2,4-Diphenyl-6-isopropylpyrylium perchlorate

• 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: 2,4-Diphenyl-6-isopropylpyrylium perchlorate
• 英文别名: 2-isopropyl-4,6-diphenyl-pyrylium; perchlorate；2-Isopropyl-4,6-diphenyl-pyrylium; Perchlorat；2,4-Diphenyl-6-propan-2-ylpyrylium;perchlorate
• 化学式: C₂₀H₁₉O*ClO₄
• 分子量: 374.821
• InChiKey: XXIKFNQIXUSSIP-UHFFFAOYSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  1.26
• 重原子数：
  26
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  75.3
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2,4-Diphenyl-6-isopropylpyrylium perchlorate 在 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 乙腈 为溶剂， 反应 22.0h， 生成 1-N-[(4-guanidinosulfonyl-phenyl)aminocarbonylmethyl]-2-isopropyl-4,6-diphenylpyridinium perchlorate
  参考文献：
  名称：

  蛋白酶抑制剂-第3部分。非碱性凝血酶抑制剂的合成，在P1位点掺入吡啶鎓-磺胺基胍基部分。

  摘要：

  以苄am和磺胺胍为先导分子，通过磺胺胍与吡喃鎓盐，分别与甘氨酸的吡啶鎓衍生物和与β-丙氨酸的吡啶鎓衍生物反应，制备了三个系列的衍生物。测定了新化合物作为两种丝氨酸蛋白酶，凝血酶和胰蛋白酶的抑制剂。研究表明，与铅相比，新的衍生物对凝血酶的K（I）分别约为100-300 nM，对胰蛋白酶的K（I）约为1200-1500 nM，对铅的抑制常数为15-50 nM。凝血酶，而它们对胰蛋白酶的亲和力仍然较低。β-丙氨酸的衍生物比相应的Gly衍生物更具活性，其反过来比磺胺胍的吡啶鎓衍生物在吡啶鎓环上具有相同的取代方式更具抑制性。因此，本研究提出了两种制备高亲和力，特异性凝血酶抑制剂的新颖方法：在已经很大的精氨酸/ am基抑制剂家族中，即SO（2）N = C（NH （2））（2）基团，以及通过在疏水结合位点掺入烷基-/芳基取代的吡啶鎓部分而获得的新型非拟肽支架。第一个对于获得可生物利用的凝血酶抑制剂很重要，因为缺乏常用的精氨酸/

  DOI：

  10.1016/s0223-5234(99)00115-4
• 作为产物：
  描述：

  Alpha-甲基-Β-苯甲酰基苯乙烯 、 异丁酸酐 在 高氯酸 作用下， 以19%的产率得到2,4-Diphenyl-6-isopropylpyrylium perchlorate
  参考文献：
  名称：

  Farcasiu, Dan; Kizirian, Mark, Journal of Heterocyclic Chemistry, 1990, vol. 27, # 7, p. 2041 - 2045

  摘要：

  DOI：

文献信息

• Carbonic Anhydrase Activators:  Design of High Affinity Isozymes I, II, and IV Activators, Incorporating Tri-/Tetrasubstituted-pyridinium-azole Moieties
  作者：Monica Ilies、Mircea D. Banciu、Marc A. Ilies、Andrea Scozzafava、Miron T. Caproiu、Claudiu T. Supuran

  DOI：10.1021/jm011031n

  日期：2002.1.1

  bovine isozymes), for which some of the new compounds showed affinities in the low nanomolar range, whereas against hCA II, their affinities were in the range of 95-150 nM. Substitution patterns of the pyridinium ring leading to best activity included 4-phenyl-2,6-dialkyl moieties or 2,4,6-tri- and 2,3,4,6-tetraalkyl groups. Ex vivo experiments showed some of the new activators to strongly enhance CA activity

  通过氨基唑（3-氨基吡唑，2-氨基咪唑和5-氨基四唑）与三或四取代的吡啶鎓盐的反应获得了一系列紧密结合的碳酸酐酶（CA）活化剂。事实证明，这里报道的许多结合了吡咯部分的新吡啶鎓盐都是三种CA同工酶CA I，II和IV的有效体外活化剂。对hCA I和bCA IV（h =人； b =牛同工酶）检测到非常好的活性，其中一些新化合物显示出低纳摩尔范围的亲和力，而对hCA II的亲和力在95范围内-150 nM。导致最佳活性的吡啶鎓环的取代方式包括4-苯基-2,6-二烷基部分或2,4,6-三-和2,3,4,6-四烷基。体外实验显示，一些新的激活剂在与人红细胞孵育后能显着增强CA活性。此外，由于它们的阳离子性质，这些化合物中的一些（咪唑和吡唑衍生物）是不渗透膜的，因此可区分胞质和膜结合的CA同工酶。本文是膜不透CA激活剂的首次报道。另一方面，吡啶鎓四唑衍生物确实穿透生物膜。此类CA激活剂可能会导致药物
• Carbonic Anhydrase Inhibitors. Design of Selective, Membrane-Impermeant Inhibitors Targeting the Human Tumor-Associated Isozyme IX
  作者：Joseph. R. Casey、Patricio E. Morgan、Daniela Vullo、Andrea Scozzafava、Antonio Mastrolorenzo、Claudiu T. Supuran

  DOI：10.1021/jm031079w

  日期：2004.4.1

  A series of positively charged sulfonamides were obtained by reaction of aminobenzolamide [5-(4-aminobenzenesulfonylamino)-1,3,4-thiadiazole-2-sulfonamide] with tri-/tetrasubstituted pyrilium salts possessing alkyl-, aryl- or combinations of alkyl and aryl groups at the pyridinium ring. The new compounds reported here were assayed for the inhibition of four physiologically relevant carbonic anhydrase

  通过氨基苯甲酰胺[5-（4-氨基苯磺酰基氨基）-1,3,4-噻二唑-2-磺酰胺]与具有烷基，芳基或烷基组合的三/四取代substituted盐反应，可获得一系列带正电荷的磺酰胺吡啶环上的芳基。分析了此处报道的新化合物对四种生理相关的碳酸酐酶（CA，EC 4.2.1.1）同工酶的抑制作用：胞质hCA I和II，膜锚定的bCA IV和与膜结合的，与肿瘤相关的同工酶hCA IX。它们显示出对所有研究的同功酶的有效抑制活性，尽管具有不同的特征。对于CA I，新衍生物显示出的抑制常数在3-12 nM范围内，对于CA II在0.20-5.96 nM范围内，对CA IV在2.0-10.3 nM范围内，和针对CA IX的范围分别为3-45 nM。这些新化合物由于具有类似盐的特性而不会渗透膜。还测试了其中一些衍生物对Cl（-）/ HCO（3）（-）阴离子交换剂AE1的抑制活性：两种衍生物在低微摩尔范围内显示
• Carbonic anhydrase inhibitors — Part 53. Synthesis of substituted-pyridinium derivatives of aromatic sulfonamides: The first non-polymeric membrane-impermeable inhibitors with selectivity for isozyme IV
  作者：Claudiu T. Supuran、Andrea Scozzafava、Marc A. Ilies、Bogdan Iorga、Teodora Cristea、Fabrizio Briganti、Filip Chiraleu、Mircea D. Banciu

  DOI：10.1016/s0223-5234(98)80017-2

  日期：1998.7

  Reaction of three aromatic sulfonamides containing a free amino group, i.e., sulfanilamide, homosulfanilamide and 4-(2-aminoethyl)-benzenesulfonamide with di-, tri- or tetra-substituted pyrylium salts afforded three series of cationic sulfonamides, containing a large variety of moieties substituting the pyridinium ring. The new derivatives were assayed as inhibitors of three carbonic anhydrase (CA) isozymes, CA I, II (cytosolic forms) and IV (membrane-bound form). Efficient inhibition was observed against all three isozymes, but due to the cationic nature of these inhibitors, in vivo and ex vivo experiments showed that only CA IV is selectively inhibited to a high degree, without affecting the cytosolic isozymes, present in appreciable concentrations in the experimental model used. This is the first example of selective in vivo inhibition of only one physiologically relevant CA isozyme with non-polymeric inhibitors and might lead to more selective drugs from this class of pharmacological agents. (C) Elsevier, Paris.
• Dimroth,K. et al., Tetrahedron, Supplement, 1964, vol. 6, p. 361 - 381
  作者：Dimroth,K. et al.

  DOI：——

  日期：——
• Carbonic anhydrase activators. Part 17. Synthesis and activation study of a series of 1-(1,2,4-triazole-(1H)-3-yl)-2,4,6-trisubstituted-pyridinium salts against isozymes I, II and IV
  作者：MA Ilies、MD Banciu、M Ilies、F Chiraleu、F Briganti、A Scozzafava、CT Supuran

  DOI：10.1016/s0223-5234(97)82777-8

  日期：1997.11

  A series of pyridinium salts were prepared by reaction of 3-amino-(1H)-1,2,4-triazole with 2,4,6-trisubatituted pyrylium salts. The new compounds have been characterized by standard procedures and were assayed for their interaction with three carbonic anhydrase (CA) isozymes, the cytosolic CA I and CA II, as well as the membrane-bound CA IV. The pyridinium salts activate the three isozymes in a different manner, with CA IV being the most susceptible to activation, followed by CA I, whereas CA II is the least sensitive to this class of activators. Compounds possessing 2,6-dialkyl-4-phenyl substituents at the pyridinium ring were the most effective activators. This is the first study of comparative activation for several CA isozymes, proving that activators, similarly to inhibitors possess isozyme-specificity.