2-甲基-2-丙基(1R,4S)-3-氧代-2-氮杂双环[2.2.1]庚-5-烯-2-羧酸酯 | 151792-53-9

• 物质功能分类: 医药中间体 - 杂环化合物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 中文名称: 2-甲基-2-丙基(1R,4S)-3-氧代-2-氮杂双环[2.2.1]庚-5-烯-2-羧酸酯
• 英文名称: tert-butyl (1R,4S)-(-)-3-oxo-2-azabicyclo[2.2.1]hept-5-ene-2-carboxylate
• 英文别名: (-)-(1R,4S)-tert-butyl 3-oxo-2-azabicyclo(2.2.1)hept-5-ene-2-carboxylate；tert-butyl (1S,4R)-2-oxo-3-azabicyclo[2.2.1]hept-5-ene-3-carboxylate；(1R,4S)-tert-Butyl 3-oxo-2-azabicyclo[2.2.1]hept-5-ene-2-carboxylate；tert-butyl (1R,4S)-3-oxo-2-azabicyclo[2.2.1]hept-5-ene-2-carboxylate
• CAS: 151792-53-9
• 化学式: C₁₁H₁₅NO₃
• 分子量: 209.245
• InChiKey: NQIZWJGHIYDHRL-SFYZADRCSA-N

物化性质

• 熔点：
  85.0-86.5 °C
• 沸点：
  339.8±31.0 °C(Predicted)
• 密度：
  1?+-.0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  46.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-甲基-2-丙基(1R,4S)-3-氧代-2-氮杂双环[2.2.1]庚-5-烯-2-羧酸酯 在 咪唑 、 sodium tetrahydroborate 、 水 、 间氯过氧苯甲酸 、 红铝 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 24.5h， 生成 (+)-(1S,2R,4R)-4-氨基-2-(羟甲基)-1-环戊醇
  参考文献：
  名称：

  Base Pairing and Replicative Processing of the Formamidopyrimidine-dG DNA Lesion

  摘要：

  The 2,6-diamino-4-hydroxy-5-formamidopyrimidine of 2'-deoxyguanosine (FaPydG) is one of the major DNA lesions found after oxidative stress in cells. To clarify the base pairing and coding potential of this major DNA lesion with the aim to estimate its mutagenic effect, we prepared oligonucleotides containing a cyclopentane based analogue of the DNA lesion (cFaPydG). In addition, oligonucleoticles containing the cyclopentane analogue of 2'-deoxyguanosine (cdG), and oligonucleotides containing 8-oxo-7,8-dihydro2'-deoxyguanosine (8-oxodG) were synthesized. The thermodynamic stability of duplexes containing these building blocks and all canonical counterbases were determined by concentration dependent melting-point measurements (van't Hoff plots). The data reveal that cFaPydG greatly destabilizes a DNA duplex (Delta Delta G(o)298K approximate to 2-4 kcal mol(-1)). The optimal base pairing partner for the cFaPydG lesion is dC. Investigation of duplexes containing dG and cdG shows that the effect of substituting the deoxyribose by a cyclopentane moiety is marginal. The data also provide strong evidence that the FaPydG lesion is unable to form a base pair with dA. Our computational studies indicate that the syn-conformation required for base pairing with dA is energetically unfavorable. This is in contrast to 8-oxodG for which the syn-conformation represents the energetic minimum. Kinetic primer extension studies using S. cerevisiae Pol eta reveal that cFaPydG is replicated in an error-free fashion. dC is inserted 2-3 orders of magnitude more efficiently than dT or CIA, showing that FaPydG is a lesion which retains the coding potential of dG. This is also in contrast to 8-oxodG, for which base pairing with dC and dA was established.

  DOI：

  10.1021/ja0549188
• 作为产物：
  描述：

  2-氮杂双环[2.2.1]庚-5-烯-3-酮 在 4-二甲氨基吡啶 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 2-甲基-2-丙基(1R,4S)-3-氧代-2-氮杂双环[2.2.1]庚-5-烯-2-羧酸酯
  参考文献：
  名称：

  Development of the biocatalytic resolution of 2-azabicyclo[2.2.1]hept-5-en-3-one as an entry to single-enantiomer carbocyclic nucleosides

  摘要：

  For the resolution of the bicyclic lactam 2-azabicyclo[2.2.1]hept-5-en-3-one, efficient whole cell biocatalysts have been identified and from these, enzymes (lactamases) have been isolated. While the two enzymes obtained act on different enantiomers of the lactam, either can be used in scaleable processes to obtain synthons for carbocyclic nucleosides having the natural configuration.

  DOI：

  10.1016/s0957-4166(00)80218-9

文献信息

• [EN] NOVEL DIPEPTIDYL PEPTIDASE IV INHIBITORS; PROCESSES FOR THEIR PREPARATION AND COMPOSITIONS THEREOF<br/>[FR] NOUVEAUX INHIBITEURS DE DIPEPTIDYLE PEPTIDASE IV, LEUR PROCEDES DE PREPARATION ET COMPOSITIONS EN COMPORTANT
  申请人：GLENMARK PHARMACEUTICALS LTD

  公开号：WO2005075426A1

  公开（公告）日：2005-08-18

  The present invention relates to novel dipeptidyl peptidase IV (DPP-IV) inhibitors or general formula (1) useful for treating diabetes, non-insulin dependent diabetes mellitus, impaired glucose tolerance, inflammatory bowel disease, ulcerative colitis,Chron’s disease, obesity, and metabolic syndrome.

  本发明涉及一种新型二肽基肽酶IV（DPP-IV）抑制剂，其一般式（1）用于治疗糖尿病、非胰岛素依赖型糖尿病、糖耐量受损、炎症性肠病、溃疡性结肠炎、克罗恩病、肥胖症和代谢综合征。
• Novel Tricyclic Compounds
  申请人：Wishart Neil

  公开号：US20090312338A1

  公开（公告）日：2009-12-17

  The invention provides a compound of Formula (I) pharmaceutically acceptable salts, pro-drugs, biologically active metabolites, stereoisomers and isomers thereof wherein the variable are defined herein. The compounds of the invention are useful for treating immunological and oncological conditions.

  这项发明提供了一个符合Formula (I)的化合物，其中包括药用盐、前药、生物活性代谢物、立体异构体和同分异构体，其中变量在此处定义。该发明的化合物对治疗免疫和肿瘤疾病有用。
• PESTICIDAL COMPOSITIONS AND PROCESSES RELATED THERETO
  申请人：DOW AGROSCIENCES LLC

  公开号：US20130288893A1

  公开（公告）日：2013-10-31

  This document discloses molecules having the following formula (“Formula One”): and processes related thereto.

  这份文件公开了具有以下公式（“公式一”）的分子以及与之相关的过程。
• PESTICIDAL COMPOSITIONS AND RELATED METHODS
  申请人：DOW AGROSCIENCES LLC

  公开号：US20150111734A1

  公开（公告）日：2015-04-23

  A pesticidal composition comprises at least one compounds selected from a compound of formula, or any agriculturally acceptable salt thereof, wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6, R 7 , R 8 , Q, Z, L, L a , and x are as described herein. A method of controlling pests comprises applying the pesticidal composition near a population of pests.

  一种杀虫组合物包括至少一种选择自以下化合物的化合物或其任何农业上可接受的盐，其中R1、R2、R3、R4、R5、R6、R7、R8、Q、Z、L、La和x如本文所述。一种控制害虫的方法包括在害虫种群附近施用该杀虫组合物。
• [EN] NOVEL DIPEPTIDYL PEPTIDASE IV INHIBITORS; PROCESS FOR THEIR PREPARATION AND COMPOSITIONS CONTAINING THEM<br/>[FR] NOUVEAUX INHIBITEURS DE LA DIPEPTIDYL PEPTIDASE IV, PROCEDE DE PREPARATION DE CES INHIBITEURS ET COMPOSITIONS CONTENANT CES INHIBITEURS
  申请人：GLENMARK PHARMACEUTICALS LTD

  公开号：WO2006011035A1

  公开（公告）日：2006-02-02

  The present invention relates to novel organic compounds, more particularly, novel Dipeptidyl peptidase IV (DPP-IV) inhibitors of general formula (I) wherein: Y is -S(O)m-, -CH2-, -CHF-, or -CF2; X and Z are independently -C(=O)-, -NR3-, - O- or -S(O)m-; each occurrence of m is independently 0, 1 or 2; a is 0, 1 or 2; b is 0, 1 or 2; the dotted line [----] in the carbocyclic ring represents an optional double bond; R1 is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkylalkyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocyclic ring, substituted or unsubstituted heterocyclylalkyl, or substituted or unsubstituted heteroarylalkyl; R2 is hydrogene, nitrile (-CN), COOH, or an isostere of carboxylic; or analogs, tautomers, enantiomers, diastereomers, regioisomers, stereoisomers, polymorphs, pharmaceutically acceptable salts, N-oxides, pharmaceutically acceptable solvates and pharmaceutical compositions containing them.

  该发明涉及新型有机化合物，更特别地，一般式（I）的新型二肽基肽酶IV（DPP-IV）抑制剂，其中：Y为-S(O)m-，-CH2-，-CHF-或-CF2；X和Z独立地为-C(=O)-，-NR3-，-O-或-S(O)m-；m的每次出现独立地为0，1或2；a为0，1或2；b为0，1或2；在碳环中的虚线[----]表示一个可选的双键；R1为取代或未取代的烷基，取代或未取代的烯基，取代或未取代的炔基，取代或未取代的环烷基，取代或未取代的环烷基烷基，取代或未取代的环烯基，取代或未取代的芳基，取代或未取代的芳基烷基，取代或未取代的杂芳基，取代或未取代的杂环烷基，或取代或未取代的杂芳基烷基；R2为氢，腈（-CN），COOH，或羧基的同分异构体；或其类似物，互变异构体，对映异构体，非对映异构体，位置异构体，立体异构体，多晶型，药学上可接受的盐，N-氧化物，药学上可接受的溶剂化合物和含有它们的药物组合物。