CN101336246B - 膦酸二酯衍生物及其制造方法 - Google Patents
膦酸二酯衍生物及其制造方法 Download PDFInfo
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- CN101336246B CN101336246B CN2006800524284A CN200680052428A CN101336246B CN 101336246 B CN101336246 B CN 101336246B CN 2006800524284 A CN2006800524284 A CN 2006800524284A CN 200680052428 A CN200680052428 A CN 200680052428A CN 101336246 B CN101336246 B CN 101336246B
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- -1 Phosphonic acid diester Chemical class 0.000 title abstract description 123
- 238000004519 manufacturing process Methods 0.000 title description 8
- 125000000217 alkyl group Chemical group 0.000 claims description 54
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 34
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 25
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 24
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 22
- 150000005690 diesters Chemical class 0.000 claims description 19
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 14
- 125000006575 electron-withdrawing group Chemical group 0.000 claims description 13
- 125000004432 carbon atom Chemical group C* 0.000 claims description 12
- 125000005843 halogen group Chemical group 0.000 claims description 8
- 238000010494 dissociation reaction Methods 0.000 claims description 6
- 230000005593 dissociations Effects 0.000 claims description 6
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 3
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 3
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 3
- NAWXUBYGYWOOIX-SFHVURJKSA-N (2s)-2-[[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]benzoyl]amino]-4-methylidenepentanedioic acid Chemical compound C1=CC2=NC(N)=NC(N)=C2C=C1CCC1=CC=C(C(=O)N[C@@H](CC(=C)C(O)=O)C(O)=O)C=C1 NAWXUBYGYWOOIX-SFHVURJKSA-N 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 description 130
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- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 85
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- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 84
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 82
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 72
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- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 66
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- 239000000203 mixture Substances 0.000 description 55
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 53
- 101710107035 Gamma-glutamyltranspeptidase Proteins 0.000 description 53
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- 239000002904 solvent Substances 0.000 description 52
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 44
- 238000005160 1H NMR spectroscopy Methods 0.000 description 40
- 238000004679 31P NMR spectroscopy Methods 0.000 description 39
- 125000001424 substituent group Chemical group 0.000 description 39
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 37
- 238000005259 measurement Methods 0.000 description 36
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- 101000926208 Homo sapiens Inactive glutathione hydrolase 2 Proteins 0.000 description 34
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- 102000012194 human gamma-glutamyltransferase Human genes 0.000 description 34
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- 125000003118 aryl group Chemical group 0.000 description 24
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- DDOQBQRIEWHWBT-UHFFFAOYSA-N 2-azaniumyl-4-phosphonobutanoate Chemical class OC(=O)C(N)CCP(O)(O)=O DDOQBQRIEWHWBT-UHFFFAOYSA-N 0.000 description 23
- 239000012043 crude product Substances 0.000 description 23
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- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 16
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- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 14
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- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 13
- 239000000126 substance Substances 0.000 description 13
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 238000004108 freeze drying Methods 0.000 description 12
- 230000007062 hydrolysis Effects 0.000 description 12
- 238000006460 hydrolysis reaction Methods 0.000 description 12
- 239000003960 organic solvent Substances 0.000 description 12
- VONGZNXBKCOUHB-UHFFFAOYSA-N Phenylmethyl butanoate Chemical compound CCCC(=O)OCC1=CC=CC=C1 VONGZNXBKCOUHB-UHFFFAOYSA-N 0.000 description 11
- 238000010828 elution Methods 0.000 description 11
- FEMOMIGRRWSMCU-UHFFFAOYSA-N ninhydrin Chemical compound C1=CC=C2C(=O)C(O)(O)C(=O)C2=C1 FEMOMIGRRWSMCU-UHFFFAOYSA-N 0.000 description 11
- 238000012360 testing method Methods 0.000 description 11
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 10
- 239000013078 crystal Substances 0.000 description 10
- 230000009257 reactivity Effects 0.000 description 10
- 239000002585 base Substances 0.000 description 9
- 239000003054 catalyst Substances 0.000 description 9
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- 229950008427 acivicin Drugs 0.000 description 8
- QAWIHIJWNYOLBE-OKKQSCSOSA-N acivicin Chemical compound OC(=O)[C@@H](N)[C@@H]1CC(Cl)=NO1 QAWIHIJWNYOLBE-OKKQSCSOSA-N 0.000 description 7
- 150000001340 alkali metals Chemical class 0.000 description 7
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 7
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 7
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 7
- 125000001476 phosphono group Chemical group [H]OP(*)(=O)O[H] 0.000 description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
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- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
- 125000003277 amino group Chemical group 0.000 description 6
- 125000002029 aromatic hydrocarbon group Chemical group 0.000 description 6
- 238000003556 assay Methods 0.000 description 6
- 239000003921 oil Substances 0.000 description 6
- 239000000047 product Substances 0.000 description 6
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- 0 Cc(cc1)cc(O2)c1C(*)=CC2=O Chemical compound Cc(cc1)cc(O2)c1C(*)=CC2=O 0.000 description 5
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 5
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 5
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- 150000008044 alkali metal hydroxides Chemical class 0.000 description 5
- 125000003368 amide group Chemical group 0.000 description 5
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- 229910052744 lithium Inorganic materials 0.000 description 5
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- WDYVUKGVKRZQNM-UHFFFAOYSA-N 6-phosphonohexylphosphonic acid Chemical compound OP(O)(=O)CCCCCCP(O)(O)=O WDYVUKGVKRZQNM-UHFFFAOYSA-N 0.000 description 4
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
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- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
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- KSNCZXRLRAAAQD-UHFFFAOYSA-N [4-oxo-4-phenylmethoxy-3-(phenylmethoxycarbonylamino)butyl]phosphonic acid Chemical compound C=1C=CC=CC=1COC(=O)C(CCP(O)(=O)O)NC(=O)OCC1=CC=CC=C1 KSNCZXRLRAAAQD-UHFFFAOYSA-N 0.000 description 3
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- 125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 description 3
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- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 3
- ABLZXFCXXLZCGV-UHFFFAOYSA-N phosphonic acid group Chemical group P(O)(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 description 3
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- JISIBLCXFLGVJX-UHFFFAOYSA-M sodium;butanedioic acid;hydroxide Chemical compound [OH-].[Na+].OC(=O)CCC(O)=O JISIBLCXFLGVJX-UHFFFAOYSA-M 0.000 description 3
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- DURPTKYDGMDSBL-UHFFFAOYSA-N 1-butoxybutane Chemical compound CCCCOCCCC DURPTKYDGMDSBL-UHFFFAOYSA-N 0.000 description 2
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- ZYVYEJXMYBUCMN-UHFFFAOYSA-N 1-methoxy-2-methylpropane Chemical compound COCC(C)C ZYVYEJXMYBUCMN-UHFFFAOYSA-N 0.000 description 2
- ZQAYBCWERYRAMF-UHFFFAOYSA-N 1-methoxy-3-methylbutane Chemical compound COCCC(C)C ZQAYBCWERYRAMF-UHFFFAOYSA-N 0.000 description 2
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- NTFPDEDRMYYPAC-UHFFFAOYSA-N 2-amino-4-[[3-(carboxymethyl)phenoxy]-methoxyphosphoryl]butanoic acid Chemical compound OC(=O)C(N)CCP(=O)(OC)OC1=CC=CC(CC(O)=O)=C1 NTFPDEDRMYYPAC-UHFFFAOYSA-N 0.000 description 2
- YCQNYEOXASVRCZ-UHFFFAOYSA-N 2-amino-4-[butoxy(phenoxy)phosphoryl]butanoic acid Chemical compound CCCCOP(=O)(CCC(N)C(O)=O)OC1=CC=CC=C1 YCQNYEOXASVRCZ-UHFFFAOYSA-N 0.000 description 2
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Images
Classifications
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- C—CHEMISTRY; METALLURGY
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- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
- C07F9/3804—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)] not used, see subgroups
- C07F9/3808—Acyclic saturated acids which can have further substituents on alkyl
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- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
- C07F9/40—Esters thereof
- C07F9/4003—Esters thereof the acid moiety containing a substituent or a structure which is considered as characteristic
- C07F9/4025—Esters of poly(thio)phosphonic acids
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- C07F9/40—Esters thereof
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- C07F9/28—Phosphorus compounds with one or more P—C bonds
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- C07F9/40—Esters thereof
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- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
- C07F9/576—Six-membered rings
- C07F9/5765—Six-membered rings condensed with carbocyclic rings or carbocyclic ring systems
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- C07F9/655—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having oxygen atoms, with or without sulfur, selenium, or tellurium atoms, as the only ring hetero atoms
- C07F9/6552—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having oxygen atoms, with or without sulfur, selenium, or tellurium atoms, as the only ring hetero atoms the oxygen atom being part of a six-membered ring
- C07F9/65522—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having oxygen atoms, with or without sulfur, selenium, or tellurium atoms, as the only ring hetero atoms the oxygen atom being part of a six-membered ring condensed with carbocyclic rings or carbocyclic ring systems
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
Description
实施例 | 取代基:X |
1 | CH3 |
2 | OCH3 |
3 | H |
4 | Cl |
5 | CF3 |
6 | CN |
7 | NO2 |
溶剂 | pH | 水解率(%) |
0.1N Na2CO3 | 11.6 | 100 |
0.1N NaHCO3 | 8.3 | 100 |
D2O | 7 | 49 |
0.1N CH3COOD | 2.9 | 40 |
0.1N CF3COOD | <1 | 0 |
0.1N DCl | <1 | 0 |
0.1N DCl+MeOH | <1 | 0 |
Claims (5)
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JP2005354121 | 2005-12-07 | ||
JP354121/2005 | 2005-12-07 | ||
JP188282/2006 | 2006-07-07 | ||
JP2006188282 | 2006-07-07 | ||
PCT/JP2006/324412 WO2007066705A1 (ja) | 2005-12-07 | 2006-11-30 | ホスホン酸ジエステル誘導体およびその製造方法 |
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CN101336246A CN101336246A (zh) | 2008-12-31 |
CN101336246B true CN101336246B (zh) | 2012-11-28 |
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US (1) | US8129557B2 (zh) |
JP (1) | JP5082102B2 (zh) |
CN (1) | CN101336246B (zh) |
HK (1) | HK1132746A1 (zh) |
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JP5686365B2 (ja) * | 2009-04-24 | 2015-03-18 | 公立大学法人大阪市立大学 | コラーゲン産生促進剤、光老化防止剤、保湿機能改善剤および皮膚用剤組成物 |
JP5787246B2 (ja) * | 2010-09-15 | 2015-09-30 | 国立大学法人京都大学 | 角化細胞遊走・増殖促進剤を含む、創傷治癒剤および褥瘡(床ずれ)治療薬 |
JP2012116776A (ja) * | 2010-11-30 | 2012-06-21 | Kyoto Univ | ホスホン酸ジエステル誘導体の製造法 |
CN103804446A (zh) * | 2014-02-27 | 2014-05-21 | 苏州东南药业股份有限公司 | 一种3,5-二苯甲酰基-2-去氧-2-氟-2甲基-D-核糖-γ-内酯的制备方法 |
JP6457292B2 (ja) * | 2015-02-15 | 2019-01-23 | 株式会社ナールスコーポレーション | 植物の鮮度保持剤組成物、植物の育成促進剤組成物、植物、並びに、植物の製造方法及び植物の処理方法 |
JP6550656B2 (ja) * | 2015-02-23 | 2019-07-31 | 株式会社ナールスコーポレーション | 炎症性皮膚疾患の予防または治療用製剤 |
JP6778362B2 (ja) * | 2015-12-01 | 2020-11-04 | 株式会社ナールスコーポレーション | グルタチオン産生促進剤 |
JP6778361B2 (ja) * | 2015-12-01 | 2020-11-04 | 株式会社ナールスコーポレーション | フィラグリン遺伝子発現促進剤 |
JP6826333B2 (ja) * | 2016-09-14 | 2021-02-03 | 株式会社ナールスコーポレーション | ナールスゲンの光学分割方法 |
JP7280562B2 (ja) * | 2018-08-31 | 2023-05-24 | 株式会社ナールスコーポレーション | 体臭抑制剤 |
CN109608494B (zh) * | 2018-12-19 | 2021-05-14 | 上海辉文生物技术股份有限公司 | 含有膦酰基的羧酸盐、其制备方法和应用 |
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2006
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2009
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Non-Patent Citations (7)
Title |
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Han,L.et al.γ-(Monophenyl)phosphono glutamate analogues as mechanism-based inhibitors of γ-glutamyl transpeptidase.《Bioorganic & Medicinal Chemistry》.2006,第14卷第6043-6045. |
Han,L.et al.γ-(Monophenyl)phosphono glutamate analogues as mechanism-based inhibitors of γ-glutamyl transpeptidase.《Bioorganic & * |
Hiratake J. et al.Enzyme Inhibitors as Chemical Tools to Study Enzyme Catalysis: Rational Design |
Hiratake,J. et al.Enzyme Inhibitors as Chemical Tools to Study Enzyme Catalysis: Rational Design, Synthesis, and Applications.《The Chemical Record》.2005,第5卷第209-228页. * |
Inoue,M. et al.Identification of catalytic nucleophile of Escherichia coli γ-glutamyltranspeptidase by γ-monofluorophosphono derivative of glutamic acid: N-terminal Thr-391 in small subunit is the nucleophile.《Biochemistry》.2000,第39卷(第26期),第7764-7771页. * |
Lherbet,C.et al.Probing the stereochemistry of the active site of gamma-glutamyl transpeptidase using sulfur derivatives of L-glutamic acid.《Organic Biomolecular Chemistry》.2004,第2卷(第2期),第238-245页. * |
Medicinal Chemistry》.2006,第14卷第6043-6045. * |
Also Published As
Publication number | Publication date |
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US20090163725A1 (en) | 2009-06-25 |
HK1132746A1 (en) | 2010-03-05 |
JPWO2007066705A1 (ja) | 2009-05-21 |
CN101336246A (zh) | 2008-12-31 |
JP5082102B2 (ja) | 2012-11-28 |
US8129557B2 (en) | 2012-03-06 |
WO2007066705A1 (ja) | 2007-06-14 |
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