DL-N-乙酰基-3-硝基苯丙氨酸 | 170157-49-0

• 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: DL-N-乙酰基-3-硝基苯丙氨酸
• 英文名称: DL-N-acetyl-3-nitrophenylalanine
• 英文别名: N-acetyl-3-nitro-(D/L)-phenylalanine；Propanoic acid, 2-acetylamino-3-(3-nitrophenyl)-；2-acetamido-3-(3-nitrophenyl)propanoic acid
• CAS: 170157-49-0
• 化学式: C₁₁H₁₂N₂O₅
• mdl: MFCD00219815
• 分子量: 252.227
• InChiKey: KIOSEOFZTDAFBP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.272
• 拓扑面积：
  112
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  DL-N-乙酰基-3-硝基苯丙氨酸 在 palladium on activated charcoal 盐酸 、 sodium hydroxide 、 氯化亚砜 、 氢气 、 溶剂黄146 作用下， 以 乙醇 、 水 、 乙腈 、 叔丁醇 为溶剂， -20.0~42.0 ℃ 、289.58 kPa 条件下， 反应 18.0h， 生成 BOC-3-氨基苯丙氨酸
  参考文献：
  名称：

  Gonadotropin-Releasing Hormone Antagonists: Novel Members of the Azaline B Family

  摘要：

  A series of antagonists of gonadotropin-releasing hormone (GnRH) homologous to azaline B ([Ac-DNal(1),DCpa(2),DPal(3),Aph(5)(Atz),DAph(6)(Atz),ILys(8),DAla(10)]GnRH) was synthesized, characterized, and tested in a rat antiovulatory assay (AOA). Selected analogues were also tested in both an in vitro dispersed rat pituitary cell culture assay for inhibition of GnRH-stimulated luteinizing hormone release and an in. vitro histamine release assay. The duration of action of some of the most potent and safest analogues in those assays was also determined in the castrated male rat in order to measure the extent (efficacy and duration of action) of inhibition of luteinizing hormone release. Structurally, this series of analogues has novel substitutions (X and Y) in the structure of the azaline B precursor: [Ac-DNal(1),DCpa(2),DPal(3),-Aph(5)(X),DAph(6)(Y),ILys(8),DAla(10)]GnRH. These substitutions were designed to confer increased hydrophilicity as compared to that of azaline B (determined by relative retention times on a C-18 reverse phase column using a triethylammonium phosphate buffer at pH 7.3) or to make them more easily accessible synthetically. Some bulky substituents were introduced in order to probe the spatial limitations of the receptor's cavity. These substitutions include acylated 4-aminophenylalanine at positions 5 and/or 6 (29 analogues), N-alpha-methylated backbone substitutions (six analogues), N-omega-isopropylaminophenylalanine at position 8, and hydrophilic amino acids at position 1. Out of 20 novel analogues tested for long duration position 8, and hydrophilic amino acids at position 1. Out of 20 novel analogues tested for long duration of action in this series, only seven ([Ac-DNal(1),DCpa(2),DPal(3),Aph(5),DAph(6),ILys(8),DAla(10)]GnRH, [Ac-DNal(1),DCpa(2),DPal(3), Aph(5)(For),DAph(6)(For), ILys(8),DAla(10)]GnRH, [Ac-DNal(1),DCpa(2),DPal(3),Aph(5)(Ac),DAph(6)(Ac),- ILys(8),DAla(10)]GnRH (acyline), [Ac-DNal(1),DCpa(2),DPal(3),Aph(5)(Pio),DAph(6)(Pio),ILys(8,)DAla(10)]GnRh, [Ac-DNal(1),DCpa(2),DPal(3),Aph(5)(Atz),DAph(6)(Ac),ILys(8),DAla(10)]GnRH, [Ac-DNalDCpa(2),DPal(3),Aph(5)(Atz-beta Ala),DAph(6)(Atz- beta Ala),ILys(8),DAla(10)]GnRH, [Ac-DNal(1),DCpa2,DPal(3),Aph(5)(Atz-Gab),DAph(6)(Atz-Gab),ILys(8),DAla(10)]GnRH) had relative potencies and/or duration of action comparable to those of azaline B. The others were one-half to one-tenth as effective as azaline B. N-alpha-Methylated backbone substitutions at position 5 yielded analogues that were significantly more hydrophilic presumably because of the breakage of the NH alpha-Tyr(5) to Arg(8)-CO hydrogen bond reported to stabilize a beta-turn encompassing residues 5-8 and which favored beta-sheet formation as shown earlier by Haviv et al.(2) This substitution resulted, however, in an increased potency in the histamine release assay and in significantly shorter duration of action.(3) Similarly, attempts at replacing isopropyllysine in position 8 by either isopropyl-4-aminophenylalanine or isopropyl-4(aminomethyl)phenylalanine resulted in loss of potency in the AOA.Changes in chirality at position 1 or 10 resulted in analogues that were one-tenth and one-half as potent, respectively, as acyline. Introduction of a relatively hydrophilic acetylated residue in position 1 (Ac-4-aminophenylalanine, Ac-2-quinolylalanine, Ac-3-quinolylalanine) also resulted in potent analogues in the AOA in the latter two cases (yet very short acting in the case of ([Ac-D2Qal(1),DCpa(2),DPal(3),Aph(5)(Atz),DAph(6)(Atz),ILys(8),DAla(10)]-GnRH). Introduction of either mesityl, (2-chlorophenyl)isourea, or (3-chlorophenyl)isourea as a substituent on the 4-amino function at residues 5 and 6 of the azaline B precursor was considerably less successful. In this article, we describe in details, improved synthetic protocols for all novel amino acis, N alpha-methylation of amino acids on the resin, and elimination of the undesired N omega-methylation of pyridylalanine at position 3 as the result of base treatment (piperidine or hydrazine) during the deprotection of the Fmoc group or formation of the triazole moiety in the presence of CH2Cl2.

  DOI：

  10.1021/jm00014a017
• 作为产物：
  描述：

  间硝基氯化苄 在 盐酸 、 sodium hydroxide 、 sodium ethanolate 作用下， 反应 36.5h， 生成 DL-N-乙酰基-3-硝基苯丙氨酸
  参考文献：
  名称：

  Gonadotropin-Releasing Hormone Antagonists: Novel Members of the Azaline B Family

  摘要：

  A series of antagonists of gonadotropin-releasing hormone (GnRH) homologous to azaline B ([Ac-DNal(1),DCpa(2),DPal(3),Aph(5)(Atz),DAph(6)(Atz),ILys(8),DAla(10)]GnRH) was synthesized, characterized, and tested in a rat antiovulatory assay (AOA). Selected analogues were also tested in both an in vitro dispersed rat pituitary cell culture assay for inhibition of GnRH-stimulated luteinizing hormone release and an in. vitro histamine release assay. The duration of action of some of the most potent and safest analogues in those assays was also determined in the castrated male rat in order to measure the extent (efficacy and duration of action) of inhibition of luteinizing hormone release. Structurally, this series of analogues has novel substitutions (X and Y) in the structure of the azaline B precursor: [Ac-DNal(1),DCpa(2),DPal(3),-Aph(5)(X),DAph(6)(Y),ILys(8),DAla(10)]GnRH. These substitutions were designed to confer increased hydrophilicity as compared to that of azaline B (determined by relative retention times on a C-18 reverse phase column using a triethylammonium phosphate buffer at pH 7.3) or to make them more easily accessible synthetically. Some bulky substituents were introduced in order to probe the spatial limitations of the receptor's cavity. These substitutions include acylated 4-aminophenylalanine at positions 5 and/or 6 (29 analogues), N-alpha-methylated backbone substitutions (six analogues), N-omega-isopropylaminophenylalanine at position 8, and hydrophilic amino acids at position 1. Out of 20 novel analogues tested for long duration position 8, and hydrophilic amino acids at position 1. Out of 20 novel analogues tested for long duration of action in this series, only seven ([Ac-DNal(1),DCpa(2),DPal(3),Aph(5),DAph(6),ILys(8),DAla(10)]GnRH, [Ac-DNal(1),DCpa(2),DPal(3), Aph(5)(For),DAph(6)(For), ILys(8),DAla(10)]GnRH, [Ac-DNal(1),DCpa(2),DPal(3),Aph(5)(Ac),DAph(6)(Ac),- ILys(8),DAla(10)]GnRH (acyline), [Ac-DNal(1),DCpa(2),DPal(3),Aph(5)(Pio),DAph(6)(Pio),ILys(8,)DAla(10)]GnRh, [Ac-DNal(1),DCpa(2),DPal(3),Aph(5)(Atz),DAph(6)(Ac),ILys(8),DAla(10)]GnRH, [Ac-DNalDCpa(2),DPal(3),Aph(5)(Atz-beta Ala),DAph(6)(Atz- beta Ala),ILys(8),DAla(10)]GnRH, [Ac-DNal(1),DCpa2,DPal(3),Aph(5)(Atz-Gab),DAph(6)(Atz-Gab),ILys(8),DAla(10)]GnRH) had relative potencies and/or duration of action comparable to those of azaline B. The others were one-half to one-tenth as effective as azaline B. N-alpha-Methylated backbone substitutions at position 5 yielded analogues that were significantly more hydrophilic presumably because of the breakage of the NH alpha-Tyr(5) to Arg(8)-CO hydrogen bond reported to stabilize a beta-turn encompassing residues 5-8 and which favored beta-sheet formation as shown earlier by Haviv et al.(2) This substitution resulted, however, in an increased potency in the histamine release assay and in significantly shorter duration of action.(3) Similarly, attempts at replacing isopropyllysine in position 8 by either isopropyl-4-aminophenylalanine or isopropyl-4(aminomethyl)phenylalanine resulted in loss of potency in the AOA.Changes in chirality at position 1 or 10 resulted in analogues that were one-tenth and one-half as potent, respectively, as acyline. Introduction of a relatively hydrophilic acetylated residue in position 1 (Ac-4-aminophenylalanine, Ac-2-quinolylalanine, Ac-3-quinolylalanine) also resulted in potent analogues in the AOA in the latter two cases (yet very short acting in the case of ([Ac-D2Qal(1),DCpa(2),DPal(3),Aph(5)(Atz),DAph(6)(Atz),ILys(8),DAla(10)]-GnRH). Introduction of either mesityl, (2-chlorophenyl)isourea, or (3-chlorophenyl)isourea as a substituent on the 4-amino function at residues 5 and 6 of the azaline B precursor was considerably less successful. In this article, we describe in details, improved synthetic protocols for all novel amino acis, N alpha-methylation of amino acids on the resin, and elimination of the undesired N omega-methylation of pyridylalanine at position 3 as the result of base treatment (piperidine or hydrazine) during the deprotection of the Fmoc group or formation of the triazole moiety in the presence of CH2Cl2.

  DOI：

  10.1021/jm00014a017

文献信息

• [DE] HYDROXYAMIDIN- UND HYDROXYGUANIDIN-VERBINDUNGEN ALS UROKINASE-HEMMSTOFFE<br/>[EN] HYDROXYAMIDINE AND HYDROXYGUANIDINE COMPOUNDS AS UROKINASE INHIBITORS<br/>[FR] COMPOSES COMPORTANT DES GROUPES HYDROXYAMIDINE ET HYDROXYGUANIDINE UTILISES EN TANT QU'INHIBITEURS DE L'UROKINASE
  申请人：WILEX AG

  公开号：WO2004103984A1

  公开（公告）日：2004-12-02

  Die vorliegende Erfindung betrifft neue Verbindungen zu Hemmung des Urokinase-Plasminogen-Aktivators (uPA) mit hoher Bioverfügbarkeit und oraler Verabreichbarkeit sowie deren Verwendung als therapeutische Wirkstoffe zur Behandlung von Urokinase oder/und Urokinase-Rezeptor assoziierten Erkrankungen, wie z.B. Tumore und Metastasierung. Die Erfindung betrifft insbesondere Hydroxyamidin- oder Hydroxyguanidingruppen enthaltende Verbindungen. Formel (I) oder Formel (II) worin E eine Gruppe aus Formel (III), Formel (IV) bedeutet.

  本发明涉及具有高生物利用度和口服可给性的新型抑制尿激酶-纤溶酶原激活物（uPA）的化合物，以及它们作为治疗性药物用于治疗与尿激酶或/和尿激酶受体相关的疾病，如肿瘤和转移等。该发明特别涉及含有羟基胺基或羟基胍基的化合物。其中，E代表来自公式（III）或公式（IV）的基团。
• STREPTOGRAMINS AND METHOD FOR PREPARING SAME BY MUTASYNTHESIS
  申请人：Aventis Pharma, S.A.

  公开号：US20020142947A1

  公开（公告）日：2002-10-03

  Novel group B streptogramine-like compounds of general formula (I), and a method for preparing streptogramines by muta-synthesis using a mutated micro-organism to influence the biosynthesis of at least one of the precursors of group B streptogramines, are disclosed. Novel nucleotide sequences involved in the biosynthesis of said precursors, and their uses, are also disclosed.

  本发明公开了通式(I)的新型B组链球菌素类化合物，以及通过使用突变的微生物进行muta合成来影响B组链球菌素的至少一个前体的生物合成的制备方法。还公开了参与所述前体生物合成的新型核苷酸序列及其用途。
• DERIVES DE 2-AMINOTHIAZOLINE ET LEUR UTILISATION COMME INHIBITEURS DE NO-SYNTHASE
  申请人：Aventis Pharma S.A.

  公开号：EP1299365B1

  公开（公告）日：2005-09-28
• US6352839B1
  申请人：——

  公开号：US6352839B1

  公开（公告）日：2002-03-05
• US6833382B2
  申请人：——

  公开号：US6833382B2

  公开（公告）日：2004-12-21