Salomen, L. M., Ellermann, M. & Diederich, F. Aromatic rings in chemical and biological recognition: energetics and structures. Angew. Chem. Int. Edn 50, 4808–4842 (2011).
Google Scholar
Locke, G. M., Bernhard, S. S. R. & Senge, M. O. Nonconjugated hydrocarbons as rigid‐linear motifs: isosteres for material sciences and bioorganic and medicinal chemistry. Chem. Eur. J. 25, 4590–4647 (2019).CAS
PubMed
Google Scholar
Nishihara, Y. (ed.) Applied Cross-Coupling Reactions Vol. 80 (Springer, 2013).Dalvie, D., Nair, S., Kang, P. & Loi., C.-M. in Metabolism, Pharmacokinetics and Toxicity of Functional Groups (ed. Smith, D. A.) 275–327 (Royal Society of Chemistry, 2010).Lovering, F., Bikker, J. & Humblet, C. Escape from flatland: increasing saturation as an approach to improving clinical success. J. Med. Chem. 52, 6752–6756 (2009).CAS
PubMed
Google Scholar
Ritchie, T. J. & Macdonald, S. F. J. The impact of aromatic ring count on compound developability—are too many aromatic rings a liability in drug design? Drug Discov. Today 14, 1011–1020 (2009).CAS
PubMed
Google Scholar
Lovering, F. Escape from Flatland 2: complexity and promiscuity. Med. Chem. Commun. 4, 515–519 (2013).CAS
Google Scholar
Mykhailiuk, P. K. Saturated bioisosteres of benzene: where to go next? Org. Biomol. Chem. 17, 2839–2849 (2019).CAS
PubMed
Google Scholar
Stepan, F. F. et al. Application of the bicyclo[1.1.1]pentane motif as a nonclassical phenyl ring bioisostere in the design of a potent and orally active γ-secretase inhibitor. J. Med. Chem. 55, 3414–3424 (2012).CAS
PubMed
Google Scholar
Frank, N. et al. Synthesis of meta-substituted arene bioisosteres from [3.1.1]propellane. Nature 611, 721–726 (2022).ADS
CAS
PubMed
Google Scholar
Iida, T. et al. Practical and facile access to bicyclo[3.1.1]heptanes: potent bioisosteres of meta-substituted benzenes. J. Am. Chem. Soc. 144, 21848–21852 (2022).CAS
PubMed
Google Scholar
Wiesenfeldt, M. P. et al. General access to cubanes as benzene bioisosteres. Nature 618, 513–518 (2023).ADS
CAS
PubMed
PubMed Central
Google Scholar
Kazi, N., Aublette, M. C., Allinson, S. L. & Coote, S. C. A practical synthesis of 1,3-disubstituted cubane derivatives. Chem. Commun. 59, 7971–7973 (2023).CAS
Google Scholar
Yang, Y. et al. An intramolecular coupling approach to alkyl bioisosteres for the synthesis of multisubstituted bicycloalkyl boronates. Nat. Chem. 13, 950–955 (2021).CAS
PubMed
PubMed Central
Google Scholar
Rigotti, T. & Bach, T. Bicyclo[2.1.1]hexanes by visible light-driven intramolecular crossed [2 + 2] photocycloadditions. Org. Lett. 24, 8821–8825 (2022).CAS
PubMed
Google Scholar
Levterov, V. V., Panasyuk, Y., Pivnytska, V. O. & Mykhailiuk, P. K. Water‐soluble non‐classical benzene mimetics. Angew. Chem. Int. Edn 59, 7161–7167 (2020).CAS
Google Scholar
Levterov, V. V. et al. 2‐Oxabicyclo[2.1.1]hexanes: synthesis, properties, and validation as bioisosteres of ortho‐ and meta‐benzenes. Angew. Chem. Int. Edn 63, e202319831 (2024).CAS
Google Scholar
Zhao, J.-X. et al. 1,2-Difunctionalized bicyclo[1.1.1]pentanes: long–sought-after mimetics for ortho/meta-substituted arenes. Proc. Natl Acad. Sci. USA 118, e2108881118 (2021).CAS
PubMed
PubMed Central
Google Scholar
Epplin, R. C. et al. [2]-Ladderanes as isosteres for meta-substituted aromatic rings and rigidified cyclohexanes. Nat. Commun. 13, 6056 (2022).ADS
CAS
PubMed
PubMed Central
Google Scholar
Smith, E. et al. Silver(I)-catalyzed synthesis of cuneanes from cubanes and their investigation as isosteres. J. Am. Chem. Soc. 145, 16365–16373 (2023).CAS
PubMed
PubMed Central
Google Scholar
Son, J.-Y. et al. Exploring cuneanes as potential benzene isosteres and energetic materials: scope and mechanistic investigations into regioselective rearrangements from cubanes. J. Am. Chem. Soc. 145, 16355–16364 (2023).CAS
PubMed
PubMed Central
Google Scholar
Fujiwara, K. et al. Biological evaluation of isosteric applicability of 1,3-substituted cuneanes as m-substituted benzenes enabled by selective isomerization of 1,4-substituted cubanes. Chem. Eur. J. 30, e202303548 (2023).
Google Scholar
Nguyen, L. A., He, H. & Pham-Huy, C. Chiral drugs: an overview. Int. J. Biomed. Sci. 2, 85–100 (2006).CAS
PubMed
PubMed Central
Google Scholar
de Groot, C. O. et al. A cell biologist’s field guide to aurora kinase inhibitors. Front. Oncol. 5, 285 (2015).PubMed
PubMed Central
Google Scholar
Lake, E. W. et al. Quantitative conformational profiling of kinase inhibitors reveals origins of selectivity for Aurora kinase activation states. Proc. Natl Acad. Sci. USA 115, E11894–E11903 (2018).ADS
CAS
PubMed
PubMed Central
Google Scholar
Martin, H.-D. & Mayer, B. Proximity effects in organic chemistry—the photoelectron spectroscopic investigation of non-bonding and transannular interactions. Angew. Chem. Int. Edn 22, 283–314 (1983).
Google Scholar
Houk, K. N. et al. Ionization potentials, electron affinities, and molecular orbitals of 2-substituted norbornadienes. Theory of 1,2 and homo-1,4 carbene cycloaddition selectivities. J. Am. Chem. Soc. 105, 5563–5569 (1983).CAS
Google Scholar
Winstein, S. & Shatavsky, M. 2,6-Homoconjugate addition to bicycloheptadiene. Chem. Ind. 1956, 56–57 (1956).
Google Scholar
Matteson, D. S. & Waldbillig, J. O. A preferred inversion in an electrophilic displacement: mercurideboronation of exo- and endo-5-norbornene-2-boronic acids. J. Am. Chem. Soc. 85, 1019–1020 (1963).CAS
Google Scholar
Tang, W. et al. Efficient monophosphorus ligands for palladium-catalyzed Miyaura borylation. Org. Lett. 13, 1366–1369 (2011).CAS
PubMed
Google Scholar
Liang, H. & Morken, J. P. Stereospecific transformations of alkylboronic esters enabled by direct boron-to-zinc transmetalation. J. Am. Chem. Soc. 145, 9976–9981 (2023).CAS
PubMed
PubMed Central
Google Scholar
Xu, N., Liang, H. & Morken, J. P. Copper-catalyzed stereospecific transformations of alkylboronic esters. J. Am. Chem. Soc. 144, 11546–11552 (2022).CAS
PubMed
PubMed Central
Google Scholar
Mlynarski, S. N., Karns, A. S. & Morken, J. P. Direct stereospecific amination of alkyl and aryl pinacol boronates. J. Am. Chem. Soc. 134, 16449–16451 (2012).CAS
PubMed
PubMed Central
Google Scholar
Sadhu, K. M. & Matteson, D. S. (Chloromethyl)lithium: efficient generation and capture by boronic esters and a simple preparation of diisopropyl (chloromethyl)boronate. Organometallics 4, 1687–1689 (1985).CAS
Google Scholar
Xu, N., Kong, Z., Wang, J. Z., Lovinger, G. J. & Morken, J. P. Copper-catalyzed coupling of alkyl vicinal bis(boronic esters) to an array of electrophiles. J. Am. Chem. Soc. 144, 17815–17823 (2022).CAS
PubMed
PubMed Central
Google Scholar
Zhang, M., Lee, P. S., Allais, C., Singer, R. A. & Morken, J. P. Desymmetrization of vicinal bis(boronic) esters by enantioselective Suzuki–Miyaura cross-coupling reaction. J. Am. Chem. Soc. 145, 8308–8313 (2023).CAS
Google Scholar
Chen, C., Hou, L., Cheng, M., Su, J. & Tong, X. Palladium(0)‐catalyzed iminohalogenation of alkenes: synthesis of 2‐halomethyl dihydropyrroles and mechanistic insights into the alkyl halide bond formation. Angew. Chem. Int. Edn 54, 3092–3096 (2015).CAS
Google Scholar
Chen, X. et al. Pd(0)-catalyzed asymmetric carbohalogenation: H-bonding-driven C(sp3)–halogen reductive elimination under mild conditions. J. Am. Chem. Soc. 143, 1924–1931 (2021).CAS
PubMed
Google Scholar
McDonald, R. I., Liu, G. & Stahl, S. S. Palladium(II)-catalyzed alkene functionalization via nucleopalladation: stereochemical pathways and enantioselective catalytic applications. Chem. Rev. 111, 2981–3019 (2011).CAS
PubMed
PubMed Central
Google Scholar
Saunders, M., Laidig, K. E. & Wolfsberg, M. Theoretical calculation of equilibrium isotope effects using ab initio force constants: application to NMR isotope perturbation studies. J. Am. Chem. Soc. 111, 8989–8994 (1989).CAS
Google Scholar
Franz, D. E., Singleton, D. A. & Snyder, J. P. 13C kinetic isotope effects for the addition of lithium dibutylcuprate to cyclohexenone. Reductive elimination is rate-determining. J. Am. Chem. Soc. 119, 3383–3384 (1997).
Google Scholar
Kathuria, S. et al. Modulation of anxiety through blockade of anandamide hydrolysis. Nat. Med. 9, 76–81 (2003).CAS
PubMed
Google Scholar
Piomelli, D. et al. Pharmacological profile of the selective FAAH inhibitor KDS‐4103 (URB597). CNS Drug Rev. 12, 21–38 (2006).CAS
PubMed
PubMed Central
Google Scholar
Van Esbroeck, A. C. M. et al. Activity-based protein profiling reveals off-target proteins of the FAAH inhibitor BIA 10-2474. Science 356, 1084–1087 (2017).ADS
PubMed
PubMed Central
Google Scholar
Chen, J. K. I only have eye for ewe: the discovery of cyclopamine and development of Hedgehog pathway-targeting drugs. Nat. Prod. Rep. 33, 595–601 (2016).CAS
PubMed
PubMed Central
Google Scholar
Pan, S. et al. Discovery of NVP-LDE225, a potent and selective smoothened antagonist. ACS Med. Chem. Lett. 1, 130–134 (2010).CAS
PubMed
PubMed Central
Google Scholar
Taipale, J. et al. Effects of oncogenic mutations in Smoothened and Patched can be reversed by cyclopamine. Nature 406, 1005–1009 (2000).ADS
CAS
PubMed
Google Scholar
Jain, N. & Yalkowsky, S. H. Estimation of the aqueous solubility I: application to organic nonelectrolytes. J. Pharm. Sci. 90, 234–252 (2001).CAS
PubMed
Google Scholar
Nicolaou, K. C. et al. Synthesis and biopharmaceutical evaluation of imatinib analogues featuring unusual structural motifs. ChemMedChem 11, 31–37 (2016).CAS
PubMed
Google Scholar
Perez-Riverol, Y. et al. The PRIDE database resources in 2022: a hub for mass spectrometry-based proteomics evidences. Nucleic Acids Res. 50, D543–D552 (2022).CAS
PubMed
Google Scholar