CN105330595A - 吡啶衍生物及其作为抗分支杆菌的应用 - Google Patents
吡啶衍生物及其作为抗分支杆菌的应用 Download PDFInfo
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- CN105330595A CN105330595A CN201410335196.XA CN201410335196A CN105330595A CN 105330595 A CN105330595 A CN 105330595A CN 201410335196 A CN201410335196 A CN 201410335196A CN 105330595 A CN105330595 A CN 105330595A
- Authority
- CN
- China
- Prior art keywords
- dimethylamino
- naphthalen
- phenylbutan
- methoxy
- methoxypyridin
- 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.)
- Granted
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- 241000186359 Mycobacterium Species 0.000 title abstract description 6
- 150000003222 pyridines Chemical class 0.000 title abstract description 6
- 238000011282 treatment Methods 0.000 claims abstract description 15
- 241000187479 Mycobacterium tuberculosis Species 0.000 claims abstract description 11
- 238000002360 preparation method Methods 0.000 claims abstract description 8
- -1 C3-10Cycloalkyl radical Chemical class 0.000 claims description 266
- 238000006243 chemical reaction Methods 0.000 claims description 155
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 136
- 150000001875 compounds Chemical class 0.000 claims description 128
- 238000000034 method Methods 0.000 claims description 113
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 claims description 106
- 229910052757 nitrogen Inorganic materials 0.000 claims description 86
- 150000003839 salts Chemical class 0.000 claims description 46
- 239000002904 solvent Substances 0.000 claims description 34
- 125000005842 heteroatom Chemical group 0.000 claims description 28
- 150000003254 radicals Chemical class 0.000 claims description 26
- 201000008827 tuberculosis Diseases 0.000 claims description 25
- 125000003118 aryl group Chemical group 0.000 claims description 22
- 229910052717 sulfur Inorganic materials 0.000 claims description 21
- 125000000217 alkyl group Chemical group 0.000 claims description 20
- 239000003814 drug Substances 0.000 claims description 20
- 125000004429 atom Chemical group 0.000 claims description 19
- 229910052794 bromium Inorganic materials 0.000 claims description 18
- 229910052740 iodine Inorganic materials 0.000 claims description 18
- 229910052799 carbon Inorganic materials 0.000 claims description 17
- 229910052801 chlorine Inorganic materials 0.000 claims description 16
- 229910052739 hydrogen Inorganic materials 0.000 claims description 16
- 229940002612 prodrug Drugs 0.000 claims description 16
- 239000000651 prodrug Substances 0.000 claims description 16
- 229910052736 halogen Inorganic materials 0.000 claims description 15
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 14
- 150000002367 halogens Chemical class 0.000 claims description 14
- 125000001072 heteroaryl group Chemical group 0.000 claims description 14
- 229910052731 fluorine Inorganic materials 0.000 claims description 13
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 13
- BTANRVKWQNVYAZ-UHFFFAOYSA-N butan-2-ol Chemical compound CCC(C)O BTANRVKWQNVYAZ-UHFFFAOYSA-N 0.000 claims description 12
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 claims description 11
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 claims description 9
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 9
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 claims description 8
- 125000003545 alkoxy group Chemical group 0.000 claims description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 8
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 7
- 125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 claims description 5
- ZYKRAYUKWIUQOX-UHFFFAOYSA-N 1-[5-(4-bromophenyl)-2-methoxypyridin-3-yl]-2-(2,5-difluorophenyl)-4-(dimethylamino)-1-phenylbutan-2-ol Chemical compound BrC1=CC=C(C=C1)C=1C=C(C(=NC=1)OC)C(C(CCN(C)C)(O)C1=C(C=CC(=C1)F)F)C1=CC=CC=C1 ZYKRAYUKWIUQOX-UHFFFAOYSA-N 0.000 claims description 5
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 5
- 125000001188 haloalkyl group Chemical group 0.000 claims description 5
- 125000004076 pyridyl group Chemical group 0.000 claims description 5
- 125000000335 thiazolyl group Chemical group 0.000 claims description 5
- QSLPNSWXUQHVLP-UHFFFAOYSA-N $l^{1}-sulfanylmethane Chemical compound [S]C QSLPNSWXUQHVLP-UHFFFAOYSA-N 0.000 claims description 4
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 4
- GMHDARFEKOSUDQ-UHFFFAOYSA-N 1-(2,3-dimethoxyphenyl)-4-(dimethylamino)-1-(2-methoxy-5-phenylpyridin-3-yl)-2-phenylbutan-2-ol Chemical compound COC1=C(C=CC=C1OC)C(C(CCN(C)C)(O)C1=CC=CC=C1)C=1C(=NC=C(C=1)C1=CC=CC=C1)OC GMHDARFEKOSUDQ-UHFFFAOYSA-N 0.000 claims description 4
- GELDIDQBCNEDGK-UHFFFAOYSA-N 1-(4-chlorophenyl)-4-(dimethylamino)-1-(2-methoxy-5-phenylpyridin-3-yl)-2-phenylbutan-2-ol Chemical compound ClC1=CC=C(C=C1)C(C(CCN(C)C)(O)C1=CC=CC=C1)C=1C(=NC=C(C=1)C1=CC=CC=C1)OC GELDIDQBCNEDGK-UHFFFAOYSA-N 0.000 claims description 4
- BJMDHWYJIAOAAQ-UHFFFAOYSA-N 1-[5-(4-bromophenyl)-2-methoxypyridin-3-yl]-2-(2,3-difluorophenyl)-4-(dimethylamino)-1-phenylbutan-2-ol Chemical compound BrC1=CC=C(C=C1)C=1C=C(C(=NC=1)OC)C(C(CCN(C)C)(O)C1=C(C(=CC=C1)F)F)C1=CC=CC=C1 BJMDHWYJIAOAAQ-UHFFFAOYSA-N 0.000 claims description 4
- NREBMYGXQZIUPN-UHFFFAOYSA-N 1-[5-(4-chlorophenyl)-2-methoxypyridin-3-yl]-2-(2,3-dichlorophenyl)-4-(dimethylamino)-1-phenylbutan-2-ol Chemical compound ClC1=CC=C(C=C1)C=1C=C(C(=NC=1)OC)C(C(CCN(C)C)(O)C1=C(C(=CC=C1)Cl)Cl)C1=CC=CC=C1 NREBMYGXQZIUPN-UHFFFAOYSA-N 0.000 claims description 4
- BQYDRBJRZCEUPJ-UHFFFAOYSA-N 1-[5-(4-chlorophenyl)-2-methoxypyridin-3-yl]-2-(2,5-dichlorophenyl)-4-(dimethylamino)-1-phenylbutan-2-ol Chemical compound ClC1=CC=C(C=C1)C=1C=C(C(=NC=1)OC)C(C(CCN(C)C)(O)C1=C(C=CC(=C1)Cl)Cl)C1=CC=CC=C1 BQYDRBJRZCEUPJ-UHFFFAOYSA-N 0.000 claims description 4
- LFQDWGNGLJACQJ-UHFFFAOYSA-N 1-[5-(4-chlorophenyl)-2-methoxypyridin-3-yl]-2-(3,5-dichlorophenyl)-4-(dimethylamino)-1-phenylbutan-2-ol Chemical compound ClC1=CC=C(C=C1)C=1C=C(C(=NC=1)OC)C(C(CCN(C)C)(O)C1=CC(=CC(=C1)Cl)Cl)C1=CC=CC=C1 LFQDWGNGLJACQJ-UHFFFAOYSA-N 0.000 claims description 4
- HEPMHOQVHUVMLT-UHFFFAOYSA-N 1-naphthalen-1-yl-1-phenylbutan-2-ol Chemical compound C1(=CC=CC2=CC=CC=C12)C(C(CC)O)C1=CC=CC=C1 HEPMHOQVHUVMLT-UHFFFAOYSA-N 0.000 claims description 4
- VMPZVYITNYGGBA-UHFFFAOYSA-N 2-(2,3-difluorophenyl)-4-(dimethylamino)-1-(2-methoxy-5-phenylpyridin-3-yl)-1-phenylbutan-2-ol Chemical compound FC1=C(C=CC=C1F)C(C(C1=CC=CC=C1)C=1C(=NC=C(C=1)C1=CC=CC=C1)OC)(CCN(C)C)O VMPZVYITNYGGBA-UHFFFAOYSA-N 0.000 claims description 4
- LZBVBDRJQSWPCR-UHFFFAOYSA-N 2-(2,5-difluorophenyl)-4-(dimethylamino)-1-(2-methoxy-5-phenylpyridin-3-yl)-1-phenylbutan-2-ol Chemical compound FC1=C(C=C(C=C1)F)C(C(C1=CC=CC=C1)C=1C(=NC=C(C=1)C1=CC=CC=C1)OC)(CCN(C)C)O LZBVBDRJQSWPCR-UHFFFAOYSA-N 0.000 claims description 4
- YINZHWYSPJSJNX-UHFFFAOYSA-N 2-(3,5-dichlorophenyl)-1-(2,3-dimethoxyphenyl)-4-(dimethylamino)-1-(2-methoxy-5-phenylpyridin-3-yl)butan-2-ol Chemical compound ClC=1C=C(C=C(C=1)Cl)C(C(C=1C(=NC=C(C=1)C1=CC=CC=C1)OC)C1=C(C(=CC=C1)OC)OC)(CCN(C)C)O YINZHWYSPJSJNX-UHFFFAOYSA-N 0.000 claims description 4
- XKGIRBCBLXKCQE-UHFFFAOYSA-N 2-(3,5-difluorophenyl)-4-(dimethylamino)-1-(2-methoxy-5-phenylpyridin-3-yl)-1-phenylbutan-2-ol Chemical compound FC=1C=C(C=C(C=1)F)C(C(C1=CC=CC=C1)C=1C(=NC=C(C=1)C1=CC=CC=C1)OC)(CCN(C)C)O XKGIRBCBLXKCQE-UHFFFAOYSA-N 0.000 claims description 4
- DUSKKVUQPINRTA-UHFFFAOYSA-N 2-(3-chlorophenyl)-1-(2,3-dimethoxyphenyl)-4-(dimethylamino)-1-(2-methoxy-5-phenylpyridin-3-yl)butan-2-ol Chemical compound ClC=1C=C(C=CC=1)C(C(C=1C(=NC=C(C=1)C1=CC=CC=C1)OC)C1=C(C(=CC=C1)OC)OC)(CCN(C)C)O DUSKKVUQPINRTA-UHFFFAOYSA-N 0.000 claims description 4
- VGZXSOYMXCHKPY-UHFFFAOYSA-N 2-benzyl-4-(dimethylamino)-1-(2-methoxy-5-phenylpyridin-3-yl)-1-phenylbutan-2-ol Chemical compound C(C1=CC=CC=C1)C(C(C1=CC=CC=C1)C=1C(=NC=C(C=1)C1=CC=CC=C1)OC)(CCN(C)C)O VGZXSOYMXCHKPY-UHFFFAOYSA-N 0.000 claims description 4
- QFZICLOYWDOENT-UHFFFAOYSA-N 2-cyclohexyl-4-(dimethylamino)-1-(2-methoxy-5-phenylpyridin-3-yl)-1-phenylbutan-2-ol Chemical compound C1(CCCCC1)C(C(C1=CC=CC=C1)C=1C(=NC=C(C=1)C1=CC=CC=C1)OC)(CCN(C)C)O QFZICLOYWDOENT-UHFFFAOYSA-N 0.000 claims description 4
- LMJWFCKAICCNPE-UHFFFAOYSA-N 4-(dimethylamino)-1-(2-fluoro-3-methoxyphenyl)-1-(2-methoxy-5-phenylpyridin-3-yl)-2-phenylbutan-2-ol Chemical compound CN(CCC(C(C=1C(=NC=C(C=1)C1=CC=CC=C1)OC)C1=C(C(=CC=C1)OC)F)(O)C1=CC=CC=C1)C LMJWFCKAICCNPE-UHFFFAOYSA-N 0.000 claims description 4
- ZLMGKTYCDQNHNW-UHFFFAOYSA-N 4-(dimethylamino)-1-(2-fluorophenyl)-1-(2-methoxy-5-phenylpyridin-3-yl)-2-phenylbutan-2-ol Chemical compound CN(CCC(C(C=1C(=NC=C(C=1)C1=CC=CC=C1)OC)C1=C(C=CC=C1)F)(O)C1=CC=CC=C1)C ZLMGKTYCDQNHNW-UHFFFAOYSA-N 0.000 claims description 4
- HMHABHYPAJNZEJ-UHFFFAOYSA-N 4-(dimethylamino)-1-(2-methoxy-5-phenylpyridin-3-yl)-2-phenyl-1-[2-(trifluoromethyl)phenyl]butan-2-ol Chemical compound CN(CCC(C(C1=C(C=CC=C1)C(F)(F)F)C=1C(=NC=C(C=1)C1=CC=CC=C1)OC)(O)C1=CC=CC=C1)C HMHABHYPAJNZEJ-UHFFFAOYSA-N 0.000 claims description 4
- WRLUDWFQPGQRCB-UHFFFAOYSA-N 4-(dimethylamino)-1-(3-fluorophenyl)-1-(2-methoxy-5-phenylpyridin-3-yl)-2-phenylbutan-2-ol Chemical compound CN(CCC(C(C=1C(=NC=C(C=1)C1=CC=CC=C1)OC)C1=CC(=CC=C1)F)(O)C1=CC=CC=C1)C WRLUDWFQPGQRCB-UHFFFAOYSA-N 0.000 claims description 4
- GRCMMTWZXILJNH-UHFFFAOYSA-N 4-(dimethylamino)-1-(4-fluorophenyl)-1-(2-methoxy-5-phenylpyridin-3-yl)-2-phenylbutan-2-ol Chemical compound CN(CCC(C(C=1C(=NC=C(C=1)C1=CC=CC=C1)OC)C1=CC=C(C=C1)F)(O)C1=CC=CC=C1)C GRCMMTWZXILJNH-UHFFFAOYSA-N 0.000 claims description 4
- 125000002541 furyl group Chemical group 0.000 claims description 4
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical compound [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 claims description 4
- 230000008569 process Effects 0.000 claims description 4
- 125000001544 thienyl group Chemical group 0.000 claims description 4
- NBTICIKJPRWAHJ-UHFFFAOYSA-N 1-(3-chlorophenyl)-4-(dimethylamino)-1-(2-methoxy-5-phenylpyridin-3-yl)-2-phenylbutan-2-ol Chemical compound ClC=1C=C(C=CC=1)C(C(CCN(C)C)(O)C1=CC=CC=C1)C=1C(=NC=C(C=1)C1=CC=CC=C1)OC NBTICIKJPRWAHJ-UHFFFAOYSA-N 0.000 claims description 3
- RFBIRGFVRMVMCQ-UHFFFAOYSA-N 1-[5-(4-bromophenyl)-2-methoxypyridin-3-yl]-2-(3,5-dichlorophenyl)-4-(dimethylamino)-1-phenylbutan-2-ol Chemical compound BrC1=CC=C(C=C1)C=1C=C(C(=NC=1)OC)C(C(CCN(C)C)(O)C1=CC(=CC(=C1)Cl)Cl)C1=CC=CC=C1 RFBIRGFVRMVMCQ-UHFFFAOYSA-N 0.000 claims description 3
- MELJKSLQZVRKQZ-UHFFFAOYSA-N 1-[5-(4-bromophenyl)-2-methoxypyridin-3-yl]-2-(3-chlorophenyl)-4-(dimethylamino)-1-phenylbutan-2-ol Chemical compound BrC1=CC=C(C=C1)C=1C=C(C(=NC=1)OC)C(C(CCN(C)C)(O)C1=CC(=CC=C1)Cl)C1=CC=CC=C1 MELJKSLQZVRKQZ-UHFFFAOYSA-N 0.000 claims description 3
- XRYBXNVVRDXBEL-UHFFFAOYSA-N 1-[5-(4-chlorophenyl)-2-methoxypyridin-3-yl]-2-(2,5-difluorophenyl)-4-(dimethylamino)-1-phenylbutan-2-ol Chemical compound ClC1=CC=C(C=C1)C=1C=C(C(=NC=1)OC)C(C(CCN(C)C)(O)C1=C(C=CC(=C1)F)F)C1=CC=CC=C1 XRYBXNVVRDXBEL-UHFFFAOYSA-N 0.000 claims description 3
- LOLGSQVEKPPNEI-UHFFFAOYSA-N 1-[5-(4-chlorophenyl)-2-methoxypyridin-3-yl]-2-(3,4-dichlorophenyl)-4-(dimethylamino)-1-phenylbutan-2-ol Chemical compound ClC1=CC=C(C=C1)C=1C=C(C(=NC=1)OC)C(C(CCN(C)C)(O)C1=CC(=C(C=C1)Cl)Cl)C1=CC=CC=C1 LOLGSQVEKPPNEI-UHFFFAOYSA-N 0.000 claims description 3
- PGJONTMWRUFXDV-UHFFFAOYSA-N 1-[5-(4-chlorophenyl)-2-methoxypyridin-3-yl]-4-(dimethylamino)-2-(3-fluorophenyl)-1-phenylbutan-2-ol Chemical compound ClC1=CC=C(C=C1)C=1C=C(C(=NC=1)OC)C(C(CCN(C)C)(O)C1=CC(=CC=C1)F)C1=CC=CC=C1 PGJONTMWRUFXDV-UHFFFAOYSA-N 0.000 claims description 3
- ISWYDIMJOBFXGZ-UHFFFAOYSA-N 2-(3,5-difluorophenyl)-1-(2,3-dimethoxyphenyl)-4-(dimethylamino)-1-(2-methoxy-5-phenylpyridin-3-yl)butan-2-ol Chemical compound FC=1C=C(C=C(C=1)F)C(C(C=1C(=NC=C(C=1)C1=CC=CC=C1)OC)C1=C(C(=CC=C1)OC)OC)(CCN(C)C)O ISWYDIMJOBFXGZ-UHFFFAOYSA-N 0.000 claims description 3
- LIEBYPUUMVVAMW-UHFFFAOYSA-N 2-(3-chlorophenyl)-1-[5-(4-chlorophenyl)-2-methoxypyridin-3-yl]-4-(dimethylamino)-1-phenylbutan-2-ol Chemical compound ClC=1C=C(C=CC=1)C(C(C1=CC=CC=C1)C=1C(=NC=C(C=1)C1=CC=C(C=C1)Cl)OC)(CCN(C)C)O LIEBYPUUMVVAMW-UHFFFAOYSA-N 0.000 claims description 3
- CJNDNFFGJPXZMJ-UHFFFAOYSA-N 4-(dimethylamino)-1-(2-methoxy-6-phenylpyridin-3-yl)-1,2-diphenylbutan-2-ol Chemical compound CN(CCC(C(C1=CC=CC=C1)C=1C(=NC(=CC=1)C1=CC=CC=C1)OC)(O)C1=CC=CC=C1)C CJNDNFFGJPXZMJ-UHFFFAOYSA-N 0.000 claims description 3
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- 125000006716 (C1-C6) heteroalkyl group Chemical group 0.000 claims description 2
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 2
- MGHIMPYHVMDTSI-UHFFFAOYSA-N 1-[5-(4-bromophenyl)-2-methoxypyridin-3-yl]-4-(dimethylamino)-2-(3-fluorophenyl)-1-phenylbutan-2-ol Chemical compound BrC1=CC=C(C=C1)C=1C=C(C(=NC=1)OC)C(C(CCN(C)C)(O)C1=CC(=CC=C1)F)C1=CC=CC=C1 MGHIMPYHVMDTSI-UHFFFAOYSA-N 0.000 claims description 2
- XNDJTBRCFKLWDP-UHFFFAOYSA-N 2-cyclopentyl-4-(dimethylamino)-1-(2-methoxy-5-phenylpyridin-3-yl)-1-phenylbutan-2-ol Chemical compound C1(CCCC1)C(C(C1=CC=CC=C1)C=1C(=NC=C(C=1)C1=CC=CC=C1)OC)(CCN(C)C)O XNDJTBRCFKLWDP-UHFFFAOYSA-N 0.000 claims description 2
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- Pyridine Compounds (AREA)
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Abstract
Description
Claims (14)
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BR112017000764-9A BR112017000764B1 (pt) | 2014-07-14 | 2015-07-09 | Composto, método para preparar o composto e uso do composto |
CA2954872A CA2954872C (en) | 2014-07-14 | 2015-07-09 | Pyridine derivatives and anti-mycobacterial use thereof |
RU2017103451A RU2664587C1 (ru) | 2014-07-14 | 2015-07-09 | Производные пиридина и их применение против микобактерий |
PCT/CN2015/083626 WO2016008381A1 (zh) | 2014-07-14 | 2015-07-09 | 吡啶衍生物及其作为抗分支杆菌的应用 |
EP15821285.2A EP3170810B1 (en) | 2014-07-14 | 2015-07-09 | Pyridine derivatives and anti-mycobacterial use thereof |
US15/325,824 US9878982B2 (en) | 2014-07-14 | 2015-07-09 | Pyridine derivatives and anti-mycobacterial use thereof |
JP2017502218A JP6362235B2 (ja) | 2014-07-14 | 2015-07-09 | ピリジン誘導体およびその抗マイコバクテリウムにおける使用 |
TW104122817A TWI572592B (zh) | 2014-07-14 | 2015-07-14 | 吡啶衍生物及其作為抗分枝桿菌的應用 |
ZA2017/01066A ZA201701066B (en) | 2014-07-14 | 2017-02-13 | Pyridine derivatives and anti-mycobacterial use thereof |
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Cited By (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2017121323A1 (zh) * | 2016-01-13 | 2017-07-20 | 辰欣药业股份有限公司 | 一种吡啶衍生物类化合物的制备方法及其中间体和晶型 |
CN108699047A (zh) * | 2016-03-03 | 2018-10-23 | 科学与工业研究委员会 | 作为抗分枝杆菌药剂的取代的橙酮生物碱 |
CN108840857A (zh) * | 2018-07-10 | 2018-11-20 | 湖南华腾制药有限公司 | 一种喹啉衍生物的制备方法 |
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WO2023217279A1 (zh) * | 2022-05-13 | 2023-11-16 | 广州嘉越医药科技有限公司 | 一种吡啶衍生物、中间体、制备方法和应用 |
WO2023227123A1 (zh) * | 2022-05-27 | 2023-11-30 | 广州嘉越医药科技有限公司 | 吡啶衍生物的用途 |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1671667A (zh) * | 2002-07-25 | 2005-09-21 | 詹森药业有限公司 | 喹啉衍生物及其作为分枝杆菌抑制剂的应用 |
CN101232884A (zh) * | 2005-06-08 | 2008-07-30 | 詹森药业有限公司 | 作为抗菌剂的喹啉衍生物 |
CN101547907A (zh) * | 2006-12-06 | 2009-09-30 | 詹森药业有限公司 | 抗菌的喹啉衍生物 |
CN101553470A (zh) * | 2006-12-06 | 2009-10-07 | 詹森药业有限公司 | 抗菌的喹啉衍生物 |
CN1976704B (zh) * | 2004-05-28 | 2012-12-05 | 詹森药业有限公司 | 取代的喹啉衍生物在治疗耐药性分枝杆菌性疾病中的用途 |
-
2014
- 2014-07-14 CN CN201410335196.XA patent/CN105330595B/zh active Active
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1671667A (zh) * | 2002-07-25 | 2005-09-21 | 詹森药业有限公司 | 喹啉衍生物及其作为分枝杆菌抑制剂的应用 |
CN1976704B (zh) * | 2004-05-28 | 2012-12-05 | 詹森药业有限公司 | 取代的喹啉衍生物在治疗耐药性分枝杆菌性疾病中的用途 |
CN101232884A (zh) * | 2005-06-08 | 2008-07-30 | 詹森药业有限公司 | 作为抗菌剂的喹啉衍生物 |
CN101547907A (zh) * | 2006-12-06 | 2009-09-30 | 詹森药业有限公司 | 抗菌的喹啉衍生物 |
CN101553470A (zh) * | 2006-12-06 | 2009-10-07 | 詹森药业有限公司 | 抗菌的喹啉衍生物 |
Cited By (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2017121323A1 (zh) * | 2016-01-13 | 2017-07-20 | 辰欣药业股份有限公司 | 一种吡啶衍生物类化合物的制备方法及其中间体和晶型 |
CN108699047A (zh) * | 2016-03-03 | 2018-10-23 | 科学与工业研究委员会 | 作为抗分枝杆菌药剂的取代的橙酮生物碱 |
CN108699047B (zh) * | 2016-03-03 | 2022-03-11 | 科学与工业研究委员会 | 作为抗分枝杆菌药剂的取代的橙酮生物碱 |
CN108929310A (zh) * | 2018-06-29 | 2018-12-04 | 湖南华腾制药有限公司 | 一种二芳基喹啉衍生物的制备方法 |
CN108840857A (zh) * | 2018-07-10 | 2018-11-20 | 湖南华腾制药有限公司 | 一种喹啉衍生物的制备方法 |
CN113100085A (zh) * | 2021-04-21 | 2021-07-13 | 铜陵博锋实业有限公司 | 一种透亮、高吸水度的淀粉猫砂及其制备工艺 |
CN113100085B (zh) * | 2021-04-21 | 2023-12-22 | 铜陵博锋实业有限公司 | 一种透亮、高吸水度的淀粉猫砂及其制备工艺 |
WO2023217279A1 (zh) * | 2022-05-13 | 2023-11-16 | 广州嘉越医药科技有限公司 | 一种吡啶衍生物、中间体、制备方法和应用 |
WO2023227123A1 (zh) * | 2022-05-27 | 2023-11-30 | 广州嘉越医药科技有限公司 | 吡啶衍生物的用途 |
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