<2-(tritylamino)thiazol-4-yl>acetic acid | 64220-26-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: <2-(tritylamino)thiazol-4-yl>acetic acid
• 英文别名: 2-tritylamino-4-thiazolyl acetic acid；2-(2-(tritylamino)thiazol-4-yl)acetic acid；2-Tritylamino-4-thiazolylessigsaeure；[2-[(triphenyl-methyl)-amino]-thiazol-4-yl] acetic acid；2-[2-(triphenylmethylamino)thiazol-4-yl]acetic acid；(2-tritylamino-thiazol-4-yl)-acetic acid；2-tritylaminothiazole-4-acetic acid；{2-[(Triphenylmethyl)amino]-1,3-thiazol-4-yl}acetic acid；2-[2-(tritylamino)-1,3-thiazol-4-yl]acetic acid
• CAS: 64220-26-4
• 化学式: C₂₄H₂₀N₂O₂S
• 分子量: 400.501
• InChiKey: YHMZKBZQZGAGOE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  29
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  90.5
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  <2-(tritylamino)thiazol-4-yl>acetic acid 在 甲酸 、 草酰氯 作用下， 以 吡啶 、 乙醚 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 17.58h， 生成 头孢地尼杂质B
  参考文献：
  名称：

  Oral absorption of cephalosporin antibiotics. 1. Synthesis, biological properties and oral bioavailability of 7-arylacetamido-3-chloro cephalosporins in animals

  摘要：

  A number of 7-(arylacetamido)-3-substituted cephalosporins were prepared and tested in animals for oral absorbability. Bioavailability in mice, rats, dogs, and monkeys was determined after oral or parenteral administration. Oral bioavailability of five compounds selected for more intensive study was generally higher than that of penicillin V in all species tested. The results of ED50 testing against experimental infections in mice generally supported the bioavailability studies. Antibiotic activities were evaluated against Gram-positive and Gram-negative organisms with some derivatives expressing in vitro activity similar to cefaclor. The plasma half-life in rats was relatively short and the plasma curves were strongly influenced by probenecid, indicating rapid renal secretion. Some 7-(arylacetamido)-3-chloro cephalosporins are orally absorbed in animals to a greater extent than penicillin V, and antibacterial agent of proven clinical utility.

  DOI：

  10.1021/jm00118a022
• 作为产物：
  描述：

  2-氨基-4-噻唑乙酸甲酯 在 甲醇 、 三乙胺 、 sodium hydroxide 作用下， 以 二氯甲烷 为溶剂， 反应 16.0h， 生成 <2-(tritylamino)thiazol-4-yl>acetic acid
  参考文献：
  名称：

  Thiazole- and imidazole-containing peptidomimetic inhibitors of protein farnesyltransferase

  摘要：

  Mimetics of the C-terminal CAAX tetrapeptide of Ras protein were designed replacing internal dipeptide AA with 4-amino-2-phenylbenzoic acid and cysteine (C) with 2-amino-4-thiazolyl-, 2-mercapto-4-thiazolyl-, 2-mercapto-4-imidazolyl- and 2-methylmercapto-4-thiazolyl-acetic or propionic acid. The compound in which C is replaced by 2-amino-4-thiazolylacetic acid inhibited FTase activity in the low nanomolar range and showed antiproliferative effect on rat aortic smooth muscle cells interfering with Ras farnesylation. On the basis of these results, 2-aminothiazole can be considered as an alternative to heterocycles, such as pyridine and imidazole, normally used in FTase inhibitors designed as non-thiol CAAX mimetics. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.07.003

文献信息

• Cephalosporin derivatives
  申请人：Imperial Chemical Industries PLC

  公开号：US04492692A1

  公开（公告）日：1985-01-08

  A cephalosporin derivative of the formula: ##STR1## in which R.sup.0 is a hydrogen atom or a methyl radical, R.sup.1 is any one of the C-3 substituents from antibacterially-active cephalosporins known in the art; R.sup.2 is any one of the C-4 substituents from antibacterially-active cephalosporins known in the art; R.sup.3 is a hydrogen atom or a 1-6C alkoxy or 1-6C alkylthio radical; X.sup.1 is a sulphur or oxygen atom, a CH.sub.2 radical or a radical of the formula NR.sup.7 in which R.sup.7 is a hydrogen atom, a 1-6C alkyl, formyl or benzyl radical; X.sup.2 is a nitrogen atom or a radical of the formula N.sup..sym. -R.sup.7 ; R.sup.4 and R.sup.7, and R.sup.5 and R.sup.6 are a variety of substituents which are described in the specification; and the pharmaceutically-acceptable acid- or base-addition salts thereof. Pharmaceutical compositions, manufacturing processes and intermediates are also described.

  一种头孢菌素衍生物的化学式：##STR1## 其中 R.sup.0 是氢原子或甲基基团，R.sup.1 是来自已知具有抗菌活性的头孢菌素的C-3取代基之一；R.sup.2 是来自已知具有抗菌活性的头孢菌素的C-4取代基之一；R.sup.3 是氢原子或1-6C烷氧基或1-6C烷硫基团；X.sup.1 是硫或氧原子，CH.sub.2基团或化学式NR.sup.7中的基团，其中R.sup.7是氢原子，1-6C烷基，甲酰基或苄基基团；X.sup.2 是氮原子或化学式N.sup..sym. -R.sup.7的基团；R.sup.4和R.sup.7，以及R.sup.5和R.sup.6是说明书中描述的各种取代基；以及其药学上可接受的酸盐或碱盐。还描述了制药组合物、制造过程和中间体。
• Antibiotic derivatives of
  申请人：Eli Lilly and Company

  公开号：US04683227A1

  公开（公告）日：1987-07-28

  7.beta.-Heterocyclicacetylamino-(and 7.beta.-heterocyclicthioacetamido)-3-chloro-3-cephem-4-carboxylic acids and pharmaceutically acceptable salts thereof, e.g., 7.beta.-[2-(2-aminothiazol-4-yl)acetamido]-3-chloro-3-cephem-4-carboxylic acid and salts thereof, exhibit surprising peroral bioavailability and are useful in a method for treating infections in man and animals and in formulations for oral administration.

  7-beta-杂环乙酰胺基-(和7-beta-杂环硫代乙酰胺基)-3-氯-3-头孢-4-羧酸及其药用盐，例如7-beta-[2-(2-氨基噻唑-4-基)乙酰胺基]-3-氯-3-头孢-4-羧酸及其盐，表现出惊人的口服生物利用度，在治疗人和动物感染的方法和口服制剂中有用。
• Cephalosporines a chaines amino-2 thiazolyl-4 acetyles
  作者：R. Bucourt、R. Heymes、A. Lutz、L. Pénasse、J. Perronnet

  DOI：10.1016/0040-4020(78)89034-6

  日期：1978.1

  The syntheses of 2-(2-amino-4-thiazolyl) 2-(hydroxy or alkoxy)-imino acetic acid derivatives, with the anti (E) and syn (Z) configurations, are described. By means of these compounds, the acylation of the amino-group of 7β-amino cephalosporanic acid (7-ACA) has been achieved. The two resulting series of cephalosporin derivatives-anti and syn-are markedly different with respect to their antibiotic activity

  描述了具有反（E）和顺（Z）构型的2-（2-氨基-4-噻唑基）2-（羟基或烷氧基）-亚氨基乙酸衍生物的合成。通过这些化合物，已经实现了7β-氨基头孢烷酸（7-ACA）的氨基的酰化。这两个由此带来的一系列的头孢derivatives-防和顺式相对于它们的抗菌活性-are明显不同。一些合成化合物具有迄今为止所观察到的最高的抗菌活性。
• Synthesis and biological evaluation of 4β-(thiazol-2-yl)amino-4′-O-demethyl-4-deoxypodophyllotoxins as topoisomerase-II inhibitors
  作者：Chun-Yan Sang、Heng-Zhi Tian、Yue Chen、Jian-Fei Liu、Shi-Wu Chen、Ling Hui

  DOI：10.1016/j.bmcl.2017.12.012

  日期：2018.1

  ypodophyllotoxins were synthesized, and their cytotoxicities were evaluated against four human cancer cell lines (A549, HepG2, HeLa, and LOVO cells) and normal human diploid fibroblast line WI-38. Some of the compounds exhibited promising antitumor activity and less toxicity than the anticancer drug etoposide. Among them, compounds 15 and 17 were found to be the most potent synthetic derivatives as

  合成了一系列4β-（噻唑-2-基）氨基-4'- O-脱甲基-4-脱氧鬼臼毒素，并评估了它们对四种人类癌细胞系（A549，HepG2，HeLa和LOVO细胞）的细胞毒性。正常人二倍体成纤维细胞系WI-38。与抗癌药依托泊苷相比，某些化合物具有良好的抗肿瘤活性和较低的毒性。其中，化合物15和17被发现是最有效的合成衍生物，作为topo-II抑制剂，可通过p73 / ATM途径以及A549细胞中的H2AX磷酸化诱导DNA双链断裂。这些化合物还可以通过调节cyclinB1 / cdc2（p34）阻滞A549细胞在G2 / M期循环。综上所述，这些结果表明一系列化合物是潜在的抗癌剂。
• Synthesis and biological activity of substituted [[3(S)-(acylamino)-2-oxo-1-azetidinyl]oxy]acetic acids. A new class of heteroatom-activated .beta.-lactam antibiotics
  作者：Steven R. Woulfe、Marvin J. Miller

  DOI：10.1021/jm00148a013

  日期：1985.10

  dimethyl sulfoxide. The Cbz group was replaced with the 2-(2-amino-4-thiazolyl)-2(Z)-(methoxyimino)acetamido side chain by catalytic hydrogenation followed by treatment with 21. Removal of the 2-(trimethylsilyl)ethyl ester with fluoride ion provided derivatives suitable for antimicrobial evaluation. In vitro tests showed that the title compounds possess significant activity predominantly against Gram-negative

  描述了取代的[[3（S）-（酰基氨基）-2-氧代-1-氮杂环丁烷基]氧基]乙酸（1）的合成。在THF / H 2 O中，在碳酸钾的存在下，将由丝氨酸和苏氨酸制备的3-[（碳苄氧基）氨基] -N-羟基-2-氮杂环丁酮（13a，b）与溴化2-（三甲基甲硅烷基）乙基乙酸乙酯烷基化。用仲α-溴代酯的烷基化反应是用氢氧化钾在二甲基亚砜中完成的。通过催化加氢，然后用21处理，将Cbz基团替换为2-（2-氨基-4-噻唑基）-2（Z）-（甲氧基亚氨基）乙酰氨基侧链，然后用21处理。将2-（三甲基甲硅烷基）乙酯去除。氟离子提供的衍生物适合进行抗菌评估。体外试验表明，标题化合物主要对革兰氏阴性菌具有重要活性。