benzhydrylamidine | 7581-11-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: benzhydrylamidine
• 英文别名: 2,2-diphenyl-acetamidine；2,2-Diphenyl-acetamidin；Diphenylacetamidin；2,2-Diphenylacetamidine；2,2-diphenylethanimidamide
• CAS: 7581-11-5
• 化学式: C₁₄H₁₄N₂
• mdl: MFCD09745995
• 分子量: 210.279
• InChiKey: CLCMSGXEVLGRNG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.071
• 拓扑面积：
  49.9
• 氢给体数：
  2
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  benzhydrylamidine 在 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 、 sodium hydroxide 作用下， 以 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.25h， 生成 (2-benzhydryl-4-phenyl-1H-imidazole-5-carbonyl)-L-arginine
  参考文献：
  名称：

  Potent Heterocyclic Ligands for Human Complement C3a Receptor

  摘要：

  The G-protein coupled receptor (C3aR) for human inflammatory protein complement C3a is an important component of immune, inflammatory, and metabolic diseases. A flexible compound (N2-[(2,2-diphenylethoxy)acetyl]-l-arginine, 4), known as a weak C3aR antagonist (IC50 mu M), was transformed here into potent agonists (EC50 nM) of human macrophages (Ca2+ release in HMDM) by incorporating aromatic heterocycles. Antagonists were also identified. A linear correlation between binding affinity for C3aR and calculated hydrogen-bond interaction energy of the heteroatom indicated that its hydrogen-bonding capacity influenced ligand affinity and function mediated by C3aR. Hydrogen-bond accepting heterocycles (e.g., imidazole) conferred the highest affinity and agonist potency (e.g., 21, EC50 24 nM, Ca2+, HMDM) with comparable efficacy and immunostimulatory activity as that of C3a in activating human macrophages (Ca2+, IL1 beta, TNF alpha, CCL3). These potent and selective modulators of C3aR, inactivated by a C3aR antagonist, are stable C3a surrogates for interrogating roles for C3aR in physiology and disease.

  DOI：

  10.1021/jm500956p
• 作为产物：
  描述：

  二苯乙腈 在 三甲基铝 、 氯化铵 作用下， 生成 benzhydrylamidine
  参考文献：
  名称：

  Potent Heterocyclic Ligands for Human Complement C3a Receptor

  摘要：

  The G-protein coupled receptor (C3aR) for human inflammatory protein complement C3a is an important component of immune, inflammatory, and metabolic diseases. A flexible compound (N2-[(2,2-diphenylethoxy)acetyl]-l-arginine, 4), known as a weak C3aR antagonist (IC50 mu M), was transformed here into potent agonists (EC50 nM) of human macrophages (Ca2+ release in HMDM) by incorporating aromatic heterocycles. Antagonists were also identified. A linear correlation between binding affinity for C3aR and calculated hydrogen-bond interaction energy of the heteroatom indicated that its hydrogen-bonding capacity influenced ligand affinity and function mediated by C3aR. Hydrogen-bond accepting heterocycles (e.g., imidazole) conferred the highest affinity and agonist potency (e.g., 21, EC50 24 nM, Ca2+, HMDM) with comparable efficacy and immunostimulatory activity as that of C3a in activating human macrophages (Ca2+, IL1 beta, TNF alpha, CCL3). These potent and selective modulators of C3aR, inactivated by a C3aR antagonist, are stable C3a surrogates for interrogating roles for C3aR in physiology and disease.

  DOI：

  10.1021/jm500956p

文献信息

• [EN] SUBSTITUTED THIAZOLEACETIC AS CRTH2 LIGANDS<br/>[FR] ACIDES THIAZOLEACETIQUES SUBSTITUES EN TANT QUE LIGANDS CRTH2
  申请人：7TM PHARMA AS

  公开号：WO2005116001A1

  公开（公告）日：2005-12-08

  Compounds of formula (I) are useful for the treatment of disease responsive to modulation of CRTH2 receptor activity, such as asthma, rhinitis, allergic airway syndrome, and allergic rhinobronchitis; wherein X1 is -S-, -O-, -N=N-. -NR7-, -CR7=CR8-, -CR7=N-, wherein R7 and R8 are independently hydrogen or C1-C3 alkyl; A is a carboxyl group -COOH, or a carboxyl bioisostere; rings Ar2 and Ar3 each independently represent a phenyl or 5- or 6­-membered monocyclic heteroaryl ring, or a bicyclic ring system consisting of a 5- or 6-membered carbocyclic or heterocyclic ring which is benz-fused or fused to a 5- or 6-membered monocyclic heteroaryl ring, said ring or ring system being optionally substituted; ring B is as defined for Ar2 and Ar3, or an optionally substituted N-­pyrrolidinyl, N-piperidinyl or N-azepinyl ring; s is 0 or 1; L1, L2 and L4 are linker radicals as defined in the description; Q1 and Q2 represent substituents as defined in the description.

  式(I)的化合物对于治疗对CRTH2受体活性调节敏感的疾病有用，如哮喘、鼻炎、过敏性气道综合征和过敏性鼻支气管炎；其中X1为-S-，-O-，-N=N-，-NR7-，-CR7=CR8-，-CR7=N-，其中R7和R8独立地为氢或C1-C3烷基；A为羧基-COOH，或羧基生物异构体；环Ar2和环Ar3各自独立地表示苯基或5-或6-成员的单环杂芳基环，或由5-或6-成员的碳环或杂环环组成的双环系统，该环或环系可以选择性地被取代；环B的定义与环Ar2和环Ar3相同，或者是一个可选择性取代的N-吡咯烷基，N-哌啶基或N-氮杂七元环；s为0或1；L1、L2和L4为描述中定义的连接基；Q1和Q2表示描述中定义的取代基。
• Substituted Thiazoleacetic Acid as Crth2 Ligands
  申请人：Ulven Trond

  公开号：US20080119456A1

  公开（公告）日：2008-05-22

  Compounds of formula (I) are useful for the treatment of disease responsive to modulation of CRTH2 receptor activity, such as asthma, rhinitis, allergic airway syndrome, and allergic rhinobronchitis; wherein X 1 is —S—, —O—, —N═N—. —NR 7 —, —CR 7 ═CR 8 —, —CR 7 ═N—, wherein R 7 and R 8 are independently hydrogen or C 1 -C 3 alkyl; A is a carboxyl group —COOH, or a carboxyl bioisostere; rings Ar 2 and Ar 3 each independently represent a phenyl or 5- or 6-membered monocyclic heteroaryl ring, or a bicyclic ring system consisting of a 5- or 6-membered carbocyclic or heterocyclic ring which is benz-fused or fused to a 5- or 6-membered monocyclic heteroaryl ring, said ring or ring system being optionally substituted; ring B is as defined for Ar 2 and Ar 3 , or an optionally substituted N-pyrrolidinyl, N-piperidinyl or N-azepinyl ring; s is 0 or 1; L1, L2 and L4 are linker radicals as defined in the description; Q 1 and Q 2 represent substituents as defined in the description.

  式(I)的化合物对于治疗对CRTH2受体活性调节敏感的疾病，如哮喘、鼻炎、过敏性气道综合症和过敏性鼻支气管炎是有用的；其中X1为—S—、—O—、—N═N—、—NR7—、—CR7═CR8—、—CR7═N—，其中R7和R8独立地为氢或C1-C3烷基；A为羧基—COOH，或羧基生物同位素；环Ar2和Ar3各自表示苯基或5-或6-成员单环杂芳基环，或由5-或6-成员碳环或杂环环组成的双环系统，该环或环系统可以选择性地被取代；环B与Ar2和Ar3的定义相同，或是一个可以选择性地被取代的N-吡咯烷基、N-哌啶基或N-氮杂环己基环；s为0或1；L1、L2和L4为描述中定义的连接基团；Q1和Q2表示描述中定义的取代基。
• 42. Some amidines and dihydroglyoxalines of the 1 : 1-diphenylethane and 1 : 1-diphenylpropane series
  作者：J. O. Jílek、M. Protiva

  DOI：10.1039/jr9500000188

  日期：——
• Nagao, Yuuki; Takahashi, Kanji; Torisu, Kazuhiko, Heterocycles, 1996, vol. 42, # 2, p. 517 - 523
  作者：Nagao, Yuuki、Takahashi, Kanji、Torisu, Kazuhiko、Kondo, Kigen、Hamanaka, Nobuyuki

  DOI：——

  日期：——
• Busch; Hobein, Chemische Berichte, 1907, vol. 40, p. 4297
  作者：Busch、Hobein

  DOI：——

  日期：——