N-methyl-D-proline

• 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: N-methyl-D-proline
• 英文别名: (2R)-1-methylpyrrolidine-2-carboxylic acid；methyl-D-proline；(2R)-1-methylpyrrolidin-1-ium-2-carboxylate
• 化学式: C₆H₁₁NO₂
• 分子量: 129.159
• InChiKey: CWLQUGTUXBXTLF-RXMQYKEDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.9
• 重原子数：
  9
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  40.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-methyl-D-proline 在 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 12.5h， 生成 (R)-1-methyl-N-(2,3,4-tribromo-5-methoxyphenethyl)pyrrolidine-2-carboxamide
  参考文献：
  名称：

  Synthesis of Reported and Revised Structures of Amathamide D and Synthesis of Convolutamine F, H and Lutamide A, C

  摘要：

  Total synthesis of the published structure of amathamide D is described. Methyl 2,3,4-tribromo-5-hydroxybenzoate was selected as starting compound because it is readily accessible via acid-mediated Grob fragmentation- aromatization reaction of 1,4,5,6-tetrabromo-7,7-dimethoxybicyclo[2.2.1]hept-5-en-2-one. The aforementioned ester was transformed into the reported structure of amathamide D through methylation of a hydroxyl group and conversion of the ester moiety to a beta-aminoethyl side chain. The NMR data of the synthetic compound did not conform to the reported natural product structure possessing contiguously positioned beta-aminoethyl side chain, a set of three adjacent bromines, and a methyl ether linkage on the phenyl ring. This prompted us to redefine the natural product structure by synthesizing a product whose spectral data exactly matched with the reported data of amathamide D. The convolutamine H, with completely substituted phenyl ring adorned with an extra methyl ether functional group, has also been synthesized by application of Grob fragmentation-aromatization strategy to 3-(benzyloxy)-1,4,5,6-tetrabromo-7,7-dimethoxybicyclo[2.2.1]hept-5-en-2-one. This approach furnished directly methyl 2,3,4-tribromo-5,6-dimethoxybenzoate, which was converted straightforwardly into convolutamine H. Further, synthesis of convolutamine F and lutamide A and C is also described.

  DOI：

  10.1021/jo3000173
• 作为产物：
  描述：

  聚合甲醛 、 D-脯氨酸 在 氢气 作用下， 以96%的产率得到N-methyl-D-proline
  参考文献：
  名称：

  Amino Acid Derivatives with Anticonvulsant Activity.

  摘要：

  一系列N-烷基化、N-酰基化或自由的九环和一个直链氨基酸的苄胺衍生物作为潜在的抗癫痫药物已被合成。所得化合物的结构设计基于先前确定的结构和物理化学性质/抗癫痫活性关系，这是根据以前合成的这类化合物而设计的。通过腹腔注射(ip)给药后的小鼠，通过最大电惊厥发作测试(MES测试)、皮下(sc)戊四氮测试(sc PTZ测试)以及通过旋转棒神经毒性测试(Tox测试)对所得化合物进行评估。结果是根据它们在国家卫生研究院(NIH)的抗癫痫药物开发计划(ADDP)中的抗癫痫筛查项目(ASP)中的分类，分为三种类别之一。选取的三种化合物在口服给药后的大鼠中进行了定量测试。确定了MES ED50、sc PTZ ED50、Tox TD50并计算了它们的保护指数(PI)值。最有希望的化合物(15)在不同癫痫模型中的抗癫痫活性被检查。该化合物的相应ED50和PI值如下：对抗苯二氯酮，73和1.4；对抗戊四氮，47和2.2；对抗士的宁，73和1.4；对抗毛果芸香碱，156和0.7；对抗海人藻酸(2-羧基-4-异丙烯基-3-吡咯烷乙酸)，39和2.6；对抗AMPA(α-氨基-3-羟基-5-甲基-4-异噁唑丙酸)，10和10.3；对抗NMDA(N-甲基-D-天冬氨酸)，114和0.9。

  DOI：

  10.1248/cpb.49.629

文献信息

• [EN] A CONJUGATE OF A TUBULYSIN ANALOG WITH BRANCHED LINKERS<br/>[FR] CONJUGUÉ D'UN ANALOGUE DE TUBULYSINE AVEC DES LIEURS RAMIFIÉS
  申请人：HANGZHOU DAC BIOTECH CO LTD

  公开号：WO2019127607A1

  公开（公告）日：2019-07-04

  The present invention relates to the conjugation of a tubulysin analog compound to a cell-binding molecule with branched/side-chain linkers for having better delivery of the conjugate compound and targeted treatment of abnormal cells. It also relates to a branched-linkage method of conjugation of a tubulysin analog molecule to a cell-binding ligand, as well as methods of using the conjugate in targeted treatment of cancer, infection and autoimmune disease.

  本发明涉及将一种管腔霉素类似物化合物与具有分支/侧链连接物的细胞结合分子结合，以实现结合物的更好传递和靶向治疗异常细胞。它还涉及一种将管腔霉素类似物分子与细胞结合配体结合的分支连接方法，以及在靶向治疗癌症、感染和自身免疫疾病中使用结合物的方法。
• [EN] METABOLICALLY ROBUST ANALOGS OF CYP-EICOSANOIDS FOR THE TREATMENT OF CARDIAC DISEASE<br/>[FR] ANALOGUES ROBUSTES SUR LE PLAN MÉTABOLIQUE DES CYP-EICOSANOÏDES POUR LE TRAITEMENT DES MALADIES CARDIAQUES
  申请人：OMEICOS THERAPEUTICS GMBH

  公开号：WO2017013265A1

  公开（公告）日：2017-01-26

  The present invention relates to compounds according to general formula (I) which are metabolically robust analogues of bioactive lipid mediators derived from omega-3 polyunsaturated fatty acids (n-3 PUFAs).The present invention further relates to compositions containing one or more of these compounds and to the use of these compounds or compositions for the treatment or prevention of cardiovascular diseases.

  本发明涉及符合一般式（I）的化合物，这些化合物是从ω-3多不饱和脂肪酸（n-3 PUFAs）衍生的生物活性脂质介质的代谢稳健类似物。本发明还涉及含有这些化合物中的一个或多个的组合物，以及利用这些化合物或组合物治疗或预防心血管疾病。
• [EN] COMPOSITIONS AND METHODS FOR THE TREATMENT OF BACTERIAL INFECTIONS<br/>[FR] COMPOSÉS ET MÉTHODES POUR LE TRAITEMENT D'INFECTIONS BACTÉRIENNES
  申请人：CIDARA THERAPEUTICS INC

  公开号：WO2018006063A1

  公开（公告）日：2018-01-04

  Compositions and methods for the treatment of bacterial infections include compounds containing dimers of cyclic heptapeptides conjugated to one or more monosaccharide or oligosaccharide moieties. In particular, compounds can be used in the treatment of bacterial infections caused by Gram-negative bacteria.

  用于治疗细菌感染的组合物和方法包括含有环七肽二聚体与一个或多个单糖或寡糖基团结合的化合物。特别是，这些化合物可用于治疗由革兰氏阴性细菌引起的细菌感染。
• [EN] PEPTIDE-BASED MULTIPLE-DRUG DELIVERY VEHICLE<br/>[FR] VÉHICULE D'ADMINISTRATION DE MÉDICAMENTS MULTIPLES À BASE DE PEPTIDES
  申请人：ARIEL-UNIVERSITY RES AND DEV COMPANY LTD

  公开号：WO2017068577A1

  公开（公告）日：2017-04-27

  A molecular structure comprising a targeting moiety, a multi-functional peptide platform and a plurality of controllably released bioactive agents attached thereto is provided herein.

  本文提供了一种包括靶向基团、多功能肽平台和附着在其上的多种可控释放的生物活性剂的分子结构。
• Hepatitis C Virus Inhibitors
  申请人：Belema Makonen

  公开号：US20100080772A1

  公开（公告）日：2010-04-01

  The present disclosure relates to compounds, compositions and methods for the treatment of hepatitis C virus (HCV) infection. Also disclosed are pharmaceutical compositions containing such compounds and methods for using these compounds in the treatment of HCV infection.

  本公开涉及化合物、组合物和治疗丙型肝炎病毒（HCV）感染的方法。还公开了含有这些化合物的药物组合物以及使用这些化合物治疗HCV感染的方法。