1,3-Dihydro-3-(phenylmethyl)-2H-imidazo<4,5-b>pyridin-2-one | 41010-46-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并吡啶类
• 英文名称: 1,3-Dihydro-3-(phenylmethyl)-2H-imidazo<4,5-b>pyridin-2-one
• 英文别名: 3-benzyl-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one；3-benzyl-2,3-dihydro-1H-imidazo[4,5-b]pyridin-2-one；3-benzyl-1,3-dihydro-imidazo[4,5-b]pyridin-2-one；3-benzyl-1,3-dihydro-imidazo[4,5-b]pyridin-2-one；3-benzyl-1,3-dihydro-imadazo[4,5-b]pyridin-2-one；3-Benzylimidazo<4,5-b>-pyridin-2-on；3-benzyl-2-hydroxy-3H-imidazo[4,5-b]pyridine；3-benzyl-1H-imidazo[4,5-b]pyridin-2-one
• CAS: 41010-46-2
• 化学式: C₁₃H₁₁N₃O
• mdl: MFCD00184163
• 分子量: 225.25
• InChiKey: RJOUSKOGXRNRBW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.076
• 拓扑面积：
  45.2
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1,3-Dihydro-3-(phenylmethyl)-2H-imidazo<4,5-b>pyridin-2-one 在 四(三苯基膦)钯 、 五氯化磷 、 三溴化硼 、 sodium carbonate 、 三苯基膦 、 偶氮二甲酸二乙酯 、 三氯氧磷 作用下， 以 乙二醇二甲醚 、 二氯甲烷 、 苯 为溶剂， 反应 24.5h， 生成
  参考文献：
  名称：

  新型苯并呋喃和苯并噻吩联苯作为具有抗高血糖特性的蛋白酪氨酸磷酸酶1B的抑制剂。

  摘要：

  肝和外周组织中的胰岛素抵抗以及胰腺细胞缺陷是2型糖尿病的常见病因。现在已经认识到，胰岛素抵抗可以由胰岛素受体信号系统中在胰岛素与其受体结合后的位点的缺陷引起。蛋白酪氨酸磷酸酶（PTPases）已被证明是胰岛素受体的负调节剂。抑制PTPases可能是治疗2型糖尿病的有效方法。我们已经确定了两个新颖的苯并呋喃/苯并噻吩联苯氧代乙酸和磺酰水杨酸系列作为具有良好口服降血糖活性的有效PTP1B抑制剂。为了帮助设计这些抑制剂，晶体学研究试图鉴定酶抑制剂的相互作用。晶体配合物的拆分表明抑制剂与酶的活性位点结合，并通过在两个疏水口袋中形成的氢键和范德华相互作用而保持在适当的位置。在含氧乙酸系列中，苯并呋喃/苯并噻吩联苯骨架第2位的疏水取代基与催化位点的Phe182相互作用，对分子的内在活性至关重要。催化位点口袋的疏水区被氧代乙酸部分的α-碳或邻位芳族位置的疏水取代基所利用和利用。水杨酸型抑制剂上类似的邻位

  DOI：

  10.1021/jm990560c
• 作为产物：
  描述：

  3-(Phenylmethyl)-2,3-dihydro-2-oxo-1H-imidazo<4,5-b>pyridine-1-carboxylic acid ethyl ester 在 sodium hydroxide 作用下， 以 甲醇 为溶剂， 以92%的产率得到1,3-Dihydro-3-(phenylmethyl)-2H-imidazo<4,5-b>pyridin-2-one
  参考文献：
  名称：

  Regiospecific Functionalization of 1,3-Dihydro-2H-benzimidazol-2-one and Structurally Related Cyclic Urea Derivatives

  摘要：

  Methods for selectively protecting one of the degenerate nitrogen atoms of the cyclic urea derivatives 1,3-dihydro-2H-benzimidazol-2-one (6a), 1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one (11), 1,3-dihydro-2H-imidazo[4,5-b]quinolin-2-ones (20), 1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one (22), and 1,3-dihydro-4-phenyl-2H-imidazol-2-one (27) were developed. Heating these cyclic ureas with ethyl 2-pyridyl carbonate in the presence of a base in CH3CN at reflux or DMF at 100 degrees C cleanly provided the monoethoxycarbonyl derivatives 7a, 12, 21, 23, and 28, respectively. Alternatively, treatment of 6a with an excess of diethyl pyrocarbonate or di-tert-butyl dicarbonate afforded the bis-alkoxycarbonyl derivatives 8a and 8b, respectively, which underwent disproportionation to 7a and 7b upon heating with 1 mol equiv of 6a and K2CO3 in CH3CN at reflux. The regiochemistry of the introduction of alkoxycarbonyl groups to benzimidazol-2-one derivatives was not significantly influenced by an electron-withdrawing (CF3, 6b) or an electron-donating (OCH3, 6c) substituent at C-5 of the heterocyclic ring. However, the reaction was found to be sensitive to steric factors since a chlorine substituent ortho to one of the urea N atoms (6e) completely directed the alkoxycarbonyl moiety to the less sterically encumbered N atom, affording a single product (7f, 7g). Alkylation of 7a-g proceeded efficiently to provide products 10a-10ag after removal of the protecting group. Halogenation of monoprotected benzimidazol-2-one 7a occurred regiospecifically to give the monohalo derivatives 7h, 7i, and 7k, the identity of which were readily established from the characteristic chemical shift and spin coupling pattern in their 1H NMR spectra. A protecting group interchange strategy that took advantage of the distinctive chemical reactivities of the EtO(2)C and t-BuO(2)C protecting groups toward isopropylamine was developed that provided access to the isomerically substituted series of monohalo, mono-N-alkylated benzimidazol-2-ones 71 and 7m. The efficient derivatization of the unprotected N atom of these monoprotected cyclic urea derivatives was accomplished by treating with activated and unactivated halides in the. presence of K2CO3 or exposure to alcohols under Mitsunobu conditions. In several cases, mixtures of O- and N-alkylated products were produced which were readily separated by chromatography. Alkylation of 7h with activated halides, using K2CO3 in CH3CN at reflux, occurred without protecting group equilibration; however, a mixture of isomeric alkylated products was obtained when 7h was heated at 110 degrees C in DMF with cyclohexylmethyl bromide in the presence of K2CO3 as the base. Derivatization of 7h under Mitsunobu reaction conditions proceeded with retention of the topological substituent relationships. Subsequent removal of the alkoxycarbonyl moiety afforded monoalkylated cyclic urea derivatives.

  DOI：

  10.1021/jo00111a014

文献信息

• Biphenyl oxo-acetic acids useful in the treatment of insulin resistance and hyperglycemia
  申请人：American Home Products Corporation

  公开号：US06232322B1

  公开（公告）日：2001-05-15

  This invention provides compounds of Formula I having the structure wherein A, R3, R4, and R5 are as defined hereinbefore in the specification, 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化合物，其中A、R3、R4和R5如前述说明中所定义，或其药学上可接受的盐，这些化合物在治疗与胰岛素抵抗或高血糖相关的代谢紊乱方面是有用的。
• Pharmacologically active aminoimidazopyridines
  申请人：Dompe Farmaceutici S.p.A.

  公开号：US05023256A1

  公开（公告）日：1991-06-11

  Novel imidazopyridine derivatives of formula: ##STR1## wherein, R represents an alkoxyalky radical having 4-6 carbon atoms or a benzyl radical optionally substituted by a halogen atom, an alkyl or alkoxy radical having up to 3 carbon atoms, X represents hydrogen or an alkyl radical having up to 3 carbon atoms, n represents 0 or 1 m represents an integer of from 2 to 5 inclusive, R.sub.1 and R.sub.2 may be the same or different and represent a saturated or unsaturated alkyl radical containing up to 4 carbon atoms or they, taken together with the adjacent nitrogen atom, may form a pyrrolidine, piperazine or homopiperazine ring which may be optionally substituted by an alkyl radical containing up to 3 carbon atoms, provided that when n is zero also m is zero and --N(R.sub.1)R.sub.2 represents the above defined piperazine or homopiperazine ring. The compounds (I) have an antihistaminic activity.

  化合物(I)是一种新型咪唑吡啶衍生物，其化学式为：##STR1##其中，R代表具有4-6个碳原子的烷氧基烷基基团或苄基基团，该苄基基团可以选择性地被卤素原子、具有最多3个碳原子的烷基或烷氧基替换，X代表氢原子或具有最多3个碳原子的烷基基团，n代表0或1，m代表2至5的整数，R.sub.1和R.sub.2可以相同也可以不同，代表含有最多4个碳原子的饱和或不饱和烷基基团，或者它们与相邻的氮原子结合形成吡咯烷、哌嗪或同源哌嗪环，该环可以选择性地被含有最多3个碳原子的烷基基团替换，但当n为零时，m也为零，且--N(R.sub.1)R.sub.2代表上述定义的哌嗪或同源哌嗪环。该化合物(I)具有抗组胺活性。
• Synthesis of 1-and 3-substituted imidazo[4,5-b]pyridin-2-ones
  作者：Yu. M. Yutilov、N. N. Smolyar、D. A. Lomov

  DOI：10.1134/s1070428006060145

  日期：2006.6

  1- and 3-Substituted imidazo[4,5-b]pyridin-2-ones were synthesized by heating equimolar amounts of 3-amino-2-chloropyridine or 2-chloro-3-methylaminopyridine, urea, and the corresponding arylamine at 150-210 degrees C. The reaction of 3-amino-2-chloropyridine with urea and p-phenylenediamine or p,p'-diaminobiphenyl at a ratio of 2:2:1 under analogous conditions gave 1,4-bis-(2-oxoimidazo[4,5-b]pyridin-3-yl)benzene or 1,4-bis(2-oxoimidazo[4,5-b]pyridin-3-yl)biphenyl, respectively.
• Design, synthesis and characterization of novel N-heterocyclic-1-benzyl-1H-benzo[d]imidazole-2-amines as selective TRPC5 inhibitors leading to the identification of the selective compound, AC1903
  作者：Swagat H. Sharma、Juan Lorenzo Pablo、Monica Suarez Montesinos、Anna Greka、Corey R. Hopkins

  DOI：10.1016/j.bmcl.2018.12.007

  日期：2019.1

  The transient receptor potential cation channel 5 (TRPC5) has been previously shown to affect podocyte survival in the kidney. As such, inhibitors of TRPC5 are interesting candidates for the treatment of chronic kidney disease (CKD). Herein, we report the synthesis and biological characterization of a series of N-heterocyclic-1-benzyl-1H-benzo[d]imidazole-2-amines as selective TRPC5 inhibitors. Work reported here evaluates the benzimidazole scaffold and substituents resulting in the discovery of AC1903, a TRPC5 inhibitor that is active in multiple animal models of CKD.
• BIPHENYL OXO-ACETIC ACIDS USEFUL IN THE TREATMENT OF INSULIN RESISTANCE AND HYPERGLYCEMIA
  申请人：Wyeth

  公开号：EP1077967B1

  公开（公告）日：2002-12-04