Exceptional reactivity of the bridgehead amine on bicyclo[1.1.1]pentane

被引：0

作者：

Lu, Yong ^{[1
]}

Chen, Chuo ^{[1
]}

机构：

[1] UT SouthWestern Med Ctr, Dept Biochem, 5323 Harry Hines Blvd, Dallas, TX 75390 USA

来源：

ARKIVOC | 2023年

关键词：

Bicyclo[1.1.1]pentane (BCP); bridgehead amine; steric hindrance; intrinsic nucleophilicity; POTENT; DISRUPTION; INHIBITORS; DISCOVERY;

D O I：

10.24820/ark.5550190.p012.003

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

Bicyclo[1.1.1]pentane (BCP) has received substantial interest in the field of synthetic chemistry recently for its potential use as a benzene isostere in medicinal chemistry. Whereas bicyclo[2.2.2]octane (BCO) has also been used as a bioisostere of benzene, the condensation of BCP-amine with nadic anhydride is significantly easier than that of BCO-amine. Analyses of the geometries and the frontier molecular orbitals of these amines suggest that the low steric hindrance and high intrinsic nucleophilicity of BCP-amine together contribute to its exceptional reactivity. [GRAPHICS] .

引用

页数：8

共 32 条

[1] Discovery of 4-((3′R,4′S,5′R)-6"-Chloro-4′-(3-chloro-2-fluorophenyl)-1′-ethyl-2"-oxodispiro[cyclohexane-1,2′-pyrrolidine-3′,3"-indoline]-5′-carboxamido)bicyclo[2.2.2]octane-1-carboxylic Acid (AA-115/APG-115): A Potent and Orally Active Murine Double Minute 2 (MDM2) Inhibitor in Clinical Development [J].

Aguilar, Angelo ;

Lu, Jianfeng ;

Liu, Liu ;

Du, Ding ;

Bernard, Denzil ;

McEachern, Donna ;

Przybranowski, Sally ;

Li, Xiaoqin ;

Luo, Ruijuan ;

Wen, Bo ;

Sun, Duxin ;

Wang, Hengbang ;

Wen, Jianfeng ;

Wang, Guangfeng ;

Zhai, Yifan ;

Guo, Ming ;

Yang, Dajun ;

Wang, Shaomeng .

JOURNAL OF MEDICINAL CHEMISTRY, 2017, 60 (07) :2819-2839

[2] Bridge Functionalisation of Bicyclo[1.1.1]pentane Derivatives [J].

Anderson, Joseph M. ;

Measom, Nicholas D. ;

Murphy, John A. ;

Poole, Darren L. .

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2021, 60 (47) :24754-24769

[3] POLAR SUBSTITUENT EFFECTS IN 1,3-DISUBSTITUTED BICYCLO[1.1.1]PENTANES [J].

APPLEQUIST, DE ;

RENKEN, TL ;

WHEELER, JW .

JOURNAL OF ORGANIC CHEMISTRY, 1982, 47 (25) :4985-4995

[4] Improving Nonspecific Binding and Solubility: Bicycloalkyl Groups and Cubanes as para-Phenyl Bioisosteres [J].

Auberson, Yves P. ;

Brocklehurst, Cara ;

Furegati, Markus ;

Fessard, Thomas C. ;

Koch, Guido ;

Decker, Andrea ;

La Vecchia, Luigi ;

Briard, Emmanuelle .

CHEMMEDCHEM, 2017, 12 (08) :590-598

[5] Evaluation of selective inhibitors of 11β-HSD1 for the treatment of hypertension [J].

Bauman, David R. ;

Whitehead, Alan ;

Contino, Lisa C. ;

Cui, Jisong ;

Garcia-Calvo, Margarita ;

Gu, Xin ;

Kevin, Nancy ;

Ma, Xiuying ;

Pai, Lee-yuh ;

Shah, Kashmira ;

Shen, Xiaolan ;

Stribling, Sloan ;

Zokian, Hratch J. ;

Metzger, Joe ;

Shevell, Diane E. ;

Waddell, Sherman T. .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2013, 23 (12) :3650-3653

[6] Discovery of a Potent, Selective, and Orally Efficacious Pyrimidinooxazinyl Bicyclooctaneacetic Acid Diacylglycerol Acyltransferase-1 Inhibitor [J].

Birch, Alan M. ;

Birtles, Susan ;

Buckett, Linda K. ;

Kemmitt, Paul D. ;

Smith, Graham J. ;

Smith, Tim J. D. ;

Turnbull, Andrew V. ;

Wang, Steven J. Y. .

JOURNAL OF MEDICINAL CHEMISTRY, 2009, 52 (06) :1558-1568

[7] Small molecule-mediated disruption of Wnt-dependent signaling in tissue regeneration and cancer [J].

Chen, Baozhi ;

Dodge, Michael E. ;

Tang, Wei ;

Lu, Jianming ;

Ma, Zhiqiang ;

Fan, Chih-Wei ;

Wei, Shuguang ;

Hao, Wayne ;

Kilgore, Jessica ;

Williams, Noelle S. ;

Roth, Michael G. ;

Amatruda, James F. ;

Chen, Chuo ;

Lum, Lawrence .

NATURE CHEMICAL BIOLOGY, 2009, 5 (02) :100-107

[8] Nucleophilic Reactivities of Primary and Secondary Amines in Acetonitrile [J].

Kanzian, Tanja ;

Nigst, Tobias A. ;

Maier, Andreas ;

Pichl, Stefan ;

Mayr, Herbert .

EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, 2009, 2009 (36) :6379-6385

[9] A PRACTICAL PHOTOCHEMICAL-SYNTHESIS OF BICYCLO[1.1.1]PENTANE-1,3-DICARBOXYLIC ACID [J].

KASZYNSKI, P ;

MICHL, J .

JOURNAL OF ORGANIC CHEMISTRY, 1988, 53 (19) :4593-4594

[10] Potent and orally bioavailable 8-bicyclo[2.2.2]octylxanthines as adenosine A1 receptor antagonists [J].

Kiesman, William F. ;

Zhao, Jin ;

Conlon, Patrick R. ;

Dowling, James E. ;

Petter, Russell C. ;

Lutterodt, Frank ;

Jin, Xiaowei ;

Smits, Glenn ;

Fure, Mary ;

Jayaraj, Andrew ;

Kim, John ;

Sullivan, Gail ;

Linden, Joel .

JOURNAL OF MEDICINAL CHEMISTRY, 2006, 49 (24) :7119-7131

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