(2R,3R)-2-((tert-butyloxycarbonyl)amino)-3-((4-methylbenzyl)thio)-3-phenylpropionic acid | 136620-85-4

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (2R,3R)-2-((tert-butyloxycarbonyl)amino)-3-((4-methylbenzyl)thio)-3-phenylpropionic acid
• 英文别名: (2R,3R)-3-[(4-methylphenyl)methylsulfanyl]-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-phenylpropanoic acid
• CAS: 136620-85-4
• 化学式: C₂₂H₂₇NO₄S
• 分子量: 401.527
• InChiKey: OJVMVGVBLUQGPR-RBUKOAKNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  28
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  101
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  methyl (2R,3R)-2-((tert-butyloxycarbonyl)amino)-3-((4-methylbenzyl)thio)-3-phenylpropionic acid 在 lithium chloride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 96.0h， 以77%的产率得到(2R,3R)-2-((tert-butyloxycarbonyl)amino)-3-((4-methylbenzyl)thio)-3-phenylpropionic acid
  参考文献：
  名称：

  Enantioselective routes to protected syn- and anti-.beta.-phenylcysteines

  摘要：

  DOI：

  10.1021/jo00038a048

文献信息

• Cyclic anti-aggregatory peptides
  申请人：SmithKline Beecham Corporation

  公开号：US05643872A1

  公开（公告）日：1997-07-01

  This invention relates to compounds of the formula: ##STR1## wherein: A' is absent, Asn, Gln, Ala or Abu; A is absent or a D- or L-amino acid chosen from Arg, HArg, (Me.sub.2)Arg, (Et.sub.2)Arg, Abu, Ala, Gly, His, Lys, or an .alpha.-R' substituted derivative thereof, Dtc, Tpr and Pro; B is a D- or L-amino acid chosen from Arg, HArg, NArg, (Me.sub.2)Arg, (Et.sub.2)Arg and Lys or an .alpha.-R' substituted derivative thereof; Q is absent or a D or L amino acid chosen from Tyr, (Alk)Tyr, Phe, (4'W)Phe, HPhe, Phg, Pro, Trp, His, Ser, (Alk)Ser, Thr, (Alk)Thr, (Alk)Cys, (Alk)Pen, Ala, Val, Nva, Met, Leu, Ile, Nle and Nal, or an .alpha.-R' substituted derivative thereof; M is absent or Gly or a D- or L-amino acid chosen from Glu, Phe, Pro, Lys and Ser or, provided n is 1, B-Gly-Glu-Q; W is halogen or Alk; R' is Alk or PhCH.sub.2 ; ##STR2## wherein Z.sub.1 and Z.sub.2 are linked via a covalent bond between L.sup.1 and L.sup.2 ; or Z.sub.1 and Z.sub.2 are, taken together, a covalent bond between the amino terminal residue and the carboxy terminal residue; L.sup.1 and L.sup.2 are --S-- or --(CH.sub.2).sub.p --; X is R.sub.4 R.sub.5 N or H; Y is H, CONR.sub.1 R.sub.2 or CO.sub.2 R.sub.2 ; R.sub.1 and R.sub.2 are H, Alk or (CH.sub.2).sub.p Ar; R.sub.3 and R.sub.3' are H, Alk, (CH.sub.2).sub.p Ar or taken together are --(CH.sub.2).sub.4 -- or --(CH.sub.2).sub.5 --; R.sub.4 is H or Alk; R.sub.5 is R.sub.11, R.sub.11 CO, R.sub.11 OCO, R.sub.11 OCH(R.sub.11')CO, R.sub.11 NHCH(R.sub.11')CO, R.sub.11 SCH(R.sub.11')CO, R.sub.11 SO.sub.2 or R.sub.11 SO; R.sub.6 is Alk, OAlk, halogen or X; R.sub.7 is H, Alk, OAlk, halogen or Y; R.sub.8 and R.sub.8' are H, Alk, (CH.sub.2).sub.p Ph, (CH.sub.2).sub.p Nph or taken together are --(CH.sub.2).sub.4 -- or --(CH.sub.2).sub.5 --; R.sub.9 is H, Alk or Y; R.sub.10 is H or Alk; R.sub.11 and R.sub.11' are H, C.sub.1-5 alkyl, C.sub.3-7 cycloalkyl, Ar, Ar--C.sub.1-5 alkyl, Ar--C.sub.3-7 cycloalkyl; Ar is phenyl or phenyl substituted by one or two C.sub.1-5 alkyl, trifluoromethyl, hydroxy, C.sub.1-5 alkoxy or halogen groups; n is 1 or 2; q is 0 or 1; and p is 0, 1, 2 or 3; or a pharmaceutically acceptable salt thereof; which are effective for inhibiting platelet aggregation, pharmaceutical compositions for effecting such activity, a method for inhibiting platelet aggregation and clot formation in a mammal, and a method for inhibiting reocclusion of a blood vessel following fibrinolytic therapy.

  本发明涉及以下式的化合物：## STR1 ## 其中：A'不存在，Asn，Gln，Ala或Abu；A不存在或为D-或L-氨基酸，选择自Arg，HArg，（Me.sub.2）Arg，（Et.sub.2）Arg，Abu，Ala，Gly，His，Lys或其α-R'取代衍生物，Dtc，Tpr和Pro; B为D-或L-氨基酸，选择自Arg，HArg，NArg，（Me.sub.2）Arg，（Et.sub.2）Arg和Lys或其α-R'取代衍生物; Q不存在或为D或L氨基酸，选择自Tyr，（Alk）Tyr，Phe，（4'W）Phe，HPhe，Phg，Pro，Trp，His，Ser，（Alk）Ser，Thr，（Alk）Thr，（Alk）Cys，（Alk）Pen，Ala，Val，Nva，Met，Leu，Ile，Nle和Nal或其α-R'取代衍生物; M不存在或为Gly或D-或L-氨基酸，选择自Glu，Phe，Pro，Lys和Ser或，如果n为1，则为B-Gly-Glu-Q; W为卤素或Alk; R'为Alk或PhCH.sub.2; ## STR2 ## 其中Z.sub.1和Z.sub.2通过L.sup.1和L.sup.2之间的共价键连接; 或Z.sub.1和Z.sub.2一起取自氨基末端残基和羧基末端残基之间的共价键; L.sup.1和L.sup.2为--S--或--（CH.sub.2）.sub.p--; X为R.sub.4 R.sub.5 N或H; Y为H，CONR.sub.1 R.sub.2或CO.sub.2 R.sub.2; R.sub.1和R.sub.2为H，Alk或（CH.sub.2）.sub.p Ar; R.sub.3和R.sub.3'为H，Alk，（CH.sub.2）.sub.p Ar或一起取为--（CH.sub.2）.sub.4--或--（CH.sub.2）.sub.5--; R.sub.4为H或Alk; R.sub.5为R.sub.11，R.sub.11 CO，R.sub.11 OCO，R.sub.11 OCH（R.sub.11'）CO，R.sub.11 NHCH（R.sub.11'）CO，R.sub.11 SCH（R.sub.11'）CO，R.sub.11 SO.sub.2或R.sub.11 SO; R.sub.6为Alk，OAlk，卤素或X; R.sub.7为H，Alk，OAlk，卤素或Y; R.sub.8和R.sub.8'为H，Alk，（CH.sub.2）.sub.p Ph，（CH.sub.2）.sub.p Nph或一起为--（CH.sub.2）.sub.4--或--（CH.sub.2）.sub.5--; R.sub.9为H，Alk或Y; R.sub.10为H或Alk; R.sub.11和R.sub.11'为H，C.sub.1-5烷基，C.sub.3-7环烷基，Ar，Ar--C.sub.1-5烷基，Ar--C.sub.3-7环烷基; Ar为苯基或被一个或两个C.sub.1-5烷基，三氟甲基，羟基，C.sub.1-5烷氧基或卤素基取代的苯基; n为1或2; q为0或1; p为0,1,2或3;或其药学上可接受的盐。它们对抑制血小板聚集有效，制备此类活性的药物组合物，一种抑制哺乳动物中血小板聚集和血栓形成的方法，以及一种抑制纤溶疗法后血管再闭塞的方法。
• Side-Chain Extended Ligation
  申请人：Botti Paolo

  公开号：US20090192300A1

  公开（公告）日：2009-07-30

  The invention is directed to methods and compositions for chemical ligation of a first component that includes a carboxythioester and a second component that includes an amino-functionalized compound bearing a branched side chain that includes a removable thiol auxiliary, to give a ligation product having an amide bond at the ligation site. The reactants of the invention are chemoselective and the thiol moiety is removable from the ligation product. Removal of the thiol can be exploited to generate a native side chain at the ligation site. The methods and compositions of the invention are particularly useful for ligation of peptides and polypeptides. The ligation system of the invention is applicable to a wide variety of molecules, and thus can be exploited to generate peptides, polypeptides and other amino acid containing polymers.

  本发明涉及一种化学连接的方法和组合物，用于将包括羧基硫酯的第一组分和包括带有可移除巯基辅助剂的分支侧链的氨基功能化合物的第二组分进行化学连接，从而在连接位点上形成酰胺键的连接产物。本发明的反应物具有化学选择性，而巯基部分可从连接产物中移除。利用巯基的去除可以在连接位点上生成天然侧链。本发明的方法和组合物特别适用于肽和多肽的连接。本发明的连接系统适用于各种分子，因此可以用于生成肽，多肽和其他含氨基酸的聚合物。
• SIDE-CHAIN EXTENDED LIGATION
  申请人：AMYLIN PHARMACEUTICALS, INC.

  公开号：EP1904515A1

  公开（公告）日：2008-04-02
• US5643872A
  申请人：——

  公开号：US5643872A

  公开（公告）日：1997-07-01
• [EN] SIDE-CHAIN EXTENDED LIGATION<br/>[FR] LIGATION ETENDUE DE CHAINE LATERALE
  申请人：GENEPROT INC

  公开号：WO2006133962A1

  公开（公告）日：2006-12-21

  [EN] The invention is directed to methods and compositions for chemical ligation of a first component that includes a carboxythioester and a second component that includes an amino-functionalized compound bearing a branched side chain that includes a removable thiol auxiliary, to give a ligation product having an amide bond at the ligation site. The reactants of the invention are chemoselective and the thiol moiety is removable from the ligation product. Removal of the thiol can be exploited to generate a native side chain at the ligation site. The methods and compositions of the invention are particularly useful for ligation of peptides and polypeptides. The ligation system of the invention is applicable to a wide variety of molecules, and thus can be exploited to generate peptides, polypeptides and other amino acid containing polymers.
  [FR] L'invention concerne des procédés et des compositions destinés à la ligation chimique d'un premier composant qui comprend un carboxythioester et un second composant qui comprend un composé amino fonctionnalisé supportant une chaîne latérale ramifiée contenant un auxiliaire thiol amovible, afin de produire un produit de ligation présentant une liaison d'amide au niveau du site de ligation. Les réactifs de l'invention sont chimiosélectifs et la fraction thiol est amovible du produit de ligation. Le retrait du thiol peut être exploité afin de générer une chaîne latérale native au niveau du site de ligation. Les procédés et les compositions de l'invention sont particulièrement utiles dans la ligation de peptides et de polypeptides. Le système de ligation de l'invention est applicable à une large variété de molécules, et peut ainsi être exploité afin de générer des peptides, des polypeptides et d'autres polymères contenant des acides aminés.