TWI399203B - 作為TAFIa抑制劑之脲衍生物及磺醯二胺衍生物 - Google Patents

作為TAFIa抑制劑之脲衍生物及磺醯二胺衍生物 Download PDF

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TWI399203B
TWI399203B TW096145997A TW96145997A TWI399203B TW I399203 B TWI399203 B TW I399203B TW 096145997 A TW096145997 A TW 096145997A TW 96145997 A TW96145997 A TW 96145997A TW I399203 B TWI399203 B TW I399203B
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Taiwan
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alkyl
alkylene
phenyl
group
substituted
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TW096145997A
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Chinese (zh)
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TW200838498A (en
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Christopher Kallus
Mark Broenstrup
Werngard Czechtizky
Andreas Evers
Markus Follmann
Nis Halland
Herman Schreuder
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Sanofi Aventis
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    • 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
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    • C07D261/06—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members
    • C07D261/08—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
    • C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
    • C07D295/18—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carboxylic acids, or sulfur or nitrogen analogues thereof
    • C07D295/182—Radicals derived from carboxylic acids
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
    • C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
    • C07D317/44—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D317/46—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems condensed with one six-membered ring
    • C07D317/48—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring
    • C07D317/50—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to atoms of the carbocyclic ring
    • C07D317/58—Radicals substituted by nitrogen atoms
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    • C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
    • C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
    • C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
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    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
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MX2010012793A (es) 2008-06-06 2010-12-14 Sanofi Aventis Derivados de urea macrociclicos y de sulfamida como inhibidores de tafia.
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US8354444B2 (en) 2008-09-18 2013-01-15 Hoffmann-La Roche Inc. Substituted pyrrolidine-2-carboxamides
AU2009310841A1 (en) * 2008-10-29 2010-05-06 Taisho Pharmaceutical Co., Ltd. Compounds having TAFIa inhibitory activity
RU2015156612A (ru) * 2013-06-10 2017-07-17 Санофи Макроциклические производные мочевины в качестве ингибиторов tafia, их получение и их применение в качестве фармацевтических средств
CN104529859B (zh) * 2015-01-13 2016-08-17 佛山市赛维斯医药科技有限公司 含苯胺和二烯氟代金刚烷结构的化合物、其制备方法和用途
RU2687254C1 (ru) * 2018-10-03 2019-05-08 Федеральное государственное бюджетное учреждение науки Новосибирский институт органической химии им. Н.Н. Ворожцова Сибирского отделения Российской академии наук (НИОХ СО РАН) N-гетероциклические производные борниламина в качестве ингибиторов ортопоксвирусов

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0611776A2 (de) * 1993-02-15 1994-08-24 Bayer Ag Neue antiviral wirksame Pseudopeptide
EP0641779A1 (de) * 1993-09-07 1995-03-08 F. Hoffmann-La Roche Ag Neue 1-Amidinopiperidine und 4-Amidinomorphozine als Aggregationshemmer
WO1999011606A2 (en) * 1997-08-28 1999-03-11 Pharmacia & Upjohn Company Inhibitors of protein tyrosine phosphatase
WO2000044335A2 (en) * 1999-01-28 2000-08-03 Microcide Pharmaceuticals, Inc. Uridyl peptide antibiotic (upa) derivatives, their synthesis and use
US20060105995A1 (en) * 2004-10-05 2006-05-18 Schering Aktiengesellschaft TAFI inhibitors and their use to treat pulmonary fibrosis

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU3631500A (en) * 1999-03-19 2000-10-09 Du Pont Pharmaceuticals Company N-adamant-1-yl-n'-(4-chlorobenzothiazol-2-yl) urea useful in the treatment of inflammation and as an anticancer radiosensitizing agent
US6359129B1 (en) * 2000-08-15 2002-03-19 University Of Kansas Amino acid-derived, 7-membered cyclic sulfamides and methods of synthesizing the same
PT1311488E (pt) * 2000-08-17 2009-12-30 Pfizer Ltd Imidazóis substituídos utilizados como inibidores de tafia
DE102004020186A1 (de) * 2004-04-22 2005-11-17 Aventis Pharma Deutschland Gmbh Heterocyclylessigsäuren als Inhibitoren von TAFla

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0611776A2 (de) * 1993-02-15 1994-08-24 Bayer Ag Neue antiviral wirksame Pseudopeptide
EP0641779A1 (de) * 1993-09-07 1995-03-08 F. Hoffmann-La Roche Ag Neue 1-Amidinopiperidine und 4-Amidinomorphozine als Aggregationshemmer
WO1999011606A2 (en) * 1997-08-28 1999-03-11 Pharmacia & Upjohn Company Inhibitors of protein tyrosine phosphatase
WO2000044335A2 (en) * 1999-01-28 2000-08-03 Microcide Pharmaceuticals, Inc. Uridyl peptide antibiotic (upa) derivatives, their synthesis and use
US20060105995A1 (en) * 2004-10-05 2006-05-18 Schering Aktiengesellschaft TAFI inhibitors and their use to treat pulmonary fibrosis

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
Pavel Majer and Pamnarayan S. Randad, A Safe and Efficient Method for Preparation of N,N'-Unsymmetrically Disubstituted Ureas Utilizing Triphosgene, Journal of Organic Chemistry, 59(7), 1937-1938, 1994 *
T. Shin-Watanabe et al., The Structure of beta-MAPI, a novel Proteinase Inhibitor, Tetrahedron, 38(12), 1775-1780, 1982. *

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