L-谷氨酸,N-[4-[[(2,4-二氨基-6-蝶啶基)甲基]氨基]-3-甲基苯甲酰]- | 103503-71-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 蝶啶及其衍生物
• 中文名称: L-谷氨酸,N-[4-[[(2,4-二氨基-6-蝶啶基)甲基]氨基]-3-甲基苯甲酰]-
• 英文名称: N-<4-(N'-(2,4-diaminopteridin-6-ylmethyl)amino)-3-methylbenzoyl>-L-glutamic acid
• 英文别名: N-{4-[(2,4-diamino-pteridin-6-ylmethyl)-amino]-3-methyl-benzoyl}-L-glutamic acid；N-{4-[(2,4-Diamino-pteridin-6-ylmethyl)-amino]-3-methyl-benzoyl}-L-glutaminsaeure；(2S)-2-[[4-[(2,4-diaminopteridin-6-yl)methylamino]-3-methylbenzoyl]amino]pentanedioic acid
• CAS: 103503-71-5
• 化学式: C₂₀H₂₂N₈O₅
• 分子量: 454.445
• InChiKey: VCJSRDBDCVROQC-ZDUSSCGKSA-N

物化性质

• 密度：
  1.548±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1.6
• 重原子数：
  33
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  219
• 氢给体数：
  6
• 氢受体数：
  12

反应信息

• 作为产物：
  描述：

  3-甲基-4-硝基苯酰肼 在 盐酸 、 溶剂黄146 、 sodium nitrite 作用下， 生成 L-谷氨酸,N-[4-[[(2,4-二氨基-6-蝶啶基)甲基]氨基]-3-甲基苯甲酰]-
  参考文献：
  名称：

  Analogs of Pteroylglutamic Acid. IX. Derivatives with Substituents on the Benzene Ring¹

  摘要：

  DOI：

  10.1021/ja01115a017

文献信息

• Antirheumatic Agents. II. Novel Methotrexate Derivatives Bearing an Alkyl-Substituted Benzene Ring.
  作者：Hiroharu MATSUOKA、Noriaki MARUYAMA、Hiroshi SUZUKI、Toshio KUROKI、Keiichiro TSUJI、Nobuaki KATO、Nobuhiro OHI、Masahiko MIHARA、Yasuhisa TAKEDA、Keiichi YANO

  DOI：10.1248/cpb.44.2287

  日期：——

  Novel methotrexate (MTX) derivatives with either a mono- or dialkyl-substituted benzene ring were synthesized and initially tested for in vitro anti-proliferative activities using human perpheral blood mononuclear cells (hPBMC)derived from healthy volunteers and synovial cells (hSC) derived from patients with rheumatoid arthritis (RA).Compounds with potent activities were further evaluated in an in vivo adjuvant arthritis model. In comparison with MTX, a glutamate derivative 3a was more potent as a suppressor of the in vitro cell proliferation and the in vivo experimental arthritis, and a homoglutamate derivative, 3e, exhibited fairly good activities in vitro and considerable activity in vivo in a dose-dependent manner. As expected, 3e did not act as a substrate of folylpolyglutamate synthetase (FPGS), and thus did not undergo polyglutamation, which is thought to be responsible for side-effects that occur during MTX therapy.

  合成了新型甲氨蝶呤（MTX）衍生物，这些衍生物具有单烷基或双烷基取代的苯环，并初步通过来自健康志愿者的外周血单核细胞（hPBMC）和来自类风湿关节炎（RA）患者的滑膜细胞（hSC）对其进行体外抗增殖活性测试。具有较强活性的化合物进一步在体内佐剂性关节炎模型中进行了评估。与MTX相比，氨基酸衍生物3a在体外细胞增殖抑制剂和体内实验性关节炎方面的效力更强，而同氨基酸衍生物3e在体外表现出相当好的活性，并在体内具有显著的剂量依赖性活性。如预期的那样，3e并未作为叶酸多谷氨酸合成酶（FPGS）的底物，因此没有经历多谷氨酸化，这被认为是MTX治疗过程中出现副作用的原因。
• SELECTIVE INHIBITION OF PHOSPHOENOLPYRUVATE CARBOXYLASES OF C4 PLANTS
  申请人：Heinrich Heine Universität Düsseldorf

  公开号：EP2797417A1

  公开（公告）日：2014-11-05
• SELECTIVE INHIBITION OF C4-PEP CARBOXYLASES
  申请人：Heinrich Heine Universitat Dusseldorf

  公开号：US20150216167A1

  公开（公告）日：2015-08-06

  The present invention relates to the use of a compound, a salt or solvate thereof as C4 plant selective herbicide wherein said compound comprises a cyclic alkyl, aryl, heterocycloalkyl or heteroaryl group, and wherein said compound further comprises a) at least a functional group Z being —C(═Y z )R 1 , wherein Y z is selected from the group consisting of O, NH and S, preferably wherein Y z is O, and wherein R 1 is selected from the group consisting of H, OH and N(R 2 R 3 ), —O(R 2 ) and —S(R 2 ), wherein R 2 and R 3 , are independently of each other, selected from the group consisting of H, alkyl, cycolalkyl, aryl and heteroaryl and a functional group Q which is —C(═Y Q )R 4 , wherein Y Q is selected from the group consisting of O, NH and S, preferably wherein Y Q is O, and wherein R 4 is selected from the group consisting of H, OH and NR 4# R 5# , OR 4# , SR 4# wherein R 4# and R 5# , are independently of each other, selected from the group consisting of H, alkyl, cycloalkyl, aryl and heteroaryl, or b) at least one electron donating group selected from the group consisting of OH, —SH, —O—R p , S—R p —NR p R q and O—C(═Y p )R r , wherein R p and R q are, independently of each other, selected from the group consisting of H, alkyl, cycloalkyl and heteroaryl, and wherein R r is —OH, —NH 2 , —NH-Alkyl, —O-Alkyl or —NH-Alkyl, and wherein Y p is selected from the group consisting of —S—, —O—, —NH, said compound being capable of binding to the malate binding site comprised by a phosphoenolpyruvate carboxylase from a C4 plant, thereby inhibiting said phosphoenolpyruvate carboxylase, and wherein the cyclic alkyl, aryl, heterocycloalkyl or heteroaryl group inhibits binding to the malate binding site of a phosphoenolpyruvate carboxylase from a C3 plant.
• [EN] SELECTIVE INHIBITION OF PHOSPHOENOLPYRUVATE CARBOXYLASES OF C4 PLANTS<br/>[FR] INHIBITION SÉLECTIVE DE PHOSPHOÉNOLPYRUVATE CARBOXYLASES DE PLANTES C4
  申请人：UNIV DUESSELDORF H HEINE

  公开号：WO2013093007A1

  公开（公告）日：2013-06-27

  The present invention relates to the use of a compound, a salt or solvate thereof as C4 plant selective herbicide wherein said compound comprises a cyclic alkyl, aryl, heterocycloalkyl or heteroaryl group, and wherein said compound further comprises a) at least a functional group Z being -C(=Yz)R1, wherein Yz is selected from the group consisting of O, NH and S, preferably wherein Yz is O, and wherein R1 is selected from the group consisting of H, OH and N(R2R3), -O(R2) and -S(R2), wherein R2 and R3, are independently of each other, selected from the group consisting of H, Alkyl, cycolalkyl, aryl and heteroaryl and a functional group Q which is -C(=YQ)R4, wherein YQ is selected from the group consisting of O, NH and S, preferably wherein YQ is O, and wherein R4 is selected from the group consisting of H, OH and NR4#R5#, OR4#, SR4# wherein R4# and R5#, are independently of each other, selected from the group consisting of H, alkyl, cycloalkyl, aryl and heteroaryl, or b) at least one electron donating group selected from the group consisting of OH, -SH, -O-Rp, -S-Rp -NRpRq and O-C(=Yp)Rr, wherein Rp and Rq are, independently of each other, selected from the group consisting of H, alkyl, cycloalkyl and heteroaryl, and wherein Rr is -OH, -NH2, -NH-Alkyl, -O-Alkyl or -NH-Alkyl, and wherein Yp is selected from the group consisting of -S-, -O-, -NH, said compound being capable of binding to the malate binding site comprised by a phosphoenolpyruvate carboxylase from a C4 plant, thereby inhibiting said phosphoenolpyruvate carboxylase, and wherein the cyclic alkyl, aryl, heterocycloalkyl or heteroaryl group inhibits binding to the malate binding site of a phosphoenolpyruvate carboxylase from a C3 plant.
• Analogs of Pteroylglutamic Acid. IX. Derivatives with Substituents on the Benzene Ring¹
  作者：Donna B. Cosulich、Doris R. Seeger、Marvin J. Fahrenbach、Kenneth H. Collins、Barbara Roth、Martin E. Hultquist、James M. Smith

  DOI：10.1021/ja01115a017

  日期：1953.10