(=CC=CC=1)F)C)C(O1)=NN=C1C1=CC=CC=C1 HYBZWVLPALMACV-KRWDZBQOSA-N 0.000 description 1
• PQZGKIYKVFSJGA-DYESRHJHSA-N [5-methoxy-2-(triazol-2-yl)phenyl]-[(1r,6s)-4-(6-methyl-2-propan-2-ylpyrimidin-4-yl)-4,7-diazabicyclo[4.2.0]octan-7-yl]methanone Chemical compound C([C@@H]1CN([C@@H]1C1)C(=O)C=2C(=CC=C(C=2)OC)N2N=CC=N2)CN1C1=CC(C)=NC(C(C)C)=N1 PQZGKIYKVFSJGA-DYESRHJHSA-N 0.000 description 1
• APHGASWWWGONQU-IEBWSBKVSA-N [6-methyl-2-(triazol-1-yl)pyridin-3-yl]-[(1r,6s)-4-(4,5,6-trimethylpyrimidin-2-yl)-4,7-diazabicyclo[4.2.0]octan-7-yl]methanone Chemical compound C([C@@H]1CN([C@@H]1C1)C(=O)C2=CC=C(N=C2N2N=NC=C2)C)CN1C1=NC(C)=C(C)C(C)=N1 APHGASWWWGONQU-IEBWSBKVSA-N 0.000 description 1
• XOSXOHWJVQVDNG-FCEFMSTGSA-N [C@H]12CNCC[C@@H]2CN1C(=O)OCC1=CC=CC=C1.CC1=NC(=NC(=C1)C)N1C[C@H]2N(C[C@H]2CC1)C(=O)OCC1=CC=CC=C1 Chemical compound [C@H]12CNCC[C@@H]2CN1C(=O)OCC1=CC=CC=C1.CC1=NC(=NC(=C1)C)N1C[C@H]2N(C[C@H]2CC1)C(=O)OCC1=CC=CC=C1 XOSXOHWJVQVDNG-FCEFMSTGSA-N 0.000 description 1
• 238000010521 absorption reaction Methods 0.000 description 1
• IPBVNPXQWQGGJP-UHFFFAOYSA-N acetic acid phenyl ester Natural products CC(=O)OC1=CC=CC=C1 IPBVNPXQWQGGJP-UHFFFAOYSA-N 0.000 description 1
• RRUDCFGSUDOHDG-UHFFFAOYSA-N acetohydroxamic acid Chemical compound CC(O)=NO RRUDCFGSUDOHDG-UHFFFAOYSA-N 0.000 description 1
• 229960001171 acetohydroxamic acid Drugs 0.000 description 1
• YTIVTFGABIZHHX-UHFFFAOYSA-L acetylenedicarboxylate(2-) Chemical compound [O-]C(=O)C#CC([O-])=O YTIVTFGABIZHHX-UHFFFAOYSA-L 0.000 description 1
• 239000008186 active pharmaceutical agent Substances 0.000 description 1
• 230000001154 acute effect Effects 0.000 description 1
• 235000004279 alanine Nutrition 0.000 description 1
• 229960003767 alanine Drugs 0.000 description 1
• 201000007930 alcohol dependence Diseases 0.000 description 1
• IAJILQKETJEXLJ-RSJOWCBRSA-N aldehydo-D-galacturonic acid Chemical compound O=C[C@H](O)[C@@H](O)[C@@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-RSJOWCBRSA-N 0.000 description 1
• IAJILQKETJEXLJ-QTBDOELSSA-N aldehydo-D-glucuronic acid Chemical compound O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-QTBDOELSSA-N 0.000 description 1
• 235000010443 alginic acid Nutrition 0.000 description 1
• 239000000783 alginic acid Substances 0.000 description 1
• 229920000615 alginic acid Polymers 0.000 description 1
• 229960001126 alginic acid Drugs 0.000 description 1
• 150000004781 alginic acids Chemical class 0.000 description 1
• 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
• 229910001860 alkaline earth metal hydroxide Inorganic materials 0.000 description 1
• 150000003973 alkyl amines Chemical class 0.000 description 1
• 239000008168 almond oil Substances 0.000 description 1
• 229940061720 alpha hydroxy acid Drugs 0.000 description 1
• 150000001280 alpha hydroxy acids Chemical class 0.000 description 1
• 235000010210 aluminium Nutrition 0.000 description 1
• 229910052782 aluminium Inorganic materials 0.000 description 1
• XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
• CEGOLXSVJUTHNZ-UHFFFAOYSA-K aluminium tristearate Chemical compound [Al+3].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CEGOLXSVJUTHNZ-UHFFFAOYSA-K 0.000 description 1
• 229940063655 aluminum stearate Drugs 0.000 description 1
• 231100000540 amenorrhea Toxicity 0.000 description 1
• 238000010640 amide synthesis reaction Methods 0.000 description 1
• 125000003277 amino group Chemical group 0.000 description 1
• 125000004103 aminoalkyl group Chemical group 0.000 description 1
• 235000019270 ammonium chloride Nutrition 0.000 description 1
• 229940025084 amphetamine Drugs 0.000 description 1
• 238000002266 amputation Methods 0.000 description 1
• 238000004458 analytical method Methods 0.000 description 1
• JFCQEDHGNNZCLN-UHFFFAOYSA-N anhydrous glutaric acid Natural products OC(=O)CCCC(O)=O JFCQEDHGNNZCLN-UHFFFAOYSA-N 0.000 description 1
• 238000010171 animal model Methods 0.000 description 1
• 208000022531 anorexia Diseases 0.000 description 1
• 230000008485 antagonism Effects 0.000 description 1
• 229940053202 antiepileptics carboxamide derivative Drugs 0.000 description 1
• 239000012736 aqueous medium Substances 0.000 description 1
• 239000007900 aqueous suspension Substances 0.000 description 1
• ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
• 159000000032 aromatic acids Chemical class 0.000 description 1
• 206010003119 arrhythmia Diseases 0.000 description 1
• 230000006793 arrhythmia Effects 0.000 description 1
• 230000004872 arterial blood pressure Effects 0.000 description 1
• 235000010323 ascorbic acid Nutrition 0.000 description 1
• 229960005070 ascorbic acid Drugs 0.000 description 1
• 239000011668 ascorbic acid Substances 0.000 description 1
• 235000003704 aspartic acid Nutrition 0.000 description 1
• RKUNBYITZUJHSG-SPUOUPEWSA-N atropine Chemical compound O([C@H]1C[C@H]2CC[C@@H](C1)N2C)C(=O)C(CO)C1=CC=CC=C1 RKUNBYITZUJHSG-SPUOUPEWSA-N 0.000 description 1
• 229960000396 atropine Drugs 0.000 description 1
• 230000003542 behavioural effect Effects 0.000 description 1
• 150000003936 benzamides Chemical class 0.000 description 1
• 150000001558 benzoic acid derivatives Chemical class 0.000 description 1
• MHHNVRRIANKNON-CHWSQXEVSA-N benzyl (1r,6s)-4,7-diazabicyclo[4.2.0]octane-7-carboxylate Chemical compound N1([C@@H]2CNCC[C@@H]2C1)C(=O)OCC1=CC=CC=C1 MHHNVRRIANKNON-CHWSQXEVSA-N 0.000 description 1
• QRXDMGQDNTUTTO-UHFFFAOYSA-N benzyl 2-methylpyrrolidine-1-carboxylate Chemical compound CC1CCCN1C(=O)OCC1=CC=CC=C1 QRXDMGQDNTUTTO-UHFFFAOYSA-N 0.000 description 1
• UVYCLXXPQAPHKR-UHFFFAOYSA-N benzyl 3-(hydroxymethyl)-4-[(2-methylpropan-2-yl)oxycarbonylamino]pyrrolidine-1-carboxylate Chemical compound C1C(CO)C(NC(=O)OC(C)(C)C)CN1C(=O)OCC1=CC=CC=C1 UVYCLXXPQAPHKR-UHFFFAOYSA-N 0.000 description 1
• FQFDLNYJBIFCOO-UHFFFAOYSA-N benzyl 3-[(2-methylpropan-2-yl)oxycarbonylamino]-4-(methylsulfonyloxymethyl)pyrrolidine-1-carboxylate Chemical compound C1C(COS(C)(=O)=O)C(NC(=O)OC(C)(C)C)CN1C(=O)OCC1=CC=CC=C1 FQFDLNYJBIFCOO-UHFFFAOYSA-N 0.000 description 1
• HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 0.000 description 1
• SGVVZHZJVANCRU-UHFFFAOYSA-N benzyl n-(2,2-dimethoxyethyl)carbamate Chemical compound COC(OC)CNC(=O)OCC1=CC=CC=C1 SGVVZHZJVANCRU-UHFFFAOYSA-N 0.000 description 1
• USNPGPXWVWTJSS-UHFFFAOYSA-N benzyl n-(2-hydroxyiminoethyl)-n-prop-2-enylcarbamate Chemical compound ON=CCN(CC=C)C(=O)OCC1=CC=CC=C1 USNPGPXWVWTJSS-UHFFFAOYSA-N 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
• OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
• 125000002619 bicyclic group Chemical group 0.000 description 1
• 238000004166 bioassay Methods 0.000 description 1
• 230000033228 biological regulation Effects 0.000 description 1
• 230000036983 biotransformation Effects 0.000 description 1
• 239000012455 biphasic mixture Substances 0.000 description 1
• KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 1
• 239000004327 boric acid Substances 0.000 description 1
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
• 229910052794 bromium Inorganic materials 0.000 description 1
• 239000007853 buffer solution Substances 0.000 description 1
• KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
• MWPLVEDNUUSJAV-UHFFFAOYSA-N c1cc2cc3ccccc3cc2cc1 Chemical compound c1cc2cc3ccccc3cc2cc1 MWPLVEDNUUSJAV-UHFFFAOYSA-N 0.000 description 1
• YNPNZTXNASCQKK-UHFFFAOYSA-N c1cc2ccc(cccc3)c3c2cc1 Chemical compound c1cc2ccc(cccc3)c3c2cc1 YNPNZTXNASCQKK-UHFFFAOYSA-N 0.000 description 1
• 150000004657 carbamic acid derivatives Chemical class 0.000 description 1
• 235000011089 carbon dioxide Nutrition 0.000 description 1
• MMCOUVMKNAHQOY-UHFFFAOYSA-N carbonoperoxoic acid Chemical class OOC(O)=O MMCOUVMKNAHQOY-UHFFFAOYSA-N 0.000 description 1
• 239000001768 carboxy methyl cellulose Substances 0.000 description 1
• 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
• 125000002843 carboxylic acid group Chemical group 0.000 description 1
• 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
• 230000000747 cardiac effect Effects 0.000 description 1
• 238000006555 catalytic reaction Methods 0.000 description 1
• 206010007776 catatonia Diseases 0.000 description 1
• 230000030833 cell death Effects 0.000 description 1
• 239000001913 cellulose Substances 0.000 description 1
• 235000010980 cellulose Nutrition 0.000 description 1
• 229920002678 cellulose Polymers 0.000 description 1
• 150000005829 chemical entities Chemical class 0.000 description 1
• 239000003795 chemical substances by application Substances 0.000 description 1
• KVSASDOGYIBWTA-UHFFFAOYSA-N chloro benzoate Chemical compound ClOC(=O)C1=CC=CC=C1 KVSASDOGYIBWTA-UHFFFAOYSA-N 0.000 description 1
• 150000005698 chloropyrimidines Chemical class 0.000 description 1
• OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
• 229960001231 choline Drugs 0.000 description 1
• 235000013985 cinnamic acid Nutrition 0.000 description 1
• 229930016911 cinnamic acid Natural products 0.000 description 1
• 229960002173 citrulline Drugs 0.000 description 1
• 235000013477 citrulline Nutrition 0.000 description 1
• 229910017052 cobalt Inorganic materials 0.000 description 1
• 239000010941 cobalt Substances 0.000 description 1
• GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 description 1
• 239000003240 coconut oil Substances 0.000 description 1
• 235000019864 coconut oil Nutrition 0.000 description 1
• 208000010877 cognitive disease Diseases 0.000 description 1
• 230000007370 cognitive improvement Effects 0.000 description 1
• 238000010668 complexation reaction Methods 0.000 description 1
• 230000021615 conjugation Effects 0.000 description 1
• 229910052802 copper Inorganic materials 0.000 description 1
• 239000010949 copper Substances 0.000 description 1
• 230000008878 coupling Effects 0.000 description 1
• 238000010168 coupling process Methods 0.000 description 1
• 238000005859 coupling reaction Methods 0.000 description 1
• 239000013058 crude material Substances 0.000 description 1
• 238000002425 crystallisation Methods 0.000 description 1
• 230000008025 crystallization Effects 0.000 description 1
• GHVNFZFCNZKVNT-UHFFFAOYSA-M decanoate Chemical compound CCCCCCCCCC([O-])=O GHVNFZFCNZKVNT-UHFFFAOYSA-M 0.000 description 1
• GHVNFZFCNZKVNT-UHFFFAOYSA-N decanoic acid Chemical compound CCCCCCCCCC(O)=O GHVNFZFCNZKVNT-UHFFFAOYSA-N 0.000 description 1
• 206010061428 decreased appetite Diseases 0.000 description 1
• YSMODUONRAFBET-UHFFFAOYSA-N delta-DL-hydroxylysine Natural products NCC(O)CCC(N)C(O)=O YSMODUONRAFBET-UHFFFAOYSA-N 0.000 description 1
• 230000001419 dependent effect Effects 0.000 description 1
• 230000005595 deprotonation Effects 0.000 description 1
• 238000010537 deprotonation reaction Methods 0.000 description 1
• 229910052805 deuterium Inorganic materials 0.000 description 1
• GOWQBFVDZPZZFA-UHFFFAOYSA-N diethyl 2-fluoropropanedioate Chemical compound CCOC(=O)C(F)C(=O)OCC GOWQBFVDZPZZFA-UHFFFAOYSA-N 0.000 description 1
• NBIIXXVUZAFLBC-UHFFFAOYSA-M dihydrogenphosphate Chemical compound OP(O)([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-M 0.000 description 1
• LVTYICIALWPMFW-UHFFFAOYSA-N diisopropanolamine Chemical compound CC(O)CNCC(C)O LVTYICIALWPMFW-UHFFFAOYSA-N 0.000 description 1
• VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 1
• PSHRANCNVXNITH-UHFFFAOYSA-N dimethylamino acetate Chemical compound CN(C)OC(C)=O PSHRANCNVXNITH-UHFFFAOYSA-N 0.000 description 1
• XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 description 1
• 235000011180 diphosphates Nutrition 0.000 description 1
• 235000014632 disordered eating Nutrition 0.000 description 1
• 238000009826 distribution Methods 0.000 description 1
• PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 description 1
• 229960003638 dopamine Drugs 0.000 description 1
• 239000003210 dopamine receptor blocking agent Substances 0.000 description 1
• 239000008298 dragée Substances 0.000 description 1
• 238000009510 drug design Methods 0.000 description 1
• 238000009509 drug development Methods 0.000 description 1
• 238000007876 drug discovery Methods 0.000 description 1
• 230000009977 dual effect Effects 0.000 description 1
• 229940125504 dual orexin 1/2 receptor antagonist Drugs 0.000 description 1
• 235000005686 eating Nutrition 0.000 description 1
• 230000007937 eating Effects 0.000 description 1
• 229910001651 emery Inorganic materials 0.000 description 1
• 238000003821 enantio-separation Methods 0.000 description 1
• 239000002702 enteric coating Substances 0.000 description 1
• 238000009505 enteric coating Methods 0.000 description 1
• 210000000105 enteric nervous system Anatomy 0.000 description 1
• YSMODUONRAFBET-UHNVWZDZSA-N erythro-5-hydroxy-L-lysine Chemical compound NC[C@H](O)CC[C@H](N)C(O)=O YSMODUONRAFBET-UHNVWZDZSA-N 0.000 description 1
• 238000010931 ester hydrolysis Methods 0.000 description 1
• 230000032050 esterification Effects 0.000 description 1
• 238000005886 esterification reaction Methods 0.000 description 1
• CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
• BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
• 125000001033 ether group Chemical group 0.000 description 1
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
• 235000019197 fats Nutrition 0.000 description 1
• 239000000945 filler Substances 0.000 description 1
• 235000019634 flavors Nutrition 0.000 description 1
• 125000001153 fluoro group Chemical group F* 0.000 description 1
• 235000013355 food flavoring agent Nutrition 0.000 description 1
• 235000003599 food sweetener Nutrition 0.000 description 1
• 229940050411 fumarate Drugs 0.000 description 1
• 239000001530 fumaric acid Substances 0.000 description 1
• 229960002598 fumaric acid Drugs 0.000 description 1
• 229960003692 gamma aminobutyric acid Drugs 0.000 description 1
• 229940083124 ganglion-blocking antiadrenergic secondary and tertiary amines Drugs 0.000 description 1
• 210000001035 gastrointestinal tract Anatomy 0.000 description 1
• 239000000499 gel Substances 0.000 description 1
• 235000001727 glucose Nutrition 0.000 description 1
• 239000008103 glucose Substances 0.000 description 1
• 229940097043 glucuronic acid Drugs 0.000 description 1
• 235000013922 glutamic acid Nutrition 0.000 description 1
• 239000004220 glutamic acid Substances 0.000 description 1
• 229940074045 glyceryl distearate Drugs 0.000 description 1
• 229940075507 glyceryl monostearate Drugs 0.000 description 1
• 235000013905 glycine and its sodium salt Nutrition 0.000 description 1
• 229960004275 glycolic acid Drugs 0.000 description 1
• 239000008187 granular material Substances 0.000 description 1
• 150000004795 grignard reagents Chemical class 0.000 description 1
• 230000003370 grooming effect Effects 0.000 description 1
• 229910052736 halogen Inorganic materials 0.000 description 1
• 150000002367 halogens Chemical class 0.000 description 1
• 230000036541 health Effects 0.000 description 1
• 208000019622 heart disease Diseases 0.000 description 1
• MNWFXJYAOYHMED-UHFFFAOYSA-N heptanoic acid Chemical compound CCCCCCC(O)=O MNWFXJYAOYHMED-UHFFFAOYSA-N 0.000 description 1
• 125000000623 heterocyclic group Chemical group 0.000 description 1
• KKLGDUSGQMHBPB-UHFFFAOYSA-N hex-2-ynedioic acid Chemical compound OC(=O)CCC#CC(O)=O KKLGDUSGQMHBPB-UHFFFAOYSA-N 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
• 230000000742 histaminergic effect Effects 0.000 description 1
• 150000004677 hydrates Chemical class 0.000 description 1
• 230000036571 hydration Effects 0.000 description 1
• 238000006703 hydration reaction Methods 0.000 description 1
• 150000003840 hydrochlorides Chemical class 0.000 description 1
• 150000002431 hydrogen Chemical class 0.000 description 1
• XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
• 238000005984 hydrogenation reaction Methods 0.000 description 1
• QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
• QJHBJHUKURJDLG-UHFFFAOYSA-N hydroxy-L-lysine Natural products NCCCCC(NO)C(O)=O QJHBJHUKURJDLG-UHFFFAOYSA-N 0.000 description 1
• 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 1
• 229960002591 hydroxyproline Drugs 0.000 description 1
• 239000005457 ice water Substances 0.000 description 1
• 238000010191 image analysis Methods 0.000 description 1
• 150000005235 imidazopyrazines Chemical class 0.000 description 1
• 150000005237 imidazopyrimidines Chemical class 0.000 description 1
• 230000006872 improvement Effects 0.000 description 1
• 239000003701 inert diluent Substances 0.000 description 1
• 208000021267 infertility disease Diseases 0.000 description 1
• 230000002401 inhibitory effect Effects 0.000 description 1
• 239000003999 initiator Substances 0.000 description 1
• 239000007972 injectable composition Substances 0.000 description 1
• 229910017053 inorganic salt Inorganic materials 0.000 description 1
• 230000010354 integration Effects 0.000 description 1
• 238000007918 intramuscular administration Methods 0.000 description 1
• 238000007912 intraperitoneal administration Methods 0.000 description 1
• 125000002346 iodo group Chemical group I* 0.000 description 1
• 150000002500 ions Chemical class 0.000 description 1
• 229910052742 iron Inorganic materials 0.000 description 1
• 230000007794 irritation Effects 0.000 description 1
• 229940045996 isethionic acid Drugs 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
• KQNPFQTWMSNSAP-UHFFFAOYSA-N isobutyric acid Chemical compound CC(C)C(O)=O KQNPFQTWMSNSAP-UHFFFAOYSA-N 0.000 description 1
• 125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 1
• VFQXVTODMYMSMJ-UHFFFAOYSA-N isonicotinamide Chemical compound NC(=O)C1=CC=NC=C1 VFQXVTODMYMSMJ-UHFFFAOYSA-N 0.000 description 1
• QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-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
• 239000004310 lactic acid Substances 0.000 description 1
• 235000014655 lactic acid Nutrition 0.000 description 1
• 229960000448 lactic acid Drugs 0.000 description 1
• 239000008101 lactose Substances 0.000 description 1
• 210000003796 lateral hypothalamic area Anatomy 0.000 description 1
• 229940033355 lauric acid Drugs 0.000 description 1
• 239000000787 lecithin Substances 0.000 description 1
• 235000010445 lecithin Nutrition 0.000 description 1
• 229940067606 lecithin Drugs 0.000 description 1
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 1
• 229940057995 liquid paraffin Drugs 0.000 description 1
• 229910052744 lithium Inorganic materials 0.000 description 1
• 239000012280 lithium aluminium hydride Substances 0.000 description 1
• 230000033001 locomotion Effects 0.000 description 1
• 230000006742 locomotor activity Effects 0.000 description 1
• 230000007774 longterm Effects 0.000 description 1
• 239000011777 magnesium Substances 0.000 description 1
• 229910052749 magnesium Inorganic materials 0.000 description 1
• 235000001055 magnesium Nutrition 0.000 description 1
• 238000011418 maintenance treatment Methods 0.000 description 1
• IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical compound [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 description 1
• 229960002510 mandelic acid Drugs 0.000 description 1
• WPBNNNQJVZRUHP-UHFFFAOYSA-L manganese(2+);methyl n-[[2-(methoxycarbonylcarbamothioylamino)phenyl]carbamothioyl]carbamate;n-[2-(sulfidocarbothioylamino)ethyl]carbamodithioate Chemical compound [Mn+2].[S-]C(=S)NCCNC([S-])=S.COC(=O)NC(=S)NC1=CC=CC=C1NC(=S)NC(=O)OC WPBNNNQJVZRUHP-UHFFFAOYSA-L 0.000 description 1
• 239000000594 mannitol Substances 0.000 description 1
• 235000010355 mannitol Nutrition 0.000 description 1
• 239000011159 matrix material Substances 0.000 description 1
• 238000002844 melting Methods 0.000 description 1
• 230000008018 melting Effects 0.000 description 1
• 108020004999 messenger RNA Proteins 0.000 description 1
• 125000005341 metaphosphate group Chemical group 0.000 description 1
• 229940098779 methanesulfonic acid Drugs 0.000 description 1
• OKKJLVBELUTLKV-VMNATFBRSA-N methanol-d1 Chemical compound [2H]OC OKKJLVBELUTLKV-VMNATFBRSA-N 0.000 description 1
• FCMQMRAFVRTHCR-UHFFFAOYSA-N methyl 2-bromo-5-fluorobenzoate Chemical compound COC(=O)C1=CC(F)=CC=C1Br FCMQMRAFVRTHCR-UHFFFAOYSA-N 0.000 description 1
• UDNUZHWPCUOGJC-UHFFFAOYSA-N methyl 2-fluoro-6-(3-methyl-1,2,4-oxadiazol-5-yl)benzoate Chemical compound COC(=O)C1=C(F)C=CC=C1C1=NC(C)=NO1 UDNUZHWPCUOGJC-UHFFFAOYSA-N 0.000 description 1
• KRBBXOCBQBADHY-UHFFFAOYSA-N methyl 2-fluoro-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate Chemical compound COC(=O)C1=C(F)C=CC=C1B1OC(C)(C)C(C)(C)O1 KRBBXOCBQBADHY-UHFFFAOYSA-N 0.000 description 1
• IGNCVPBULCJIRO-UHFFFAOYSA-N methyl 2-fluoro-6-iodobenzoate Chemical compound COC(=O)C1=C(F)C=CC=C1I IGNCVPBULCJIRO-UHFFFAOYSA-N 0.000 description 1
• VFWHJJKKMBKSSG-UHFFFAOYSA-N methyl 2-fluoro-6-pyrimidin-2-ylbenzoate Chemical compound COC(=O)C1=C(F)C=CC=C1C1=NC=CC=N1 VFWHJJKKMBKSSG-UHFFFAOYSA-N 0.000 description 1
• HAMZTFVEACVCBK-UHFFFAOYSA-N methyl 3-fluoro-2-(3-methyl-1,2,4-oxadiazol-5-yl)benzoate Chemical compound COC(=O)C1=CC=CC(F)=C1C1=NC(C)=NO1 HAMZTFVEACVCBK-UHFFFAOYSA-N 0.000 description 1
• DCNAAOVAUVQRQD-UHFFFAOYSA-N methyl 5-fluoro-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate Chemical compound COC(=O)C1=CC(F)=CC=C1B1OC(C)(C)C(C)(C)O1 DCNAAOVAUVQRQD-UHFFFAOYSA-N 0.000 description 1
• FCIVFGJJCBYNFY-UHFFFAOYSA-N methyl 5-fluoro-2-pyrimidin-2-ylbenzoate Chemical compound COC(=O)C1=CC(F)=CC=C1C1=NC=CC=N1 FCIVFGJJCBYNFY-UHFFFAOYSA-N 0.000 description 1
• 229940095102 methyl benzoate Drugs 0.000 description 1
• 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
• 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
• WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 1
• 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
• 239000008108 microcrystalline cellulose Substances 0.000 description 1
• 229940016286 microcrystalline cellulose Drugs 0.000 description 1
• 239000011259 mixed solution Substances 0.000 description 1
• 239000012046 mixed solvent Substances 0.000 description 1
• 229960005181 morphine Drugs 0.000 description 1
• 230000004899 motility Effects 0.000 description 1
• 230000035772 mutation Effects 0.000 description 1
• LNOPIUAQISRISI-UHFFFAOYSA-N n'-hydroxy-2-propan-2-ylsulfonylethanimidamide Chemical compound CC(C)S(=O)(=O)CC(N)=NO LNOPIUAQISRISI-UHFFFAOYSA-N 0.000 description 1
• WQEPLUUGTLDZJY-UHFFFAOYSA-N n-Pentadecanoic acid Natural products CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 description 1
• DVDIIPQLDCMPFY-UHFFFAOYSA-N n-[2-(3,4-dimethoxyphenyl)ethyl]-n-methylnaphthalene-1-carboxamide Chemical compound C1=C(OC)C(OC)=CC=C1CCN(C)C(=O)C1=CC=CC2=CC=CC=C12 DVDIIPQLDCMPFY-UHFFFAOYSA-N 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-N naphthalene-1-sulfonic acid Chemical compound C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1 PSZYNBSKGUBXEH-UHFFFAOYSA-N 0.000 description 1
• KVBGVZZKJNLNJU-UHFFFAOYSA-N naphthalene-2-sulfonic acid Chemical compound C1=CC=CC2=CC(S(=O)(=O)O)=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-N 0.000 description 1
• 230000004770 neurodegeneration Effects 0.000 description 1
• 208000015122 neurodegenerative disease Diseases 0.000 description 1
• 229960002715 nicotine Drugs 0.000 description 1
• SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 description 1
• 229910017604 nitric acid Inorganic materials 0.000 description 1
• 239000012299 nitrogen atmosphere Substances 0.000 description 1
• AKRYBBWYDSDZHG-UHFFFAOYSA-N nitrosobis(2-oxopropyl)amine Chemical compound CC(=O)CN(N=O)CC(C)=O AKRYBBWYDSDZHG-UHFFFAOYSA-N 0.000 description 1
• 239000002687 nonaqueous vehicle Substances 0.000 description 1
• WWZKQHOCKIZLMA-UHFFFAOYSA-M octanoate Chemical compound CCCCCCCC([O-])=O WWZKQHOCKIZLMA-UHFFFAOYSA-M 0.000 description 1
• ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
• 229960002969 oleic acid Drugs 0.000 description 1
• 210000000956 olfactory bulb Anatomy 0.000 description 1
• 239000004006 olive oil Substances 0.000 description 1
• 235000008390 olive oil Nutrition 0.000 description 1
• 238000011017 operating method Methods 0.000 description 1
• 230000003287 optical effect Effects 0.000 description 1
• 239000007935 oral tablet Substances 0.000 description 1
• 229940125636 orexin 1 receptor antagonist Drugs 0.000 description 1
• 239000003960 organic solvent Substances 0.000 description 1
• 229960003104 ornithine Drugs 0.000 description 1
• ILUJQPXNXACGAN-UHFFFAOYSA-N ortho-methoxybenzoic acid Natural products COC1=CC=CC=C1C(O)=O ILUJQPXNXACGAN-UHFFFAOYSA-N 0.000 description 1
• 229940116315 oxalic acid Drugs 0.000 description 1
• 235000006408 oxalic acid Nutrition 0.000 description 1
• 125000004043 oxo group Chemical group O=* 0.000 description 1
• 125000004430 oxygen atom Chemical group O* 0.000 description 1
• 230000020477 pH reduction Effects 0.000 description 1
• YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
• 229940098695 palmitic acid Drugs 0.000 description 1
• FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
• 210000002963 paraventricular hypothalamic nucleus Anatomy 0.000 description 1
• 230000008506 pathogenesis Effects 0.000 description 1
• 239000000312 peanut oil Substances 0.000 description 1
• 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
• 229940124531 pharmaceutical excipient Drugs 0.000 description 1
• 239000008196 pharmacological composition Substances 0.000 description 1
• DYUMLJSJISTVPV-UHFFFAOYSA-N phenyl propanoate Chemical compound CCC(=O)OC1=CC=CC=C1 DYUMLJSJISTVPV-UHFFFAOYSA-N 0.000 description 1
• 229940049953 phenylacetate Drugs 0.000 description 1
• WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
• 125000005541 phosphonamide group Chemical group 0.000 description 1
• 229910052698 phosphorus Inorganic materials 0.000 description 1
• 239000011574 phosphorus Substances 0.000 description 1
• XNGIFLGASWRNHJ-UHFFFAOYSA-L phthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC=C1C([O-])=O XNGIFLGASWRNHJ-UHFFFAOYSA-L 0.000 description 1
• 230000004962 physiological condition Effects 0.000 description 1
• 150000003053 piperidines Chemical class 0.000 description 1
• 230000007505 plaque formation Effects 0.000 description 1
• 229920001467 poly(styrenesulfonates) Polymers 0.000 description 1
• 125000003367 polycyclic group Chemical group 0.000 description 1
• 229920000573 polyethylene Polymers 0.000 description 1
• 229920001223 polyethylene glycol Polymers 0.000 description 1
• 229940068918 polyethylene glycol 400 Drugs 0.000 description 1
• 229920001184 polypeptide Polymers 0.000 description 1
• 229910052700 potassium Inorganic materials 0.000 description 1
• 239000011591 potassium Substances 0.000 description 1
• 229910000027 potassium carbonate Inorganic materials 0.000 description 1
• 230000003389 potentiating effect Effects 0.000 description 1
• 238000001556 precipitation Methods 0.000 description 1
• 230000002265 prevention Effects 0.000 description 1
• 150000003141 primary amines Chemical class 0.000 description 1
• 102000004196 processed proteins & peptides Human genes 0.000 description 1
• 108010007439 proline transporter Proteins 0.000 description 1
• KCXFHTAICRTXLI-UHFFFAOYSA-N propane-1-sulfonic acid Chemical compound CCCS(O)(=O)=O KCXFHTAICRTXLI-UHFFFAOYSA-N 0.000 description 1
• 235000019260 propionic acid Nutrition 0.000 description 1
• 229940095574 propionic acid Drugs 0.000 description 1
• 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
• 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
• QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 1
• 108090000623 proteins and genes Proteins 0.000 description 1
• 230000005588 protonation Effects 0.000 description 1
• DMYLUKNFEYWGCH-UHFFFAOYSA-N pyridazine-3-carboxamide Chemical class NC(=O)C1=CC=CN=N1 DMYLUKNFEYWGCH-UHFFFAOYSA-N 0.000 description 1
• 125000000714 pyrimidinyl group Chemical group 0.000 description 1
• 229940076788 pyruvate Drugs 0.000 description 1
• 229940107700 pyruvic acid Drugs 0.000 description 1
• IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
• 230000005855 radiation Effects 0.000 description 1
• 238000003653 radioligand binding assay Methods 0.000 description 1
• 229940044551 receptor antagonist Drugs 0.000 description 1
• 239000002464 receptor antagonist Substances 0.000 description 1
• 229940075993 receptor modulator Drugs 0.000 description 1
• 238000011084 recovery Methods 0.000 description 1
• 230000001105 regulatory effect Effects 0.000 description 1
• 238000012552 review Methods 0.000 description 1
• YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
• 229960004889 salicylic acid Drugs 0.000 description 1
• 239000012047 saturated solution Substances 0.000 description 1
• 201000000980 schizophrenia Diseases 0.000 description 1
• 229940116351 sebacate Drugs 0.000 description 1
• CXMXRPHRNRROMY-UHFFFAOYSA-L sebacate(2-) Chemical compound [O-]C(=O)CCCCCCCCC([O-])=O CXMXRPHRNRROMY-UHFFFAOYSA-L 0.000 description 1
• DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 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
• 150000003335 secondary amines Chemical class 0.000 description 1
• 235000021391 short chain fatty acids Nutrition 0.000 description 1
• 150000004666 short chain fatty acids Chemical class 0.000 description 1
• 238000010898 silica gel chromatography Methods 0.000 description 1
• 239000000377 silicon dioxide 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
• 150000003384 small molecules Chemical class 0.000 description 1
• 235000010413 sodium alginate Nutrition 0.000 description 1
• 239000000661 sodium alginate Substances 0.000 description 1
• 229940005550 sodium alginate Drugs 0.000 description 1
• 239000001488 sodium phosphate Substances 0.000 description 1
• 229910000162 sodium phosphate Inorganic materials 0.000 description 1
• 239000008109 sodium starch glycolate Substances 0.000 description 1
• 229920003109 sodium starch glycolate Polymers 0.000 description 1
• 229940079832 sodium starch glycolate Drugs 0.000 description 1
• 239000012321 sodium triacetoxyborohydride Substances 0.000 description 1
• 238000007614 solvation Methods 0.000 description 1
• 239000004334 sorbic acid Substances 0.000 description 1
• 235000010199 sorbic acid Nutrition 0.000 description 1
• 229940075582 sorbic acid Drugs 0.000 description 1
• 238000001228 spectrum Methods 0.000 description 1
• 210000000278 spinal cord Anatomy 0.000 description 1
• 239000007921 spray Substances 0.000 description 1
• 238000003860 storage Methods 0.000 description 1
• 238000007920 subcutaneous administration Methods 0.000 description 1
• TYFQFVWCELRYAO-UHFFFAOYSA-L suberate(2-) Chemical compound [O-]C(=O)CCCCCCC([O-])=O TYFQFVWCELRYAO-UHFFFAOYSA-L 0.000 description 1
• 210000000470 submucous plexus Anatomy 0.000 description 1
• 208000011117 substance-related disease Diseases 0.000 description 1
• 125000003107 substituted aryl group Chemical group 0.000 description 1
• 239000000758 substrate Substances 0.000 description 1
• KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
• 150000008163 sugars Chemical class 0.000 description 1
• 229940124530 sulfonamide Drugs 0.000 description 1
• 150000003456 sulfonamides Chemical class 0.000 description 1
• BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
• 150000003871 sulfonates Chemical class 0.000 description 1
• 150000003460 sulfonic acids Chemical class 0.000 description 1
• 125000004963 sulfonylalkyl group Chemical group 0.000 description 1
• 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
• 239000000375 suspending agent Substances 0.000 description 1
• JYTNQNCOQXFQPK-MRXNPFEDSA-N suvorexant Chemical compound C([C@H]1C)CN(C=2OC3=CC=C(Cl)C=C3N=2)CCN1C(=O)C1=CC(C)=CC=C1N1N=CC=N1 JYTNQNCOQXFQPK-MRXNPFEDSA-N 0.000 description 1
• 239000003765 sweetening agent Substances 0.000 description 1
• 239000006188 syrup Substances 0.000 description 1
• 235000020357 syrup Nutrition 0.000 description 1
• 239000000454 talc Substances 0.000 description 1
• 235000012222 talc Nutrition 0.000 description 1
• 229910052623 talc Inorganic materials 0.000 description 1
• 230000008685 targeting Effects 0.000 description 1
• 239000011975 tartaric acid Substances 0.000 description 1
• 235000002906 tartaric acid Nutrition 0.000 description 1
• 229940095064 tartrate Drugs 0.000 description 1
• 238000003419 tautomerization reaction Methods 0.000 description 1
• LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
• VDIYTKLZDDFJTI-CZUORRHYSA-N tert-butyl (1r,6s)-7-[3-fluoro-2-(triazol-2-yl)benzoyl]-4,7-diazabicyclo[4.2.0]octane-4-carboxylate Chemical compound C([C@H]1CCN(C[C@H]11)C(=O)OC(C)(C)C)N1C(=O)C1=CC=CC(F)=C1N1N=CC=N1 VDIYTKLZDDFJTI-CZUORRHYSA-N 0.000 description 1
• NNQILRJQUZTJFW-GDBMZVCRSA-N tert-butyl (1r,6s)-7-[6-methyl-2-(triazol-1-yl)pyridine-3-carbonyl]-4,7-diazabicyclo[4.2.0]octane-4-carboxylate Chemical compound N=1C(C)=CC=C(C(=O)N2[C@@H]3CN(CC[C@@H]3C2)C(=O)OC(C)(C)C)C=1N1C=CN=N1 NNQILRJQUZTJFW-GDBMZVCRSA-N 0.000 description 1
• ZRRQJEOGSURZRN-XIRDDKMYSA-N tert-butyl (1s,6r)-7-[(1s)-1-phenylethyl]-4,7-diazabicyclo[4.2.0]octane-4-carboxylate Chemical compound C1([C@@H](N2[C@H]3CN(CC[C@H]3C2)C(=O)OC(C)(C)C)C)=CC=CC=C1 ZRRQJEOGSURZRN-XIRDDKMYSA-N 0.000 description 1
• FQJRZOYTUCCBQR-UHFFFAOYSA-N tert-butyl 2-methylheptanoate Chemical compound CCCCCC(C)C(=O)OC(C)(C)C FQJRZOYTUCCBQR-UHFFFAOYSA-N 0.000 description 1
• YPCQQZHIBTVQAB-UHFFFAOYSA-N tert-butyl 3,6-diazabicyclo[3.2.0]heptane-6-carboxylate Chemical compound C1NCC2N(C(=O)OC(C)(C)C)CC21 YPCQQZHIBTVQAB-UHFFFAOYSA-N 0.000 description 1
• DXDPYNMZBVKTDD-UHFFFAOYSA-N tert-butyl 3-quinoxalin-2-yl-3,6-diazabicyclo[3.2.0]heptane-6-carboxylate Chemical compound C1=CC=CC2=NC(N3CC4CN(C4C3)C(=O)OC(C)(C)C)=CN=C21 DXDPYNMZBVKTDD-UHFFFAOYSA-N 0.000 description 1
• UOUFRTFWWBCVPV-UHFFFAOYSA-N tert-butyl 4-(2,4-dioxo-1H-thieno[3,2-d]pyrimidin-3-yl)piperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(CC1)n1c(=O)[nH]c2ccsc2c1=O UOUFRTFWWBCVPV-UHFFFAOYSA-N 0.000 description 1
• PAPSFUPQVJVKIJ-UHFFFAOYSA-N tert-butyl 7-(2,4-dimethylphenyl)sulfonyl-4,7-diazabicyclo[4.2.0]octane-4-carboxylate Chemical compound CC1=CC(C)=CC=C1S(=O)(=O)N1C2CN(C(=O)OC(C)(C)C)CCC2C1 PAPSFUPQVJVKIJ-UHFFFAOYSA-N 0.000 description 1
• LRMPBBTXTXELIH-UHFFFAOYSA-N tert-butyl 7-[4-(2-fluorophenyl)-2-methyl-1,3-thiazole-5-carbonyl]-4,7-diazabicyclo[4.2.0]octane-4-carboxylate Chemical class C1C2CCN(C(=O)OC(C)(C)C)CC2N1C(=O)C=1SC(C)=NC=1C1=CC=CC=C1F LRMPBBTXTXELIH-UHFFFAOYSA-N 0.000 description 1
• YZOGZTSRYKCKAC-UHFFFAOYSA-N tert-butyl 7-benzyl-4,7-diazabicyclo[4.2.0]octane-4-carboxylate Chemical compound C12CN(C(=O)OC(C)(C)C)CCC2CN1CC1=CC=CC=C1 YZOGZTSRYKCKAC-UHFFFAOYSA-N 0.000 description 1
• GUBRMMYIMWWHQX-UHFFFAOYSA-N tert-butyl bicyclo[4.2.0]octane-3-carboxylate Chemical compound C1C(C(=O)OC(C)(C)C)CCC2CCC21 GUBRMMYIMWWHQX-UHFFFAOYSA-N 0.000 description 1
• FQFILJKFZCVHNH-UHFFFAOYSA-N tert-butyl n-[3-[(5-bromo-2-chloropyrimidin-4-yl)amino]propyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCCNC1=NC(Cl)=NC=C1Br FQFILJKFZCVHNH-UHFFFAOYSA-N 0.000 description 1
• 125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• 125000005207 tetraalkylammonium group Chemical group 0.000 description 1
• CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
• WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
• 229940124597 therapeutic agent Drugs 0.000 description 1
• 125000004001 thioalkyl group Chemical group 0.000 description 1
• 150000003568 thioethers Chemical class 0.000 description 1
• 230000000699 topical effect Effects 0.000 description 1
• 231100000419 toxicity Toxicity 0.000 description 1
• 230000001988 toxicity Effects 0.000 description 1
• 230000037317 transdermal delivery Effects 0.000 description 1
• LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
• 229960000281 trometamol Drugs 0.000 description 1
• 206010048828 underweight Diseases 0.000 description 1
• 150000003672 ureas Chemical class 0.000 description 1
• 229940005605 valeric acid Drugs 0.000 description 1
• 235000015112 vegetable and seed oil Nutrition 0.000 description 1
• 239000008158 vegetable oil Substances 0.000 description 1
• 239000003981 vehicle Substances 0.000 description 1
• 238000005406 washing Methods 0.000 description 1
• 239000000080 wetting agent Substances 0.000 description 1
• 229940071104 xylenesulfonate Drugs 0.000 description 1
• 229910052725 zinc Inorganic materials 0.000 description 1
• 239000011701 zinc Substances 0.000 description 1