penicillin G N-ethylpiperidine salt | 39879-63-5

• 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
• 英文名称: penicillin G N-ethylpiperidine salt
• 英文别名: Penicillin G N-ethylpiperidine salt；(2S,5R,6R)-3,3-dimethyl-7-oxo-6-[(2-phenylacetyl)amino]-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid;1-ethylpiperidine
• CAS: 39879-63-5
• 化学式: C₇H₁₅N*C₁₆H₁₈N₂O₄S
• 分子量: 447.599
• InChiKey: KLNSFLVJJKLEDK-LQDWTQKMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.35
• 重原子数：
  31
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  115
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  penicillin G N-ethylpiperidine salt 以 二氯甲烷 为溶剂， 反应 4.0h， 生成 (2S,5R,6R)-3,3-Dimethyl-7-oxo-6-phenylacetylamino-4-thia-1-aza-bicyclo[3.2.0]heptane-2-carboxylic acid ethylamide
  参考文献：
  名称：

  青霉素衍生的C2对称二聚体是HIV-1蛋白酶的新型抑制剂。

  摘要：

  DOI：

  10.1021/jm00094a024

文献信息

• Synthesis and structure-activity relationships of a series of penicillin-derived HIV proteinase inhibitors containing a stereochemically unique peptide isostere
  作者：Duncan S. Holmes、Richard C. Bethell、Nicholas Cammack、Ian R. Clemens、John Kitchin、Peter McMeekin、Chi L. Mo、David C. Orr、Binakumari Patel

  DOI：10.1021/jm00073a012

  日期：1993.10

  A series of HIV-1 proteinase inhibitors was synthesized based upon a single penicillin derived thiazolidine moiety. Reaction of the C-4 carboxyl group with (R)-phenylalaninol gave amide 10 which was a moderately potent inhibitor of HIV-1 proteinase (IC50 = 0.15 microM). Further modifications based on molecular modeling studies led to compound 48 which contained a stereochemically unique statine-based

  基于单个青霉素衍生的噻唑烷部分合成了一系列HIV-1蛋白酶抑制剂。C-4羧基与（R）-苯丙氨醇的反应得到酰胺10，它是HIV-1蛋白酶的中等有效抑制剂（IC50 ＝0.15μM）。基于分子模型研究的进一步修饰导致化合物48包含立体化学独特的基于他汀类的等排物。这是一种有效的竞争性抑制剂（Ki = 0.25 nM），在体外具有针对HIV-1的抗病毒活性（5 microM）。试图修饰苄基以改善与S2'口袋的相互作用，或者引入氢键供体基团以与残基Gly48'相互作用均未导致改善的抑制或抗病毒活性。
• A series of penicillin-derived C2-symmetric inhibitors of HIV-1 proteinase: synthesis, mode of interaction, and structure-activity relationships
  作者：David C. Humber、Mark J. Bamford、Richard C. Bethell、Nicholas Cammack、Kevin Cobley、Derek N. Evans、Norman M. Gray、Michael M. Hann、David C. Orr

  DOI：10.1021/jm00073a011

  日期：1993.10

  formation in infected C8166 cells, with no evidence of cytotoxicity. The compounds showed no activity against other aspartyl proteinases (renin, pepsin, and cathepsin D). Structure-activity relationships support a symmetrical interaction with the enzyme. Pharmacokinetic evaluation of the ethylamide 3 revealed it was subject to rapid plasma clearance and had low oral bioavailability.

  通过随机筛选将C2对称二酯1鉴定为HIV-1蛋白酶的新型抑制剂。这导致了从容易获得的青霉素制备一系列相关的更有效的酰胺。许多化合物在感染HIV-1的MT-4细胞中显示出有效的抗病毒活性，并具有在感染的C8166细胞中抑制合胞体形成的能力，而没有细胞毒性的证据。该化合物对其他天冬氨酰蛋白酶（肾素，胃蛋白酶和组织蛋白酶D）无活性。结构-活性关系支持与酶的对称相互作用。乙酰胺3的药代动力学评估表明，乙酰胺3血浆清除迅速，口服生物利用度低。
• Synthesis and Structure-Activity Relationships of a Series of Penicillin-Derived HIV Proteinase Inhibitors: Heterocyclic Ring Systems Containing P1' and P2' Substituents
  作者：John Kitchin、Richard C. Bethell、Nicholas Cammack、Simon Dolan、Derek N. Evans、Stuart Holman、Duncan S. Holmes、Peter McMeekin、Chi L. Mo

  DOI：10.1021/jm00048a007

  日期：1994.10

  As an extension of our earlier work based upon a single penicillin-derived thiazolidine moiety we have found that the decahydroisoquinoline grouping, also present in Ro 31-8959, is an effective replacement for one of the thiazolidine units in C2 symmetric penicillin-derived dimers. Reaction of racemic epoxide 6 with [3S-[3 alpha, 4a alpha, 8a alpha]]-decahydro-N-(1,1-dimethylethyl)-3- isoquinolinecarboxamide

  作为我们基于单个青霉素衍生的噻唑烷部分的早期工作的扩展，我们发现十氢异喹啉基团（也存在于Ro 31-8959中）可有效替代C2对称青霉素衍生的二聚体中的噻唑烷单元之一。外消旋环氧化合物6与[3S- [3α，4aα，8aα]]-十氢-N-（1，1-二甲基乙基）-3-异喹啉羧酰胺的反应得到非对映异构体34a和34b。确定34a的羟基的立体化学为（S）。衍生自34a和34b的胺与噻唑烷8a的反应分别得到50和51。化合物50是有效的HIV蛋白酶抑制剂（IC50 = 23 nM），在体外具有针对HIV-1的抗病毒活性（EC50 C8166细胞= 50 nM）。但是，狗体内化合物50及其类似物的药代动力学较差，
• Transformations of penicillin. Part II. NN′-Di-isopropyihylrazine, a new reagent for protection of carboxylic acids
  作者：D. H. R. Barton、M. Girijavallabhan、P. G. Sammes

  DOI：10.1039/p19720000929

  日期：——

  NN′-Di-isopropylhydrazine is a useful reagent for the protection of carboxylic acids. The derived hydrazides can be reconverted by selective oxidation, with, for example, lead tetra-acetate, into the parent acids in very high yield. The protecting group has been used for penicillins. Acid-catalysed rearrangement of the NN′-di-isopropyl-hydrazide from 6β-phenylacetamidopenicillanic acid (S)-sulphoxide

  NN ' -二异丙基肼为羧酸保护的有用试剂。衍生的酰肼可以通过选择性氧化，例如用四乙酸铅，以很高的收率转化成母体酸。该保护基已用于青霉素。酸催化的重排NN ' -二异丙基-酰肼从6β-phenylacetamidopenicillanic酸（小号）-sulphoxide，其次是保护基团，得到相应的去乙酰酸的氧化裂解。6β-苯基乙酰胺基openicillanic酸（S）-亚砜的N-异丙基酰肼的热重排产生了适度的脱水青霉素。
• Stereoselective synthesis of a thiazolane amide using molecular recognition in the triazolyl-activated ester intermediate
  作者：Peter Styring、Sannie S.F. Chong

  DOI：10.1016/j.tetlet.2006.01.047

  日期：2006.3

  An amide derived from penicillin V and racemic (R/S)-2-aminobutanol was prepared with 83% de and shows significantly higher toxicity than the pure diastereomers prepared from homochiral 2-aminobutanol. This has been attributed to conformational changes in the resolved product brought about through hydrogen-bonded self-assembly in the intermediate. (c) 2006 Elsevier Ltd. All rights reserved.