(1R,2R,3S,4R,5S)-4-(2,6-dichloropurin-9-yl)-1-hydroxymethyl-2,3-O-isopropylidenebicyclo[3.1.0]hexane | 352552-14-8

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 核苷和核苷酸类似物
• 英文名称: (1R,2R,3S,4R,5S)-4-(2,6-dichloropurin-9-yl)-1-hydroxymethyl-2,3-O-isopropylidenebicyclo[3.1.0]hexane
• 英文别名: (1'S,2'R,3'S,4'R,5'S)-4'-(2,6-dichloropurin-9-yl)-1-(hydroxymethyl)bicyclo[3.1.0]hexane-2,3-(O-isopropylidine)；(1'R,2'R,3'S,4'R,5'S)-4-(2,6-dichloropurin-9-yl)-1-[hydroxymethyl]bicyclo[3.1.0]hexane-2,3-(O-isopropylidine)；[(1R,2R,4S,5R,6S)-5-(2,6-dichloropurin-9-yl)-8,8-dimethyl-7,9-dioxatricyclo[4.3.0.02,4]nonan-2-yl]methanol
• CAS: 352552-14-8
• 化学式: C₁₅H₁₆Cl₂N₄O₃
• 分子量: 371.223
• InChiKey: AFAQFXYGTOURIK-RFXZSQAESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  24
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  82.3
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (1R,2R,3S,4R,5S)-4-(2,6-dichloropurin-9-yl)-1-hydroxymethyl-2,3-O-isopropylidenebicyclo[3.1.0]hexane 在 ruthenium(IV) oxide 、 sodium periodate 、 草酰氯 、 TEA 、 potassium carbonate 作用下， 以 甲醇 、 二氯甲烷 、 氯仿 、 乙腈 为溶剂， 反应 26.0h， 生成
  参考文献：
  名称：

  Ring-Constrained (N)-Methanocarba nucleosides as adenosine receptor agonists: independent 5′-Uronamide and 2′-deoxy modifications

  摘要：

  Novel methanocarba adenosine analogues, having the pseudo-ribose northern (N) conformation preferred at adenosine receptors (ARs), were synthesized and tested in binding assays. The 5'-uronamide modification preserved [N-6-(3-iodobenzyl)] or enhanced (N-6-methyl) affinity at A(3)ARs, while the 2'-deoxy modification reduced affinity and efficacy in a functional assay. Published by Elsevier Science Ltd.

  DOI：

  10.1016/s0960-894x(01)00213-x
• 作为产物：
  描述：

  (1'R,2'R,3'S,4'R,5'S)-4-(2,6-dichloropurin-9-yl)-1-[(phenylmethoxy)methyl]bicyclo[3.1.0]hexane-2,3-(O-isopropylidene) 在 三氯化硼 、 邻苯二甲酸二甲酯 、 对甲苯磺酸 作用下， 以 二氯甲烷 、 丙酮 为溶剂， 生成 (1R,2R,3S,4R,5S)-4-(2,6-dichloropurin-9-yl)-1-hydroxymethyl-2,3-O-isopropylidenebicyclo[3.1.0]hexane
  参考文献：
  名称：

  Ring-Constrained (N)-Methanocarba nucleosides as adenosine receptor agonists: independent 5′-Uronamide and 2′-deoxy modifications

  摘要：

  Novel methanocarba adenosine analogues, having the pseudo-ribose northern (N) conformation preferred at adenosine receptors (ARs), were synthesized and tested in binding assays. The 5'-uronamide modification preserved [N-6-(3-iodobenzyl)] or enhanced (N-6-methyl) affinity at A(3)ARs, while the 2'-deoxy modification reduced affinity and efficacy in a functional assay. Published by Elsevier Science Ltd.

  DOI：

  10.1016/s0960-894x(01)00213-x

文献信息

• [EN] A3 ADENOSINE RECEPTOR AGONISTS FOR USE IN MEDICINE<br/>[FR] ANALOGUES DU RÉCEPTEUR A3 DE L'ADÉNOSINE POUR LE TRAITEMENT D'UNE MALADIE
  申请人：BIOINTERVENE INC

  公开号：WO2022040241A1

  公开（公告）日：2022-02-24

  The disclosure provides adenosine analogs for the treatment of disease such as pain and inflammatory conditions.

  该披露提供了用于治疗疾病如疼痛和炎症症状的腺苷类似物。
• Structure−Activity Relationship of (<i>N</i>)-Methanocarba Phosphonate Analogues of 5′-AMP as Cardioprotective Agents Acting Through a Cardiac P2X Receptor
  作者：T. Santhosh Kumar、Si-Yuan Zhou、Bhalchandra V. Joshi、Ramachandran Balasubramanian、Tiehong Yang、Bruce T. Liang、Kenneth A. Jacobson

  DOI：10.1021/jm9018542

  日期：2010.3.25

  P2X receptor activation protects in heart failure models. MRS2339 3, a 2-chloro-AMP derivative containing a (N)-methanocarba (bicyclo[3.1.0]hexane) system, activates this cardioprotective channel. Michaelis-Arbuzov and Wittig reactions provided phosphonate analogues of 3, expected to be stable in vivo due to the C P bond. After chronic administration via a mini-osmotic pump (Alzet), some analogues significantly increased intact heart contractile function in calsequestrin-overexpressing mice (genetic model of heart failure) compared to vehicle-infused mice (all inactive at the vasodilatory P2Y(1) receptor). Two phosphonates, (1'S,2'R,3',5,4'R,5'S)-4'-(6-amino-2-chloropurin-9-y1)-2',3'-(dihydroxy)-1'-(phosphonomethylene)-bicyclo[3.1.0]hexane, 4 (MRS2775), and its homologue 9 (MRS2935), both 5'-saturated, containing a 2-Cl substitution, improved echocardiography-derived fractional shortening (20.25% and 19.26%, respectively, versus 13.78% in controls), while unsaturated 5'-extended phosphonates, all 2-H analogues, and a CH3-phosphonate were inactive. Thus, chronic administration of nucleotidase-resistant phosphonates conferred a beneficial effect, likely via cardiac P2X receptor activation. Thus, we have greatly expanded the range of carbocyclic nucleotide analogues that represent potential candidates for the treatment of heart failure.
• WO2006/91905
  申请人：——

  公开号：——

  公开（公告）日：——
• Synthesis of Ethyl (1<i>S</i>,2<i>R</i>,3<i>S</i>,4<i>S,</i>5<i>S</i>)-2,3-<i>O</i>-(Isopropylidene)-4-Hydroxy-Bicyclo[3.1.0]Hexane-Carboxylate from L-Ribose: A Versatile Chiral Synthon for Preparation of Adenosine and P2 Receptor Ligands
  作者：Bhalchandra V. Joshi、Artem Melman、Richard L. Mackman、Kenneth A. Jacobson

  DOI：10.1080/15257770701845253

  日期：2008.2.8

  Substitution of the ribose moiety of various nucleosides and nucleotides with the (N)-methanocarba ring system increases the potency and selectivity as ligands at certain subtypes of adenosine and P2 receptors. We have prepared a key intermediate in the synthesis of these derivatives, ethyl (1S,2R,3S,4S,5S)-Z3-O-(isopropylidene)-4-hydroxybicyclo[3.1.0]hexane-carboxylate (15), starting from L-ribose (8) as a readily available, enantiopure building block. L-ribose was converted to the corresponding 5'-iodo derivative (9), which was cleaved reductively with Zn. Improvements were made in subsequent steps corresponding to a published route to biologically important (N)-methanocarba 5'-uronamido nucleosides, and new steps were added to prepare related 5'-nucleotides.
• AMP DERIVATIVES FOR TREATING CARDIAC DISEASES
  申请人：University of Connecticut

  公开号：EP2539352B1

  公开（公告）日：2017-10-04