O^2'_,O3'-isopropylidene-O²-methyl-isoguanosine | 66748-44-5

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 英文名称: O^2'_,O3'-isopropylidene-O²-methyl-isoguanosine
• 英文别名: 2',3'-O-isopropylidene-2-methoxy-adenosine；[(3aR,4R,6R,6aR)-4-(6-amino-2-methoxypurin-9-yl)-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-6-yl]methanol
• CAS: 66748-44-5
• 化学式: C₁₄H₁₉N₅O₅
• 分子量: 337.335
• InChiKey: JYZUZGKYIZVGJY-WOUKDFQISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.6
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  127
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  O^2'_,O3'-isopropylidene-O²-methyl-isoguanosine 在 氢氧化钾 、 potassium permanganate 、 三乙胺 、 三氟乙酸 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 17.0h， 生成 (2S,3S,4R,5R)-5-(6-amino-2-methoxypurin-9-yl)-3,4-dihydroxy-N-phenyloxolane-2-carboxamide
  参考文献：
  名称：

  [EN] ADENOSINE RECEPTOR AGONISTS
  [FR] COMPOSES THERAPEUTIQUES

  摘要：

  公开号：

  WO2005084653A3
• 作为产物：
  描述：

  海绵核苷 、 丙酮 在 对甲苯磺酸 作用下， 以 水 为溶剂， 反应 1.0h， 生成 O^2'_,O3'-isopropylidene-O²-methyl-isoguanosine
  参考文献：
  名称：

  Selective inhibition of TRPM2 channel by two novel synthesized ADPR analogues

  摘要：

  Transient receptor potential melastatin‐2 (TRPM2) channel critical for monitoring internal body temperature is implicated in the pathological processes such as neurodegeneration. However, lacking selective and potent TRPM2 inhibitors impedes investigation and validation of the channel as a drug target. To discover novel and selective TRPM2 inhibitors, a series of adenosine 5′‐diphosphoribose analogues were synthesized, and their activities and selectivity were evaluated. Whole‐cell patch‐clamp recordings were employed for screen and evaluation of synthesized compounds. Two compounds, 7i and 8a, were identified as TRPM2 inhibitors with IC50 of 5.7 and 5.4 μm, respectively. Both 7i and 8a inhibited TRPM2 current without affecting TRPM7, TRPM8, TRPV1 and TRPV3. These two TRPM2 inhibitors can serve as new pharmacological tools for further investigation and validation of TRPM2 channel as a drug target, and the summarized structure–activity relationship (SAR) may also provide insights into further improving existing inhibitors as potential lead compounds.

  DOI：

  10.1111/cbdd.13119

文献信息

• Therapeutic Compounds
  申请人：Pritchard Martyn

  公开号：US20080221060A1

  公开（公告）日：2008-09-11

  Use of compounds of general formula (A) as medicaments is described, in particular for the treatment of pain or inflammation; wherein: (I) when X=OH, R 2 =NH 2 , R 5 =CH 2 OH, R 6 =H, R 1 is C 5 -C 6 alkoxy, OCH 2 Cyclopropyl, O-(2,2,3,3-tetrafluoro-cycloButyl), phenoxy, substituted phenoxy, OCH 2 CH 2 OH, or OCH 2 CHF 2 , (5-indanyl)oxy, C 1 , C 2 , C 5 , or C 6 alkylamino, (R) or (S)-sec-Butylamino, C 5 or C 6 cycloalkylamino, exo-norbornane amino, (N-methyl, N-isoamylamino), phenylamino, phenylamino with either methoxy or fluoro substituents, a C 2 sulfone group, a C 2 alkyl group, a cyano group, a CONH 2 group, or 3,5-dimethylphenyl; or when X=H, R 2 =NH 2 , R 5 =CH 2 OH, R 6 =H, R 1 is n-hexyloxy; or (II) when X=OH, R 1 =H, R 5 =CH 2 OH, R 6 =H, R 2 is NMe 2 , N-(2-isopentenyl), piperazinyl, (N-Me, N-benzyl), (N-Me, N—CH 2 Ph(3-Br)), (N-Me, N—CH 2 Ph(3-CF 3 )), or (N-Me, N-(2-methoxyethyl)), or OCH 2 Cyclopentyl; or (III) when X=OH, R 5 =CONHR 3 , R 6 =H: R 1 is H, R 3 is an isopropyl group, and R 2 is either NH 2 or a methylamino group (NHMe) or an isoamyl group (CH 2 CH 2 CHMe 2 ); or R 1 is H, R 3 is H, and R 2 is NH 2 ; or R 1 is OMe, R 3 is Ph, and R 2 is NH 2 ; or R 1 is NHCH 2 CH 2 CH 2 CH 2 CH 2 Me, R 3 is CH 2 CH 2 CH 2 Me, and R 2 is NH 2 ; or (IV) when X=OH, R 1 =H, R 2 =NH 2 , R 5 =CH 2 NHCOR 4 , R 6 =H, R 1 is n-propyl or NHCH 2 CH 3 ; or (V) when X=OH, R 5 =CH 2 OH, R 6 =H: R 1 is NHCyclohexyl when R 2 is NMe 2 ; or R 1 is OMe when R 2 is NHBenzyl; or (VI) when X=OH, R 2 =NH 2 , R 5 =CH 2 OH, R 6 =Me, R1 is NHCyclohexyl or NHCyclopentyl.

  描述了一般式（A）化合物的药物应用，特别是用于治疗疼痛或炎症；其中：（I）当X = OH，R2 = NH2，R5 = CH2OH，R6 = H，R1为C5-C6烷氧基，OCH2环丙基，O-（2,2,3,3-四氟-环丁基），苯氧基，取代苯氧基，OCH2CH2OH或OCH2CHF2，（5-吲哚基）氧基，C1，C2，C5或C6烷基氨基，（R）或（S）-sec-丁基氨基，C5或C6环烷基氨基，外-去环辛烷氨基，（N-甲基，N-异戊基氨基），苯基氨基，带有甲氧基或氟代取代基的苯基氨基，C2磺酰基，C2烷基，氰基，CONH2基或3,5-二甲基苯基；或当X = H，R2 = NH2，R5 = CH2OH，R6 = H，R1为正己氧基；或（II）当X = OH，R1 = H，R5 = CH2OH，R6 = H，R2为NMe2，N-（2-异戊烯基），哌嗪基，（N-Me，N-苄基），（N-Me，N-CH2Ph（3-Br）），（N-Me，N-CH2Ph（3-CF3））或（N-Me，N-（2-甲氧基乙基）），或OCH2环戊基；或（III）当X = OH，R5 = CONHR3，R6 = H：R1为H，R3为异丙基基团，R2为NH2或甲基氨基（NHMe）或异戊基基团（CH2CH2CHMe2）；或R1为H，R3为H，R2为NH2；或R1为OMe，R3为Ph，R2为NH2；或R1为NHCH2CH2CH2CH2CH2Me，R3为CH2CH2CH2Me，R2为NH2；或（IV）当X = OH，R1 = H，R2 = NH2，R5 = CH2NHCOR4，R6 = H，R1为正丙基或NHCH2CH3；或（V）当X = OH，R5 = CH2OH，R6 = H：当R2为NMe2时，R1为NHCyclohexyl；或当R2为NHBenzyl时，R1为OMe；或（VI）当X = OH，R2 = NH2，R5 = CH2OH，R6 = Me，R1为NHCyclohexyl或NHCyclopentyl。
• SAR around (l)-S-adenosyl-l-homocysteine, an inhibitor of human DNA methyltransferase (DNMT) enzymes
  作者：Oscar M. Saavedra、Ljubomir Isakovic、David B. Llewellyn、Lijie Zhan、Naomy Bernstein、Stephen Claridge、Franck Raeppel、Arkadii Vaisburg、Nadine Elowe、Andrea J. Petschner、Jubrail Rahil、Norman Beaulieu、A. Robert MacLeod、Daniel Delorme、Jeffrey M. Besterman、Amal Wahhab

  DOI：10.1016/j.bmcl.2009.03.113

  日期：2009.5

  The inhibitory activity of base-modified SAH analogues and the specificity of inhibiting human DNMT1 and DNMT3b2 enzymes was explored. The 6-amino group was essential while the 7-N of the adenine ring of SAH could be replaced by CH- without loss of activity against both enzymes. The introduction of small groups at the 2-position of the adenine moiety favors DNMT1 over DNMT3b2 inhibition whereas alkylation of the N-6-amino moiety favors the inhibition of DNMT3b2 enzyme. (C) 2009 Elsevier Ltd. All rights reserved.
• ADENOSINE RECEPTOR AGONISTS
  申请人：Cambridge Biotechnology Ltd

  公开号：EP1749016A2

  公开（公告）日：2007-02-07
• [EN] THERAPEUTIC COMPOUNDS<br/>[FR] COMPOSES THERAPEUTIQUES
  申请人：CAMBRIDGE BIOTECHNOLOGY LTD

  公开号：WO2005084653A2

  公开（公告）日：2005-09-15

  Use of compounds of general formula (A) as medicaments is described, in particular for the treatment of pain or inflammation; wherein: (I) when X = OH, R2 = NH2, R5 = CH2OH, R6 = H , R1 is C5-C6 alkoxy, OCH2Cyclopropyl, O-(2,2,3,3-tetrafluoro-cycloButyl), phenoxy, substituted phenoxy, OCH2CH2OH, or OCH2CHF2, (5-indanyl)oxy, C1, C2, C5, or C6 alkylamino, (R) or (S)-sec-Butylamino, C5 or C6 cycloalkylamino, exo-norbornane amino, (N-methyl, N-­isoamylamino), phenylamino, phenylamino with either rnethoxy or fluoro substituents, a C2 sulfone group, a C2 alkyl group, a cyano group, a CONH2 group, or 3,5-dimethylphenyl; or when X = H, R2 = NH2, R5 = CH2OH , R6 = H, R1 is n-hexyloxy; or (II) when X = OH , R1 = H, R5 = CH2OH, R6 = H, R2 is NMe2, N-(2-isopentenyl), piperazinyl, (N-Me, N-benzyl), (N-Me, N-CH2Ph(3-Br)), (N-Me, N-­CH2Ph(3-CF3)), or (N-Me, N-(2-rnethoxyethyl)), or OCH2Cyclopentyl; or (III) when X = OH, R5 = CONHR3, R6 = H: R1 is H, R3 is an isopropyl group, and R2 is either NH2 or a methylamino group (NHMe) or an isoamyl group (CH2CH2CHMe2); or R1 is H, R3 is H, and R2 is NH2; or R1 is OMe, R3 is Ph, and R2 is NH2; or R1 is NHCH2CH2CH2CH2CH2Me, R3 is CH2CH2CH2Me, and R2 is NH2; or (IV) when X = OH, R1 = H, R2 = NH2, R5 = CH2NHCOR.4, R6 = H, R4 is n-propyl or NHCH2CH3; or (V) when X = OH, R5 = CH2OH, R6 = H: R1 is NHCyclohexyl when R2 is NMe2; or R1 is OMe when R2 is NHBenzyl; or (VI) when X = OH , R2 = NH2, R5 = CH2OH, R6 = Me, R1 is NHCyclohexyl or NHCyclopentyl.
• Selective inhibition of TRPM2 channel by two novel synthesized ADPR analogues
  作者：Xiao Luo、Meng Li、Kaiyu Zhan、Wei Yang、Lihe Zhang、KeWei Wang、Peilin Yu、Liangren Zhang

  DOI：10.1111/cbdd.13119

  日期：2018.2

  Transient receptor potential melastatin‐2 (TRPM2) channel critical for monitoring internal body temperature is implicated in the pathological processes such as neurodegeneration. However, lacking selective and potent TRPM2 inhibitors impedes investigation and validation of the channel as a drug target. To discover novel and selective TRPM2 inhibitors, a series of adenosine 5′‐diphosphoribose analogues were synthesized, and their activities and selectivity were evaluated. Whole‐cell patch‐clamp recordings were employed for screen and evaluation of synthesized compounds. Two compounds, 7i and 8a, were identified as TRPM2 inhibitors with IC50 of 5.7 and 5.4 μm, respectively. Both 7i and 8a inhibited TRPM2 current without affecting TRPM7, TRPM8, TRPV1 and TRPV3. These two TRPM2 inhibitors can serve as new pharmacological tools for further investigation and validation of TRPM2 channel as a drug target, and the summarized structure–activity relationship (SAR) may also provide insights into further improving existing inhibitors as potential lead compounds.