CNF-2024

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: CNF-2024
• 英文别名: 9-{2-[(2,2-dimethylpropyl)amino]ethyl}-8-[(2-iodo-5-methoxyphenyl)sulfanyl]-9H-purin-6-amine；9-[2-(2,2-dimethylpropylamino)ethyl]-8-(2-iodo-5-methoxyphenyl)sulfanylpurin-6-amine
• 化学式: C₁₉H₂₅IN₆OS
• 分子量: 512.418
• InChiKey: FGUVIEZMWVLUBS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  28
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  116
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  CNF-2024 、 2-噻吩硼酸 在 bis-triphenylphosphine-palladium(II) chloride 碳酸氢钠 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 以71%的产率得到8-(5-methoxy-2-(thiophen-2-yl)phenylthio)-9-(2-(neopentylamino)ethyl)-9H-purin-6-amine
  参考文献：
  名称：

  [EN] PURINE DERIVATIVES USEFUL AS HSP90 INHIBITORS
  [FR] DÉRIVÉS DE PURINE CONVENANT COMME INHIBITEURS DE HSP90

  摘要：

  本申请提供所示公式的取代嘌呤衍生物及相关化合物。这些化合物作为HSP90抑制剂具有用途，因此可用于治疗相关疾病。（公式）Z1-Z3、Xa-Xc、X2、X4、Y和R的定义见说明书。

  公开号：

  WO2011044394A1
• 作为产物：
  描述：

  acetic acid 2-(6-aminopurin-9-yl)-ethyl ester 在 甲醇 、 acetate buffer 、 溴 、 potassium carbonate 、 三乙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 35.5h， 生成 CNF-2024
  参考文献：
  名称：

  Orally Active Purine-Based Inhibitors of the Heat Shock Protein 90

  摘要：

  Orally active Hsp90 inhibitors are of interest as potential chemotherapeutic agents. Recently, fully synthetic 8-benzyladenines and 8-sulfanyladenines such as 4 were disclosed as Hsp90 inhibitors, but these compounds are not water soluble and consequently have unacceptably low oral bioavailabilities. We now report that water-solubility can be achieved by inserting an amino functionality in the N(9) side chain. This results in compounds that are potent, soluble in aqueous media, and orally bioavailable. In an HER-2 degradation assay, the highest potency was achieved with the neopentylamine 42 (HER-2 IC50 = 90 nM). In a murine tumor xenograft model (using the gastric cancer cell line N87), the H3PO4 salts of the amines 38, 39, and 42 induced tumor growth inhibition when administered orally at 200 mg/kg/day. The amines 38, 39, and 42 are the first Hsp90 inhibitors shown to inhibit tumor growth upon oral dosage.

  DOI：

  10.1021/jm0503087

文献信息

• HSP90 INHIBITING INDAZOLE DERIVATIVES, COMPOSITIONS CONTAINING SAME AND USE THEREOF
  申请人：Bertin Luc

  公开号：US20120010241A1

  公开（公告）日：2012-01-12

  The invention relates to novel products having formula (I), wherein: R4 represents H, CH3, CH2CH3, CF3, F, Cl, Br, I; Het represents a heterocycle optionally substituted by one or more R1 or R′1 radicals selected from H, halogen, CF3, nitro, cyano, alkyl, hydroxy, mercapto, amino, alkylamino, dialkylamino, alkoxy, phenylalkoxy, alkylthio, carboxy that is free or sterified with an alkyl radical, carboxamide, CO—NH(alkyl), CON(alkyl)2, NH—CO-alkyl, sulfonamide, NH—SO2-alkyl, S(O)2-NHalkyl, S(O2)-N(alkyl)2, all of the alkyl, alkoxy and alkylthio radicals being optionally substituted; R being selected from the group comprising (A′), (B), (C), (D) and (F), wherein W1, W2, W3 represent independently CH or N, X represents O, S, NR2, C(O), S(O) or S(O)2; V represents H, Hal, —O—R2 or —NH—R2 with R2 representing H, alkyl, cycloalkyl or heterocycloalkyl, optionally substituted; said products being in all isomer forms, as well as the salts and intended for use as drugs.

  本发明涉及具有公式(I)的新产品，其中：R4代表H，CH3，CH2CH3，CF3，F，Cl，Br，I；Het代表一个杂环，可选地由一个或多个R1或R'1自由基取代，这些自由基选自H，卤素，CF3，硝基，腈基，烷基，羟基，巯基，氨基，烷基氨基，二烷基氨基，烷氧基，苯基烷氧基，烷基硫醚，游离或与烷基自由基酯化的羧基，羧酰胺，CO—NH(烷基)，CON(烷基)2，NH—CO-烷基，磺酰胺，NH—SO2-烷基，S(O)2-NH烷基，S(O2)-N(烷基)2，所有烷基，烷氧基和烷基硫醚自由基都是可选取代的；R选自包括(A′)，(B)，(C)，(D)和(F)的组，其中W1，W2，W3独立代表CH或N，X代表O，S，NR2，C(O)，S(O)或S(O)2；V代表H，Hal，—O—R2或—NH—R2，R2代表H，烷基，环烷基或杂环烷基，可选取代；所述产品为所有异构体形式，以及盐，用于作为药物使用。
• FUSED AMINO PYRIDINES FOR THE TREATMENT OF BRAIN TUMORS
  申请人：Cai Xiong

  公开号：US20100184801A1

  公开（公告）日：2010-07-22

  The present invention relates to the use of compounds with fused amino pyridine core for the treatment of malignancies associated with brain and lung. The oral administration of compounds of the instant application results in effective brain penetration and provides for non-intrusive treatment of brain and lung tumors.

  本发明涉及使用具有融合氨基吡啶核的化合物治疗与大脑和肺部相关的恶性肿瘤。本申请的化合物经口给药可有效穿透大脑，并提供对大脑和肺部肿瘤的非侵入性治疗。
• Fused Amino Pyridines for the Treatment of Lung Cancer
  申请人：Curis, Inc.

  公开号：US20160317508A1

  公开（公告）日：2016-11-03

  The present invention relates to the use of compounds with fused amino pyridine core for the treatment of malignancies associated with brain and lung. The oral administration of compounds of the instant application results in effective brain penetration and provides for non-intrusive treatment of brain and lung tumors.

  本发明涉及使用具有融合氨基吡啶核的化合物治疗与大脑和肺部相关的恶性肿瘤。本申请的化合物经口服后能有效穿透大脑，并实现对大脑和肺部肿瘤的非侵入性治疗。
• COMBINATIONS OF PYRAZOLE DERIVATIVES FOR THE INHIBITION OF CDKS AND GSK'S
  申请人：Lyons John Francis

  公开号：US20100021420A1

  公开（公告）日：2010-01-28

  A combination comprising (a) a compound of formula (0): or salts or tautomers or N-oxides or solvates thereof; wherein X is R 1 -A-NR 4 — or a 5- or 6-membered carbocyclic or heterocyclic ring; A is a bond, SO 2 , C═O, NR 9 (C═O) or 0(C═O) wherein R 9 is hydrogen or C 1-4 hydrocarbyl optionally substituted by hydroxy or C 1-4 alkoxy; Y is a bond or an alkylene chain of 1 to 3 carbon atoms; R 1 is hydrogen; a carbocyclic or heterocyclic group having from 3 to 12 ring members; or an optionally substituted C 1-8 hydrocarbyl group wherein 1 or 2 of the carbon atoms of the hydrocarbyl group may optionally be replaced by an atom or group selected from O, S, NH, SO, SO 2 ; R 2 is hydrogen; halogen; C 1-4 alkoxy; or a C 1-4 hydrocarbyl group optionally substituted by halogen, hydroxyl or C 1-4 alkoxy; R 3 is selected from hydrogen and carbocyclic and heterocyclic groups having from 3 to 12 ring members; and R 4 is hydrogen or a C 1-4 hydrocarbyl group optionally substituted by halogen, hydroxyl or C 1-4 alkoxy; and (b) a compound of formula (I′″) or salts, tautomers, solvates and N-oxides thereof: wherein R 1 is 2,6-dichlorophenyl; R 2a and R 2b are both hydrogen; and R 3 is a group: formula (A) where R 4 is C 1-4 alkyl.

  一个组合物，包括（a）式（0）的化合物：或其盐或互变异构体或N-氧化物或溶剂合物；其中X为R1-A-NR4-或5-或6-成员的碳环或杂环环；A为键，SO2，C═O，NR9（C═O）或0（C═O），其中R9为氢或C1-4烃基，可选择地被羟基或C1-4烷氧基取代；Y为键或1至3个碳原子的烷基链；R1为氢；具有3至12个环成员的碳环或杂环基；或可选择地被卤代、羟基或C1-4烷氧基取代的C1-8烃基，其中烃基的1或2个碳原子可选择地被从O、S、NH、SO、SO2中选择的原子或基团取代；R2为氢；卤素；C1-4烷氧基；或可选择地被卤代、羟基或C1-4烷氧基取代的C1-4烃基；R3选自氢和具有3至12个环成员的碳环或杂环基；和R4为氢或可选择地被卤代、羟基或C1-4烷氧基取代的C1-4烃基；和（b）式（I′″）的化合物或其盐、互变异构体、溶剂合物和N-氧化物：其中R1为2,6-二氯苯基；R2a和R2b均为氢；和R3为一个基团：式（A），其中R4为C1-4烷基。
• NOVEL HSP90 INHIBITORY CARBAZOLE DERIVATIVES, COMPOSITIONS CONTAINING SAME AND USE THEREOF
  申请人：RUXER Jean-Marie

  公开号：US20110166169A1

  公开（公告）日：2011-07-07

  The invention relates to the novel substances in Formula (I): wherein Het is a heterocycle optionally substituted by one or a plurality of radicals R1 or R′1; R is selected from the group comprising Formula (A′), (B), (C), (D), or (E), with R1 and/or R′1 selected from H, halogen, CF3, nitro, cyano, alkyl, hydroxyl, mercapto, amino, alkylamino, dialkylamino, alkoxy, phenylalcoxy, alkylhio, or carboxy that is free or esterified by an alkyl, carboxamide, CO—NH(alkyl), CON(alkyl)2, NH—CO-alkyl, sulfonamide, NH—S02-alkyl, S(0)2-NHalkyl, or S(02)-N(alkyl)2 radical; all these radicals are optionally substituted; W1, W2, and W3 independently are CH or N; X is 0, S, NR2, C(O), S(O), or S(0)2; Z is optionally substituted H, Hal, -0-R2 or —NH—R2 with R2 being H, alkyl, cycloalkyl, or heterocycloalkyl; and these substances are all isomeric forms and salts thereof, used as drugs.

  该发明涉及式（I）中的新物质：其中Het是一种杂环，可选择地由一个或多个基团R1或R′1取代；R从包括式（A′）、（B）、（C）、（D）或（E）的基团中选择，其中R1和/或R′1从H、卤素、CF3、硝基、氰基、烷基、羟基、巯基、氨基、烷基氨基、二烷基氨基、烷氧基、苯基氧基、烷硫基或自由或被烷基、羧酰胺、CO—NH（烷基）、CON（烷基）2、NH—CO-烷基、磺酰胺、NH—S02-烷基、S(0)2-NH烷基或S(02)-N(烷基)2基团中选择；所有这些基团可选择地被取代；W1、W2和W3独立地是CH或N；X是0、S、NR2、C(O)、S(O)或S(0)2；Z是可选择地取代的H、卤素、-0-R2或—NH—R2，其中R2是H、烷基、环烷基或杂环烷基；这些物质都是同分异构体和其盐，用作药物。