KR102365952B1 - 선택적으로 치환된 퀴놀린 화합물 - Google Patents
선택적으로 치환된 퀴놀린 화합물 Download PDFInfo
- Publication number
- KR102365952B1 KR102365952B1 KR1020167009292A KR20167009292A KR102365952B1 KR 102365952 B1 KR102365952 B1 KR 102365952B1 KR 1020167009292 A KR1020167009292 A KR 1020167009292A KR 20167009292 A KR20167009292 A KR 20167009292A KR 102365952 B1 KR102365952 B1 KR 102365952B1
- Authority
- KR
- South Korea
- Prior art keywords
- methylpiperidin
- cyanoquinolin
- amino
- mmol
- methyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 125000002943 quinolinyl group Chemical class N1=C(C=CC2=CC=CC=C12)* 0.000 title abstract 2
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 21
- 150000001875 compounds Chemical class 0.000 claims description 108
- -1 dioxidothiopyranyl Chemical group 0.000 claims description 47
- 150000003839 salts Chemical class 0.000 claims description 46
- 238000000034 method Methods 0.000 claims description 38
- 206010025135 lupus erythematosus Diseases 0.000 claims description 32
- 201000000596 systemic lupus erythematosus Diseases 0.000 claims description 28
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 20
- 238000011282 treatment Methods 0.000 claims description 19
- 101000669402 Homo sapiens Toll-like receptor 7 Proteins 0.000 claims description 16
- 229920006395 saturated elastomer Polymers 0.000 claims description 15
- 208000005777 Lupus Nephritis Diseases 0.000 claims description 14
- 102000045715 human TLR7 Human genes 0.000 claims description 14
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 13
- 230000004913 activation Effects 0.000 claims description 11
- 229910002091 carbon monoxide Inorganic materials 0.000 claims description 7
- 230000001419 dependent effect Effects 0.000 claims description 7
- 108091003079 Bovine Serum Albumin Proteins 0.000 claims description 6
- 102000003945 NF-kappa B Human genes 0.000 claims description 6
- 108010057466 NF-kappa B Proteins 0.000 claims description 6
- 125000000217 alkyl group Chemical group 0.000 claims description 6
- 125000004122 cyclic group Chemical group 0.000 claims description 6
- 239000012091 fetal bovine serum Substances 0.000 claims description 6
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 claims description 5
- MPGCORKREKQAST-WCQYABFASA-N 5-[(3r,5s)-3-amino-5-methylpiperidin-1-yl]quinoline-8-carbonitrile Chemical compound C1[C@@H](C)C[C@@H](N)CN1C1=CC=C(C#N)C2=NC=CC=C12 MPGCORKREKQAST-WCQYABFASA-N 0.000 claims description 4
- 206010063663 Neuropsychiatric lupus Diseases 0.000 claims description 4
- 150000001408 amides Chemical class 0.000 claims description 4
- 125000004432 carbon atom Chemical group C* 0.000 claims description 4
- 238000004020 luminiscence type Methods 0.000 claims description 4
- ROSDSFDQCJNGOL-UHFFFAOYSA-N protonated dimethyl amine Natural products CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 claims description 4
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 4
- ATUOYWHBWRKTHZ-UHFFFAOYSA-N dimethylmethane Natural products CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 125000002757 morpholinyl group Chemical group 0.000 claims description 3
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 2
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 2
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
- 125000002971 oxazolyl group Chemical group 0.000 claims description 2
- 125000003566 oxetanyl group Chemical group 0.000 claims description 2
- 125000005476 oxopyrrolidinyl group Chemical group 0.000 claims description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
- 239000001294 propane Substances 0.000 claims description 2
- 125000004076 pyridyl group Chemical group 0.000 claims description 2
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 2
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 2
- 125000001984 thiazolidinyl group Chemical group 0.000 claims description 2
- QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 claims 5
- CIIFKVFOVFJZDM-UHFFFAOYSA-N quinoline-8-carbonitrile Chemical compound C1=CN=C2C(C#N)=CC=CC2=C1 CIIFKVFOVFJZDM-UHFFFAOYSA-N 0.000 claims 2
- GBSNGTLITPOAQM-DKZVUGQWSA-N (2R)-2-amino-N-[(3R,5S)-1-(8-cyanoquinolin-5-yl)-5-methylpiperidin-3-yl]-2-phenylacetamide Chemical compound N[C@@H](C(=O)N[C@H]1CN(C[C@H](C1)C)C1=C2C=CC=NC2=C(C=C1)C#N)C1=CC=CC=C1 GBSNGTLITPOAQM-DKZVUGQWSA-N 0.000 claims 1
- SBQCLFUIJZXTLT-XTQGRXLLSA-N (2R)-2-amino-N-[(3R,5S)-1-(8-cyanoquinolin-5-yl)-5-methylpiperidin-3-yl]-3,3,3-trifluoropropanamide Chemical compound N[C@H](C(=O)N[C@H]1CN(C[C@H](C1)C)C1=C2C=CC=NC2=C(C=C1)C#N)C(F)(F)F SBQCLFUIJZXTLT-XTQGRXLLSA-N 0.000 claims 1
- KKKANZIUJZIJFN-JGGQBBKZSA-N (2R)-2-amino-N-[(3R,5S)-1-(8-cyanoquinolin-5-yl)-5-methylpiperidin-3-yl]-3-hydroxypropanamide Chemical compound N[C@@H](C(=O)N[C@H]1CN(C[C@H](C1)C)C1=C2C=CC=NC2=C(C=C1)C#N)CO KKKANZIUJZIJFN-JGGQBBKZSA-N 0.000 claims 1
- SXCUBAMGHCAYRX-UCNVEGJOSA-N (2R)-2-amino-N-[(3R,5S)-1-(8-cyanoquinolin-5-yl)-5-methylpiperidin-3-yl]-3-phenylpropanamide Chemical compound N[C@@H](C(=O)N[C@H]1CN(C[C@H](C1)C)C1=C2C=CC=NC2=C(C=C1)C#N)CC1=CC=CC=C1 SXCUBAMGHCAYRX-UCNVEGJOSA-N 0.000 claims 1
- HKBSADXDDOGWRG-KVSKMBFKSA-N (2R)-2-amino-N-[(3R,5S)-1-(8-cyanoquinolin-5-yl)-5-methylpiperidin-3-yl]-4-methylpentanamide Chemical compound N[C@@H](C(=O)N[C@H]1CN(C[C@H](C1)C)C1=C2C=CC=NC2=C(C=C1)C#N)CC(C)C HKBSADXDDOGWRG-KVSKMBFKSA-N 0.000 claims 1
- KKQHXOGKPYDXJU-JGGQBBKZSA-N (2R)-2-amino-N-[(3R,5S)-1-(8-cyanoquinolin-5-yl)-5-methylpiperidin-3-yl]butanediamide Chemical compound N[C@@H](C(=O)N[C@H]1CN(C[C@H](C1)C)C1=C2C=CC=NC2=C(C=C1)C#N)CC(=O)N KKQHXOGKPYDXJU-JGGQBBKZSA-N 0.000 claims 1
- MCLARVHBNPVJFY-GZBFAFLISA-N (2R)-2-amino-N-[(3R,5S)-1-(8-cyanoquinolin-5-yl)-5-methylpiperidin-3-yl]propanamide Chemical compound N[C@@H](C(=O)N[C@H]1CN(C[C@H](C1)C)C1=C2C=CC=NC2=C(C=C1)C#N)C MCLARVHBNPVJFY-GZBFAFLISA-N 0.000 claims 1
- GLHTYUAPUWZVHX-YXJHDRRASA-N (2R)-N-[(3R,5S)-1-(8-cyanoquinolin-5-yl)-5-methylpiperidin-3-yl]pyrrolidine-2-carboxamide Chemical compound C(#N)C=1C=CC(=C2C=CC=NC=12)N1C[C@@H](C[C@@H](C1)C)NC(=O)[C@@H]1NCCC1 GLHTYUAPUWZVHX-YXJHDRRASA-N 0.000 claims 1
- AUHYXZSAEUYFAD-BJJXKVORSA-N (2S)-2-amino-N'-[(3R,5S)-1-(8-cyanoquinolin-5-yl)-5-methylpiperidin-3-yl]butanediamide Chemical compound N[C@@H](CC(=O)N[C@H]1CN(C[C@H](C1)C)C1=C2C=CC=NC2=C(C=C1)C#N)C(=O)N AUHYXZSAEUYFAD-BJJXKVORSA-N 0.000 claims 1
- GBSNGTLITPOAQM-NBCNXNJRSA-N (2S)-2-amino-N-[(3R,5S)-1-(8-cyanoquinolin-5-yl)-5-methylpiperidin-3-yl]-2-phenylacetamide Chemical compound N[C@H](C(=O)N[C@H]1CN(C[C@H](C1)C)C1=C2C=CC=NC2=C(C=C1)C#N)C1=CC=CC=C1 GBSNGTLITPOAQM-NBCNXNJRSA-N 0.000 claims 1
- SBQCLFUIJZXTLT-PPHDSNJXSA-N (2S)-2-amino-N-[(3R,5S)-1-(8-cyanoquinolin-5-yl)-5-methylpiperidin-3-yl]-3,3,3-trifluoropropanamide Chemical compound N[C@@H](C(=O)N[C@H]1CN(C[C@H](C1)C)C1=C2C=CC=NC2=C(C=C1)C#N)C(F)(F)F SBQCLFUIJZXTLT-PPHDSNJXSA-N 0.000 claims 1
- CQZCCOHOBPOSTD-YYFZDKIDSA-N (2S)-2-amino-N-[(3R,5S)-1-(8-cyanoquinolin-5-yl)-5-methylpiperidin-3-yl]-3,3-dimethylbutanamide Chemical compound N[C@H](C(=O)N[C@H]1CN(C[C@H](C1)C)C1=C2C=CC=NC2=C(C=C1)C#N)C(C)(C)C CQZCCOHOBPOSTD-YYFZDKIDSA-N 0.000 claims 1
- ZLRSIGBLBQPCOY-YJLNNSPDSA-N (2S)-2-amino-N-[(3R,5S)-1-(8-cyanoquinolin-5-yl)-5-methylpiperidin-3-yl]-3-(1H-imidazol-5-yl)propanamide Chemical compound N[C@H](C(=O)N[C@H]1CN(C[C@H](C1)C)C1=C2C=CC=NC2=C(C=C1)C#N)CC1=CN=CN1 ZLRSIGBLBQPCOY-YJLNNSPDSA-N 0.000 claims 1
- NJWZTPBTBUXEBK-LXZKKBNFSA-N (2S)-2-amino-N-[(3R,5S)-1-(8-cyanoquinolin-5-yl)-5-methylpiperidin-3-yl]-3-methoxypropanamide Chemical compound N[C@H](C(=O)N[C@H]1CN(C[C@H](C1)C)C1=C2C=CC=NC2=C(C=C1)C#N)COC NJWZTPBTBUXEBK-LXZKKBNFSA-N 0.000 claims 1
- PLVSEUMUWNDIQD-GMBSWORKSA-N (2S)-2-amino-N-[(3R,5S)-1-(8-cyanoquinolin-5-yl)-5-methylpiperidin-3-yl]-3-methylbutanamide Chemical compound N[C@H](C(=O)N[C@H]1CN(C[C@H](C1)C)C1=C2C=CC=NC2=C(C=C1)C#N)C(C)C PLVSEUMUWNDIQD-GMBSWORKSA-N 0.000 claims 1
- WDHGJVKAUNBBRU-WDYCEAGBSA-N (2S)-2-amino-N-[(3R,5S)-1-(8-cyanoquinolin-5-yl)-5-methylpiperidin-3-yl]-4,4-dimethylpentanamide Chemical compound N[C@H](C(=O)N[C@H]1CN(C[C@H](C1)C)C1=C2C=CC=NC2=C(C=C1)C#N)CC(C)(C)C WDHGJVKAUNBBRU-WDYCEAGBSA-N 0.000 claims 1
- HKBSADXDDOGWRG-WDYCEAGBSA-N (2S)-2-amino-N-[(3R,5S)-1-(8-cyanoquinolin-5-yl)-5-methylpiperidin-3-yl]-4-methylpentanamide Chemical compound N[C@H](C(=O)N[C@H]1CN(C[C@H](C1)C)C1=C2C=CC=NC2=C(C=C1)C#N)CC(C)C HKBSADXDDOGWRG-WDYCEAGBSA-N 0.000 claims 1
- KKQHXOGKPYDXJU-BJJXKVORSA-N (2S)-2-amino-N-[(3R,5S)-1-(8-cyanoquinolin-5-yl)-5-methylpiperidin-3-yl]butanediamide Chemical compound N[C@H](C(=O)N[C@H]1CN(C[C@H](C1)C)C1=C2C=CC=NC2=C(C=C1)C#N)CC(=O)N KKQHXOGKPYDXJU-BJJXKVORSA-N 0.000 claims 1
- TXJBTONEIKYJNZ-LESCRADOSA-N (2S)-2-amino-N-[(3R,5S)-1-(8-cyanoquinolin-5-yl)-5-methylpiperidin-3-yl]pentanamide Chemical compound N[C@H](C(=O)N[C@H]1CN(C[C@H](C1)C)C1=C2C=CC=NC2=C(C=C1)C#N)CCC TXJBTONEIKYJNZ-LESCRADOSA-N 0.000 claims 1
- PLNCXRCXYXDWDI-LXZKKBNFSA-N (2S)-2-amino-N-[(3R,5S)-1-(8-cyanoquinolin-5-yl)-5-methylpiperidin-3-yl]pentanediamide Chemical compound N[C@H](C(=O)N[C@H]1CN(C[C@H](C1)C)C1=C2C=CC=NC2=C(C=C1)C#N)CCC(=O)N PLNCXRCXYXDWDI-LXZKKBNFSA-N 0.000 claims 1
- MCLARVHBNPVJFY-KCQAQPDRSA-N (2S)-2-amino-N-[(3R,5S)-1-(8-cyanoquinolin-5-yl)-5-methylpiperidin-3-yl]propanamide Chemical compound N[C@H](C(=O)N[C@H]1CN(C[C@H](C1)C)C1=C2C=CC=NC2=C(C=C1)C#N)C MCLARVHBNPVJFY-KCQAQPDRSA-N 0.000 claims 1
- UPOXTVMUMIGFQX-HQRMLTQVSA-N (2S)-N-[(3R,5S)-1-(8-cyanoquinolin-5-yl)-5-methylpiperidin-3-yl]-2-(methylamino)hexanamide Chemical compound C(#N)C=1C=CC(=C2C=CC=NC=12)N1C[C@@H](C[C@@H](C1)C)NC([C@H](CCCC)NC)=O UPOXTVMUMIGFQX-HQRMLTQVSA-N 0.000 claims 1
- FXJIMRHADQSNDK-OFQRWUPVSA-N (2S)-N-[(3R,5S)-1-(8-cyanoquinolin-5-yl)-5-methylpiperidin-3-yl]-2-(methylamino)propanamide Chemical compound C(#N)C=1C=CC(=C2C=CC=NC=12)N1C[C@@H](C[C@@H](C1)C)NC([C@H](C)NC)=O FXJIMRHADQSNDK-OFQRWUPVSA-N 0.000 claims 1
- UBHKMWMJXZIKEV-NBQZKYEYSA-N (2S)-N-[(3R,5S)-1-(8-cyanoquinolin-5-yl)-5-methylpiperidin-3-yl]-2-hydroxy-3-methylbutanamide Chemical compound C(#N)C=1C=CC(=C2C=CC=NC=12)N1C[C@@H](C[C@@H](C1)C)NC([C@H](C(C)C)O)=O UBHKMWMJXZIKEV-NBQZKYEYSA-N 0.000 claims 1
- SRQWPXHCVOEYJC-COCVIAQXSA-N (2S,3S)-2-amino-N-[(3R,5S)-1-(8-cyanoquinolin-5-yl)-5-methylpiperidin-3-yl]-3-methylpentanamide Chemical compound N[C@H](C(=O)N[C@H]1CN(C[C@H](C1)C)C1=C2C=CC=NC2=C(C=C1)C#N)[C@H](CC)C SRQWPXHCVOEYJC-COCVIAQXSA-N 0.000 claims 1
- RFXZAMLCCZJCPH-ZDRJDWQYSA-N (2S,4R)-N-[(3R,5S)-1-(8-cyanoquinolin-5-yl)-5-methylpiperidin-3-yl]-4-hydroxypyrrolidine-2-carboxamide Chemical compound C[C@H]1C[C@H](CN(C1)c1ccc(C#N)c2ncccc12)NC(=O)[C@@H]1C[C@@H](O)CN1 RFXZAMLCCZJCPH-ZDRJDWQYSA-N 0.000 claims 1
- WEGPVDHTUARHOU-KVSKMBFKSA-N (3R)-3-amino-N-[(3R,5S)-1-(8-cyanoquinolin-5-yl)-5-methylpiperidin-3-yl]-4-methylpentanamide Chemical compound N[C@H](CC(=O)N[C@H]1CN(C[C@H](C1)C)C1=C2C=CC=NC2=C(C=C1)C#N)C(C)C WEGPVDHTUARHOU-KVSKMBFKSA-N 0.000 claims 1
- NRQDUIUHNZFHAQ-SQWLQELKSA-N (3R)-3-amino-N-[(3R,5S)-1-(8-cyanoquinolin-5-yl)-5-methylpiperidin-3-yl]butanamide Chemical compound N[C@@H](CC(=O)N[C@H]1CN(C[C@H](C1)C)C1=C2C=CC=NC2=C(C=C1)C#N)C NRQDUIUHNZFHAQ-SQWLQELKSA-N 0.000 claims 1
- ZAHKIMGEERWNKN-YXJHDRRASA-N (3R)-N-[(3R,5S)-1-(8-cyanoquinolin-5-yl)-5-methylpiperidin-3-yl]morpholine-3-carboxamide Chemical compound C(#N)C=1C=CC(=C2C=CC=NC=12)N1C[C@@H](C[C@@H](C1)C)NC(=O)[C@@H]1NCCOC1 ZAHKIMGEERWNKN-YXJHDRRASA-N 0.000 claims 1
- WEGPVDHTUARHOU-WDYCEAGBSA-N (3S)-3-amino-N-[(3R,5S)-1-(8-cyanoquinolin-5-yl)-5-methylpiperidin-3-yl]-4-methylpentanamide Chemical compound N[C@@H](CC(=O)N[C@H]1CN(C[C@H](C1)C)C1=C2C=CC=NC2=C(C=C1)C#N)C(C)C WEGPVDHTUARHOU-WDYCEAGBSA-N 0.000 claims 1
- NRQDUIUHNZFHAQ-OFQRWUPVSA-N (3S)-3-amino-N-[(3R,5S)-1-(8-cyanoquinolin-5-yl)-5-methylpiperidin-3-yl]butanamide Chemical compound N[C@H](CC(=O)N[C@H]1CN(C[C@H](C1)C)C1=C2C=CC=NC2=C(C=C1)C#N)C NRQDUIUHNZFHAQ-OFQRWUPVSA-N 0.000 claims 1
- ZAHKIMGEERWNKN-LESCRADOSA-N (3S)-N-[(3R,5S)-1-(8-cyanoquinolin-5-yl)-5-methylpiperidin-3-yl]morpholine-3-carboxamide Chemical compound C(#N)C=1C=CC(=C2C=CC=NC=12)N1C[C@@H](C[C@@H](C1)C)NC(=O)[C@H]1NCCOC1 ZAHKIMGEERWNKN-LESCRADOSA-N 0.000 claims 1
- WPOSDRYKVRISBO-YSVLISHTSA-N (4S)-N-[(3R,5S)-1-(8-cyanoquinolin-5-yl)-5-methylpiperidin-3-yl]-1,3-thiazolidine-4-carboxamide Chemical compound C(#N)C=1C=CC(=C2C=CC=NC=12)N1C[C@@H](C[C@@H](C1)C)NC(=O)[C@@H]1NCSC1 WPOSDRYKVRISBO-YSVLISHTSA-N 0.000 claims 1
- GUFOZQLBETZPLW-YPSXYOJZSA-N 1-amino-N-[(3R,5S)-1-(8-cyanoquinolin-5-yl)-5-methylpiperidin-3-yl]-3-hydroxycyclopentane-1-carboxamide Chemical compound NC1(CC(CC1)O)C(=O)N[C@H]1CN(C[C@H](C1)C)C1=C2C=CC=NC2=C(C=C1)C#N GUFOZQLBETZPLW-YPSXYOJZSA-N 0.000 claims 1
- RZSGTJOBEJJBKU-VFGXLCBOSA-N 1-amino-N-[(3R,5S)-1-(8-cyanoquinolin-5-yl)-5-methylpiperidin-3-yl]-4-hydroxycyclohexane-1-carboxamide Chemical compound C[C@H]1C[C@H](CN(C1)C1=C2C=CC=NC2=C(C=C1)C#N)NC(=O)C1(N)CCC(O)CC1 RZSGTJOBEJJBKU-VFGXLCBOSA-N 0.000 claims 1
- KCYVXOKULNIGRK-DZGCQCFKSA-N 1-amino-N-[(3R,5S)-1-(8-cyanoquinolin-5-yl)-5-methylpiperidin-3-yl]cyclopropane-1-carboxamide Chemical compound NC1(CC1)C(=O)N[C@H]1CN(C[C@H](C1)C)C1=C2C=CC=NC2=C(C=C1)C#N KCYVXOKULNIGRK-DZGCQCFKSA-N 0.000 claims 1
- JZQAXVGNYWSACD-WMLDXEAASA-N 2-(azetidin-3-yl)-N-[(3R,5S)-1-(8-cyanoquinolin-5-yl)-5-methylpiperidin-3-yl]acetamide Chemical compound N1CC(C1)CC(=O)N[C@H]1CN(C[C@H](C1)C)C1=C2C=CC=NC2=C(C=C1)C#N JZQAXVGNYWSACD-WMLDXEAASA-N 0.000 claims 1
- JCWJKRBBQCWFPE-AZUAARDMSA-N 2-[1-(aminomethyl)cyclohexyl]-N-[(3R,5S)-1-(8-cyanoquinolin-5-yl)-5-methylpiperidin-3-yl]acetamide Chemical compound C[C@H]1C[C@H](CN(C1)c1ccc(C#N)c2ncccc12)NC(=O)CC1(CN)CCCCC1 JCWJKRBBQCWFPE-AZUAARDMSA-N 0.000 claims 1
- JLXRLGIMDBMAHT-GOEBONIOSA-N 2-[[(3R,5S)-1-(8-cyanoquinolin-5-yl)-5-methylpiperidin-3-yl]amino]-N,N-dimethylacetamide Chemical compound C(#N)C=1C=CC(=C2C=CC=NC12)N1C[C@@H](C[C@@H](C1)C)NCC(=O)N(C)C JLXRLGIMDBMAHT-GOEBONIOSA-N 0.000 claims 1
- IOOALLPKMLPOPP-GOEBONIOSA-N 2-[[(3R,5S)-1-(8-cyanoquinolin-5-yl)-5-methylpiperidin-3-yl]amino]-N-ethylacetamide Chemical compound C(#N)C=1C=CC(=C2C=CC=NC12)N1C[C@@H](C[C@@H](C1)C)NCC(=O)NCC IOOALLPKMLPOPP-GOEBONIOSA-N 0.000 claims 1
- NJTBNHUTGHYSNP-DZGCQCFKSA-N 2-[[(3R,5S)-1-(8-cyanoquinolin-5-yl)-5-methylpiperidin-3-yl]amino]-N-methylacetamide Chemical compound C(#N)C=1C=CC(=C2C=CC=NC12)N1C[C@@H](C[C@@H](C1)C)NCC(=O)NC NJTBNHUTGHYSNP-DZGCQCFKSA-N 0.000 claims 1
- HMMMOIOPDPFULC-GXTWGEPZSA-N 2-[[(3R,5S)-1-(8-cyanoquinolin-5-yl)-5-methylpiperidin-3-yl]amino]acetamide Chemical compound C(#N)C=1C=CC(=C2C=CC=NC=12)N1C[C@@H](C[C@@H](C1)C)NCC(=O)N HMMMOIOPDPFULC-GXTWGEPZSA-N 0.000 claims 1
- DAJXLHINMWNLRE-DZGCQCFKSA-N 2-amino-N-[(3R,5S)-1-(8-cyanoquinolin-5-yl)-5-methylpiperidin-3-yl]-2-methylpropanamide Chemical compound NC(C(=O)N[C@H]1CN(C[C@H](C1)C)C1=C2C=CC=NC2=C(C=C1)C#N)(C)C DAJXLHINMWNLRE-DZGCQCFKSA-N 0.000 claims 1
- CQZCCOHOBPOSTD-DBMQZSJKSA-N 2-amino-N-[(3R,5S)-1-(8-cyanoquinolin-5-yl)-5-methylpiperidin-3-yl]-3,3-dimethylbutanamide Chemical compound NC(C(=O)N[C@H]1CN(C[C@H](C1)C)C1=C2C=CC=NC2=C(C=C1)C#N)C(C)(C)C CQZCCOHOBPOSTD-DBMQZSJKSA-N 0.000 claims 1
- PLVSEUMUWNDIQD-FSGMKPHLSA-N 2-amino-N-[(3R,5S)-1-(8-cyanoquinolin-5-yl)-5-methylpiperidin-3-yl]-3-methylbutanamide Chemical compound NC(C(=O)N[C@H]1CN(C[C@H](C1)C)C1=C2C=CC=NC2=C(C=C1)C#N)C(C)C PLVSEUMUWNDIQD-FSGMKPHLSA-N 0.000 claims 1
- LFUFLUYPSJXLDE-QJZXMCBYSA-N 2-amino-N-[(3R,5S)-1-(8-cyanoquinolin-5-yl)-5-methylpiperidin-3-yl]-4-methylsulfanylbutanamide Chemical compound CSCCC(N)C(=O)N[C@@H]1C[C@H](C)CN(C1)c1ccc(C#N)c2ncccc12 LFUFLUYPSJXLDE-QJZXMCBYSA-N 0.000 claims 1
- TZVWRTYMVFXDOZ-GXTWGEPZSA-N 2-amino-N-[(3R,5S)-1-(8-cyanoquinolin-5-yl)-5-methylpiperidin-3-yl]acetamide Chemical compound NCC(=O)N[C@H]1CN(C[C@H](C1)C)C1=C2C=CC=NC2=C(C=C1)C#N TZVWRTYMVFXDOZ-GXTWGEPZSA-N 0.000 claims 1
- MSJIFXMFGWHORA-DZGCQCFKSA-N 2-amino-N-[(3R,5S)-1-(8-cyanoquinolin-5-yl)-5-methylpiperidin-3-yl]ethanesulfonamide Chemical compound NCCS(=O)(=O)N[C@H]1CN(C[C@H](C1)C)C1=C2C=CC=NC2=C(C=C1)C#N MSJIFXMFGWHORA-DZGCQCFKSA-N 0.000 claims 1
- UCEPVFBTJALCAW-KUARMEPBSA-N 2-hydroxypropane-1,2,3-tricarboxylic acid 5-[(3R,5S)-3-(2-methoxyethylamino)-5-methylpiperidin-1-yl]quinoline-8-carbonitrile Chemical compound OC(=O)CC(O)(CC(O)=O)C(O)=O.COCCN[C@@H]1C[C@H](C)CN(C1)c1ccc(C#N)c2ncccc12 UCEPVFBTJALCAW-KUARMEPBSA-N 0.000 claims 1
- JZKTYEFKAWMJFO-DZGCQCFKSA-N 3-amino-N-[(3R,5S)-1-(8-cyanoquinolin-5-yl)-5-methylpiperidin-3-yl]oxetane-3-carboxamide Chemical compound NC1(COC1)C(=O)N[C@H]1CN(C[C@H](C1)C)C1=C2C=CC=NC2=C(C=C1)C#N JZKTYEFKAWMJFO-DZGCQCFKSA-N 0.000 claims 1
- DSCIPMDWPNFYCH-HNAYVOBHSA-N 4-amino-N-[(3R,5S)-1-(8-cyanoquinolin-5-yl)-5-methylpiperidin-3-yl]benzamide Chemical compound NC1=CC=C(C(=O)N[C@H]2CN(C[C@H](C2)C)C2=C3C=CC=NC3=C(C=C2)C#N)C=C1 DSCIPMDWPNFYCH-HNAYVOBHSA-N 0.000 claims 1
- FPQMWWMZLQHZPA-GFCCVEGCSA-N 5-[(3R)-3-aminopiperidin-1-yl]quinoline-8-carbonitrile Chemical compound N[C@H]1CN(CCC1)C1=C2C=CC=NC2=C(C=C1)C#N FPQMWWMZLQHZPA-GFCCVEGCSA-N 0.000 claims 1
- QFNVHAQBOVHSOU-GXTWGEPZSA-N 5-[(3R,5S)-3-(2,2-difluoroethylamino)-5-methylpiperidin-1-yl]quinoline-8-carbonitrile Chemical compound FC(CN[C@H]1CN(C[C@H](C1)C)C1=C2C=CC=NC2=C(C=C1)C#N)F QFNVHAQBOVHSOU-GXTWGEPZSA-N 0.000 claims 1
- GHANVXHUGKFIAO-GOEBONIOSA-N 5-[(3R,5S)-3-(2-methoxyethylamino)-5-methylpiperidin-1-yl]quinoline-8-carbonitrile Chemical compound COCCN[C@H]1CN(C[C@H](C1)C)C1=C2C=CC=NC2=C(C=C1)C#N GHANVXHUGKFIAO-GOEBONIOSA-N 0.000 claims 1
- HAGFOKHKURKKCU-DZGCQCFKSA-N 5-[(3R,5S)-3-(cyanomethylamino)-5-methylpiperidin-1-yl]quinoline-8-carbonitrile Chemical compound C(#N)CN[C@H]1CN(C[C@H](C1)C)C1=C2C=CC=NC2=C(C=C1)C#N HAGFOKHKURKKCU-DZGCQCFKSA-N 0.000 claims 1
- GARXROVFNAHNAJ-DZGCQCFKSA-N 5-[(3R,5S)-3-(dimethylamino)-5-methylpiperidin-1-yl]quinoline-8-carbonitrile Chemical compound CN([C@H]1CN(C[C@H](C1)C)C1=C2C=CC=NC2=C(C=C1)C#N)C GARXROVFNAHNAJ-DZGCQCFKSA-N 0.000 claims 1
- LIFMBQPGDWHVQT-DZGCQCFKSA-N 5-[(3R,5S)-3-(ethylamino)-5-methylpiperidin-1-yl]quinoline-8-carbonitrile Chemical compound C(C)N[C@H]1CN(C[C@H](C1)C)C1=C2C=CC=NC2=C(C=C1)C#N LIFMBQPGDWHVQT-DZGCQCFKSA-N 0.000 claims 1
- FCHISKFXARNLGD-MAUKXSAKSA-N 5-[(3R,5S)-3-[(1,1-dioxothian-4-yl)amino]-5-methylpiperidin-1-yl]quinoline-8-carbonitrile Chemical compound O=S1(CCC(CC1)N[C@H]1CN(C[C@H](C1)C)C1=C2C=CC=NC2=C(C=C1)C#N)=O FCHISKFXARNLGD-MAUKXSAKSA-N 0.000 claims 1
- JJBZSAZSDMFAGM-GBJJWRMUSA-N 5-[(3R,5S)-3-[(2-cyanocyclopentyl)amino]-5-methylpiperidin-1-yl]quinoline-8-carbonitrile Chemical compound C(#N)C1C(CCC1)N[C@H]1CN(C[C@H](C1)C)C1=C2C=CC=NC2=C(C=C1)C#N JJBZSAZSDMFAGM-GBJJWRMUSA-N 0.000 claims 1
- NCGXZHMHDAABFZ-KBXCAEBGSA-N 5-[(3R,5S)-3-[(3,5-dimethyl-1,2-oxazol-4-yl)methylamino]-5-methylpiperidin-1-yl]quinoline-8-carbonitrile Chemical compound CC1=NOC(=C1CN[C@H]1CN(C[C@H](C1)C)C1=C2C=CC=NC2=C(C=C1)C#N)C NCGXZHMHDAABFZ-KBXCAEBGSA-N 0.000 claims 1
- DQIQXORDOXJJCS-GOEBONIOSA-N 5-[(3R,5S)-3-[(3-aminooxetan-3-yl)methylamino]-5-methylpiperidin-1-yl]quinoline-8-carbonitrile Chemical compound NC1(COC1)CN[C@H]1CN(C[C@H](C1)C)C1=C2C=CC=NC2=C(C=C1)C#N DQIQXORDOXJJCS-GOEBONIOSA-N 0.000 claims 1
- OPSVQCCVHUYOAA-WDEREUQCSA-N 5-[(3R,5S)-3-amino-5-methylpiperidin-1-yl]quinoline-8-carboxamide Chemical compound N[C@H]1CN(C[C@H](C1)C)C1=C2C=CC=NC2=C(C=C1)C(=O)N OPSVQCCVHUYOAA-WDEREUQCSA-N 0.000 claims 1
- OUHZCESHQZMEFR-WCQYABFASA-N 5-[(3R,5S)-3-hydroxy-5-methylpiperidin-1-yl]quinoline-8-carbonitrile Chemical compound O[C@H]1CN(C[C@H](C1)C)C1=C2C=CC=NC2=C(C=C1)C#N OUHZCESHQZMEFR-WCQYABFASA-N 0.000 claims 1
- UCIDSRZJTOTWCF-GOEBONIOSA-N 5-[(3S,5R)-3-methyl-5-(1,3-oxazol-2-ylmethylamino)piperidin-1-yl]quinoline-8-carbonitrile Chemical compound C[C@@H]1CN(C[C@@H](C1)NCC=1OC=CN=1)C1=C2C=CC=NC2=C(C=C1)C#N UCIDSRZJTOTWCF-GOEBONIOSA-N 0.000 claims 1
- RDPKDSKQGOIHDG-LVLJQFTKSA-N 5-[(3S,5R)-3-methyl-5-(1-pyridin-2-ylethylamino)piperidin-1-yl]quinoline-8-carbonitrile Chemical compound C[C@@H]1CN(C[C@@H](C1)NC(C)C1=NC=CC=C1)C1=C2C=CC=NC2=C(C=C1)C#N RDPKDSKQGOIHDG-LVLJQFTKSA-N 0.000 claims 1
- OFNXRPSQEYZPMJ-WMLDXEAASA-N 5-[(3S,5R)-3-methyl-5-(1H-pyrazol-5-ylmethylamino)piperidin-1-yl]quinoline-8-carbonitrile Chemical compound N1N=CC=C1CN[C@H]1CN(C[C@H](C1)C)C1=C2C=CC=NC2=C(C=C1)C#N OFNXRPSQEYZPMJ-WMLDXEAASA-N 0.000 claims 1
- WNZGOINMOSRHKN-GXTWGEPZSA-N 5-[(3S,5R)-3-methyl-5-(2,2,2-trifluoroethylamino)piperidin-1-yl]quinoline-8-carbonitrile Chemical compound C[C@@H]1CN(C[C@@H](C1)NCC(F)(F)F)C1=C2C=CC=NC2=C(C=C1)C#N WNZGOINMOSRHKN-GXTWGEPZSA-N 0.000 claims 1
- FLJRGMXVSGCSRI-DZGCQCFKSA-N 5-[(3S,5R)-3-methyl-5-(3,3,3-trifluoropropylamino)piperidin-1-yl]quinoline-8-carbonitrile Chemical compound C[C@@H]1CN(C[C@@H](C1)NCCC(F)(F)F)C1=C2C=CC=NC2=C(C=C1)C#N FLJRGMXVSGCSRI-DZGCQCFKSA-N 0.000 claims 1
- QZEAQDXUYGUVRF-DOTOQJQBSA-N 5-[(3S,5R)-3-methyl-5-(3-methylsulfonylpropylamino)piperidin-1-yl]quinoline-8-carbonitrile Chemical compound C[C@@H]1CN(C[C@@H](C1)NCCCS(=O)(=O)C)C1=C2C=CC=NC2=C(C=C1)C#N QZEAQDXUYGUVRF-DOTOQJQBSA-N 0.000 claims 1
- IMXGIEMHMXNTEI-GXTWGEPZSA-N 5-[(3S,5R)-3-methyl-5-(methylamino)piperidin-1-yl]quinoline-8-carbonitrile Chemical compound C[C@@H]1CN(C[C@@H](C1)NC)C1=C2C=CC=NC2=C(C=C1)C#N IMXGIEMHMXNTEI-GXTWGEPZSA-N 0.000 claims 1
- MYXMZVJRGRJRSK-DKKDMOBXSA-N 5-[(3S,5R)-3-methyl-5-(oxan-3-ylamino)piperidin-1-yl]quinoline-8-carbonitrile Chemical compound C[C@@H]1CN(C[C@@H](C1)NC1COCCC1)C1=C2C=CC=NC2=C(C=C1)C#N MYXMZVJRGRJRSK-DKKDMOBXSA-N 0.000 claims 1
- AGLANHZQTXXUMX-MAUKXSAKSA-N 5-[(3S,5R)-3-methyl-5-(oxan-4-ylamino)piperidin-1-yl]quinoline-8-carbonitrile Chemical compound C[C@@H]1CN(C[C@@H](C1)NC1CCOCC1)C1=C2C=CC=NC2=C(C=C1)C#N AGLANHZQTXXUMX-MAUKXSAKSA-N 0.000 claims 1
- ULLJMMWMNOCMIB-DZGCQCFKSA-N 5-[(3S,5R)-3-methyl-5-(oxetan-3-ylamino)piperidin-1-yl]quinoline-8-carbonitrile Chemical compound C[C@@H]1CN(C[C@@H](C1)NC1COC1)C1=C2C=CC=NC2=C(C=C1)C#N ULLJMMWMNOCMIB-DZGCQCFKSA-N 0.000 claims 1
- NESPOGIWKNXEDZ-DRXWIORDSA-N 5-[(3S,5R)-3-methyl-5-(oxolan-3-ylamino)piperidin-1-yl]quinoline-8-carbonitrile Chemical compound C[C@@H]1CN(C[C@@H](C1)NC1COCC1)C1=C2C=CC=NC2=C(C=C1)C#N NESPOGIWKNXEDZ-DRXWIORDSA-N 0.000 claims 1
- FJAACKITTPXTTK-DOTOQJQBSA-N 5-[(3S,5R)-3-methyl-5-[(1-methylimidazol-4-yl)methylamino]piperidin-1-yl]quinoline-8-carbonitrile Chemical compound C[C@@H]1CN(C[C@@H](C1)NCC=1N=CN(C=1)C)C1=C2C=CC=NC2=C(C=C1)C#N FJAACKITTPXTTK-DOTOQJQBSA-N 0.000 claims 1
- HGSSICVTPZKQQL-GZJFXKPMSA-N 5-[(3S,5R)-3-methyl-5-[(2-oxopyrrolidin-3-yl)amino]piperidin-1-yl]quinoline-8-carbonitrile Chemical compound C[C@@H]1CN(C[C@@H](C1)NC1C(NCC1)=O)C1=C2C=CC=NC2=C(C=C1)C#N HGSSICVTPZKQQL-GZJFXKPMSA-N 0.000 claims 1
- QPIKVGNKSDXAHK-DOTOQJQBSA-N 5-[(3S,5R)-3-methyl-5-[(3-methyloxetan-3-yl)methylamino]piperidin-1-yl]quinoline-8-carbonitrile Chemical compound C[C@@H]1CN(C[C@@H](C1)NCC1(COC1)C)C1=C2C=CC=NC2=C(C=C1)C#N QPIKVGNKSDXAHK-DOTOQJQBSA-N 0.000 claims 1
- PVJLCOKIFNZOLE-MAUKXSAKSA-N 5-[(3S,5R)-3-methyl-5-[(4-oxocyclohexyl)amino]piperidin-1-yl]quinoline-8-carbonitrile Chemical compound C[C@@H]1CN(C[C@@H](C1)NC1CCC(CC1)=O)C1=C2C=CC=NC2=C(C=C1)C#N PVJLCOKIFNZOLE-MAUKXSAKSA-N 0.000 claims 1
- RAZDPBMHANOILQ-LYNLNPNLSA-N 5-[(3S,5R)-3-methyl-5-[1-(6-methylpyridin-2-yl)ethylamino]piperidin-1-yl]quinoline-8-carbonitrile Chemical compound C[C@@H]1CN(C[C@@H](C1)NC(C)C1=NC(=CC=C1)C)C1=C2C=CC=NC2=C(C=C1)C#N RAZDPBMHANOILQ-LYNLNPNLSA-N 0.000 claims 1
- BNGBLAFHISTXDK-HNAYVOBHSA-N 5-[(3S,5R)-3-methyl-5-[[5-(trifluoromethyl)pyridin-2-yl]methylamino]piperidin-1-yl]quinoline-8-carbonitrile Chemical compound C[C@@H]1CN(C[C@@H](C1)NCC1=NC=C(C=C1)C(F)(F)F)C1=C2C=CC=NC2=C(C=C1)C#N BNGBLAFHISTXDK-HNAYVOBHSA-N 0.000 claims 1
- ULQBBCYBMKQUMZ-MAUKXSAKSA-N 5-[(3S,5R)-3-methyl-5-[[6-(trifluoromethyl)pyridin-3-yl]methylamino]piperidin-1-yl]quinoline-8-carbonitrile Chemical compound C[C@@H]1CN(C[C@@H](C1)NCC=1C=NC(=CC=1)C(F)(F)F)C1=C2C=CC=NC2=C(C=C1)C#N ULQBBCYBMKQUMZ-MAUKXSAKSA-N 0.000 claims 1
- UIEOEMJOIWJXAL-CYBMUJFWSA-N 5-[(5R)-5-amino-3,3-dimethylpiperidin-1-yl]quinoline-8-carbonitrile Chemical compound N[C@@H]1CC(CN(C1)C1=C2C=CC=NC2=C(C=C1)C#N)(C)C UIEOEMJOIWJXAL-CYBMUJFWSA-N 0.000 claims 1
- WZLXBCNVVUIINC-HLIUYOAVSA-N 5-[(5S)-3-(1-hydroxypropan-2-ylamino)-5-methylpiperidin-1-yl]quinoline-8-carbonitrile Chemical compound OCC(C)NC1CN(C[C@H](C1)C)C1=C2C=CC=NC2=C(C=C1)C#N WZLXBCNVVUIINC-HLIUYOAVSA-N 0.000 claims 1
- ILGWKYXHVFRPQT-DOTOQJQBSA-N 5-amino-N-[(3R,5S)-1-(8-cyanoquinolin-5-yl)-5-methylpiperidin-3-yl]pentanamide Chemical compound NCCCCC(=O)N[C@H]1CN(C[C@H](C1)C)C1=C2C=CC=NC2=C(C=C1)C#N ILGWKYXHVFRPQT-DOTOQJQBSA-N 0.000 claims 1
- KKPHYFFGMRJEPY-XJKSGUPXSA-N N-[(3R,5S)-1-(8-cyanoquinolin-5-yl)-5-methylpiperidin-3-yl]-1H-pyrazole-4-carboxamide Chemical compound C(#N)C=1C=CC(=C2C=CC=NC=12)N1C[C@@H](C[C@@H](C1)C)NC(=O)C=1C=NNC=1 KKPHYFFGMRJEPY-XJKSGUPXSA-N 0.000 claims 1
- HGFFWTNRTNYXEB-WCQYABFASA-N N-[(3R,5S)-1-(8-cyanoquinolin-5-yl)-5-methylpiperidin-3-yl]-2,2,2-trifluoroacetamide Chemical compound C(#N)C=1C=CC(=C2C=CC=NC=12)N1C[C@@H](C[C@@H](C1)C)NC(C(F)(F)F)=O HGFFWTNRTNYXEB-WCQYABFASA-N 0.000 claims 1
- YUBCLCLSPGFDFI-WMLDXEAASA-N N-[(3R,5S)-1-(8-cyanoquinolin-5-yl)-5-methylpiperidin-3-yl]-2-(1H-imidazol-5-yl)acetamide Chemical compound C(#N)C=1C=CC(=C2C=CC=NC=12)N1C[C@@H](C[C@@H](C1)C)NC(CC1=CN=CN1)=O YUBCLCLSPGFDFI-WMLDXEAASA-N 0.000 claims 1
- HEBHRLKOTOQKCD-GOEBONIOSA-N N-[(3R,5S)-1-(8-cyanoquinolin-5-yl)-5-methylpiperidin-3-yl]-2-(dimethylamino)acetamide Chemical compound C(#N)C=1C=CC(=C2C=CC=NC=12)N1C[C@@H](C[C@@H](C1)C)NC(CN(C)C)=O HEBHRLKOTOQKCD-GOEBONIOSA-N 0.000 claims 1
- QKPILARUPBBPKV-DOTOQJQBSA-N N-[(3R,5S)-1-(8-cyanoquinolin-5-yl)-5-methylpiperidin-3-yl]-2-(dimethylamino)ethanesulfonamide Chemical compound C(#N)C=1C=CC(=C2C=CC=NC=12)N1C[C@@H](C[C@@H](C1)C)NS(=O)(=O)CCN(C)C QKPILARUPBBPKV-DOTOQJQBSA-N 0.000 claims 1
- YHDMSRHXHVQKBE-DZGCQCFKSA-N N-[(3R,5S)-1-(8-cyanoquinolin-5-yl)-5-methylpiperidin-3-yl]-2-(methylamino)acetamide Chemical compound C(#N)C=1C=CC(=C2C=CC=NC=12)N1C[C@@H](C[C@@H](C1)C)NC(CNC)=O YHDMSRHXHVQKBE-DZGCQCFKSA-N 0.000 claims 1
- PBNXHQVYBNHGTO-GOEBONIOSA-N N-[(3R,5S)-1-(8-cyanoquinolin-5-yl)-5-methylpiperidin-3-yl]-2-ethylsulfanylacetamide Chemical compound C(#N)C=1C=CC(=C2C=CC=NC=12)N1C[C@@H](C[C@@H](C1)C)NC(CSCC)=O PBNXHQVYBNHGTO-GOEBONIOSA-N 0.000 claims 1
- SKXVUXLIIHRWGI-GXTWGEPZSA-N N-[(3R,5S)-1-(8-cyanoquinolin-5-yl)-5-methylpiperidin-3-yl]-2-hydroxyacetamide Chemical compound C(#N)C=1C=CC(=C2C=CC=NC=12)N1C[C@@H](C[C@@H](C1)C)NC(CO)=O SKXVUXLIIHRWGI-GXTWGEPZSA-N 0.000 claims 1
- GNKFJTIVCDACAS-DZGCQCFKSA-N N-[(3R,5S)-1-(8-cyanoquinolin-5-yl)-5-methylpiperidin-3-yl]-2-methoxyacetamide Chemical compound C(#N)C=1C=CC(=C2C=CC=NC=12)N1C[C@@H](C[C@@H](C1)C)NC(COC)=O GNKFJTIVCDACAS-DZGCQCFKSA-N 0.000 claims 1
- WKGHLNKJYRNEEL-GOEBONIOSA-N N-[(3R,5S)-1-(8-cyanoquinolin-5-yl)-5-methylpiperidin-3-yl]-2-methylpyrazole-3-carboxamide Chemical compound C(#N)C=1C=CC(=C2C=CC=NC=12)N1C[C@@H](C[C@@H](C1)C)NC(=O)C1=CC=NN1C WKGHLNKJYRNEEL-GOEBONIOSA-N 0.000 claims 1
- MPNXXCLTGCJKIF-DZGCQCFKSA-N N-[(3R,5S)-1-(8-cyanoquinolin-5-yl)-5-methylpiperidin-3-yl]-2-methylsulfanylacetamide Chemical compound C(#N)C=1C=CC(=C2C=CC=NC=12)N1C[C@@H](C[C@@H](C1)C)NC(CSC)=O MPNXXCLTGCJKIF-DZGCQCFKSA-N 0.000 claims 1
- FAKDVMYSTNVMFA-DZGCQCFKSA-N N-[(3R,5S)-1-(8-cyanoquinolin-5-yl)-5-methylpiperidin-3-yl]-2-methylsulfonylacetamide Chemical compound C(#N)C=1C=CC(=C2C=CC=NC=12)N1C[C@@H](C[C@@H](C1)C)NC(CS(=O)(=O)C)=O FAKDVMYSTNVMFA-DZGCQCFKSA-N 0.000 claims 1
- JBDZURITHPRCJH-QFBILLFUSA-N N-[(3R,5S)-1-(8-cyanoquinolin-5-yl)-5-methylpiperidin-3-yl]-2-piperidin-4-ylacetamide Chemical compound C(#N)C=1C=CC(=C2C=CC=NC=12)N1C[C@@H](C[C@@H](C1)C)NC(CC1CCNCC1)=O JBDZURITHPRCJH-QFBILLFUSA-N 0.000 claims 1
- ICYSNCTWUHFDIT-DOTOQJQBSA-N N-[(3R,5S)-1-(8-cyanoquinolin-5-yl)-5-methylpiperidin-3-yl]-2-pyrazol-1-ylacetamide Chemical compound C(#N)C=1C=CC(=C2C=CC=NC=12)N1C[C@@H](C[C@@H](C1)C)NC(CN1N=CC=C1)=O ICYSNCTWUHFDIT-DOTOQJQBSA-N 0.000 claims 1
- DCSSSKNUQGKHEU-QFBILLFUSA-N N-[(3R,5S)-1-(8-cyanoquinolin-5-yl)-5-methylpiperidin-3-yl]-2-pyridin-2-ylacetamide Chemical compound C(#N)C=1C=CC(=C2C=CC=NC=12)N1C[C@@H](C[C@@H](C1)C)NC(CC1=NC=CC=C1)=O DCSSSKNUQGKHEU-QFBILLFUSA-N 0.000 claims 1
- NSNFYMJWISNRSM-NANQTSIFSA-N N-[(3R,5S)-1-(8-cyanoquinolin-5-yl)-5-methylpiperidin-3-yl]-2-pyrrolidin-3-ylacetamide Chemical compound C(#N)C=1C=CC(=C2C=CC=NC12)N1C[C@@H](C[C@@H](C1)C)NC(CC1CNCC1)=O NSNFYMJWISNRSM-NANQTSIFSA-N 0.000 claims 1
- IJACPQKFOLJSML-GXTWGEPZSA-N N-[(3R,5S)-1-(8-cyanoquinolin-5-yl)-5-methylpiperidin-3-yl]-3,3,3-trifluoropropanamide Chemical compound C(#N)C=1C=CC(=C2C=CC=NC=12)N1C[C@@H](C[C@@H](C1)C)NC(CC(F)(F)F)=O IJACPQKFOLJSML-GXTWGEPZSA-N 0.000 claims 1
- YXPHTPAGFABTNS-FUHWJXTLSA-N N-[(3R,5S)-1-(8-cyanoquinolin-5-yl)-5-methylpiperidin-3-yl]-3-(dimethylamino)propane-1-sulfonamide Chemical compound C(#N)C=1C=CC(=C2C=CC=NC=12)N1C[C@@H](C[C@@H](C1)C)NS(=O)(=O)CCCN(C)C YXPHTPAGFABTNS-FUHWJXTLSA-N 0.000 claims 1
- MUGJXJQHPJXSMK-MAUKXSAKSA-N N-[(3R,5S)-1-(8-cyanoquinolin-5-yl)-5-methylpiperidin-3-yl]-3-hydroxybenzamide Chemical compound C(#N)C=1C=CC(=C2C=CC=NC=12)N1C[C@@H](C[C@@H](C1)C)NC(C1=CC(=CC=C1)O)=O MUGJXJQHPJXSMK-MAUKXSAKSA-N 0.000 claims 1
- LOWLIXJVOKQXRP-DAPIJDQBSA-N N-[(3R,5S)-1-(8-cyanoquinolin-5-yl)-5-methylpiperidin-3-yl]-3-methyl-2-(methylamino)butanamide Chemical compound CNC(C(C)C)C(=O)N[C@@H]1C[C@H](C)CN(C1)c1ccc(C#N)c2ncccc12 LOWLIXJVOKQXRP-DAPIJDQBSA-N 0.000 claims 1
- NCSOFSYILGIFDO-GOEBONIOSA-N N-[(3R,5S)-1-(8-cyanoquinolin-5-yl)-5-methylpiperidin-3-yl]-3-methylimidazole-4-carboxamide Chemical compound C(#N)C=1C=CC(=C2C=CC=NC=12)N1C[C@@H](C[C@@H](C1)C)NC(=O)C1=CN=CN1C NCSOFSYILGIFDO-GOEBONIOSA-N 0.000 claims 1
- BMPCHFHJINHAMJ-GOEBONIOSA-N N-[(3R,5S)-1-(8-cyanoquinolin-5-yl)-5-methylpiperidin-3-yl]-3-methyloxetane-3-carboxamide Chemical compound C(#N)C=1C=CC(=C2C=CC=NC=12)N1C[C@@H](C[C@@H](C1)C)NC(=O)C1(COC1)C BMPCHFHJINHAMJ-GOEBONIOSA-N 0.000 claims 1
- WNTUNZINLPYPCF-JVPALSCHSA-N N-[(3R,5S)-1-(8-cyanoquinolin-5-yl)-5-methylpiperidin-3-yl]-3-piperidin-2-ylpropanamide Chemical compound C(#N)C=1C=CC(=C2C=CC=NC=12)N1C[C@@H](C[C@@H](C1)C)NC(CCC1NCCCC1)=O WNTUNZINLPYPCF-JVPALSCHSA-N 0.000 claims 1
- MQRKWCVYZFEFKL-NKUTVCTDSA-N N-[(3R,5S)-1-(8-cyanoquinolin-5-yl)-5-methylpiperidin-3-yl]-3-piperidin-3-ylpropanamide Chemical compound C(#N)C=1C=CC(=C2C=CC=NC=12)N1C[C@@H](C[C@@H](C1)C)NC(CCC1CNCCC1)=O MQRKWCVYZFEFKL-NKUTVCTDSA-N 0.000 claims 1
- QFFQKDMQDLOXLW-GOEBONIOSA-N N-[(3R,5S)-1-(8-cyanoquinolin-5-yl)-5-methylpiperidin-3-yl]-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine-3-carboxamide Chemical compound C(#N)C=1C=CC(=C2C=CC=NC=12)N1C[C@@H](C[C@@H](C1)C)NC(=O)C1=NNC2=C1CNCC2 QFFQKDMQDLOXLW-GOEBONIOSA-N 0.000 claims 1
- RXVJOTNEOSVBJY-MAUKXSAKSA-N N-[(3R,5S)-1-(8-cyanoquinolin-5-yl)-5-methylpiperidin-3-yl]-4-hydroxybenzamide Chemical compound C(#N)C=1C=CC(=C2C=CC=NC=12)N1C[C@@H](C[C@@H](C1)C)NC(C1=CC=C(C=C1)O)=O RXVJOTNEOSVBJY-MAUKXSAKSA-N 0.000 claims 1
- ZTHGFHGLBHJPCH-FUHWJXTLSA-N N-[(3R,5S)-1-(8-cyanoquinolin-5-yl)-5-methylpiperidin-3-yl]-4-methylpiperidine-4-carboxamide Chemical compound C(#N)C=1C=CC(=C2C=CC=NC=12)N1C[C@@H](C[C@@H](C1)C)NC(=O)C1(CCNCC1)C ZTHGFHGLBHJPCH-FUHWJXTLSA-N 0.000 claims 1
- QXUSKLVETMNXKJ-XJKSGUPXSA-N N-[(3R,5S)-1-(8-cyanoquinolin-5-yl)-5-methylpiperidin-3-yl]-5-methyl-1,2-oxazole-3-carboxamide Chemical compound C(#N)C=1C=CC(=C2C=CC=NC=12)N1C[C@@H](C[C@@H](C1)C)NC(=O)C1=NOC(=C1)C QXUSKLVETMNXKJ-XJKSGUPXSA-N 0.000 claims 1
- ODIUXRLSZQWVJO-SWLSCSKDSA-N N-[(3R,5S)-1-(8-cyanoquinolin-5-yl)-5-methylpiperidin-3-yl]acetamide Chemical compound C(#N)C=1C=CC(=C2C=CC=NC=12)N1C[C@@H](C[C@@H](C1)C)NC(C)=O ODIUXRLSZQWVJO-SWLSCSKDSA-N 0.000 claims 1
- OFXCFZYZAUNULT-FSGMKPHLSA-N N-[(3R,5S)-1-(8-cyanoquinolin-5-yl)-5-methylpiperidin-3-yl]morpholine-2-carboxamide Chemical compound C(#N)C=1C=CC(=C2C=CC=NC=12)N1C[C@@H](C[C@@H](C1)C)NC(=O)C1CNCCO1 OFXCFZYZAUNULT-FSGMKPHLSA-N 0.000 claims 1
- FCVOQQXWKSBJMX-QJZXMCBYSA-N N-[(3R,5S)-1-(8-cyanoquinolin-5-yl)-5-methylpiperidin-3-yl]piperazine-2-carboxamide Chemical compound C(#N)C=1C=CC(=C2C=CC=NC12)N1C[C@@H](C[C@@H](C1)C)NC(=O)C1NCCNC1 FCVOQQXWKSBJMX-QJZXMCBYSA-N 0.000 claims 1
- RUMKPNXYJMTARN-DKKDMOBXSA-N N-[(3R,5S)-1-(8-cyanoquinolin-5-yl)-5-methylpiperidin-3-yl]piperidine-3-carboxamide Chemical compound C(#N)C=1C=CC(=C2C=CC=NC12)N1C[C@@H](C[C@@H](C1)C)NC(=O)C1CNCCC1 RUMKPNXYJMTARN-DKKDMOBXSA-N 0.000 claims 1
- UJFGBYVXCIHRBI-MAUKXSAKSA-N N-[(3R,5S)-1-(8-cyanoquinolin-5-yl)-5-methylpiperidin-3-yl]piperidine-4-carboxamide Chemical compound C(#N)C=1C=CC(=C2C=CC=NC12)N1C[C@@H](C[C@@H](C1)C)NC(=O)C1CCNCC1 UJFGBYVXCIHRBI-MAUKXSAKSA-N 0.000 claims 1
- MZRVZCTVSIORNX-GOEBONIOSA-N N-[(3R,5S)-1-(8-cyanoquinolin-5-yl)-5-methylpiperidin-3-yl]propane-2-sulfonamide Chemical compound C(#N)C=1C=CC(=C2C=CC=NC=12)N1C[C@@H](C[C@@H](C1)C)NS(=O)(=O)C(C)C MZRVZCTVSIORNX-GOEBONIOSA-N 0.000 claims 1
- PJCJHXTWLILERM-MAUKXSAKSA-N N-[(3R,5S)-1-(8-cyanoquinolin-5-yl)-5-methylpiperidin-3-yl]pyridine-3-carboxamide Chemical compound C(#N)C=1C=CC(=C2C=CC=NC=12)N1C[C@@H](C[C@@H](C1)C)NC(C1=CN=CC=C1)=O PJCJHXTWLILERM-MAUKXSAKSA-N 0.000 claims 1
- FAPXGJRWUYKCEV-DRXWIORDSA-N N-[(3R,5S)-1-(8-cyanoquinolin-5-yl)-5-methylpiperidin-3-yl]pyrrolidine-3-carboxamide Chemical compound C(#N)C=1C=CC(=C2C=CC=NC=12)N1C[C@@H](C[C@@H](C1)C)NC(=O)C1CNCC1 FAPXGJRWUYKCEV-DRXWIORDSA-N 0.000 claims 1
- 102100039390 Toll-like receptor 7 Human genes 0.000 claims 1
- BHYICLZSGHVCJS-KUARMEPBSA-N acetic acid 5-[(3S,5R)-3-methyl-5-[methyl(oxetan-3-yl)amino]piperidin-1-yl]quinoline-8-carbonitrile Chemical compound CC(O)=O.C[C@H]1C[C@H](CN(C1)c1ccc(C#N)c2ncccc12)N(C)C1COC1 BHYICLZSGHVCJS-KUARMEPBSA-N 0.000 claims 1
- DNSISZSEWVHGLH-UHFFFAOYSA-N butanamide Chemical compound CCCC(N)=O DNSISZSEWVHGLH-UHFFFAOYSA-N 0.000 claims 1
- NQWVXZDOOQCBOP-PKOBYXMFSA-N ethyl 2-[[(3R,5S)-1-(8-cyanoquinolin-5-yl)-5-methylpiperidin-3-yl]-(2-ethoxy-2-oxoethyl)amino]acetate Chemical compound C(#N)C=1C=CC(=C2C=CC=NC=12)N1C[C@@H](C[C@@H](C1)C)N(CC(=O)OCC)CC(=O)OCC NQWVXZDOOQCBOP-PKOBYXMFSA-N 0.000 claims 1
- PCUVUWOHXHDLKB-GOEBONIOSA-N ethyl 2-[[(3R,5S)-1-(8-cyanoquinolin-5-yl)-5-methylpiperidin-3-yl]amino]acetate Chemical compound C(#N)C=1C=CC(=C2C=CC=NC=12)N1C[C@@H](C[C@@H](C1)C)NCC(=O)OCC PCUVUWOHXHDLKB-GOEBONIOSA-N 0.000 claims 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 91
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 83
- 239000000203 mixture Substances 0.000 description 75
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 66
- 102000008236 Toll-Like Receptor 7 Human genes 0.000 description 55
- 108010060825 Toll-Like Receptor 7 Proteins 0.000 description 55
- 210000004027 cell Anatomy 0.000 description 44
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 43
- 238000006243 chemical reaction Methods 0.000 description 42
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 42
- 235000019439 ethyl acetate Nutrition 0.000 description 41
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 37
- 239000000243 solution Substances 0.000 description 37
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 36
- XOJVVFBFDXDTEG-UHFFFAOYSA-N pristane Chemical compound CC(C)CCCC(C)CCCC(C)CCCC(C)C XOJVVFBFDXDTEG-UHFFFAOYSA-N 0.000 description 35
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 33
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 31
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 30
- 230000009850 completed effect Effects 0.000 description 28
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 28
- 239000000741 silica gel Substances 0.000 description 27
- 229910002027 silica gel Inorganic materials 0.000 description 27
- 239000007787 solid Substances 0.000 description 26
- 102100033110 Toll-like receptor 8 Human genes 0.000 description 24
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 23
- 102000002689 Toll-like receptor Human genes 0.000 description 21
- 108020000411 Toll-like receptor Proteins 0.000 description 21
- 239000012044 organic layer Substances 0.000 description 21
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 20
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 20
- 108010050904 Interferons Proteins 0.000 description 20
- 102000014150 Interferons Human genes 0.000 description 20
- 229940079322 interferon Drugs 0.000 description 20
- 201000010099 disease Diseases 0.000 description 19
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 18
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 18
- 239000002953 phosphate buffered saline Substances 0.000 description 18
- 101000800483 Homo sapiens Toll-like receptor 8 Proteins 0.000 description 17
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 17
- 102000008235 Toll-Like Receptor 9 Human genes 0.000 description 17
- 239000002253 acid Substances 0.000 description 17
- 239000000725 suspension Substances 0.000 description 17
- 239000011541 reaction mixture Substances 0.000 description 16
- 241000699670 Mus sp. Species 0.000 description 15
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 15
- 108010060818 Toll-Like Receptor 9 Proteins 0.000 description 15
- 239000012267 brine Substances 0.000 description 15
- 108090000623 proteins and genes Proteins 0.000 description 15
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 15
- 230000015572 biosynthetic process Effects 0.000 description 14
- 239000010410 layer Substances 0.000 description 13
- 229950010550 resiquimod Drugs 0.000 description 13
- BXNMTOQRYBFHNZ-UHFFFAOYSA-N resiquimod Chemical compound C1=CC=CC2=C(N(C(COCC)=N3)CC(C)(C)O)C3=C(N)N=C21 BXNMTOQRYBFHNZ-UHFFFAOYSA-N 0.000 description 13
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 12
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 12
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 12
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 11
- 241000699666 Mus <mouse, genus> Species 0.000 description 11
- 239000012043 crude product Substances 0.000 description 11
- 239000011734 sodium Substances 0.000 description 11
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 10
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
- 108010060752 Toll-Like Receptor 8 Proteins 0.000 description 10
- 230000014509 gene expression Effects 0.000 description 10
- 238000001727 in vivo Methods 0.000 description 10
- 239000000047 product Substances 0.000 description 10
- 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 9
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- 108020004414 DNA Proteins 0.000 description 9
- 238000002965 ELISA Methods 0.000 description 9
- 210000004369 blood Anatomy 0.000 description 9
- 239000008280 blood Substances 0.000 description 9
- 230000000694 effects Effects 0.000 description 9
- 239000000706 filtrate Substances 0.000 description 9
- 235000019253 formic acid Nutrition 0.000 description 9
- XXSMGPRMXLTPCZ-UHFFFAOYSA-N hydroxychloroquine Chemical compound ClC1=CC=C2C(NC(C)CCCN(CCO)CC)=CC=NC2=C1 XXSMGPRMXLTPCZ-UHFFFAOYSA-N 0.000 description 9
- 229960004171 hydroxychloroquine Drugs 0.000 description 9
- 239000000543 intermediate Substances 0.000 description 9
- 238000003786 synthesis reaction Methods 0.000 description 9
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical class CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 9
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 8
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 8
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 8
- 238000003556 assay Methods 0.000 description 8
- DDRJAANPRJIHGJ-UHFFFAOYSA-N creatinine Chemical compound CN1CC(=O)NC1=N DDRJAANPRJIHGJ-UHFFFAOYSA-N 0.000 description 8
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 8
- DUWWHGPELOTTOE-UHFFFAOYSA-N n-(5-chloro-2,4-dimethoxyphenyl)-3-oxobutanamide Chemical compound COC1=CC(OC)=C(NC(=O)CC(C)=O)C=C1Cl DUWWHGPELOTTOE-UHFFFAOYSA-N 0.000 description 8
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 8
- 238000002360 preparation method Methods 0.000 description 8
- 235000019260 propionic acid Nutrition 0.000 description 8
- 238000000746 purification Methods 0.000 description 8
- 238000003756 stirring Methods 0.000 description 8
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 7
- 101000669447 Homo sapiens Toll-like receptor 4 Proteins 0.000 description 7
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 7
- 230000001965 increasing effect Effects 0.000 description 7
- 239000000126 substance Substances 0.000 description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- 102000053602 DNA Human genes 0.000 description 6
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 6
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 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
- 239000002299 complementary DNA Substances 0.000 description 6
- 239000012065 filter cake Substances 0.000 description 6
- 238000001914 filtration Methods 0.000 description 6
- 239000007924 injection Substances 0.000 description 6
- 238000002347 injection Methods 0.000 description 6
- 230000000144 pharmacologic effect Effects 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- 230000001105 regulatory effect Effects 0.000 description 6
- 239000011780 sodium chloride Substances 0.000 description 6
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- 230000001225 therapeutic effect Effects 0.000 description 6
- NPLPBRIDHFAGPQ-UHFFFAOYSA-N 5-bromoquinoline-8-carbaldehyde Chemical compound C1=CC=C2C(Br)=CC=C(C=O)C2=N1 NPLPBRIDHFAGPQ-UHFFFAOYSA-N 0.000 description 5
- 241000282412 Homo Species 0.000 description 5
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 5
- 101100153388 Mus musculus Tlr7 gene Proteins 0.000 description 5
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 5
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 5
- 238000011529 RT qPCR Methods 0.000 description 5
- 239000000556 agonist Substances 0.000 description 5
- 235000019270 ammonium chloride Nutrition 0.000 description 5
- 239000005557 antagonist Substances 0.000 description 5
- 239000003430 antimalarial agent Substances 0.000 description 5
- 239000003153 chemical reaction reagent Substances 0.000 description 5
- 238000010511 deprotection reaction Methods 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- 239000002158 endotoxin Substances 0.000 description 5
- 229920006008 lipopolysaccharide Polymers 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 239000000843 powder Substances 0.000 description 5
- 238000010992 reflux Methods 0.000 description 5
- 230000000638 stimulation Effects 0.000 description 5
- 239000003981 vehicle Substances 0.000 description 5
- PAQZWJGSJMLPMG-UHFFFAOYSA-N 2,4,6-tripropyl-1,3,5,2$l^{5},4$l^{5},6$l^{5}-trioxatriphosphinane 2,4,6-trioxide Chemical compound CCCP1(=O)OP(=O)(CCC)OP(=O)(CCC)O1 PAQZWJGSJMLPMG-UHFFFAOYSA-N 0.000 description 4
- 108010088751 Albumins Proteins 0.000 description 4
- 102000009027 Albumins Human genes 0.000 description 4
- 208000023275 Autoimmune disease Diseases 0.000 description 4
- 101000800479 Homo sapiens Toll-like receptor 9 Proteins 0.000 description 4
- 102000004889 Interleukin-6 Human genes 0.000 description 4
- 108090001005 Interleukin-6 Proteins 0.000 description 4
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 102100039360 Toll-like receptor 4 Human genes 0.000 description 4
- 230000029936 alkylation Effects 0.000 description 4
- 238000005804 alkylation reaction Methods 0.000 description 4
- 230000003042 antagnostic effect Effects 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- 239000012141 concentrate Substances 0.000 description 4
- 229940109239 creatinine Drugs 0.000 description 4
- 210000003743 erythrocyte Anatomy 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 125000000623 heterocyclic group Chemical group 0.000 description 4
- 239000007928 intraperitoneal injection Substances 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 239000002609 medium Substances 0.000 description 4
- 201000008383 nephritis Diseases 0.000 description 4
- 239000000546 pharmaceutical excipient Substances 0.000 description 4
- 238000004007 reversed phase HPLC Methods 0.000 description 4
- 238000000926 separation method Methods 0.000 description 4
- 238000007920 subcutaneous administration Methods 0.000 description 4
- 210000002700 urine Anatomy 0.000 description 4
- 239000003643 water by type Substances 0.000 description 4
- 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 3
- FZENGILVLUJGJX-NSCUHMNNSA-N (E)-acetaldehyde oxime Chemical compound C\C=N\O FZENGILVLUJGJX-NSCUHMNNSA-N 0.000 description 3
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 3
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 3
- DAYKHFAZOORREQ-UHFFFAOYSA-N 5-bromoquinoline-8-carbonitrile Chemical compound C1=CC=C2C(Br)=CC=C(C#N)C2=N1 DAYKHFAZOORREQ-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
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 239000007821 HATU Substances 0.000 description 3
- 239000005089 Luciferase Substances 0.000 description 3
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 3
- 241000219061 Rheum Species 0.000 description 3
- 150000001412 amines Chemical class 0.000 description 3
- 206010003246 arthritis Diseases 0.000 description 3
- 210000003719 b-lymphocyte Anatomy 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- XMIIGOLPHOKFCH-UHFFFAOYSA-N beta-phenylpropanoic acid Natural products OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 description 3
- 229940126214 compound 3 Drugs 0.000 description 3
- 230000001276 controlling effect Effects 0.000 description 3
- OPQARKPSCNTWTJ-UHFFFAOYSA-L copper(ii) acetate Chemical compound [Cu+2].CC([O-])=O.CC([O-])=O OPQARKPSCNTWTJ-UHFFFAOYSA-L 0.000 description 3
- 230000002950 deficient Effects 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- 238000011156 evaluation Methods 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 239000007789 gas Substances 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 102000045717 human TLR4 Human genes 0.000 description 3
- 102000045720 human TLR8 Human genes 0.000 description 3
- 150000003840 hydrochlorides Chemical class 0.000 description 3
- 238000005984 hydrogenation reaction Methods 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 230000001404 mediated effect Effects 0.000 description 3
- 229920000609 methyl cellulose Polymers 0.000 description 3
- 239000001923 methylcellulose Substances 0.000 description 3
- 235000010981 methylcellulose Nutrition 0.000 description 3
- 229960002900 methylcellulose Drugs 0.000 description 3
- 238000006386 neutralization reaction Methods 0.000 description 3
- 235000001968 nicotinic acid Nutrition 0.000 description 3
- 239000011664 nicotinic acid Substances 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 102000039446 nucleic acids Human genes 0.000 description 3
- 108020004707 nucleic acids Proteins 0.000 description 3
- 150000007523 nucleic acids Chemical class 0.000 description 3
- 239000003921 oil Substances 0.000 description 3
- 235000019198 oils Nutrition 0.000 description 3
- 230000008506 pathogenesis Effects 0.000 description 3
- 230000037361 pathway Effects 0.000 description 3
- 210000005134 plasmacytoid dendritic cell Anatomy 0.000 description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 description 3
- 230000003389 potentiating effect Effects 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 230000000770 proinflammatory effect Effects 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 229920005989 resin Polymers 0.000 description 3
- 239000011347 resin Substances 0.000 description 3
- 230000011664 signaling Effects 0.000 description 3
- 229910000104 sodium hydride Inorganic materials 0.000 description 3
- 235000010288 sodium nitrite Nutrition 0.000 description 3
- 230000003595 spectral effect Effects 0.000 description 3
- 230000002269 spontaneous effect Effects 0.000 description 3
- 125000001424 substituent group Chemical group 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
- CNALVHVMBXLLIY-DTWKUNHWSA-N tert-butyl n-[(3r,5s)-5-methylpiperidin-3-yl]carbamate Chemical compound C[C@@H]1CNC[C@H](NC(=O)OC(C)(C)C)C1 CNALVHVMBXLLIY-DTWKUNHWSA-N 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 3
- WHTVZRBIWZFKQO-AWEZNQCLSA-N (S)-chloroquine Chemical compound ClC1=CC=C2C(N[C@@H](C)CCCN(CC)CC)=CC=NC2=C1 WHTVZRBIWZFKQO-AWEZNQCLSA-N 0.000 description 2
- OVBFMEVBMNZIBR-UHFFFAOYSA-N -2-Methylpentanoic acid Natural products CCCC(C)C(O)=O OVBFMEVBMNZIBR-UHFFFAOYSA-N 0.000 description 2
- JREJQAWGQCMSIY-UHFFFAOYSA-N 1-methyl-pyrazole-5-carboxylic acid Chemical compound CN1N=CC=C1C(O)=O JREJQAWGQCMSIY-UHFFFAOYSA-N 0.000 description 2
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 2
- IJFXRHURBJZNAO-UHFFFAOYSA-N 3-hydroxybenzoic acid Chemical compound OC(=O)C1=CC=CC(O)=C1 IJFXRHURBJZNAO-UHFFFAOYSA-N 0.000 description 2
- WYFCZWSWFGJODV-MIANJLSGSA-N 4-[[(1s)-2-[(e)-3-[3-chloro-2-fluoro-6-(tetrazol-1-yl)phenyl]prop-2-enoyl]-5-(4-methyl-2-oxopiperazin-1-yl)-3,4-dihydro-1h-isoquinoline-1-carbonyl]amino]benzoic acid Chemical compound O=C1CN(C)CCN1C1=CC=CC2=C1CCN(C(=O)\C=C\C=1C(=CC=C(Cl)C=1F)N1N=NN=C1)[C@@H]2C(=O)NC1=CC=C(C(O)=O)C=C1 WYFCZWSWFGJODV-MIANJLSGSA-N 0.000 description 2
- FJKROLUGYXJWQN-UHFFFAOYSA-N 4-hydroxybenzoic acid Chemical compound OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 2
- NZWHZJRPGUTRNI-NSHDSACASA-N 5-[(3S)-3-methyl-5-oxopiperidin-1-yl]quinoline-8-carbonitrile Chemical compound C[C@@H]1CN(CC(=O)C1)c1ccc(C#N)c2ncccc12 NZWHZJRPGUTRNI-NSHDSACASA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 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
- 108091008875 B cell receptors Proteins 0.000 description 2
- 238000011725 BALB/c mouse Methods 0.000 description 2
- FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 2
- JMTREPCMLJFWOF-DOTOQJQBSA-N C(#N)C=1C=CC(=C2C=CC=NC=12)N1C[C@@H](C[C@@H](C1)C)N(C(OC(C)(C)C)=O)C Chemical compound C(#N)C=1C=CC(=C2C=CC=NC=12)N1C[C@@H](C[C@@H](C1)C)N(C(OC(C)(C)C)=O)C JMTREPCMLJFWOF-DOTOQJQBSA-N 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 102000004127 Cytokines Human genes 0.000 description 2
- 108090000695 Cytokines Proteins 0.000 description 2
- 206010061818 Disease progression Diseases 0.000 description 2
- 102000015689 E-Selectin Human genes 0.000 description 2
- 108010024212 E-Selectin Proteins 0.000 description 2
- 108700039887 Essential Genes Proteins 0.000 description 2
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- 239000007995 HEPES buffer Substances 0.000 description 2
- 108010033040 Histones Proteins 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- 101150103227 IFN gene Proteins 0.000 description 2
- 108010014726 Interferon Type I Proteins 0.000 description 2
- 102000002227 Interferon Type I Human genes 0.000 description 2
- 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 2
- 108060001084 Luciferase Proteins 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- 229920000954 Polyglycolide Polymers 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 2
- 239000012980 RPMI-1640 medium Substances 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 238000000692 Student's t-test Methods 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 102000018165 U1 Small Nuclear Ribonucleoprotein Human genes 0.000 description 2
- 108010091281 U1 Small Nuclear Ribonucleoprotein Proteins 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- 239000000443 aerosol Substances 0.000 description 2
- 235000010443 alginic acid Nutrition 0.000 description 2
- 229920000615 alginic acid Polymers 0.000 description 2
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 2
- 230000008485 antagonism Effects 0.000 description 2
- 230000002583 anti-histone Effects 0.000 description 2
- 239000000427 antigen Substances 0.000 description 2
- 108091007433 antigens Proteins 0.000 description 2
- 102000036639 antigens Human genes 0.000 description 2
- 239000007900 aqueous suspension Substances 0.000 description 2
- 125000003118 aryl group Chemical group 0.000 description 2
- 230000005784 autoimmunity Effects 0.000 description 2
- 230000001580 bacterial effect Effects 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
- 230000000903 blocking effect Effects 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 238000004364 calculation method Methods 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 229920001429 chelating resin Polymers 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 229960003677 chloroquine Drugs 0.000 description 2
- WHTVZRBIWZFKQO-UHFFFAOYSA-N chloroquine Natural products ClC1=CC=C2C(NC(C)CCCN(CC)CC)=CC=NC2=C1 WHTVZRBIWZFKQO-UHFFFAOYSA-N 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 229920001577 copolymer Polymers 0.000 description 2
- 239000012228 culture supernatant Substances 0.000 description 2
- 230000016396 cytokine production Effects 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 230000007123 defense Effects 0.000 description 2
- 210000004443 dendritic cell Anatomy 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- MOTZDAYCYVMXPC-UHFFFAOYSA-N dodecyl hydrogen sulfate Chemical compound CCCCCCCCCCCCOS(O)(=O)=O MOTZDAYCYVMXPC-UHFFFAOYSA-N 0.000 description 2
- 229940043264 dodecyl sulfate Drugs 0.000 description 2
- RSOJSFYJLQADDM-UHFFFAOYSA-N ethanesulfonamide Chemical compound [CH2]CS(N)(=O)=O RSOJSFYJLQADDM-UHFFFAOYSA-N 0.000 description 2
- DEQYTNZJHKPYEZ-UHFFFAOYSA-N ethyl acetate;heptane Chemical compound CCOC(C)=O.CCCCCCC DEQYTNZJHKPYEZ-UHFFFAOYSA-N 0.000 description 2
- 230000001747 exhibiting effect Effects 0.000 description 2
- 238000003818 flash chromatography Methods 0.000 description 2
- 238000012224 gene deletion Methods 0.000 description 2
- 230000004547 gene signature Effects 0.000 description 2
- 102000045710 human TLR9 Human genes 0.000 description 2
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine hydrate Chemical compound O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 2
- 230000036039 immunity Effects 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 102000014909 interleukin-1 receptor activity proteins Human genes 0.000 description 2
- 108040006732 interleukin-1 receptor activity proteins Proteins 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 238000002794 lymphocyte assay Methods 0.000 description 2
- 239000011777 magnesium Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
- 238000004949 mass spectrometry Methods 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 238000010172 mouse model Methods 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 238000010606 normalization Methods 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 230000002018 overexpression Effects 0.000 description 2
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
- 125000004193 piperazinyl group Chemical group 0.000 description 2
- 150000003053 piperidines Chemical class 0.000 description 2
- 239000013612 plasmid Substances 0.000 description 2
- 229920000747 poly(lactic acid) Polymers 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 239000004633 polyglycolic acid Substances 0.000 description 2
- 239000004626 polylactic acid Substances 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 230000000069 prophylactic effect Effects 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 201000001474 proteinuria Diseases 0.000 description 2
- 150000003248 quinolines Chemical class 0.000 description 2
- 238000003753 real-time PCR Methods 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 238000006722 reduction reaction Methods 0.000 description 2
- 238000006268 reductive amination reaction Methods 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 238000010898 silica gel chromatography Methods 0.000 description 2
- 239000002002 slurry Substances 0.000 description 2
- 235000017281 sodium acetate Nutrition 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 239000012312 sodium hydride Substances 0.000 description 2
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 2
- 210000000952 spleen Anatomy 0.000 description 2
- 239000007929 subcutaneous injection Substances 0.000 description 2
- 238000010254 subcutaneous injection Methods 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 238000012353 t test Methods 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- 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 2
- IUFILCOKJSYFAP-GOEBONIOSA-N tert-butyl N-[(3R,5S)-1-(8-cyanoquinolin-5-yl)-5-methylpiperidin-3-yl]carbamate Chemical compound C(#N)C=1C=CC(=C2C=CC=NC=12)N1C[C@@H](C[C@@H](C1)C)NC(OC(C)(C)C)=O IUFILCOKJSYFAP-GOEBONIOSA-N 0.000 description 2
- 125000000335 thiazolyl group Chemical group 0.000 description 2
- 238000004809 thin layer chromatography Methods 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- 239000002691 unilamellar liposome Substances 0.000 description 2
- 239000013598 vector Substances 0.000 description 2
- 230000003612 virological effect Effects 0.000 description 2
- LSPHULWDVZXLIL-UHFFFAOYSA-N (+/-)-Camphoric acid Chemical compound CC1(C)C(C(O)=O)CCC1(C)C(O)=O LSPHULWDVZXLIL-UHFFFAOYSA-N 0.000 description 1
- ZQEBQGAAWMOMAI-SSDOTTSWSA-N (2r)-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidine-2-carboxylic acid Chemical compound CC(C)(C)OC(=O)N1CCC[C@@H]1C(O)=O ZQEBQGAAWMOMAI-SSDOTTSWSA-N 0.000 description 1
- HOBFSNNENNQQIU-SNVBAGLBSA-N (2r)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-2-phenylacetic acid Chemical compound CC(C)(C)OC(=O)N[C@@H](C(O)=O)C1=CC=CC=C1 HOBFSNNENNQQIU-SNVBAGLBSA-N 0.000 description 1
- ZYJPUMXJBDHSIF-LLVKDONJSA-N (2r)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-phenylpropanoic acid Chemical compound CC(C)(C)OC(=O)N[C@@H](C(O)=O)CC1=CC=CC=C1 ZYJPUMXJBDHSIF-LLVKDONJSA-N 0.000 description 1
- QVHJQCGUWFKTSE-RXMQYKEDSA-N (2r)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid Chemical compound OC(=O)[C@@H](C)NC(=O)OC(C)(C)C QVHJQCGUWFKTSE-RXMQYKEDSA-N 0.000 description 1
- MDXGYYOJGPFFJL-MRVPVSSYSA-N (2r)-4-methyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]pentanoic acid Chemical compound CC(C)C[C@H](C(O)=O)NC(=O)OC(C)(C)C MDXGYYOJGPFFJL-MRVPVSSYSA-N 0.000 description 1
- AKFYXIPCMPHHSU-HZPDHXFCSA-N (2r,3r)-2,3-bis(4-methoxyphenoxy)butanedioic acid Chemical compound C1=CC(OC)=CC=C1O[C@@H](C(O)=O)[C@H](C(O)=O)OC1=CC=C(OC)C=C1 AKFYXIPCMPHHSU-HZPDHXFCSA-N 0.000 description 1
- KWWCVCFQHGKOMI-HZPDHXFCSA-N (2r,3r)-2,3-bis[(4-methoxybenzoyl)oxy]butanedioic acid Chemical compound C1=CC(OC)=CC=C1C(=O)O[C@@H](C(O)=O)[C@H](C(O)=O)OC(=O)C1=CC=C(OC)C=C1 KWWCVCFQHGKOMI-HZPDHXFCSA-N 0.000 description 1
- HOBFSNNENNQQIU-JTQLQIEISA-N (2s)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-2-phenylacetic acid Chemical compound CC(C)(C)OC(=O)N[C@H](C(O)=O)C1=CC=CC=C1 HOBFSNNENNQQIU-JTQLQIEISA-N 0.000 description 1
- INWOAUUPYIXDHN-ZETCQYMHSA-N (2s)-2-[(2-methylpropan-2-yl)oxycarbonylamino]pentanoic acid Chemical compound CCC[C@@H](C(O)=O)NC(=O)OC(C)(C)C INWOAUUPYIXDHN-ZETCQYMHSA-N 0.000 description 1
- QVHJQCGUWFKTSE-YFKPBYRVSA-N (2s)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid Chemical compound OC(=O)[C@H](C)NC(=O)OC(C)(C)C QVHJQCGUWFKTSE-YFKPBYRVSA-N 0.000 description 1
- HYGQYTQHPSQSFF-VIFPVBQESA-N (2s)-2-[methyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]hexanoic acid Chemical compound CCCC[C@@H](C(O)=O)N(C)C(=O)OC(C)(C)C HYGQYTQHPSQSFF-VIFPVBQESA-N 0.000 description 1
- SZXBQTSZISFIAO-ZETCQYMHSA-N (2s)-3-methyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]butanoic acid Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)OC(C)(C)C SZXBQTSZISFIAO-ZETCQYMHSA-N 0.000 description 1
- PYNDHEONPQYIAN-ZCFIWIBFSA-N (3r)-3-[(2-methylpropan-2-yl)oxycarbonylamino]butanoic acid Chemical compound OC(=O)C[C@@H](C)NC(=O)OC(C)(C)C PYNDHEONPQYIAN-ZCFIWIBFSA-N 0.000 description 1
- KVXXEKIGMOEPSA-SSDOTTSWSA-N (3r)-4-[(2-methylpropan-2-yl)oxycarbonyl]morpholine-3-carboxylic acid Chemical compound CC(C)(C)OC(=O)N1CCOC[C@@H]1C(O)=O KVXXEKIGMOEPSA-SSDOTTSWSA-N 0.000 description 1
- GGPNYXIOFZLNKW-ZJIMSODOSA-N (3r)-piperidin-3-amine;dihydrochloride Chemical compound Cl.Cl.N[C@@H]1CCCNC1 GGPNYXIOFZLNKW-ZJIMSODOSA-N 0.000 description 1
- MPDDTAJMJCESGV-CTUHWIOQSA-M (3r,5r)-7-[2-(4-fluorophenyl)-5-[methyl-[(1r)-1-phenylethyl]carbamoyl]-4-propan-2-ylpyrazol-3-yl]-3,5-dihydroxyheptanoate Chemical compound C1([C@@H](C)N(C)C(=O)C2=NN(C(CC[C@@H](O)C[C@@H](O)CC([O-])=O)=C2C(C)C)C=2C=CC(F)=CC=2)=CC=CC=C1 MPDDTAJMJCESGV-CTUHWIOQSA-M 0.000 description 1
- PYNDHEONPQYIAN-LURJTMIESA-N (3s)-3-[(2-methylpropan-2-yl)oxycarbonylamino]butanoic acid Chemical compound OC(=O)C[C@H](C)NC(=O)OC(C)(C)C PYNDHEONPQYIAN-LURJTMIESA-N 0.000 description 1
- FJWNZTPXVSWUKF-ZCFIWIBFSA-N (4s)-3-[(2-methylpropan-2-yl)oxycarbonyl]-1,3-thiazolidine-4-carboxylic acid Chemical compound CC(C)(C)OC(=O)N1CSC[C@@H]1C(O)=O FJWNZTPXVSWUKF-ZCFIWIBFSA-N 0.000 description 1
- NGEWQZIDQIYUNV-BYPYZUCNSA-N (S)-2-hydroxy-3-methylbutyric acid Chemical compound CC(C)[C@H](O)C(O)=O NGEWQZIDQIYUNV-BYPYZUCNSA-N 0.000 description 1
- MIOPJNTWMNEORI-GMSGAONNSA-N (S)-camphorsulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)C[C@@H]1C2(C)C MIOPJNTWMNEORI-GMSGAONNSA-N 0.000 description 1
- HGTBAIVLETUVCG-UHFFFAOYSA-N (methylthio)acetic acid Chemical compound CSCC(O)=O HGTBAIVLETUVCG-UHFFFAOYSA-N 0.000 description 1
- 0 *C(*)(CC(C1)O*)CN1c(cc1)c(cccn2)c2c1C#N Chemical compound *C(*)(CC(C1)O*)CN1c(cc1)c(cccn2)c2c1C#N 0.000 description 1
- DIOHEXPTUTVCNX-UHFFFAOYSA-N 1,1,1-trifluoro-n-phenyl-n-(trifluoromethylsulfonyl)methanesulfonamide Chemical compound FC(F)(F)S(=O)(=O)N(S(=O)(=O)C(F)(F)F)C1=CC=CC=C1 DIOHEXPTUTVCNX-UHFFFAOYSA-N 0.000 description 1
- XFMQGQAAHOGFQS-UHFFFAOYSA-N 1,1-dioxothian-4-one Chemical compound O=C1CCS(=O)(=O)CC1 XFMQGQAAHOGFQS-UHFFFAOYSA-N 0.000 description 1
- TYHOSUCCUICRLM-UHFFFAOYSA-N 1,3-oxazole-2-carbaldehyde Chemical compound O=CC1=NC=CO1 TYHOSUCCUICRLM-UHFFFAOYSA-N 0.000 description 1
- LKBYTIDNKQGSAN-UHFFFAOYSA-N 1,4-dimethylpyrazole-3-carbaldehyde Chemical compound CC1=CN(C)N=C1C=O LKBYTIDNKQGSAN-UHFFFAOYSA-N 0.000 description 1
- FBFJOZZTIXSPPR-UHFFFAOYSA-N 1-(4-aminobutyl)-2-(ethoxymethyl)imidazo[4,5-c]quinolin-4-amine Chemical compound C1=CC=CC2=C(N(C(COCC)=N3)CCCCN)C3=C(N)N=C21 FBFJOZZTIXSPPR-UHFFFAOYSA-N 0.000 description 1
- NXILIHONWRXHFA-UHFFFAOYSA-N 1-[(2-methylpropan-2-yl)oxycarbonyl]piperidine-3-carboxylic acid Chemical compound CC(C)(C)OC(=O)N1CCCC(C(O)=O)C1 NXILIHONWRXHFA-UHFFFAOYSA-N 0.000 description 1
- JWOHBPPVVDQMKB-UHFFFAOYSA-N 1-[(2-methylpropan-2-yl)oxycarbonyl]piperidine-4-carboxylic acid Chemical compound CC(C)(C)OC(=O)N1CCC(C(O)=O)CC1 JWOHBPPVVDQMKB-UHFFFAOYSA-N 0.000 description 1
- HRMRQBJUFWFQLX-UHFFFAOYSA-N 1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidine-3-carboxylic acid Chemical compound CC(C)(C)OC(=O)N1CCC(C(O)=O)C1 HRMRQBJUFWFQLX-UHFFFAOYSA-N 0.000 description 1
- DSKCOVBHIFAJRI-UHFFFAOYSA-N 1-[(2-methylpropan-2-yl)oxycarbonylamino]cyclopropane-1-carboxylic acid Chemical compound CC(C)(C)OC(=O)NC1(C(O)=O)CC1 DSKCOVBHIFAJRI-UHFFFAOYSA-N 0.000 description 1
- YZUPZGFPHUVJKC-UHFFFAOYSA-N 1-bromo-2-methoxyethane Chemical compound COCCBr YZUPZGFPHUVJKC-UHFFFAOYSA-N 0.000 description 1
- CQZXDIHVSPZIGF-UHFFFAOYSA-N 1-methylimidazole-4-carbaldehyde Chemical compound CN1C=NC(C=O)=C1 CQZXDIHVSPZIGF-UHFFFAOYSA-N 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- ICFGFAUMBISMLR-UHFFFAOYSA-N 1h-pyrazole-5-carbaldehyde Chemical compound O=CC=1C=CNN=1 ICFGFAUMBISMLR-UHFFFAOYSA-N 0.000 description 1
- HCPVYBCAYPMANM-UHFFFAOYSA-N 2-(1,3-dioxoisoindol-2-yl)ethanesulfonyl chloride Chemical compound C1=CC=C2C(=O)N(CCS(=O)(=O)Cl)C(=O)C2=C1 HCPVYBCAYPMANM-UHFFFAOYSA-N 0.000 description 1
- 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 1
- RXWOHFUULDINMC-UHFFFAOYSA-N 2-(3-nitrothiophen-2-yl)acetic acid Chemical compound OC(=O)CC=1SC=CC=1[N+]([O-])=O RXWOHFUULDINMC-UHFFFAOYSA-N 0.000 description 1
- FKASAVXZZLJTNX-UHFFFAOYSA-N 2-(dimethylamino)acetic acid;hydrochloride Chemical compound [Cl-].C[NH+](C)CC(O)=O FKASAVXZZLJTNX-UHFFFAOYSA-N 0.000 description 1
- FPQMUQPPAYCAME-UHFFFAOYSA-N 2-Acetyl-6-methylpyridine Chemical compound CC(=O)C1=CC=CC(C)=N1 FPQMUQPPAYCAME-UHFFFAOYSA-N 0.000 description 1
- AJKVQEKCUACUMD-UHFFFAOYSA-N 2-Acetylpyridine Chemical compound CC(=O)C1=CC=CC=N1 AJKVQEKCUACUMD-UHFFFAOYSA-N 0.000 description 1
- IMUSLIHRIYOHEV-UHFFFAOYSA-N 2-[(2-methylpropan-2-yl)oxycarbonylamino]-4-methylsulfanylbutanoic acid Chemical compound CSCCC(C(O)=O)NC(=O)OC(C)(C)C IMUSLIHRIYOHEV-UHFFFAOYSA-N 0.000 description 1
- VRPJIFMKZZEXLR-UHFFFAOYSA-N 2-[(2-methylpropan-2-yl)oxycarbonylamino]acetic acid Chemical compound CC(C)(C)OC(=O)NCC(O)=O VRPJIFMKZZEXLR-UHFFFAOYSA-N 0.000 description 1
- VEFHUWJIRFTGRB-UHFFFAOYSA-N 2-[1-[(2-methylpropan-2-yl)oxycarbonyl]azetidin-3-yl]acetic acid Chemical compound CC(C)(C)OC(=O)N1CC(CC(O)=O)C1 VEFHUWJIRFTGRB-UHFFFAOYSA-N 0.000 description 1
- ZXFLMSIMHISJFV-UHFFFAOYSA-N 2-[1-[(2-methylpropan-2-yl)oxycarbonyl]piperidin-4-yl]acetic acid Chemical compound CC(C)(C)OC(=O)N1CCC(CC(O)=O)CC1 ZXFLMSIMHISJFV-UHFFFAOYSA-N 0.000 description 1
- SKEXQIJIXQSFRX-UHFFFAOYSA-N 2-[1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidin-3-yl]acetic acid Chemical compound CC(C)(C)OC(=O)N1CCC(CC(O)=O)C1 SKEXQIJIXQSFRX-UHFFFAOYSA-N 0.000 description 1
- CQVKMVQRSNNAGO-UHFFFAOYSA-N 2-[4-formyl-3-methyl-n-(2-methylsulfonyloxyethyl)anilino]ethyl methanesulfonate Chemical compound CC1=CC(N(CCOS(C)(=O)=O)CCOS(C)(=O)=O)=CC=C1C=O CQVKMVQRSNNAGO-UHFFFAOYSA-N 0.000 description 1
- YRXIMPFOTQVOHG-UHFFFAOYSA-N 2-[methyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]acetic acid Chemical compound OC(=O)CN(C)C(=O)OC(C)(C)C YRXIMPFOTQVOHG-UHFFFAOYSA-N 0.000 description 1
- VJIKFWJCVWFZIN-UHFFFAOYSA-N 2-ethylsulfanylacetic acid Chemical compound CCSCC(O)=O VJIKFWJCVWFZIN-UHFFFAOYSA-N 0.000 description 1
- YEDUAINPPJYDJZ-UHFFFAOYSA-N 2-hydroxybenzothiazole Chemical compound C1=CC=C2SC(O)=NC2=C1 YEDUAINPPJYDJZ-UHFFFAOYSA-N 0.000 description 1
- AFENDNXGAFYKQO-UHFFFAOYSA-N 2-hydroxybutyric acid Chemical compound CCC(O)C(O)=O AFENDNXGAFYKQO-UHFFFAOYSA-N 0.000 description 1
- MYHNUQVKTSTVDI-UHFFFAOYSA-N 2-methyl-2-[(2-methylpropan-2-yl)oxy]propane;potassium Chemical compound [K].CC(C)(C)OC(C)(C)C MYHNUQVKTSTVDI-UHFFFAOYSA-N 0.000 description 1
- MFNXWZGIFWJHMI-UHFFFAOYSA-N 2-methyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid Chemical compound CC(C)(C)OC(=O)NC(C)(C)C(O)=O MFNXWZGIFWJHMI-UHFFFAOYSA-N 0.000 description 1
- LBLYYCQCTBFVLH-UHFFFAOYSA-M 2-methylbenzenesulfonate Chemical compound CC1=CC=CC=C1S([O-])(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-M 0.000 description 1
- YOETUEMZNOLGDB-UHFFFAOYSA-N 2-methylpropyl carbonochloridate Chemical compound CC(C)COC(Cl)=O YOETUEMZNOLGDB-UHFFFAOYSA-N 0.000 description 1
- NYEHUAQIJXERLP-UHFFFAOYSA-N 2-methylsulfonylacetic acid Chemical compound CS(=O)(=O)CC(O)=O NYEHUAQIJXERLP-UHFFFAOYSA-N 0.000 description 1
- 229940080296 2-naphthalenesulfonate Drugs 0.000 description 1
- IPMQSLPLJDKUPI-UHFFFAOYSA-N 2-oxocyclopentane-1-carbonitrile Chemical compound O=C1CCCC1C#N IPMQSLPLJDKUPI-UHFFFAOYSA-N 0.000 description 1
- LOSKNFQZTWYZHI-UHFFFAOYSA-N 2-pyrazol-1-ylacetic acid Chemical compound OC(=O)CN1C=CC=N1 LOSKNFQZTWYZHI-UHFFFAOYSA-N 0.000 description 1
- MQVISALTZUNQSK-UHFFFAOYSA-N 2-pyridin-2-ylacetic acid;hydrochloride Chemical compound Cl.OC(=O)CC1=CC=CC=N1 MQVISALTZUNQSK-UHFFFAOYSA-N 0.000 description 1
- 108020005345 3' Untranslated Regions Proteins 0.000 description 1
- UAIUNKRWKOVEES-UHFFFAOYSA-N 3,3',5,5'-tetramethylbenzidine Chemical compound CC1=C(N)C(C)=CC(C=2C=C(C)C(N)=C(C)C=2)=C1 UAIUNKRWKOVEES-UHFFFAOYSA-N 0.000 description 1
- KSNKQSPJFRQSEI-UHFFFAOYSA-N 3,3,3-trifluoropropanoic acid Chemical compound OC(=O)CC(F)(F)F KSNKQSPJFRQSEI-UHFFFAOYSA-N 0.000 description 1
- LKXPDOQKELOUCP-UHFFFAOYSA-N 3,3,3-trifluoropropyl methanesulfonate Chemical compound CS(=O)(=O)OCCC(F)(F)F LKXPDOQKELOUCP-UHFFFAOYSA-N 0.000 description 1
- TVAYXKLCEILMEA-UHFFFAOYSA-N 3,5-dimethyl-1,2-oxazole-4-carbaldehyde Chemical compound CC1=NOC(C)=C1C=O TVAYXKLCEILMEA-UHFFFAOYSA-N 0.000 description 1
- BYKKHSIDBWTCTP-UHFFFAOYSA-N 3-(dimethylamino)propane-1-sulfonyl chloride;hydrochloride Chemical compound Cl.CN(C)CCCS(Cl)(=O)=O BYKKHSIDBWTCTP-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
- GWYFCOCPABKNJV-UHFFFAOYSA-M 3-Methylbutanoic acid Natural products CC(C)CC([O-])=O GWYFCOCPABKNJV-UHFFFAOYSA-M 0.000 description 1
- BRQMDBOVDLUBAI-UHFFFAOYSA-N 3-[1-[(2-methylpropan-2-yl)oxycarbonyl]piperidin-2-yl]propanoic acid Chemical compound CC(C)(C)OC(=O)N1CCCCC1CCC(O)=O BRQMDBOVDLUBAI-UHFFFAOYSA-N 0.000 description 1
- ZVYVZEUADCRFHK-UHFFFAOYSA-N 3-[1-[(2-methylpropan-2-yl)oxycarbonyl]piperidin-3-yl]propanoic acid Chemical compound CC(C)(C)OC(=O)N1CCCC(CCC(O)=O)C1 ZVYVZEUADCRFHK-UHFFFAOYSA-N 0.000 description 1
- PBINEGXMYGDOPT-UHFFFAOYSA-N 3-hydroxy-1-[(2-methylpropan-2-yl)oxycarbonylamino]cyclopentane-1-carboxylic acid Chemical compound CC(C)(C)OC(=O)NC1(C(O)=O)CCC(O)C1 PBINEGXMYGDOPT-UHFFFAOYSA-N 0.000 description 1
- SZXBQTSZISFIAO-UHFFFAOYSA-N 3-methyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]butanoic acid Chemical compound CC(C)C(C(O)=O)NC(=O)OC(C)(C)C SZXBQTSZISFIAO-UHFFFAOYSA-N 0.000 description 1
- XPUAXAVJMJDPDH-UHFFFAOYSA-N 3-methyl-2-[methyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]butanoic acid Chemical compound CC(C)C(C(O)=O)N(C)C(=O)OC(C)(C)C XPUAXAVJMJDPDH-UHFFFAOYSA-N 0.000 description 1
- PBEDVTDUVXFSMW-UHFFFAOYSA-N 3-methylimidazole-4-carboxylic acid Chemical compound CN1C=NC=C1C(O)=O PBEDVTDUVXFSMW-UHFFFAOYSA-N 0.000 description 1
- DUQGFIKXKISULR-UHFFFAOYSA-N 3-methyloxetane-3-carbaldehyde Chemical compound O=CC1(C)COC1 DUQGFIKXKISULR-UHFFFAOYSA-N 0.000 description 1
- PMPZEEUNGQSAIQ-UHFFFAOYSA-N 3-methyloxetane-3-carboxylic acid Chemical compound OC(=O)C1(C)COC1 PMPZEEUNGQSAIQ-UHFFFAOYSA-N 0.000 description 1
- CLUWOWRTHNNBBU-UHFFFAOYSA-N 3-methylthiopropanal Chemical compound CSCCC=O CLUWOWRTHNNBBU-UHFFFAOYSA-N 0.000 description 1
- ROADCYAOHVSOLQ-UHFFFAOYSA-N 3-oxetanone Chemical compound O=C1COC1 ROADCYAOHVSOLQ-UHFFFAOYSA-N 0.000 description 1
- XMIIGOLPHOKFCH-UHFFFAOYSA-M 3-phenylpropionate Chemical compound [O-]C(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-M 0.000 description 1
- IMBBXSASDSZJSX-UHFFFAOYSA-N 4-Carboxypyrazole Chemical compound OC(=O)C=1C=NNC=1 IMBBXSASDSZJSX-UHFFFAOYSA-N 0.000 description 1
- YRYAXQJXMBETAT-UHFFFAOYSA-N 4-[(2-methylpropan-2-yl)oxycarbonyl]piperazin-1-ium-2-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCNC(C(O)=O)C1 YRYAXQJXMBETAT-UHFFFAOYSA-N 0.000 description 1
- ZJDBQMWMDZEONW-UHFFFAOYSA-N 4-[(2-methylpropan-2-yl)oxycarbonylamino]benzoic acid Chemical compound CC(C)(C)OC(=O)NC1=CC=C(C(O)=O)C=C1 ZJDBQMWMDZEONW-UHFFFAOYSA-N 0.000 description 1
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 1
- DRBVVUBYEBFRKS-UHFFFAOYSA-N 4-hydroxy-1-[(2-methylpropan-2-yl)oxycarbonylamino]cyclohexane-1-carboxylic acid Chemical compound CC(C)(C)OC(=O)NC1(C(O)=O)CCC(O)CC1 DRBVVUBYEBFRKS-UHFFFAOYSA-N 0.000 description 1
- 229940090248 4-hydroxybenzoic acid Drugs 0.000 description 1
- SJZRECIVHVDYJC-UHFFFAOYSA-N 4-hydroxybutyric acid Chemical compound OCCCC(O)=O SJZRECIVHVDYJC-UHFFFAOYSA-N 0.000 description 1
- BXBJZYXQHHPVGO-UHFFFAOYSA-N 4-hydroxycyclohexan-1-one Chemical compound OC1CCC(=O)CC1 BXBJZYXQHHPVGO-UHFFFAOYSA-N 0.000 description 1
- OKBNEDPOUYRYNP-UHFFFAOYSA-N 4-methyl-1-[(2-methylpropan-2-yl)oxycarbonyl]piperidine-4-carboxylic acid Chemical compound CC(C)(C)OC(=O)N1CCC(C)(C(O)=O)CC1 OKBNEDPOUYRYNP-UHFFFAOYSA-N 0.000 description 1
- JJDDVGAESNBKMY-UHFFFAOYSA-N 5-(trifluoromethyl)pyridine-2-carbaldehyde Chemical compound FC(F)(F)C1=CC=C(C=O)N=C1 JJDDVGAESNBKMY-UHFFFAOYSA-N 0.000 description 1
- GFMRZAMDGJIWRB-UHFFFAOYSA-N 5-[(2-methylpropan-2-yl)oxycarbonylamino]pentanoic acid Chemical compound CC(C)(C)OC(=O)NCCCCC(O)=O GFMRZAMDGJIWRB-UHFFFAOYSA-N 0.000 description 1
- CHODTZCXWXCALP-UHFFFAOYSA-N 5-bromoquinoline Chemical compound C1=CC=C2C(Br)=CC=CC2=N1 CHODTZCXWXCALP-UHFFFAOYSA-N 0.000 description 1
- XMVNMWDLOGSUSM-UHFFFAOYSA-N 5-methyl-1,2-oxazole-3-carbonyl chloride Chemical compound CC1=CC(C(Cl)=O)=NO1 XMVNMWDLOGSUSM-UHFFFAOYSA-N 0.000 description 1
- JXUWZXFVCBODAN-UHFFFAOYSA-N 5-methylpyridin-3-amine Chemical compound CC1=CN=CC(N)=C1 JXUWZXFVCBODAN-UHFFFAOYSA-N 0.000 description 1
- MRPAGRCGPAXOGS-UHFFFAOYSA-N 6-(trifluoromethyl)pyridine-3-carbaldehyde Chemical compound FC(F)(F)C1=CC=C(C=O)C=N1 MRPAGRCGPAXOGS-UHFFFAOYSA-N 0.000 description 1
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
- 101150106774 9 gene Proteins 0.000 description 1
- 102100032814 ATP-dependent zinc metalloprotease YME1L1 Human genes 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 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
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 208000003343 Antiphospholipid Syndrome Diseases 0.000 description 1
- 208000006820 Arthralgia Diseases 0.000 description 1
- 206010003671 Atrioventricular Block Diseases 0.000 description 1
- 208000035143 Bacterial infection Diseases 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- 238000011740 C57BL/6 mouse Methods 0.000 description 1
- 101100297347 Caenorhabditis elegans pgl-3 gene Proteins 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 108020004635 Complementary DNA Proteins 0.000 description 1
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-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
- 235000019739 Dicalciumphosphate Nutrition 0.000 description 1
- DKMROQRQHGEIOW-UHFFFAOYSA-N Diethyl succinate Chemical compound CCOC(=O)CCC(=O)OCC DKMROQRQHGEIOW-UHFFFAOYSA-N 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- 208000010201 Exanthema Diseases 0.000 description 1
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
- 230000005526 G1 to G0 transition Effects 0.000 description 1
- 208000022461 Glomerular disease Diseases 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 229910004373 HOAc Inorganic materials 0.000 description 1
- 208000010271 Heart Block Diseases 0.000 description 1
- 239000004705 High-molecular-weight polyethylene Substances 0.000 description 1
- 102000006947 Histones Human genes 0.000 description 1
- 101000622123 Homo sapiens E-selectin Proteins 0.000 description 1
- 101000917826 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor II-a Proteins 0.000 description 1
- 101000917824 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor II-b Proteins 0.000 description 1
- 101001018020 Homo sapiens Lymphocyte antigen 96 Proteins 0.000 description 1
- 101000763579 Homo sapiens Toll-like receptor 1 Proteins 0.000 description 1
- 101150003028 Hprt1 gene Proteins 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 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 1
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 1
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 102100023533 Interleukin-1 receptor-associated kinase 4 Human genes 0.000 description 1
- 101710199010 Interleukin-1 receptor-associated kinase 4 Proteins 0.000 description 1
- 102000014158 Interleukin-12 Subunit p40 Human genes 0.000 description 1
- 108010011429 Interleukin-12 Subunit p40 Proteins 0.000 description 1
- 206010023232 Joint swelling Diseases 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- 229930182816 L-glutamine Natural products 0.000 description 1
- NGEWQZIDQIYUNV-UHFFFAOYSA-N L-valinic acid Natural products CC(C)C(O)C(O)=O NGEWQZIDQIYUNV-UHFFFAOYSA-N 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- 108010031801 Lipopolysaccharide Receptors Proteins 0.000 description 1
- 102000005482 Lipopolysaccharide Receptors Human genes 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 102100029204 Low affinity immunoglobulin gamma Fc region receptor II-a Human genes 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
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 102000010168 Myeloid Differentiation Factor 88 Human genes 0.000 description 1
- 108010077432 Myeloid Differentiation Factor 88 Proteins 0.000 description 1
- MDXGYYOJGPFFJL-QMMMGPOBSA-N N(alpha)-t-butoxycarbonyl-L-leucine Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)OC(C)(C)C MDXGYYOJGPFFJL-QMMMGPOBSA-N 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- 239000004677 Nylon Substances 0.000 description 1
- MHABMANUFPZXEB-UHFFFAOYSA-N O-demethyl-aloesaponarin I Natural products O=C1C2=CC=CC(O)=C2C(=O)C2=C1C=C(O)C(C(O)=O)=C2C MHABMANUFPZXEB-UHFFFAOYSA-N 0.000 description 1
- KPUNUPJPDZATGH-AWNIVKPZSA-N O/N=C/c(cc1)c2ncccc2c1Br Chemical compound O/N=C/c(cc1)c2ncccc2c1Br KPUNUPJPDZATGH-AWNIVKPZSA-N 0.000 description 1
- REYJJPSVUYRZGE-UHFFFAOYSA-N Octadecylamine Chemical compound CCCCCCCCCCCCCCCCCCN REYJJPSVUYRZGE-UHFFFAOYSA-N 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 229920001710 Polyorthoester Polymers 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 101800000795 Proadrenomedullin N-20 terminal peptide Proteins 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- 238000010802 RNA extraction kit Methods 0.000 description 1
- 239000006146 Roswell Park Memorial Institute medium Substances 0.000 description 1
- 108020004682 Single-Stranded DNA Proteins 0.000 description 1
- 102000039471 Small Nuclear RNA Human genes 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical group [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- QYTDEUPAUMOIOP-UHFFFAOYSA-N TEMPO Chemical group CC1(C)CCCC(C)(C)N1[O] QYTDEUPAUMOIOP-UHFFFAOYSA-N 0.000 description 1
- 229940124613 TLR 7/8 agonist Drugs 0.000 description 1
- 229940124614 TLR 8 agonist Drugs 0.000 description 1
- ZMZDMBWJUHKJPS-UHFFFAOYSA-M Thiocyanate anion Chemical compound [S-]C#N ZMZDMBWJUHKJPS-UHFFFAOYSA-M 0.000 description 1
- RYYWUUFWQRZTIU-UHFFFAOYSA-N Thiophosphoric acid Chemical group OP(O)(S)=O RYYWUUFWQRZTIU-UHFFFAOYSA-N 0.000 description 1
- 102100027010 Toll-like receptor 1 Human genes 0.000 description 1
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 1
- 108091026838 U1 spliceosomal RNA Proteins 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- WPRGHSMSISRIQU-LLVKDONJSA-N [(2r)-4,4-dimethyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]-5-methylsulfonyloxypentyl] methanesulfonate Chemical compound CS(=O)(=O)OCC(C)(C)C[C@H](COS(C)(=O)=O)NC(=O)OC(C)(C)C WPRGHSMSISRIQU-LLVKDONJSA-N 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- WNLRTRBMVRJNCN-UHFFFAOYSA-L adipate(2-) Chemical compound [O-]C(=O)CCCCC([O-])=O WNLRTRBMVRJNCN-UHFFFAOYSA-L 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 229940072056 alginate Drugs 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 150000007933 aliphatic carboxylic acids Chemical class 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 125000003342 alkenyl group Chemical group 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- 208000030961 allergic reaction Diseases 0.000 description 1
- AWUCVROLDVIAJX-UHFFFAOYSA-N alpha-glycerophosphate Natural products OCC(O)COP(O)(O)=O AWUCVROLDVIAJX-UHFFFAOYSA-N 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- 229920000469 amphiphilic block copolymer Polymers 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 239000002152 aqueous-organic solution Substances 0.000 description 1
- 238000003491 array Methods 0.000 description 1
- 125000004391 aryl sulfonyl group Chemical group 0.000 description 1
- 229940072107 ascorbate Drugs 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 229940009098 aspartate Drugs 0.000 description 1
- 238000002820 assay format Methods 0.000 description 1
- 238000003149 assay kit Methods 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 230000001363 autoimmune Effects 0.000 description 1
- DLGYNVMUCSTYDQ-UHFFFAOYSA-N azane;pyridine Chemical compound N.C1=CC=NC=C1 DLGYNVMUCSTYDQ-UHFFFAOYSA-N 0.000 description 1
- 125000002393 azetidinyl group Chemical group 0.000 description 1
- 229960003270 belimumab Drugs 0.000 description 1
- 229940077388 benzenesulfonate Drugs 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
- 229940050390 benzoate Drugs 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 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
- 229920002988 biodegradable polymer Polymers 0.000 description 1
- 239000004621 biodegradable polymer Substances 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 239000012503 blood component Substances 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- FATUQANACHZLRT-KMRXSBRUSA-L calcium glucoheptonate Chemical compound [Ca+2].OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)C([O-])=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)C([O-])=O FATUQANACHZLRT-KMRXSBRUSA-L 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 244000309466 calf Species 0.000 description 1
- MIOPJNTWMNEORI-UHFFFAOYSA-N camphorsulfonic acid Chemical compound C1CC2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-UHFFFAOYSA-N 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 238000012754 cardiac puncture Methods 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000000423 cell based assay Methods 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 239000008004 cell lysis buffer Substances 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- PBAYDYUZOSNJGU-UHFFFAOYSA-N chelidonic acid Natural products OC(=O)C1=CC(=O)C=C(C(O)=O)O1 PBAYDYUZOSNJGU-UHFFFAOYSA-N 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 238000004296 chiral HPLC Methods 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 230000000112 colonic effect Effects 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 239000000306 component Substances 0.000 description 1
- 235000008504 concentrate Nutrition 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 229920006037 cross link polymer Polymers 0.000 description 1
- 239000013058 crude material Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 208000004921 cutaneous lupus erythematosus Diseases 0.000 description 1
- 229960004397 cyclophosphamide Drugs 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000005595 deprotonation Effects 0.000 description 1
- 238000010537 deprotonation reaction Methods 0.000 description 1
- 239000007933 dermal patch Substances 0.000 description 1
- 238000011033 desalting Methods 0.000 description 1
- 239000011903 deuterated solvents Substances 0.000 description 1
- NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
- 229940038472 dicalcium phosphate Drugs 0.000 description 1
- 229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- POULHZVOKOAJMA-UHFFFAOYSA-M dodecanoate Chemical compound CCCCCCCCCCCC([O-])=O POULHZVOKOAJMA-UHFFFAOYSA-M 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 239000006196 drop Substances 0.000 description 1
- 229940112141 dry powder inhaler Drugs 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 238000003821 enantio-separation Methods 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- PQJJJMRNHATNKG-UHFFFAOYSA-N ethyl bromoacetate Chemical compound CCOC(=O)CBr PQJJJMRNHATNKG-UHFFFAOYSA-N 0.000 description 1
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
- 229940093471 ethyl oleate Drugs 0.000 description 1
- 230000003090 exacerbative effect Effects 0.000 description 1
- 201000005884 exanthem Diseases 0.000 description 1
- 239000013604 expression vector Substances 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 208000028327 extreme fatigue Diseases 0.000 description 1
- 210000002458 fetal heart Anatomy 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 231100000852 glomerular disease Toxicity 0.000 description 1
- 231100000853 glomerular lesion Toxicity 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 239000000122 growth hormone Substances 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 125000001072 heteroaryl group Chemical group 0.000 description 1
- 150000002391 heterocyclic compounds Chemical class 0.000 description 1
- IPCSVZSSVZVIGE-UHFFFAOYSA-M hexadecanoate Chemical compound CCCCCCCCCCCCCCCC([O-])=O IPCSVZSSVZVIGE-UHFFFAOYSA-M 0.000 description 1
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 230000009215 host defense mechanism Effects 0.000 description 1
- 102000045711 human LY96 Human genes 0.000 description 1
- 239000000017 hydrogel Substances 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- ZMZDMBWJUHKJPS-UHFFFAOYSA-N hydrogen thiocyanate Natural products SC#N ZMZDMBWJUHKJPS-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
- MWHLCFYPFGFBQO-UHFFFAOYSA-N hydron;2-(1h-imidazol-5-yl)acetic acid;chloride Chemical compound Cl.OC(=O)CC1=CN=CN1 MWHLCFYPFGFBQO-UHFFFAOYSA-N 0.000 description 1
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
- 125000004464 hydroxyphenyl group Chemical group 0.000 description 1
- 125000002140 imidazol-4-yl group Chemical group [H]N1C([H])=NC([*])=C1[H] 0.000 description 1
- 125000002632 imidazolidinyl group Chemical group 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 229940124622 immune-modulator drug Drugs 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000006749 inflammatory damage Effects 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 239000003999 initiator Substances 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 108091005434 innate immune receptors Proteins 0.000 description 1
- 230000011488 interferon-alpha production Effects 0.000 description 1
- 238000001361 intraarterial administration Methods 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 1
- 125000001786 isothiazolyl group Chemical group 0.000 description 1
- 210000001503 joint Anatomy 0.000 description 1
- 230000003907 kidney function Effects 0.000 description 1
- 229940001447 lactate Drugs 0.000 description 1
- 229940099584 lactobionate Drugs 0.000 description 1
- JYTUSYBCFIZPBE-AMTLMPIISA-N lactobionic acid Chemical compound OC(=O)[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O JYTUSYBCFIZPBE-AMTLMPIISA-N 0.000 description 1
- 229940070765 laurate Drugs 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 239000012139 lysis buffer Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 230000005499 meniscus Effects 0.000 description 1
- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 1
- 229910052753 mercury Inorganic materials 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
- RMIODHQZRUFFFF-UHFFFAOYSA-N methoxyacetic acid Chemical compound COCC(O)=O RMIODHQZRUFFFF-UHFFFAOYSA-N 0.000 description 1
- GDOPTJXRTPNYNR-UHFFFAOYSA-N methyl-cyclopentane Natural products CC1CCCC1 GDOPTJXRTPNYNR-UHFFFAOYSA-N 0.000 description 1
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 1
- 238000001471 micro-filtration Methods 0.000 description 1
- 230000000116 mitigating effect Effects 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- DAZSWUUAFHBCGE-KRWDZBQOSA-N n-[(2s)-3-methyl-1-oxo-1-pyrrolidin-1-ylbutan-2-yl]-3-phenylpropanamide Chemical compound N([C@@H](C(C)C)C(=O)N1CCCC1)C(=O)CCC1=CC=CC=C1 DAZSWUUAFHBCGE-KRWDZBQOSA-N 0.000 description 1
- KVBGVZZKJNLNJU-UHFFFAOYSA-M naphthalene-2-sulfonate Chemical compound C1=CC=CC2=CC(S(=O)(=O)[O-])=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-M 0.000 description 1
- 239000006199 nebulizer Substances 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 229960003512 nicotinic acid Drugs 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 125000001736 nosyl group Chemical group S(=O)(=O)(C1=CC=C([N+](=O)[O-])C=C1)* 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 229920001778 nylon Polymers 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- 239000004533 oil dispersion Substances 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 229940049964 oleate Drugs 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 244000039328 opportunistic pathogen Species 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 238000003305 oral gavage Methods 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 150000002895 organic esters Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- URUUZIAJVSGYRC-UHFFFAOYSA-N oxan-3-one Chemical compound O=C1CCCOC1 URUUZIAJVSGYRC-UHFFFAOYSA-N 0.000 description 1
- JMJRYTGVHCAYCT-UHFFFAOYSA-N oxan-4-one Chemical compound O=C1CCOCC1 JMJRYTGVHCAYCT-UHFFFAOYSA-N 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 150000002923 oximes Chemical class 0.000 description 1
- JLPJFSCQKHRSQR-UHFFFAOYSA-N oxolan-3-one Chemical compound O=C1CCOC1 JLPJFSCQKHRSQR-UHFFFAOYSA-N 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 125000001312 palmitoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- PIRWNASAJNPKHT-SHZATDIYSA-N pamp Chemical compound C([C@@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](C)N)C(C)C)C1=CC=CC=C1 PIRWNASAJNPKHT-SHZATDIYSA-N 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 238000005897 peptide coupling reaction Methods 0.000 description 1
- JRKICGRDRMAZLK-UHFFFAOYSA-L peroxydisulfate Chemical compound [O-]S(=O)(=O)OOS([O-])(=O)=O JRKICGRDRMAZLK-UHFFFAOYSA-L 0.000 description 1
- 230000003094 perturbing effect Effects 0.000 description 1
- 239000008177 pharmaceutical agent Chemical class 0.000 description 1
- 230000009038 pharmacological inhibition Effects 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 description 1
- 229940075930 picrate Drugs 0.000 description 1
- OXNIZHLAWKMVMX-UHFFFAOYSA-M picrate anion Chemical compound [O-]C1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-M 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 229950010765 pivalate Drugs 0.000 description 1
- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
- 210000004180 plasmocyte Anatomy 0.000 description 1
- 229920001610 polycaprolactone Polymers 0.000 description 1
- 229920002721 polycyanoacrylate Polymers 0.000 description 1
- 230000003234 polygenic effect Effects 0.000 description 1
- 229920000656 polylysine Polymers 0.000 description 1
- 102000054765 polymorphisms of proteins Human genes 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 229920006324 polyoxymethylene Polymers 0.000 description 1
- 229920001296 polysiloxane Polymers 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- XOFYZVNMUHMLCC-ZPOLXVRWSA-N prednisone Chemical compound O=C1C=C[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 XOFYZVNMUHMLCC-ZPOLXVRWSA-N 0.000 description 1
- 229960004618 prednisone Drugs 0.000 description 1
- 238000002953 preparative HPLC Methods 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- DRINJBFRTLBHNF-UHFFFAOYSA-N propane-2-sulfonyl chloride Chemical compound CC(C)S(Cl)(=O)=O DRINJBFRTLBHNF-UHFFFAOYSA-N 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- DOQJUNNMZNNQAD-UHFFFAOYSA-N pyrrolidine-2,4-dione Chemical compound O=C1CNC(=O)C1 DOQJUNNMZNNQAD-UHFFFAOYSA-N 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 125000001453 quaternary ammonium group Chemical group 0.000 description 1
- 206010037844 rash Diseases 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 230000008085 renal dysfunction Effects 0.000 description 1
- 238000010839 reverse transcription Methods 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 238000003118 sandwich ELISA Methods 0.000 description 1
- 229930195734 saturated hydrocarbon Natural products 0.000 description 1
- 238000007423 screening assay Methods 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 229920000260 silastic Polymers 0.000 description 1
- 150000004760 silicates Chemical class 0.000 description 1
- 229920002379 silicone rubber Polymers 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 231100000046 skin rash Toxicity 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 108091029842 small nuclear ribonucleic acid Proteins 0.000 description 1
- AWUCVROLDVIAJX-GSVOUGTGSA-N sn-glycerol 3-phosphate Chemical compound OC[C@@H](O)COP(O)(O)=O AWUCVROLDVIAJX-GSVOUGTGSA-N 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 229940087562 sodium acetate trihydrate Drugs 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
- 235000019345 sodium thiosulphate Nutrition 0.000 description 1
- 239000008247 solid mixture Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 125000000547 substituted alkyl group Chemical group 0.000 description 1
- 238000006467 substitution reaction Methods 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
- 239000005720 sucrose Substances 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 150000003456 sulfonamides Chemical class 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 229920001059 synthetic polymer Polymers 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- FKHIFSZMMVMEQY-UHFFFAOYSA-N talc Chemical compound [Mg+2].[O-][Si]([O-])=O FKHIFSZMMVMEQY-UHFFFAOYSA-N 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- MTMBHUYOIZWQAJ-QMMMGPOBSA-N tert-butyl (2s)-2-(aminomethyl)morpholine-4-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCO[C@@H](CN)C1 MTMBHUYOIZWQAJ-QMMMGPOBSA-N 0.000 description 1
- CXAMRLRVJOHMPL-SECBINFHSA-N tert-butyl N-[(2R)-1,5-dihydroxy-4,4-dimethylpentan-2-yl]carbamate Chemical compound OC[C@@H](CC(CO)(C)C)NC(OC(C)(C)C)=O CXAMRLRVJOHMPL-SECBINFHSA-N 0.000 description 1
- NFGAGSXCYBCWDV-MRXNPFEDSA-N tert-butyl N-[(3R)-1-(8-cyanoquinolin-5-yl)-5,5-dimethylpiperidin-3-yl]carbamate Chemical compound CC(C)(C)OC(=O)N[C@H]1CN(CC(C)(C)C1)c1ccc(C#N)c2ncccc12 NFGAGSXCYBCWDV-MRXNPFEDSA-N 0.000 description 1
- MFJHATKFYFKEOC-UONOGXRCSA-N tert-butyl N-[(3R,5S)-1-(8-carbamoylquinolin-5-yl)-5-methylpiperidin-3-yl]carbamate Chemical compound C(N)(=O)C=1C=CC(=C2C=CC=NC=12)N1C[C@@H](C[C@@H](C1)C)NC(OC(C)(C)C)=O MFJHATKFYFKEOC-UONOGXRCSA-N 0.000 description 1
- XCMHWWZDAXHISG-GOEBONIOSA-N tert-butyl N-[(3R,5S)-1-benzyl-5-methylpiperidin-3-yl]carbamate Chemical compound C[C@H]1C[C@H](CN(Cc2ccccc2)C1)NC(=O)OC(C)(C)C XCMHWWZDAXHISG-GOEBONIOSA-N 0.000 description 1
- ZVKZIVBMLICOOK-UHFFFAOYSA-N tert-butyl n-(3-formyloxetan-3-yl)carbamate Chemical compound CC(C)(C)OC(=O)NC1(C=O)COC1 ZVKZIVBMLICOOK-UHFFFAOYSA-N 0.000 description 1
- XYPVJWFXUXXBOT-UHFFFAOYSA-N tert-butyl n-(5-methylpyridin-3-yl)carbamate Chemical compound CC1=CN=CC(NC(=O)OC(C)(C)C)=C1 XYPVJWFXUXXBOT-UHFFFAOYSA-N 0.000 description 1
- PDAFIZPRSXHMCO-ZCFIWIBFSA-N tert-butyl n-[(2r)-1-hydroxypropan-2-yl]carbamate Chemical compound OC[C@@H](C)NC(=O)OC(C)(C)C PDAFIZPRSXHMCO-ZCFIWIBFSA-N 0.000 description 1
- IKUBRBJLKRGJFD-SECBINFHSA-N tert-butyl n-[(2r)-4,4-dimethylpentan-2-yl]carbamate Chemical compound CC(C)(C)C[C@@H](C)NC(=O)OC(C)(C)C IKUBRBJLKRGJFD-SECBINFHSA-N 0.000 description 1
- KRGZQPBXNUSHSW-ZETCQYMHSA-N tert-butyl n-[(2s)-1-methoxypropan-2-yl]carbamate Chemical compound COC[C@H](C)NC(=O)OC(C)(C)C KRGZQPBXNUSHSW-ZETCQYMHSA-N 0.000 description 1
- CNALVHVMBXLLIY-BDAKNGLRSA-N tert-butyl n-[(3s,5r)-5-methylpiperidin-3-yl]carbamate Chemical compound C[C@H]1CNC[C@@H](NC(=O)OC(C)(C)C)C1 CNALVHVMBXLLIY-BDAKNGLRSA-N 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- CBXCPBUEXACCNR-UHFFFAOYSA-N tetraethylammonium Chemical compound CC[N+](CC)(CC)CC CBXCPBUEXACCNR-UHFFFAOYSA-N 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- QEMXHQIAXOOASZ-UHFFFAOYSA-N tetramethylammonium Chemical compound C[N+](C)(C)C QEMXHQIAXOOASZ-UHFFFAOYSA-N 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000004797 therapeutic response Effects 0.000 description 1
- 230000008719 thickening Effects 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- 210000001541 thymus gland Anatomy 0.000 description 1
- 230000000451 tissue damage Effects 0.000 description 1
- 231100000827 tissue damage Toxicity 0.000 description 1
- 239000012049 topical pharmaceutical composition Substances 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 238000009901 transfer hydrogenation reaction Methods 0.000 description 1
- 230000009261 transgenic effect Effects 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
- ZDPHROOEEOARMN-UHFFFAOYSA-N undecanoic acid Chemical compound CCCCCCCCCCC(O)=O ZDPHROOEEOARMN-UHFFFAOYSA-N 0.000 description 1
- 230000003827 upregulation Effects 0.000 description 1
- 238000010200 validation analysis Methods 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- 239000011534 wash buffer Substances 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/42—Oxazoles
- A61K31/422—Oxazoles not condensed and containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
- A61K31/427—Thiazoles not condensed and containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/4545—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4709—Non-condensed quinolines and containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/472—Non-condensed isoquinolines, e.g. papaverine
- A61K31/4725—Non-condensed isoquinolines, e.g. papaverine containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Dermatology (AREA)
- Urology & Nephrology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201361890858P | 2013-10-14 | 2013-10-14 | |
| US61/890,858 | 2013-10-14 | ||
| PCT/US2014/060412 WO2015057655A1 (en) | 2013-10-14 | 2014-10-14 | Selectively substituted quinoline compounds |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| KR20160068775A KR20160068775A (ko) | 2016-06-15 |
| KR102365952B1 true KR102365952B1 (ko) | 2022-02-22 |
Family
ID=51842880
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020167009292A Active KR102365952B1 (ko) | 2013-10-14 | 2014-10-14 | 선택적으로 치환된 퀴놀린 화합물 |
Country Status (13)
| Country | Link |
|---|---|
| US (1) | US9663486B2 (enExample) |
| EP (1) | EP3057948B1 (enExample) |
| JP (1) | JP6483666B2 (enExample) |
| KR (1) | KR102365952B1 (enExample) |
| CN (2) | CN107935988A (enExample) |
| AU (1) | AU2014334551B2 (enExample) |
| BR (1) | BR112016008378B1 (enExample) |
| CA (1) | CA2920791C (enExample) |
| ES (1) | ES2670550T3 (enExample) |
| IL (2) | IL243926B (enExample) |
| MX (1) | MX363708B (enExample) |
| RU (1) | RU2671496C2 (enExample) |
| WO (1) | WO2015057655A1 (enExample) |
Families Citing this family (69)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2013096194A1 (en) * | 2011-12-22 | 2013-06-27 | Merck Patent Gmbh | Novel heterocyclic carboxamides as modulators of kinase activity |
| RS59911B1 (sr) | 2013-10-14 | 2020-03-31 | Eisai R&D Man Co Ltd | Selektivno supstituisana jedinjenja hinolina |
| CA2920791C (en) | 2013-10-14 | 2021-11-16 | Eisai R&D Management Co., Ltd. | Selectively substituted quinoline compounds |
| EP3889145B1 (en) * | 2015-12-17 | 2024-02-21 | Merck Patent GmbH | 8-cyano-5-piperidino-quinolines as tlr7/8 antagonists and their uses for treating immune disorders |
| US10947214B2 (en) * | 2016-08-08 | 2021-03-16 | Merck Patent Gmbh | TLR7/8 antagonists and uses thereof |
| WO2018047081A1 (en) | 2016-09-09 | 2018-03-15 | Novartis Ag | Compounds and compositions as inhibitors of endosomal toll-like receptors |
| KR20230010826A (ko) | 2016-10-14 | 2023-01-19 | 프리시젼 바이오사이언시스 인코포레이티드 | B형 간염 바이러스 게놈 내의 인식 서열에 대해 특이적인 조작된 메가뉴클레아제 |
| EP3655401B1 (en) * | 2017-07-18 | 2023-09-06 | Merck Patent GmbH | Tlr7/8 antagonists and uses thereof |
| CA3086172A1 (en) * | 2017-12-19 | 2019-06-27 | Merck Patent Gmbh | Tlr7/8 antagonists and uses thereof |
| CN111511754B (zh) | 2017-12-20 | 2023-09-12 | 捷克共和国有机化学与生物化学研究所 | 活化sting转接蛋白的具有膦酸酯键的2’3’环状二核苷酸 |
| US10966999B2 (en) | 2017-12-20 | 2021-04-06 | Institute Of Organic Chemistry And Biochemistry Ascr, V.V.I. | 3′3′ cyclic dinucleotides with phosphonate bond activating the sting adaptor protein |
| WO2019123294A2 (en) * | 2017-12-22 | 2019-06-27 | Novartis Ag | Novel uses of pyrazolo piperidine derivatives |
| EP3752505B1 (en) | 2018-02-12 | 2023-01-11 | F. Hoffmann-La Roche AG | Novel sulfone compounds and derivatives for the treatment and prophylaxis of virus infection |
| CA3091142C (en) | 2018-02-26 | 2023-04-11 | Gilead Sciences, Inc. | Substituted pyrrolizine compounds and uses thereof |
| US10870691B2 (en) | 2018-04-05 | 2020-12-22 | Gilead Sciences, Inc. | Antibodies and fragments thereof that bind hepatitis B virus protein X |
| TWI833744B (zh) | 2018-04-06 | 2024-03-01 | 捷克科學院有機化學與生物化學研究所 | 3'3'-環二核苷酸 |
| TW202005654A (zh) | 2018-04-06 | 2020-02-01 | 捷克科學院有機化學與生物化學研究所 | 2,2,─環二核苷酸 |
| TWI818007B (zh) | 2018-04-06 | 2023-10-11 | 捷克科學院有機化學與生物化學研究所 | 2'3'-環二核苷酸 |
| US11142750B2 (en) | 2018-04-12 | 2021-10-12 | Precision Biosciences, Inc. | Optimized engineered meganucleases having specificity for a recognition sequence in the Hepatitis B virus genome |
| US20190359645A1 (en) | 2018-05-03 | 2019-11-28 | Institute Of Organic Chemistry And Biochemistry Ascr, V.V.I. | 2'3'-cyclic dinucleotides comprising carbocyclic nucleotide |
| AU2019280728A1 (en) | 2018-06-05 | 2020-11-12 | F. Hoffmann-La Roche Ag | Tetrahydro-1 H-pyrazino[2,1 -ajisoindolylquinoline compounds for the treatment of autoimmune disease |
| TW202016105A (zh) | 2018-06-12 | 2020-05-01 | 瑞士商赫孚孟拉羅股份公司 | 用於治療自體免疫疾病的新穎雜芳基雜環基化合物 |
| EP3807271A1 (en) * | 2018-06-13 | 2021-04-21 | F. Hoffmann-La Roche AG | Pyridinyl heterocyclyl compounds for the treatment of autoimmune disease |
| JPWO2020017569A1 (ja) * | 2018-07-17 | 2021-12-02 | 日本ケミファ株式会社 | T型カルシウムチャネル阻害剤 |
| EP3826724B1 (en) * | 2018-07-23 | 2022-10-05 | F. Hoffmann-La Roche AG | Novel piperazine compounds for the treatment of autoimmune disease |
| JP7491900B2 (ja) * | 2018-07-31 | 2024-05-28 | メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフツング | Tlr7/8アンタゴニストおよびそれらの使用 |
| WO2020028097A1 (en) | 2018-08-01 | 2020-02-06 | Gilead Sciences, Inc. | Solid forms of (r)-11-(methoxymethyl)-12-(3-methoxypropoxy)-3,3-dimethyl-8-0x0-2,3,8,13b-tetrahydro-1h-pyrido[2,1-a]pyrrolo[1,2-c] phthalazine-7-c arboxylic acid |
| EP3847169A1 (en) | 2018-09-04 | 2021-07-14 | F. Hoffmann-La Roche AG | Benzothiazole compounds for the treatment of autoimmune diseases |
| JP2022502353A (ja) * | 2018-09-06 | 2022-01-11 | エフ.ホフマン−ラ ロシュ アーゲーF. Hoffmann−La Roche Aktiengesellschaft | 自己免疫疾患の処置のための新規の環状アミジン化合物 |
| EP3847173B1 (en) | 2018-09-06 | 2023-04-12 | F. Hoffmann-La Roche AG | Novel pyrazolopyridine compounds for the treatment of autoimmune disease |
| JP2022501326A (ja) * | 2018-09-07 | 2022-01-06 | エフ.ホフマン−ラ ロシュ アーゲーF. Hoffmann−La Roche Aktiengesellschaft | 自己免疫疾患の治療のための新規ピロリジンアミン化合物 |
| CN117105933A (zh) | 2018-10-31 | 2023-11-24 | 吉利德科学公司 | 具有hpk1抑制活性的取代的6-氮杂苯并咪唑化合物 |
| MX2021005047A (es) | 2018-10-31 | 2021-09-08 | Gilead Sciences Inc | Compuestos de 6-azabenzimidazol sustituidos como inhibidores de hpk1. |
| US11008303B2 (en) | 2019-01-30 | 2021-05-18 | Insilico Medicine Ip Limited | TLR 9 inhibitors |
| US11807622B2 (en) | 2019-01-30 | 2023-11-07 | Insilico Medicine Ip Limited | TLR 9 inhibitors |
| US10689360B1 (en) * | 2019-01-30 | 2020-06-23 | Insilico Medicine Ip Limited | TLR inhibitors |
| AU2020231115B2 (en) | 2019-03-07 | 2025-02-20 | Institute Of Organic Chemistry And Biochemistry Ascr, V.V.I. | 3'3'-cyclic dinucleotides and prodrugs thereof |
| US11766447B2 (en) | 2019-03-07 | 2023-09-26 | Institute Of Organic Chemistry And Biochemistry Ascr, V.V.I. | 3′3′-cyclic dinucleotide analogue comprising a cyclopentanyl modified nucleotide as sting modulator |
| DK3934757T3 (da) | 2019-03-07 | 2023-04-17 | Inst Of Organic Chemistry And Biochemistry Ascr V V I | 2'3'-cykliske dinukleotider og prodrugs deraf |
| JP2022081710A (ja) * | 2019-03-29 | 2022-06-01 | ユーティアイ リミテッド パートナーシップ | 関節リウマチを治療するためのt型カルシウムチャネル阻害剤の使用 |
| JPWO2020203609A1 (enExample) * | 2019-03-29 | 2020-10-08 | ||
| TWI751516B (zh) | 2019-04-17 | 2022-01-01 | 美商基利科學股份有限公司 | 類鐸受體調節劑之固體形式 |
| TW202212339A (zh) | 2019-04-17 | 2022-04-01 | 美商基利科學股份有限公司 | 類鐸受體調節劑之固體形式 |
| TWI826690B (zh) | 2019-05-23 | 2023-12-21 | 美商基利科學股份有限公司 | 經取代之烯吲哚酮化物及其用途 |
| US20220296619A1 (en) | 2019-08-19 | 2022-09-22 | Gilead Sciences, Inc. | Pharmaceutical formulations of tenofovir alafenamide |
| US20220363665A1 (en) | 2019-09-10 | 2022-11-17 | Hoffmann-La Roche Inc. | Quinoline compounds for the treatment of autoimmune disease |
| JP2022547729A (ja) | 2019-09-16 | 2022-11-15 | エフ.ホフマン-ラ ロシュ アーゲー | 自己免疫疾患を治療するためのピペリジニルアミン化合物 |
| EP4089083A1 (en) | 2019-09-23 | 2022-11-16 | Accutar Biotechnology Inc. | Piperidine-2,6-dione substituted isoindoles in the preparation of substituted quinoline-8-carbonitrile derivatives having androgen receptor degradation activity and uses thereof |
| EP4458975A3 (en) | 2019-09-30 | 2025-02-12 | Gilead Sciences, Inc. | Hbv vaccines and methods treating hbv |
| WO2021084022A1 (en) | 2019-10-31 | 2021-05-06 | F. Hoffmann-La Roche Ag | Hydropyrazino[1,2-d][1,4]diazepine compounds for the treatment of autoimmune disease |
| JP7707163B2 (ja) * | 2019-11-12 | 2025-07-14 | エフ. ホフマン-ラ ロシュ アーゲー | 自己免疫疾患の処置のためのヒドロピラジノ[1,2-b]イソキノリン化合物 |
| CN114728976B (zh) | 2019-11-19 | 2024-08-16 | 豪夫迈·罗氏有限公司 | 用于治疗自身免疫性疾病的氢-1H-吡咯并[1,2-a]吡嗪化合物 |
| US12421252B2 (en) | 2019-11-20 | 2025-09-23 | Hoffmann-La Roche Inc. | Spiro (isobenzofuranazetidine) compounds for the treatment of autoimmune disease |
| US12421229B2 (en) | 2019-12-03 | 2025-09-23 | Hoffmann-La Roche Inc. | Hydropyrido[1,2-α]pyrazine compounds for the treatment of autoimmune disease |
| EP4069729B1 (en) | 2019-12-06 | 2025-01-22 | Precision BioSciences, Inc. | Optimized engineered meganucleases having specificity for a recognition sequence in the hepatitis b virus genome |
| AR121620A1 (es) | 2020-03-20 | 2022-06-22 | Gilead Sciences Inc | Profármacos de nucleósidos 4-c-sustituidos-2-halo-2-deoxiadenosina y métodos de preparación y uso de los mismos |
| CN112649540B9 (zh) * | 2021-01-11 | 2022-02-18 | 中国科学院西北生态环境资源研究院 | 一种类异戊二烯烷烃中姥鲛烷非对映异构体快速分离方法 |
| CN115109032B (zh) * | 2021-03-18 | 2023-09-05 | 成都百裕制药股份有限公司 | 喹啉衍生物及其在医药上的应用 |
| US11661431B2 (en) | 2021-04-16 | 2023-05-30 | Gilead Sciences, Inc. | Thienopyrrole compounds |
| AU2022274607A1 (en) | 2021-05-13 | 2023-11-16 | Gilead Sciences, Inc. | COMBINATION OF A TLR8 MODULATING COMPOUND AND ANTI-HBV siRNA THERAPEUTICS |
| JP7686086B2 (ja) | 2021-06-23 | 2025-05-30 | ギリアード サイエンシーズ, インコーポレイテッド | ジアシルグリエルコール(diacylglyercol)キナーゼ調節化合物 |
| WO2022271684A1 (en) | 2021-06-23 | 2022-12-29 | Gilead Sciences, Inc. | Diacylglyercol kinase modulating compounds |
| KR20240005901A (ko) | 2021-06-23 | 2024-01-12 | 길리애드 사이언시즈, 인코포레이티드 | 디아실글리세롤 키나제 조절 화합물 |
| WO2022271659A1 (en) | 2021-06-23 | 2022-12-29 | Gilead Sciences, Inc. | Diacylglyercol kinase modulating compounds |
| CN117957234A (zh) | 2021-09-10 | 2024-04-30 | 吉利德科学公司 | 噻吩并吡咯化合物 |
| WO2025240242A1 (en) | 2024-05-13 | 2025-11-20 | Gilead Sciences, Inc. | Combination therapies with ribavirin |
| WO2025240246A1 (en) | 2024-05-13 | 2025-11-20 | Gilead Sciences, Inc. | Combination therapies with ribavirin |
| WO2025240243A1 (en) | 2024-05-13 | 2025-11-20 | Gilead Sciences, Inc. | Combination therapies with bulevirtide and an inhibitory nucleic acid targeting hepatitis b virus |
| WO2025240244A1 (en) | 2024-05-13 | 2025-11-20 | Gilead Sciences, Inc. | Combination therapies comprising bulevirtide and lonafarnib for use in the treatment of hepatitis d virus infection |
Family Cites Families (166)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NO156828C (no) | 1980-11-10 | 1987-12-02 | Otsuka Pharma Co Ltd | Analogifremgangsm te for fremstilling av antibakterielt virksomme benzoheterocykliske forbindelser. |
| IL62783A (en) | 1981-05-04 | 1987-01-30 | Usv Pharma Corp | Antihypertensive 1,4-thiazine,1,4-thiazepine and 1,4-thiazocine compounds,method for the preparation thereof and pharmaceutical compositions containing the same |
| JPS5890511A (ja) | 1981-11-25 | 1983-05-30 | Otsuka Pharmaceut Co Ltd | 抗菌剤 |
| US5358949A (en) | 1986-03-05 | 1994-10-25 | Otsuka Pharmaceutical Co., Ltd. | Carbostyril derivatives and salts thereof and anti-arrhythmic agents containing the carbostyril derivatives |
| JPS6354363A (ja) | 1986-08-26 | 1988-03-08 | Ss Pharmaceut Co Ltd | キノリン誘導体 |
| AU639529B2 (en) | 1987-03-04 | 1993-07-29 | Higuchi, Yoshinari | Carbostyril derivatives and salts thereof and anti-arrhythmic agents containing the carbostyril derivatives |
| JPH01156960A (ja) * | 1987-09-24 | 1989-06-20 | Ss Pharmaceut Co Ltd | キノリン誘導体 |
| US4933447A (en) * | 1987-09-24 | 1990-06-12 | Ss Pharmaceutical Co., Ltd. | Quinoline derivatives |
| JPH08295690A (ja) | 1995-04-26 | 1996-11-12 | Tokuyama Corp | クロメン化合物 |
| EP0934924B1 (en) | 1996-10-11 | 2008-08-13 | Kowa Co. Ltd. | Novel diamide compounds and drugs containing the same |
| DE19643048A1 (de) | 1996-10-18 | 1998-04-23 | Daimler Benz Ag | Verbindungen und deren Verwendung sowie Verfahren zur Herstellung von flüssigkristallinen Polymeren daraus |
| GB9712761D0 (en) | 1997-06-17 | 1997-08-20 | Chiroscience Ltd | Quinolines and their therapeutic use |
| US6933272B1 (en) | 1998-09-22 | 2005-08-23 | Erik Helmerhorst | Use of non-peptidyl compounds for the treatment of insulin related ailments |
| EE200100558A (et) | 1999-04-28 | 2002-12-16 | Aventis Pharma Deutschland Gmbh | Triarüülhappe derivaat, seda sisaldav farmatseutiline kompositsioon ja ühendi raviotstarbeline kasutamine |
| CN101070316A (zh) | 1999-04-28 | 2007-11-14 | 萨诺费-阿文蒂斯德国有限公司 | 作为ppar受体配体的二芳基酸衍生物 |
| DE19936437A1 (de) | 1999-08-03 | 2001-02-08 | Aventis Cropscience Gmbh | Kombinationen aus Herbiziden und Safenern |
| FR2798656B1 (fr) * | 1999-09-17 | 2004-12-17 | Aventis Pharma Sa | Derives de la quinolyl propyl piperidine, leur preparation et les compositions qui les contiennent |
| US6710205B2 (en) | 2000-02-22 | 2004-03-23 | Ono Pharmaceutical Co., Ltd. | Benzoic acid derivatives, processes for producing the same and drugs containing the same as the active ingredient |
| WO2001070734A2 (en) | 2000-03-17 | 2001-09-27 | Bristol-Myers Squibb Pharma Company | Beta-amino acid derivatives as inhibitors of matrix metalloproteases and tnf-alpha |
| CZ20023033A3 (cs) | 2000-03-17 | 2003-01-15 | Bristol-Myers Squibb Pharma Company | Deriváty cyklických beta-aminokyselin jako inhibitory matrixových metaloproteáz a TNF-alfa |
| WO2002018335A1 (en) | 2000-08-28 | 2002-03-07 | Yamanouchi Pharmaceutical Co., Ltd. | Cyclic amine derivatives |
| US20030028018A1 (en) | 2000-09-11 | 2003-02-06 | Chiron Coporation | Quinolinone derivatives |
| ES2302106T3 (es) | 2000-09-11 | 2008-07-01 | Novartis Vaccines And Diagnostics, Inc. | Procedimiento de preparacion de derivados de bencimidazol-2-il quinolina. |
| EP1217000A1 (en) | 2000-12-23 | 2002-06-26 | Aventis Pharma Deutschland GmbH | Inhibitors of factor Xa and factor VIIa |
| CN1509184A (zh) | 2001-03-19 | 2004-06-30 | �ձ���ҩ��ʽ���� | 止痒剂 |
| US20030055263A1 (en) | 2001-07-11 | 2003-03-20 | Boehringer Ingelheim Pharma Kg | Carboxylic acid derivatives, medicaments comprising these compounds, their use and processes for their production |
| CA2465978C (en) | 2001-09-14 | 2015-04-07 | Soon Hyung Woo | Inhibitors of histone deacetylase |
| US7868204B2 (en) | 2001-09-14 | 2011-01-11 | Methylgene Inc. | Inhibitors of histone deacetylase |
| US6897220B2 (en) | 2001-09-14 | 2005-05-24 | Methylgene, Inc. | Inhibitors of histone deacetylase |
| DE10222166A1 (de) | 2002-05-20 | 2003-12-11 | Fraunhofer Ges Forschung | Chirale Verbindungen und deren Verwendung |
| DE10229070A1 (de) | 2002-06-28 | 2004-01-15 | Merck Patent Gmbh | Phenylderivate 5 |
| AU2003257822A1 (en) | 2002-08-13 | 2004-04-30 | Shionogi And Co., Ltd. | Heterocyclic compound having hiv integrase inhibitory activity |
| US7825132B2 (en) | 2002-08-23 | 2010-11-02 | Novartis Vaccines And Diagnostics, Inc. | Inhibition of FGFR3 and treatment of multiple myeloma |
| US20050256157A1 (en) | 2002-08-23 | 2005-11-17 | Chiron Corporation | Combination therapy with CHK1 inhibitors |
| BR0313743A (pt) | 2002-08-23 | 2005-07-05 | Chiron Corp | Benzimidazol quinolinonas e usos destas |
| US7041693B2 (en) | 2002-10-04 | 2006-05-09 | Bristol-Myers Squibb Company | Hydantoin derivatives as inhibitors of matrix metalloproteinases and/or TNF-α converting enzyme (TACE) |
| US7074810B2 (en) | 2002-10-07 | 2006-07-11 | Bristol-Myers Squibb Company | Triazolone and triazolethione derivatives as inhibitors of matrix metalloproteinases and/or TNF-α converting enzyme |
| US20040072802A1 (en) | 2002-10-09 | 2004-04-15 | Jingwu Duan | Beta-amino acid derivatives as inhibitors of matrix metalloproteases and TNF-alpha |
| GB2396154B (en) | 2002-10-15 | 2007-02-28 | Merck Patent Gmbh | 4,5-Dicyanoimidazole derivatives and their use in liquid crystal media and liquid crystal devices |
| US7442475B2 (en) | 2003-02-22 | 2008-10-28 | Merck Patent Gmbh | Cyanopyridone derivatives as liquid crystals |
| EP1608373A4 (en) | 2003-03-19 | 2010-09-29 | Exelixis Inc | TIE-2 MODULATORS AND USE METHOD |
| WO2004087698A2 (en) | 2003-03-25 | 2004-10-14 | Vertex Pharmaceuticals Incorporated | Thiazoles useful as inhibitors of protein kinases |
| WO2004087835A1 (en) | 2003-04-01 | 2004-10-14 | Merck Patent Gmbh | Chiral polymerizable compounds |
| ZA200510028B (en) * | 2003-06-20 | 2007-03-28 | Coley Pharm Gmbh | Small molicule toll-like receptor (TLR) antagonists |
| MXPA05013922A (es) | 2003-06-20 | 2006-02-24 | Coley Pharm Group Inc | Antagonistas de receptor tipo toll de molecula pequena. |
| WO2005028488A1 (en) | 2003-09-12 | 2005-03-31 | Quatrx Pharmaceuticals Co. | Heteroaryl phosphinyl and thiophosphinyl compounds for regulation of glucose, triglycerides, and ldl/hdl levels |
| US7211671B2 (en) | 2003-10-01 | 2007-05-01 | Bristol Myers Squibb Company | Substituted 1,3-dihydro-imidazol-2-one and 1,3-dihydro-imidazol-2-thione derivatives as inhibitors of matrix metalloproteinases and/or TNF-α converting enzyme (TACE) |
| JP2005132834A (ja) | 2003-10-09 | 2005-05-26 | Kyowa Hakko Kogyo Co Ltd | キノリン誘導体 |
| GB0325956D0 (en) | 2003-11-06 | 2003-12-10 | Addex Pharmaceuticals Sa | Novel compounds |
| KR101167573B1 (ko) | 2003-11-07 | 2012-07-30 | 노바티스 백신즈 앤드 다이아그노스틱스 인코포레이티드 | 개선된 약학적 성질을 갖는 퀴놀리논 화합물의 약학적으로허용가능한 염 |
| KR101104100B1 (ko) | 2003-11-19 | 2012-01-12 | 제이엔씨 석유 화학 주식회사 | 광 중합성 액정 조성물, 그의 중합체 또는 중합체 조성물및 광학보상 소자 |
| CA2555311A1 (en) | 2004-02-04 | 2005-08-18 | Neurosearch A/S | Diazabicyclic aryl derivatives as nicotinic acetylcholine receptor ligands |
| EA200601266A1 (ru) | 2004-02-18 | 2007-02-27 | Астразенека Аб | Соединения триазола и их применение в качестве антагонистов метаботропного рецептора глутамата |
| WO2005082340A2 (en) | 2004-02-20 | 2005-09-09 | Chiron Corporation | Modulation of inflammatory and metastatic processes |
| US8404747B2 (en) | 2004-03-05 | 2013-03-26 | The General Hospital Corporation | Compositions and methods for modulating interaction between polypeptides |
| WO2005108370A1 (ja) | 2004-04-16 | 2005-11-17 | Ajinomoto Co., Inc. | ベンゼン化合物 |
| WO2005115361A2 (en) | 2004-05-17 | 2005-12-08 | Acadia Pharmaceuticals Inc. | Androgen receptor modulators and method of treating disease using the same |
| US20070004679A1 (en) | 2004-05-17 | 2007-01-04 | Nathalie Schlienger | Androgen receptor modulators and methods of treating disease using the same |
| JP2007538046A (ja) | 2004-05-19 | 2007-12-27 | ノイロサーチ アクティーゼルスカブ | 新規なアザビシクロアリール誘導体 |
| GB0418046D0 (en) | 2004-08-12 | 2004-09-15 | Prosidion Ltd | Eantioselective process |
| DE102004039789A1 (de) | 2004-08-16 | 2006-03-02 | Sanofi-Aventis Deutschland Gmbh | Arylsubstituierte polycyclische Amine, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel |
| GB0510143D0 (en) | 2005-05-18 | 2005-06-22 | Addex Pharmaceuticals Sa | Novel compounds A1 |
| US20080306055A1 (en) | 2004-12-21 | 2008-12-11 | Astrazeneca Ab | Heterocyclic Mchr1 Antagonists And Their Use In Therapy |
| US7880002B2 (en) | 2004-12-29 | 2011-02-01 | Millennium Pharmaceuticals, Inc. | Substituted piperazinyl-pyrrolidine compounds useful as chemokine receptor antagonists |
| US7317024B2 (en) | 2005-01-13 | 2008-01-08 | Bristol-Myers Squibb Co. | Heterocyclic modulators of the glucocorticoid receptor, AP-1, and/or NF-κB activity and use thereof |
| WO2006110276A2 (en) | 2005-04-08 | 2006-10-19 | Cropsolution, Inc. | Acylated thiosemicarbazides as herbicides |
| GB0510139D0 (en) | 2005-05-18 | 2005-06-22 | Addex Pharmaceuticals Sa | Novel compounds B1 |
| JP2007045752A (ja) | 2005-08-10 | 2007-02-22 | Takeda Chem Ind Ltd | 5員芳香族複素環誘導体、その製造法および用途 |
| JP2007131765A (ja) | 2005-11-11 | 2007-05-31 | Fujifilm Corp | 液晶性組成物 |
| RU2441869C2 (ru) | 2005-12-21 | 2012-02-10 | Эбботт Лэборетриз | Противовирусные соединения |
| US20070254894A1 (en) | 2006-01-10 | 2007-11-01 | Kane John L Jr | Novel small molecules with selective cytotoxicity against human microvascular endothelial cell proliferation |
| BRPI0707223A2 (pt) | 2006-01-27 | 2011-04-26 | Pfizer Prod Inc | compostos de derivados de aminoftalazina |
| AR061974A1 (es) | 2006-07-14 | 2008-08-10 | Novartis Ag | Derivados de pirimidina como inhibidores de alk, composiciones farmaceuticas y procesos de obtencion |
| US7683060B2 (en) | 2006-08-07 | 2010-03-23 | Incyte Corporation | Triazolotriazines as kinase inhibitors |
| EP1900731A1 (de) | 2006-09-07 | 2008-03-19 | Bayer Schering Pharma Aktiengesellschaft | N-(1-Phthalazin-1-yl-piperidin-4-yl)-amide als EP2-Rezeptor Modulatoren |
| EP2086974B1 (en) | 2006-11-17 | 2013-07-24 | Polyera Corporation | Diimide-based semiconductor materials and methods of preparing and using the same |
| DE102007015169A1 (de) | 2007-03-27 | 2008-10-02 | Universität des Saarlandes Campus Saarbrücken | 17Beta-Hydroxysteroid-Dehydrogenase-Typ1-Inhibitoren zur Behandlung hormonabhängiger Erkrankungen |
| MX2009010517A (es) | 2007-04-05 | 2009-10-19 | Amgen Inc | Moduladores de cinasa aurora y metodos de uso. |
| US8173639B2 (en) | 2007-04-26 | 2012-05-08 | H. Lundbeck A/S | Isoquinolinone derivatives as NK3 antagonists |
| WO2008131779A1 (en) | 2007-04-26 | 2008-11-06 | H. Lundbeck A/S | Isoquinolinone derivatives as nk3 antagonists |
| EP2167058B1 (en) | 2007-06-18 | 2015-08-12 | University Of Louisville Research Foundation, Inc. | Family of pfkfb3 inhibitors with anti-neoplastic activities |
| US8557823B2 (en) | 2007-06-18 | 2013-10-15 | Advanced Cancer Therapeutics, Llc | Family of PFKFB3 inhibitors with anti-neoplastic activities |
| AU2008266954A1 (en) | 2007-06-20 | 2008-12-24 | Merck Sharp & Dohme Corp. | CETP inhibitors derived from benzoxazole arylamides |
| CA2689523A1 (en) | 2007-06-20 | 2008-12-24 | Merck Sharp & Dohme Corp. | Cetp inhibitors derived from benzoxazole arylamides |
| JP5057056B2 (ja) | 2007-08-03 | 2012-10-24 | Jsr株式会社 | 液晶配向剤、液晶配向膜の製造方法、ポリアミック酸およびポリイミドならびにジアミン化合物 |
| CA2703980A1 (en) | 2007-10-29 | 2009-05-07 | Schering Corporation | Diamido thiazole derivatives as protein kinase inhibitors |
| JP2009108152A (ja) | 2007-10-29 | 2009-05-21 | Sumitomo Chemical Co Ltd | 重合性化合物および光学フィルム |
| CN101440062B (zh) | 2007-11-23 | 2011-09-28 | 齐齐哈尔大学 | N-酰基-8-氨基喹啉衍生物的合成及其作为荧光分子探针的应用 |
| JP2009149754A (ja) | 2007-12-20 | 2009-07-09 | Sumitomo Chemical Co Ltd | 重合性化合物および該重合性化合物を重合してなる光学フィルム |
| EP2262773A1 (en) | 2008-03-07 | 2010-12-22 | F. Hoffmann-La Roche AG | 2-aminoquinoline derivatives |
| JP5219583B2 (ja) | 2008-03-31 | 2013-06-26 | 住友化学株式会社 | 組成物、光学フィルムとその製造方法、光学部材及び表示装置 |
| US8980877B2 (en) | 2008-04-15 | 2015-03-17 | Dac S.R.L. | Spirocyclic derivatives as histone deacetylase inhibitors |
| WO2009137081A2 (en) | 2008-05-07 | 2009-11-12 | Massachusetts Institute Of Technology | Small molecule inhibitors of plasmodium falciparum dihydroorotate dehydrogenase |
| WO2009139438A1 (ja) | 2008-05-15 | 2009-11-19 | 田辺三菱製薬株式会社 | 光学活性カルボン酸の製造方法 |
| EP2299824B1 (en) | 2008-06-11 | 2013-06-19 | Merck Sharp & Dohme Corp. | Pyrazole derivatives useful as inhibitors of faah |
| CA2727245A1 (en) | 2008-06-11 | 2009-12-17 | Merck Sharp & Dohme Corp. | Imidazole derivatives useful as inhibitors of faah |
| EA201001847A1 (ru) | 2008-06-11 | 2011-08-30 | Айрм Ллк | Соединения и композиции, применяемые для лечения малярии |
| US8822513B2 (en) | 2010-03-01 | 2014-09-02 | Gtx, Inc. | Compounds for treatment of cancer |
| HUE060249T2 (hu) | 2008-06-16 | 2023-02-28 | Univ Tennessee Res Found | Vegyületek rák kezelésére |
| US20120157492A1 (en) | 2008-07-15 | 2012-06-21 | Taigen Biotechnology Co., Ltd. | Antibiotic drug |
| WO2010010187A1 (en) | 2008-07-25 | 2010-01-28 | Galapagos Nv | Novel compounds useful for the treatment of degenerative and inflammatory diseases |
| MX2011001090A (es) | 2008-07-28 | 2011-03-15 | Gilead Sciences Inc | Compuestos de inhibidor de desacetilasa de histona de cicloalquilideno y heterocicloalquilideno. |
| WO2010017079A1 (en) | 2008-08-04 | 2010-02-11 | Merck & Co., Inc. | Oxazole derivatives useful as inhibitors of faah |
| JP2011530483A (ja) | 2008-08-12 | 2011-12-22 | 武田薬品工業株式会社 | アミド化合物 |
| JP5443720B2 (ja) | 2008-09-05 | 2014-03-19 | 住友化学株式会社 | 組成物、光学フィルム及びその製造方法、光学部材ならびに表示装置 |
| JP2010066630A (ja) | 2008-09-12 | 2010-03-25 | Sumitomo Chemical Co Ltd | 光学フィルムの製造方法及び光学フィルム |
| WO2010048149A2 (en) | 2008-10-20 | 2010-04-29 | Kalypsys, Inc. | Heterocyclic modulators of gpr119 for treatment of disease |
| CA2738453C (en) | 2008-10-23 | 2017-07-04 | Boehringer Ingelheim International Gmbh | Urea derivatives of substituted nortropanes, medicaments containing such compounds and their use |
| US8987242B2 (en) | 2008-12-05 | 2015-03-24 | Merck Sharp & Dohme Corp. | Morpholinone compounds as factor IXA inhibitors |
| JP2012511008A (ja) | 2008-12-05 | 2012-05-17 | 持田製薬株式会社 | IXa因子阻害薬としてのモルホリノン化合物 |
| MX2011006332A (es) | 2008-12-23 | 2011-06-27 | Abbott Lab | Compuestos antivirales. |
| JP2012513410A (ja) | 2008-12-23 | 2012-06-14 | アボット・ラボラトリーズ | 抗ウイルス化合物 |
| CN101759683B (zh) | 2008-12-25 | 2011-12-28 | 哈尔滨誉衡药业股份有限公司 | 二氢化茚酰胺化合物制备方法、包含其的药物组合物、及其作为蛋白激酶抑制剂的应用 |
| WO2010096371A2 (en) | 2009-02-18 | 2010-08-26 | Boehringer Ingelheim International Gmbh | Heterocyclic compounds which modulate the cb2 receptor |
| JP5899607B2 (ja) | 2009-03-16 | 2016-04-06 | 住友化学株式会社 | 化合物、光学フィルム及び光学フィルムの製造方法 |
| KR101641385B1 (ko) | 2009-03-16 | 2016-07-20 | 스미또모 가가꾸 가부시끼가이샤 | 화합물, 광학 필름 및 광학 필름의 제조 방법 |
| JP2011008205A (ja) | 2009-05-27 | 2011-01-13 | Fujifilm Corp | 二軸性光学異方性膜を作製するための組成物 |
| JP2011006360A (ja) | 2009-06-26 | 2011-01-13 | Sumitomo Chemical Co Ltd | 化合物、光学フィルム及び光学フィルムの製造方法 |
| GB0912777D0 (en) | 2009-07-22 | 2009-08-26 | Eisai London Res Lab Ltd | Fused aminodihydropyrimidone derivatives |
| US20110021531A1 (en) | 2009-07-27 | 2011-01-27 | Chobanian Harry | Oxazole derivatives useful as inhibitors of faah |
| US9212177B2 (en) | 2009-08-05 | 2015-12-15 | Versitech Limited | Antiviral compounds and methods of making and using thereof |
| CN102573994B (zh) | 2009-08-06 | 2015-06-24 | 默克专利有限公司 | 双环脲化合物 |
| JP2011042606A (ja) | 2009-08-20 | 2011-03-03 | Sumitomo Chemical Co Ltd | 化合物、光学フィルム及び光学フィルムの製造方法 |
| EP2470183B1 (en) | 2009-08-26 | 2015-09-16 | Merck Sharp & Dohme Corp. | Heterocyclic amide compounds as protein kinase inhibitors |
| AU2010286933A1 (en) | 2009-08-31 | 2012-03-15 | Merck Sharp & Dohme Corp. | Morpholinone compounds as factor IXa inhibitors |
| WO2011031896A2 (en) | 2009-09-09 | 2011-03-17 | Avila Therapeutics, Inc. | Pi3 kinase inhibitors and uses thereof |
| MX2012003007A (es) | 2009-09-10 | 2012-04-11 | Novartis Ag | Sulfonamidas como inhibidores de las proteinas de la familia bcl-2 para el tratamiento de cancer. |
| KR101746250B1 (ko) | 2009-12-01 | 2017-06-12 | 스미또모 가가꾸 가부시키가이샤 | 시클로알칸디카르복실산 모노에스테르의 제조 방법 |
| CA2784748A1 (en) | 2009-12-18 | 2011-06-23 | Idenix Pharmaceuticals, Inc. | 5,5-fused arylene or heteroarylene hepatitis c virus inhibitors |
| EP2523664A4 (en) | 2010-01-13 | 2013-06-26 | Tempero Pharmaceuticals Inc | COMPOUNDS AND METHODS |
| WO2011088181A1 (en) | 2010-01-13 | 2011-07-21 | Tempero Pharmaceuticals, Inc. | Compounds and methods |
| BR112012018913A2 (pt) | 2010-01-28 | 2017-06-20 | Merck Sharp & Dohme | "composição farmacêutica, e, uso da composição" |
| CN102892288B (zh) | 2010-02-11 | 2016-02-24 | 范德比尔特大学 | 作为亲代谢性谷氨酸受体4(mGLuR4)变构增效剂的吡唑并吡啶化合物、吡唑并吡嗪化合物、吡唑并吡嘧啶化合物、吡唑并噻吩化合物和吡唑并噻唑化合物,组合物,以及其治疗神经学上的功能失调的方法 |
| AU2010347233B2 (en) | 2010-03-01 | 2015-06-18 | Oncternal Therapeutics, Inc. | Compounds for treatment of cancer |
| JP5871896B2 (ja) | 2010-03-26 | 2016-03-01 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | B−rafキナーゼインヒビター |
| US8865703B2 (en) | 2010-03-26 | 2014-10-21 | Boehringer Ingelheim International Gmbh | Pyridyltriazoles |
| US9725479B2 (en) | 2010-04-22 | 2017-08-08 | Ionis Pharmaceuticals, Inc. | 5′-end derivatives |
| JP5856606B2 (ja) | 2010-04-22 | 2016-02-10 | メルク・シャープ・エンド・ドーム・コーポレイション | Faahの調節薬として有用なオキサゾール誘導体 |
| AU2011242688B2 (en) | 2010-04-23 | 2015-01-22 | Kineta, Inc. | Anti-viral compounds |
| EP2560636A4 (en) | 2010-04-23 | 2013-11-27 | Kineta Inc | ANTIVIRAL CONNECTIONS |
| US20120149715A1 (en) | 2010-05-28 | 2012-06-14 | Yi Tsun Richard Kao | Compounds and methods for the treatment of viral infections |
| JP5652011B2 (ja) | 2010-06-10 | 2015-01-14 | 住友化学株式会社 | 光学フィルム |
| EP2593107A1 (en) | 2010-07-12 | 2013-05-22 | Merck Sharp & Dohme Corp. | Tyrosine kinase inhibitors |
| WO2012016133A2 (en) | 2010-07-29 | 2012-02-02 | President And Fellows Of Harvard College | Ros1 kinase inhibitors for the treatment of glioblastoma and other p53-deficient cancers |
| EP2609092B1 (en) | 2010-08-26 | 2015-04-01 | Boehringer Ingelheim International GmbH | Oxadiazole inhibitors of leukotriene production |
| WO2012033390A2 (en) | 2010-09-10 | 2012-03-15 | Green Cross Corporation | Novel thiophene derivative as sglt2 inhibitor and pharmaceutical composition comprising same |
| WO2012052540A1 (en) | 2010-10-21 | 2012-04-26 | Universitaet Des Saarlandes | Selective cyp11b1 inhibitors for the treatment of cortisol dependent diseases |
| EP2632898A4 (en) | 2010-10-29 | 2014-04-02 | Biogen Idec Inc | HETEROCYCLIC TYROSINE KINASE HEMMER |
| US8710055B2 (en) | 2010-12-21 | 2014-04-29 | Boehringer Ingelheim International Gmbh | Triazolylphenyl sulfonamides as serine/threonine kinase inhibitors |
| WO2012084219A1 (en) | 2010-12-23 | 2012-06-28 | Solvay Sa | Preparation of a fac-isomer for a tris homoleptic metal complex |
| US20120214803A1 (en) | 2011-02-18 | 2012-08-23 | Vifor (International) Ag | Novel Sulfonaminoquinoline Hepcidin Antagonists |
| EP2686325B1 (en) | 2011-03-14 | 2016-12-14 | Vertex Pharmaceuticals Incorporated | Morpholine-spirocyclic piperidine amides as modulators of ion channels |
| CN102675289B (zh) | 2011-03-18 | 2014-11-05 | 浙江大德药业集团有限公司 | 作为蛋白激酶抑制剂的n-苯基苯甲酰胺衍生物 |
| WO2012128582A2 (en) | 2011-03-23 | 2012-09-27 | Hyundai Pharm Co., Ltd. | A COMPOUND FOR INHIBITING HUMAN 11-β-HYDROXY STEROID DEHYDROGENASE TYPE 1, AND A PHARMACEUTICAL COMPOSITION COMPRISING THE SAME |
| US20120252721A1 (en) | 2011-03-31 | 2012-10-04 | Idenix Pharmaceuticals, Inc. | Methods for treating drug-resistant hepatitis c virus infection with a 5,5-fused arylene or heteroarylene hepatitis c virus inhibitor |
| WO2013004332A1 (en) | 2011-07-07 | 2013-01-10 | Merck Patent Gmbh | Substituted azaheterocycles for the treatment of cancer |
| WO2013009827A1 (en) | 2011-07-13 | 2013-01-17 | Tempero Pharmaceuticals, Inc. | Methods of treatment |
| WO2013009830A1 (en) | 2011-07-13 | 2013-01-17 | Tempero Pharmaceuticals, Inc. | Methods of treatment |
| WO2013009810A1 (en) | 2011-07-13 | 2013-01-17 | Tempero Pharmaceuticals, Inc. | Methods of treatment |
| CA2849726A1 (en) | 2011-09-23 | 2013-03-28 | Advinus Therapeutics Limited | Amide compounds, compositions and applications thereof |
| US8846917B2 (en) | 2011-11-09 | 2014-09-30 | Vertex Pharmaceuticals Incorporated | Compounds useful as inhibitors of ATR kinase |
| US8841450B2 (en) | 2011-11-09 | 2014-09-23 | Vertex Pharmaceuticals Incorporated | Compounds useful as inhibitors of ATR kinase |
| WO2013071090A1 (en) | 2011-11-09 | 2013-05-16 | Vertex Pharmaceuticals Incorporated | Compounds useful as inhibitors of atr kinase |
| JO3407B1 (ar) | 2012-05-31 | 2019-10-20 | Eisai R&D Man Co Ltd | مركبات رباعي هيدرو بيرازولو بيريميدين |
| CA2920791C (en) | 2013-10-14 | 2021-11-16 | Eisai R&D Management Co., Ltd. | Selectively substituted quinoline compounds |
| RS59911B1 (sr) | 2013-10-14 | 2020-03-31 | Eisai R&D Man Co Ltd | Selektivno supstituisana jedinjenja hinolina |
-
2014
- 2014-10-14 CA CA2920791A patent/CA2920791C/en active Active
- 2014-10-14 AU AU2014334551A patent/AU2014334551B2/en active Active
- 2014-10-14 US US14/908,164 patent/US9663486B2/en active Active
- 2014-10-14 ES ES14790936.0T patent/ES2670550T3/es active Active
- 2014-10-14 WO PCT/US2014/060412 patent/WO2015057655A1/en not_active Ceased
- 2014-10-14 BR BR112016008378-4A patent/BR112016008378B1/pt active IP Right Grant
- 2014-10-14 RU RU2016118624A patent/RU2671496C2/ru active
- 2014-10-14 CN CN201710963307.5A patent/CN107935988A/zh active Pending
- 2014-10-14 MX MX2016004629A patent/MX363708B/es unknown
- 2014-10-14 JP JP2016516866A patent/JP6483666B2/ja active Active
- 2014-10-14 CN CN201480056216.8A patent/CN105636945B/zh active Active
- 2014-10-14 EP EP14790936.0A patent/EP3057948B1/en active Active
- 2014-10-14 KR KR1020167009292A patent/KR102365952B1/ko active Active
-
2016
- 2016-02-03 IL IL243926A patent/IL243926B/en active IP Right Grant
-
2019
- 2019-06-02 IL IL267031A patent/IL267031B/en active IP Right Grant
Non-Patent Citations (1)
| Title |
|---|
| Organic Letters, 2003, 5, 897-900. |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2015057655A1 (en) | 2015-04-23 |
| CA2920791A1 (en) | 2015-04-23 |
| JP6483666B2 (ja) | 2019-03-13 |
| ES2670550T3 (es) | 2018-05-30 |
| CN105636945B (zh) | 2017-11-17 |
| IL267031A (en) | 2019-07-31 |
| KR20160068775A (ko) | 2016-06-15 |
| JP2016539079A (ja) | 2016-12-15 |
| MX2016004629A (es) | 2016-08-01 |
| AU2014334551B2 (en) | 2018-05-10 |
| MX363708B (es) | 2019-03-29 |
| RU2671496C2 (ru) | 2018-11-01 |
| IL267031B (en) | 2021-05-31 |
| IL243926A0 (en) | 2016-04-21 |
| US20160176841A1 (en) | 2016-06-23 |
| CA2920791C (en) | 2021-11-16 |
| RU2016118624A (ru) | 2017-11-17 |
| CN105636945A (zh) | 2016-06-01 |
| BR112016008378A2 (enExample) | 2017-10-03 |
| CN107935988A (zh) | 2018-04-20 |
| EP3057948B1 (en) | 2018-03-14 |
| IL243926B (en) | 2019-06-30 |
| BR112016008378B1 (pt) | 2022-11-08 |
| US9663486B2 (en) | 2017-05-30 |
| RU2016118624A3 (enExample) | 2018-04-25 |
| EP3057948A1 (en) | 2016-08-24 |
| AU2014334551A1 (en) | 2016-02-25 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR102365952B1 (ko) | 선택적으로 치환된 퀴놀린 화합물 | |
| US11130758B2 (en) | Tetrahydropyrazolopyrimidine compounds | |
| AU2018264036B2 (en) | Selectively substituted quinoline compounds | |
| HK1203498B (en) | Tetrahydropyrazolopyrimidine compounds |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PA0105 | International application |
Patent event date: 20160408 Patent event code: PA01051R01D Comment text: International Patent Application |
|
| PG1501 | Laying open of application | ||
| PA0201 | Request for examination |
Patent event code: PA02012R01D Patent event date: 20191011 Comment text: Request for Examination of Application |
|
| E902 | Notification of reason for refusal | ||
| PE0902 | Notice of grounds for rejection |
Comment text: Notification of reason for refusal Patent event date: 20210329 Patent event code: PE09021S01D |
|
| E701 | Decision to grant or registration of patent right | ||
| PE0701 | Decision of registration |
Patent event code: PE07011S01D Comment text: Decision to Grant Registration Patent event date: 20211116 |
|
| GRNT | Written decision to grant | ||
| PR0701 | Registration of establishment |
Comment text: Registration of Establishment Patent event date: 20220217 Patent event code: PR07011E01D |
|
| PR1002 | Payment of registration fee |
Payment date: 20220218 End annual number: 3 Start annual number: 1 |
|
| PG1601 | Publication of registration | ||
| PR1001 | Payment of annual fee |
Payment date: 20250204 Start annual number: 4 End annual number: 4 |