2-phenyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-ol | 87753-08-0

• 物质功能分类: 医药中间体
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 2-phenyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-ol
• 英文别名: 2‐phenyl‐6,7‐dihydro‐5H‐cyclopenta[d]pyrimidin‐4‐ol；2-Phenyl-5H,6H,7H-cyclopenta[D]pyrimidin-4-OL；2-phenyl-3,5,6,7-tetrahydrocyclopenta[d]pyrimidin-4-one
• CAS: 87753-08-0
• 化学式: C₁₃H₁₂N₂O
• 分子量: 212.251
• InChiKey: AGQQOLIHSSZYLE-UHFFFAOYSA-N

物化性质

• 密度：
  1.30±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  41.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-phenyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-ol 在 水 、 potassium carbonate 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 61.0h， 生成 2-(4-(2-phenyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-ylamino)phenyl)acetic acid
  参考文献：
  名称：

  Identification of the fused bicyclic 4-amino-2-phenylpyrimidine derivatives as novel and potent PDE4 inhibitors

  摘要：

  2-Phenyl-4-piperidinyl-6,7-dihydrothieno[3,4-d] pyrimidine derivative (2) was found to be a new PDE4 inhibitor with moderate PDE4B activity (IC50 = 150 nM). A number of derivatives with a variety of 4-amino substituents and fused bicyclic pyrimidines were synthesized. Among these, 5,5-dioxo-7,8-dihydro-6H-thiopyrano[3,2-d] pyrimidine derivative (18) showed potent PDE4B inhibitory activity (IC50 = 25 nM). Finally, N-propylacetamide derivative (31b) was determined as a potent inhibitor for both PDE4B (IC50 = 7.5 nM) and TNF-alpha production in mouse splenocytes (IC50 = 9.8 nM) and showed good in vivo anti-inflammatory activity in the LPS-induced lung inflammation model in mice (ID50 = 18 mg/kg). The binding mode of the new inhibitor (31e) in the catalytic site of PDE4B is presented based on an X-ray crystal structure of the ligand-enzyme complex. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.03.104
• 作为产物：
  描述：

  2-amino-1-(N-benzoylcarbamoyl)cyclopentene 以 溶剂黄146 为溶剂， 反应 0.17h， 以97%的产率得到2-phenyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-ol
  参考文献：
  名称：

  A novel ring transformation of oxazinones and azetidinones into pyrimidinones

  摘要：

  Azetidinones or oxazinones, being easily prepared from enamines and acyl isocyanates, were transformed into highly substituted 4(3H)-pyrimidinones upon treatment with ammonium acetate. This novel ring transformation was also accomplished through a one-pot reaction without isolation of the adduct.

  DOI：

  10.1021/jo00054a026

文献信息

• Pyrimidine derivatives useful in the treatment of insulin resistance and hyperglycemia
  申请人：Wyeth

  公开号：US20040110780A1

  公开（公告）日：2004-06-10

  This invention provides compounds of Formula I having the structure: 1 wherein: B is alkyl of 1-4 carbons or alkoxy of 1-4 carbons; R 1 is aryl or Het optionally substituted with R 6 ; R 2 and R 3 are each independently, alkyl of 1-4 carbons, CF 3 , aryl or Het substituted with R 6 , or R 2 and R 3 are combined to form a cycloalkyl or heterocyclic ring optionally substituted with alkyl, benzyl, or acyl; R 4 , and R 5 are each independently, hydrogen, halogen, alkyl of 1-4 carbons, CO 2 R 7 , SO 2 NHR 7 , CONHR 7 , CN, NO 2 or CF 3 ; R 6 is hydrogen, halogen, NO 2 , alkyl of 1-4 carbons, alkoxy of 1-4 carbons, alkylcarbonyloxy of 2-7 carbon atoms, alkylcarbonyl of 2-7 carbon atoms, CF 3 , or COOH; and R 7 is hydrogen, alkyl of 1-4 carbons, or alkylaryl where aryl group is substituted with R 6 ; or a pharmaceutically acceptable salt thereof, which are useful in treating metabolic disorders related to insulin resistance or hyperglycemia.

  这项发明提供了具有结构的Formula I化合物： 其中： B是1-4碳的烷基或1-4碳的烷氧基； R1是芳基或取代为R6的杂环； R2和R3分别独立地是1-4碳的烷基，CF3，芳基或取代为R6的杂环，或者R2和R3结合形成一个环烷基或杂环，可选地取代为烷基，苄基或酰基； R4和R5分别独立地是氢，卤素，1-4碳的烷基，CO2R7，SO2NHR7，CONHR7，CN，NO2或 ； R6是氢，卤素， ，1-4碳的烷基，1-4碳的烷氧基，2-7碳原子的烷基羰氧基，2-7碳原子的烷基羰基， 或COOH；以及 R7是氢，1-4碳的烷基，或芳基取代为R6的烷基芳基；或其药学上可接受的盐，用于治疗与胰岛素抵抗或高血糖相关的代谢紊乱。
• Synthesis and biological evaluation of novel 6,7-dihydro-5H-cyclopenta[d]pyrimidine and 5,6,7,8-tetrahydroquinazoline derivatives as sigma-1 (σ1) receptor antagonists for the treatment of pain
  作者：Yu Lan、Yiyan Songyang、Lingli Zhang、Yan Peng、Jinchun Song

  DOI：10.1016/j.bmcl.2016.02.077

  日期：2016.4

  The synthesis and biological evaluation of new series of 6,7-dihydro-5H-cyclopenta[d]pyrimidine and 5,6,7,8-tetrahydroquinazoline derivatives as selective sigma-1 receptor (σ1R) antagonists are reported. The receptor affinities of new compounds were evaluated in vitro in σ1 and σ2 receptor binding assays. The structure-active relationship study leads us to the most promising compound: 2-(4-chlorop

  的合成和新系列6,7-二氢5的生物学评价ħ环戊二烯并[ d（]嘧啶和5,6,7,8-四氢喹唑啉衍生物作为选择性σ-1受体σ 1个R）报道拮抗剂。新化合物的受体亲和力在体外进行了评价σ 1和σ 2受体结合试验。通过结构-活性关系研究，我们得出了最有希望的化合物：2-（4-氯苯基）-4-（3-（4-甲基哌啶-1-基）丙氧基）-5,6,7,8-四氢喹唑啉（33）。化合物33具有用于施加纳摩尔亲和力σ 1个R（ķ我σ1  = 15.6 1nM）和高σ 1 / σ 2选择性（ķ我σ 2 > 2000纳米），和鉴定为σ 1 - [R拮抗剂。在动物模型中，化合物33在福尔马林试验中表现出剂量依赖性的抗伤害感受作用。这些结果表明，化合物33可能是用于疼痛治疗的有效止痛药。
• Microwave-Assisted Copper-Powder-Catalyzed Synthesis of Pyrimidinones from β-Bromo α,β-Unsaturated Carboxylic Acids and Amidines
  作者：Chan Cho、Son Ho

  DOI：10.1055/s-0033-1340283

  日期：——

  β-Bromo α,β-unsaturated carboxylic acids were coupled and cyclized with amidine hydrochlorides by microwave irradiation in the presence of catalytic amounts of copper powder and a base to give the corresponding pyrimidinones in high yields.

  在催化量的铜粉和碱存在下，通过微波辐射将β-溴α,β-不饱和羧酸与脒盐酸盐偶联并环化，以高产率得到相应的嘧啶酮。
• 2-aryl-5,6-ring-fused pyrimidines and herbicidal use
  申请人：Rohm and Haas Company

  公开号：US05451565A1

  公开（公告）日：1995-09-19

  A class of 2-aryl-5,6-ring-fused pyrimidines which is useful in the control of weeds is of the general formula: ##STR1## wherein Ar is an optionally substituted aromatic or heteroaromatic ring; R.sup.3 is an alkynyl or alkoxyalkyl group, --R.sup.5 ----R.sup.6 -- is a fused ring moiety bonded to the pyrimidine ring at the 5 and 6 positions; and X is oxygen or sulfur.

  一类有用于控制杂草的2-芳基-5,6-环融合嘧啶的一般式为：##STR1## 其中Ar是一个可选取的取代芳香环或杂环；R.sup.3是一个炔基或烷氧基烷基；--R.sup.5 ----R.sup.6--是一个融合环基团，与嘧啶环在5和6位置连接；X是氧或硫。
• Hit discovery of novel 2‐phenyl‐substituted 4‐amino–6,7‐dihydro‐5 <i>H</i> ‐cyclopenta[ <i>d</i> ]pyrimidines as potential anti‐glioblastoma therapeutics: Design, synthesis, biological evaluation, and computational screening
  作者：Sanjay Khairnar、Anjali Sonawane、Rameshwar S. Cheke、Prashant S. Kharkar、Vishwas Gaikwad、Sambhaji Patil、Valmik Aware

  DOI：10.1002/ddr.22046

  日期：——

  success. There is an unmet medical need of molecularly-targeted therapeutics for GBM treatment. In the present work, a series of novel 2-phenyl-substituted 4-amino–6,7-dihydro-5H-cyclopenta[d]pyrimidines was designed, synthesized, purified, characterized, and evaluated for cytotoxicity against glioblastoma cell line U87-MG. The design process (virtual library enumeration around the core, physicochemical and

  多形性胶质母细胞瘤 (GBM) 是一种高度侵袭性、可怕的疾病，预后不良且临床成功率令人失望。用于 GBM 治疗的分子靶向疗法存在未满足的医疗需求。在目前的工作中，一系列新型 2-苯基取代的 4-氨基-6,7-二氢-5 H-cyclopenta[d]pyrimidines 被设计、合成、纯化、表征，并评估了对胶质母细胞瘤细胞系 U87-MG 的细胞毒性。设计过程（围绕核心的虚拟库枚举、设计的物理化学和分子特性预测/计算、过滤不需要的设计以及类先导设计的多样性分析）经过精心策划，以获得一组结构-多样化的新型分子（总共 20 个），特别关注相对未开发的核心结构，6,7-dihydro-5 H -cyclopenta[d]pyrimidine。使用 MTT 法在 10 和 100 μM 浓度的标题化合物F 1 - F 20下进行初步筛选和阳性对照顺铂，产生六次命中（10 μM 时的抑制百分比：~50%）—