(S)-3-(4-((2,7-萘啶-1-基)氨基)苯基)-2-((3-氧代螺[3.5]壬-1 | 455264-29-6

• 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
• 中文名称: (S)-3-(4-((2,7-萘啶-1-基)氨基)苯基)-2-((3-氧代螺[3.5]壬-1
• 英文名称: UCB1193394
• 英文别名: ethyl-3-[4-([2,7]naphthyridin-1-ylamino)phenyl]-2(S)-(3-oxo-spiro[3.5]non-1-en-1-ylamino)propanoate；Ethyl (2S)-3-[4-([2,7]naphthyridin-1-ylamino)phenyl]-2-(3-oxo-spiro[3.5]non-1-en-1-ylamino)propanoate；(S)-ethyl 3-(4-(2,7-naphthyridin-1-ylamino)phenyl)-2-(3-oxospiro[3.5]non-1-en-1-ylamino)propanoate；ethyl (2S)-3-[4-(2,7-naphthyridin-1-ylamino)phenyl]-2-[(3-oxospiro[3.5]non-1-en-1-yl)amino]propanoate
• CAS: 455264-29-6
• 化学式: C₂₈H₃₀N₄O₃
• 分子量: 470.571
• InChiKey: QLICADPMIPSGBE-QHCPKHFHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  35
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  93.2
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (S)-3-(4-((2,7-萘啶-1-基)氨基)苯基)-2-((3-氧代螺[3.5]壬-1 在 N-溴代丁二酰亚胺(NBS) 作用下， 以 乙酸乙酯 为溶剂， 反应 4.0h， 以92.3%的产率得到Zaurategrast乙酯
  参考文献：
  名称：

  [EN] PROCESS FOR THE PREPARATION OF PHENYLALANINE ENAMIDE DERIVATIVES
  [FR] PROCEDE DE PREPARATION DE DERIVES DE PHENYLALANINE-ENAMIDE

  摘要：

  描述了一种制备苯丙氨酸烯酰胺衍生物类的过程，其化学式为（1）其中：Ar1是一个可选择取代的芳香族或杂芳族基团；L2是从-N(R4)- [其中R4是氢原子或可选择取代的直链或支链C1-6烷基基团]，-CON(R4)-或-S(O)2N(R4)-中选择的连接基团；R1是一个羧酸（-CO2H）或其衍生物或生物立体异构体；R2是一个氢原子或一个C1-6烷基基团；Rx、Ry和Rz可以相同也可以不同，每个都是一个原子或基团-L1(Alk1)n(R3)v；以及其盐、溶剂合物、水合物和N-氧化物；所述过程包括将化合物（2）与化合物Ar1W反应，其中：Qa是一个基团-N(R4)H；以及其盐、溶剂合物、水合物和N-氧化物；其中W是从X1（其中X1是一个脱离原子或基团），-COX2（其中X2是卤原子或一个-OH基团）或-SO2X3（其中X3是卤原子）中选择的基团。

  公开号：

  WO2004007428A1
• 作为产物：
  描述：

  ethyl-3-[4-([2,7]naphthyridin-1-ylamino)phenyl]-2(S)-(3-oxo-spiro[3.5]non-1-en-1-ylamino)propanoate, di-(4-toluoyl)-2(R),3(R)-tartaric acid salt 在 potassium carbonate 作用下， 以 水 、 乙酸乙酯 为溶剂， 生成 (S)-3-(4-((2,7-萘啶-1-基)氨基)苯基)-2-((3-氧代螺[3.5]壬-1
  参考文献：
  名称：

  [EN] PROCESS FOR THE PREPARATION OF PHENYLALANINE ENAMIDE DERIVATIVES
  [FR] PROCEDE DE PREPARATION DE DERIVES DE PHENYLALANINE-ENAMIDE

  摘要：

  描述了一种制备苯丙氨酸烯酰胺衍生物类的过程，其化学式为（1）其中：Ar1是一个可选择取代的芳香族或杂芳族基团；L2是从-N(R4)- [其中R4是氢原子或可选择取代的直链或支链C1-6烷基基团]，-CON(R4)-或-S(O)2N(R4)-中选择的连接基团；R1是一个羧酸（-CO2H）或其衍生物或生物立体异构体；R2是一个氢原子或一个C1-6烷基基团；Rx、Ry和Rz可以相同也可以不同，每个都是一个原子或基团-L1(Alk1)n(R3)v；以及其盐、溶剂合物、水合物和N-氧化物；所述过程包括将化合物（2）与化合物Ar1W反应，其中：Qa是一个基团-N(R4)H；以及其盐、溶剂合物、水合物和N-氧化物；其中W是从X1（其中X1是一个脱离原子或基团），-COX2（其中X2是卤原子或一个-OH基团）或-SO2X3（其中X3是卤原子）中选择的基团。

  公开号：

  WO2004007428A1

文献信息

• [EN] PHENYLALANINE ENAMIDE DERIVATIVES<br/>[FR] DERIVES DE PHENYLALANINE ENAMIDE
  申请人：CELLTECH R&D LTD

  公开号：WO2004007494A1

  公开（公告）日：2004-01-22

  Phenylalanine enamide derivatives of formula (1) are described, wherein R1 is a -CH(CH3)2, -(CH2)2CH3; -CH2C(CH3)3, -CH2CH2OH, -CH2CH2OCH3, -CH2CH2OCH2CH2OH, -CH2CH2OCH2CH2OCH3, formula (A) group; and the salts, solvates and N-oxides thereof. Compounds according to the invention are potent and selective inhibitors of α4 integrins. The compounds are of use in modulating cell adhesion and in particular are of use in the prophylaxis and treatment of diseases or disorders including inflammation in which the extravasation of leukocytes plays a role and the invention extends to such a use and to the use of the compounds for the manufacture of a medicament for treating such diseases or disorders.

  公式（1）中描述了苯丙氨酸烯酰胺衍生物，其中R1为-CH(CH3)2，-(CH2)2CH3；-CH2C(CH3)3，-CH2CH2OH，-CH2CH2OCH3，-CH2CH2OCH2CH2OH，-CH2CH2OCH2CH2OCH3，公式（A）基团；以及它们的盐、溶剂合物和N-氧化物。根据本发明的化合物是α4整合素的有效和选择性抑制剂。这些化合物可用于调节细胞粘附，特别是可用于预防和治疗包括白细胞外渗在内的炎症等疾病或紊乱，本发明还涉及这种用途以及用于制造用于治疗此类疾病或紊乱的药物的化合物的用途。
• Process for the preparation of phenylalanine enamide derivatives
  申请人：——

  公开号：US20040073033A1

  公开（公告）日：2004-04-15

  A process for the preparation of a class of phenylalanine enamide derivatives is described: 1 wherein: Ar 1 is an optionally substituted aromatic or heteroaromatic group; L 2 is a linker group selected from —N(R 4 )—[where R 4 is a hydrogen atom or an optionally substituted straight or branched C 1-6 alkyl group], —CON(R 4 )—, or —S(O) 2 N(R 4 )—; R 1 is a carboxylic acid (—CO 2 H) or a derivative or biostere thereof; R 2 is a hydrogen atom or a C 1-6 alkyl group; R x , R y and R z which may be the same or different is each an atom or group —L 1 (Alk 1 ) n (R 3 ) v ; and the salts, solvates, hydrates and N-oxides thereof; which comprises reacting a compound of formula (2): 2 wherein: Q a is a group —N(R 4 )H; and the salts, solvates, hydrates and N-oxides thereof; with a compound Ar 1 W wherein W is a group selected from X 1 (wherein X 1 is a leaving atom or group), —COX 2 (wherein X 2 is a halogen atom or a —OH group) or —SO 2 X 3 (in which X 3 is a halogen atom).

  本发明涉及一种制备苯丙氨酸烯酰胺衍生物的方法：其中：Ar1是可选取代的芳香或杂芳基；L2是选择自—N(R4)—[其中R4是氢原子或可选取代的直链或支链C1-6烷基]、—CON(R4)—或—S(O)2N(R4)—的连接基；R1是羧酸（—CO2H）或其衍生物或生物立体异构体；R2是氢原子或C1-6烷基；Rx、Ry和Rz，它们可以相同也可以不同，每个都是原子或基团—L1(Alk1)n(R3)v；以及其盐、溶剂化物、水合物和N-氧化物；该方法包括将式（2）的化合物：其中：Qa是—N(R4)H基团；及其盐、溶剂化物、水合物和N-氧化物，与化合物Ar1W反应，其中W是选择自X1（其中X1是离去原子或基团）、—COX2（其中X2是卤素原子或—OH基团）或—SO2X3（其中X3是卤素原子）的基团。
• Phenylalanine Enamide Derivatives
  申请人：Brand Stephen

  公开号：US20070167483A1

  公开（公告）日：2007-07-19

  Phenylalanine enamide derivatives of formula (1) are described: wherein R 1 is a group Ar 1 L 2 Ar 2 Alk- in which: Ar 1 is an optionally substituted aromatic or heteroaromatic group; L 2 is a covalent bond or a linker atom or group; Ar 2 is an optionally substituted arylene or heteroarylene group; and Alk is a chain in which R is a carboxylic acid (—CO 2 H) or a derivative or biostere thereof; X is an —O— or —S— atom or —N(R 2 )— group in which: R x , R y and R z which may be the same or different is each a hydrogen atom or an optional substituent; or R z is an atom or group as previously defined and R x and R y are joined together to form an optionally substituted spiro linked cycloaliphatic or heterocycloaliphatic group; and the salts, solvates, hydrates and N-oxides thereof. The compounds are able to inhibit the binding of integrins to their ligands and are of use in the prophylaxis and treatment of immuno or inflammatory disorders or disorders involving the inappropriate growth or migration of cells.

  描述了公式（1）的苯丙氨酸烯酰衍生物：其中R1是Ar1L2Ar2Alk-基团，其中：Ar1是可选的取代芳香族或杂芳族基团；L2是共价键或连接原子或基团；Ar2是可选的取代芳烃或杂芳烃基团；Alk是链，在其中R是羧酸（-CO2H）或其衍生物或生物同分异构体；X是一个-O-或-S-原子或-N（R2）-基团，其中：Rx，Ry和Rz可相同或不同，分别是氢原子或可选的取代基团；或Rz是先前定义的原子或基团，而Rx和Ry结合在一起形成可选的取代螺环脂肪族或杂环脂肪族基团；以及其盐，溶剂化合物，水合物和N-氧化物。这些化合物能够抑制整合素与其配体的结合，并用于预防和治疗免疫或炎症性疾病或涉及细胞不适当生长或迁移的疾病。
• Monitoring and Control of Genotoxic Impurity Acetamide in the Synthesis of Zaurategrast Sulfate
  作者：Arnaud Schülé、Célal Ates、Magali Palacio、Jimmy Stofferis、Jean-Pierre Delatinne、Bruno Martin、Steven Lloyd

  DOI：10.1021/op900330e

  日期：2010.7.16

  In this article we describe the strategy adopted to minimize the risk of acetamide presence in zaurategrast sulfate drug candidate. A risk of acetamide formation (a potential genotoxic impurity) was identified in the API formation step of the process during the early development phase. In order to keep the project development timelines unchanged and without having the appropriate analytical method ready developed, we chose to minimize the risk of acetamide impurity presence by applying an adequate chemical process design. The implementation of a workup sequence involving initially three aqueous washes was later proven to be successful when an appropriate analytical method to detect acetamide below ppm levels was available. Additionally the analytical tool gave us the opportunity to assess and fine-tune the designed process for acetamide elimination by spiking experiments. Data acquired during this evaluation showed that a single aqueous wash associated with two efficient crystallization steps were finally enough to deliver API with a content of acetamide below the level defined as the acceptance criterion.
• US6951943B2
  申请人：——

  公开号：US6951943B2

  公开（公告）日：2005-10-04