2-(乙酰氨基)-3-(3-硝基苯基)丙酸乙酯 | 170157-50-3

• 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: 2-(乙酰氨基)-3-(3-硝基苯基)丙酸乙酯
• 英文名称: D,L-N-acetyl-3-nitrophenylalanine ethyl ester
• 英文别名: β-Acetamido-β-(m-nitrophenyl)propionsaeureethylester；ethyl 2-(acetylamino)-3-(3-nitrophenyl)propanoate；ethyl (R,S)-N-acetyl-3-nitrophenylalaninate；ethyl 2-acetamido-3-(3-nitrophenyl)propanoate
• CAS: 170157-50-3
• 化学式: C₁₃H₁₆N₂O₅
• 分子量: 280.28
• InChiKey: DEMVMKCQUASWND-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  20
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  101
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-(乙酰氨基)-3-(3-硝基苯基)丙酸乙酯 在 palladium on activated charcoal 盐酸 、 sodium hydroxide 、 氢气 、 溶剂黄146 作用下， 以 乙醇 、 水 、 乙腈 、 叔丁醇 为溶剂， 25.0~42.0 ℃ 、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 、 氯化亚砜 、 sodium ethanolate 作用下， 反应 36.5h， 生成 2-(乙酰氨基)-3-(3-硝基苯基)丙酸乙酯
  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

• Use of 2-aminothiazoline derivatives as inhibitors of inducible no-synthase
  申请人：——

  公开号：US20020022631A1

  公开（公告）日：2002-02-21

  The present invention relates to the use of 2-aminothiazoline derivatives of formula: 1 in which either R 1 is a hydrogen atom or an alkyl radical and R 2 is an alkyl, -alk-NH 2 , —CH 2 —R 3 , —CH 2 —S—R 4 or phenyl radical substituted with a nitro or —NH—C(═NH)CH 3 radical, or R 1 is an alkyl radical and R 2 is a hydrogen atom, R 3 is a (3-6C) cycloalkyl, pyridyl, pyridyl N-oxide, thienyl, thiazolyl, imidazolyl, pyrazinyl, triazolyl or phenyl radical or a phenyl radical substituted with a nitro, hydroxy or carboxyl radical, R 4 represents a pyridyl or pyridyl N-oxide radical, alk represents an alkylene radical, or pharmaceutically acceptable salts thereof, as inhibitors of inducible NO-synthase.

  本发明涉及通式1的2-氨基噻唑啉衍生物的用途： 其中，R1为氢原子或烷基基团，R2为烷基、-烷-NH2、—CH2—R3、—CH2—S—R4或被硝基或—NH—C(═NH)CH3基团取代的苯基基团；或者，R1为烷基基团，R2为氢原子，R3为(3-6C)环烷基、吡啶基、吡啶基N-氧化物、噻吩基、噻唑基、咪唑基、吡嗪基、三唑基或苯基基团，或被硝基、羟基或羧基基团取代的苯基基团，R4代表吡啶基或吡啶基N-氧化物基团，烷代表亚烷基基团，或其药学上可接受的盐，作为诱导型NO合酶抑制剂。
• Use of 2-aminothiazoline derivatives as inhibitors of inducible NO-synthase
  申请人：——

  公开号：US20020187987A1

  公开（公告）日：2002-12-12

  The present invention relates to the use of 2-aminothiazoline derivatives of formula I: 1 in which either R 1 is a hydrogen atom or an alkyl radical and R 2 is an alkyl, -alk-NH 2 , —CH 2 —R 3 , —CH 2 —S—R 4 or phenyl radical substituted with a nitro or —NH—C(═NH)CH 3 radical, or R 1 is an alkyl radical and R 2 is a hydrogen atom, R 3 is a (3-6C) cycloalkyl, pyridyl, pyridyl N-oxide, thienyl, thiazolyl, imidazolyl, pyrazinyl, triazolyl or phenyl radical or a phenyl radical substituted with a nitro, hydroxy or carboxyl radical, R 4 represents a pyridyl or pyridyl N-oxide radical, alk represents an alkylene radical, or pharmaceutically acceptable salts thereof, as inhibitors of inducible NO-synthase.

  本发明涉及使用公式I中的2-氨基噻唑衍生物：1其中R1为氢原子或烷基基团，R2为烷基，-烷基-NH2，—CH2—R3，—CH2—S—R4或被硝基或—NH—C（═NH）CH3基团取代的苯基基团，或R1为烷基基团，R2为氢原子，R3为（3-6C）环烷基、吡啶基、吡啶N-氧化物、噻吩基、噻唑基、咪唑基、吡嗪基、三唑基或苯基基团或被硝基、羟基或羧基取代的苯基基团，R4表示吡啶基或吡啶N-氧化物基团，烷基表示烷基基团，或其药学上可接受的盐，作为诱导型NO合酶的抑制剂。
• 2-aminothiazoline derivatives and process for preparing the same
  申请人：——

  公开号：US20020198243A1

  公开（公告）日：2002-12-26

  The present invention relates to a class of 2-aminothiazoline derivatives of formula I: 1 in which either R 1 is a hydrogen atom or an alkyl radical and R 2 is an alkyl, -alk-NH 2 , —CH 2 —R 3 , —CH 2 —S—R 4 or phenyl radical substituted with a nitro or —NH—C(═NH)CH 3 radical, or R 1 is an alkyl radical and R 2 is a hydrogen atom, R 3 is a (3-6C) cycloalkyl, pyridyl, pyridyl N-oxide, thienyl, thiazolyl, imidazolyl, pyrazinyl, triazolyl or phenyl radical or a phenyl radical substituted with a nitro, hydroxy or carboxyl radical, R 4 represents a pyridyl or pyridyl N-oxide radical, alk represents an alkylene radical, or pharmaceutically acceptable salts thereof, which are useful as inhibitors of inducible NO-synthase.

  本发明涉及一类2-氨基噻唑啉衍生物，其化学式为I:1，其中R1为氢原子或烷基基团，R2为烷基、-烷基-NH2、—CH2—R3、—CH2—S—R4或取代有硝基或—NH—C(═NH)CH3基团的苯基基团，或R1为烷基基团，R2为氢原子，R3为(3-6C)环烷基、吡啶基、吡啶N-氧化物、噻吩基、噻唑基、咪唑基、吡嗪基、三唑基或苯基基团或取代有硝基、羟基或羧基的苯基基团，R4表示吡啶基或吡啶N-氧化物基团，alk表示烷基链，或其药学上可接受的盐，其作为诱导型NO合酶的抑制剂具有用途。
• 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。
• US6352839B1
  申请人：——

  公开号：US6352839B1

  公开（公告）日：2002-03-05