Modification of Boc-Protected CAN508 via Acylation and Suzuki-Miyaura Coupling
Language English Country Switzerland Media electronic
Document type Journal Article
PubMed
29329219
PubMed Central
PMC6017724
DOI
10.3390/molecules23010149
PII: molecules23010149
Knihovny.cz E-resources
- Keywords
- Boc-protection, CDK inhibitor, Suzuki-Miyaura reaction, XPhos Pd G2, acylation, pyrazole,
- MeSH
- Acylation MeSH
- Azo Compounds chemistry MeSH
- Hydrolysis MeSH
- Protein Kinase Inhibitors chemistry MeSH
- Catalysis MeSH
- Molecular Structure MeSH
- Palladium chemistry MeSH
- Pyrazoles chemistry MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Azo Compounds MeSH
- CAN 508 MeSH Browser
- Protein Kinase Inhibitors MeSH
- Palladium MeSH
- Pyrazoles MeSH
The cyclin-dependent kinase inhibitor, CAN508, was protected with di-tert-butyl dicarbonate to access the amino-benzoylated pyrazoles. The bromo derivatives were further arylated by Suzuki-Miyaura coupling using the XPhos Pd G2 pre-catalyst. The coupling reaction provided generally the para-substituted benzoylpyrazoles in the higher yields than the meta-substituted ones. The Boc groups were only utilized as directing functionalities for the benzoylation step and were hydrolyzed under conditions of Suzuki-Miyaura coupling, which allowed for elimination of the additional deprotection step.
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Schütznerová E., Popa I., Kryštof V., Koshino H., Trávníček Z., Hradil P., Cankař P. Utilization of DmbNHNH2 in the synthesis of amino-substituted 4-((3,5-diamino-1H-pyrazol-4-yl)diazenyl)phenols. Tetrahedron. 2012;68:3996–4002. doi: 10.1016/j.tet.2012.03.063. DOI
Whittaker S.R., Mallinger A., Workman P., Clarke P.A. Inhibitors of cyclin-dependent kinases as cancer therapeutics. Pharmacol. Ther. 2017;173:83–105. doi: 10.1016/j.pharmthera.2017.02.008. PubMed DOI PMC
Sherr C.J., Beach D., Shapiro G.I. Targeting CDK4 and CDK6: From Discovery to Therapy. Cancer Discov. 2016;6:353–367. doi: 10.1158/2159-8290.CD-15-0894. PubMed DOI PMC
Kryštof V., Cankař P., Fryšová I., Slouka J., Kontopidis G., Džubák P., Hajduch M., Srovnal J., de Azevedo W.F., Jr., Orság X.M., et al. 4-Arylazo-3,5-diamino-1H-pyrazole CDK Inhibitors: SAR Study, Crystal Structure in Complex with CDK2, Selectivity, and Cellular Effects. J. Med. Chem. 2006;49:6500–6509. doi: 10.1021/jm0605740. PubMed DOI
Eskildsen J., Kristensen J., Vedso P., Begtrup M. Convergent Synthesis of 3-Arylated 1-Hydroxypyrazoles via 3-Metalated Pyrazole-1-oxides. J. Org. Chem. 2001;66:8654–8656. doi: 10.1021/jo015874y. PubMed DOI
Rzepecki P., Wehner M., Molt O., Zadmard R., Harms K., Schrader T. Aminopyrazole Oligomers for β-SheetStabilization of Peptides. Synthesis. 2003:1815–1826. doi: 10.1055/s-2003-41031. DOI
Subramanyam C. 4-Methoxybenzyl (PMB), a Versatile Protecting Group for the Regiospecific Lithiation and Functionalization of Pyrazoles. Synth. Commun. 1995;25:761–774. doi: 10.1080/00397919508011414. DOI
Eller G.A., Holzer W. The 4-Methoxybenzyl (PMB) Function as a Versatile Protecting Group in the Synthesis of N-Unsubstituted Pyrazolones. Heterocycles. 2004;63:2537–2555. doi: 10.1002/chin.200515113. DOI
Jarowicki K., Kocienski P.J. Protecting Groups. Chem. Soc. Perkin Trans. 1. 2001;18:2109–2135. doi: 10.1039/b103282h. DOI
Richters A., Basu D., Engel J., Ercanoglu M.S., Balke-Want H., Tesch R., Thomas R.K., Rauh D. Identification and Further Development of Potent TBK1 Inhibitors. ACS Chem. Biol. 2015;10:289–298. doi: 10.1021/cb500908d. PubMed DOI
Honma T., Yoshizumi T., Hashimoto N., Hayashi K., Kawanishi N., Fukasawa K., Takaki T., Ikeura C., Ikuta M., Suzuki-Takahashi I., et al. A Novel Approach for the Development of Selective Cdk4 Inhibitors: Library Design Based on Locations of Cdk4 Specific Amino Acid Residues. J. Med. Chem. 2001;44:4628–4640. doi: 10.1021/jm010326y. PubMed DOI
Pevarello P., Brasca M.G., Orsini P., Traquandi G., Longo A., Nesi M., Orzi F., Piutti C., Sansonna P., Varasi M., et al. 3-Aminopyrazole Inhibitors of CDK2/Cyclin A as Antitumor Agents. 2. Lead Optimization. J. Med. Chem. 2005;48:2944–2956. doi: 10.1021/jm0408870. PubMed DOI
Halland N., Schmidt F., Weiss T., Saas J., Li Z., Czech J., Dreyer M., Hofmeister A., Mertsch K., Dietz U., et al. Discovery of N-[4-(1H-Pyrazolo[3,4-b]pyrazin-6-yl)-phenyl]-sulfonamides as Highly Active and Selective SGK1 Inhibitors. ACS Med. Chem. Lett. 2015;6:73–78. doi: 10.1021/ml5003376. PubMed DOI PMC
Puello J.Q., Obando B.I., Forces-Forces C., Infantes L., Claramunt R.M., Cabildo P., Jimenez J.A., Elguero J. Structure and Tautomerism of 3-Amino-5-arylpyrazoles in the Solid State and in Solution: An X-Ray and NMR Study. Tetrahedron. 1997;53:10783–10802. doi: 10.1016/S0040-4020(97)00678-9. DOI
Seelen W., Schafer M., Ernst A. Selective ring N-protection of aminopyrazoles. Tetrahedron Lett. 2003;44:4491–4493. doi: 10.1016/S0040-4039(03)00988-2. DOI
Kusakiewicz-Dawid A., Gorecki L., Masiukiewicz E., Rzeszotarska B. Susceptibility of Methyl 3-Amino-1H-pyrazole-5-carboxylate to Acylation. Synth. Commun. 2009;39:4122–4132. doi: 10.1080/00397910902898536. DOI
Brinkmeyer R.S., Terando N.H. Dimerization of pyrazolyl-5-hydroxypyrrolidinones to tetrazocines. J. Heterocycl. Chem. 1989;26:1713–1717. doi: 10.1002/jhet.5570260636. DOI
Orsini P., Traquandi G., Sansonna P., Pevarello P. 3-Acylaminopyrazole derivatives via a regioselectively N-protected 3-nitropyrazole. Tetrahedron Lett. 2005;46:933–935. doi: 10.1016/j.tetlet.2004.12.054. DOI
Miyaura N., Suzuki A. Palladium-Catalyzed Cross-Coupling Reactions of Organoboron Compounds. Chem. Rev. 1995;95:2457–2483. doi: 10.1021/cr00039a007. DOI
Jedinák L., Zátopková R., Zemánková H., Šustková A., Cankař P. The Suzuki–Miyaura Cross-Coupling Reaction of Halogenated Aminopyrazoles: Method Development, Scope, and Mechanism of Dehalogenation Side Reaction. J. Org. Chem. 2017;82:157–169. doi: 10.1021/acs.joc.6b02306. PubMed DOI
Jedinák L., Cankař P. 4-Arylation of N-Acylamino- and Aminopyrazoles by the Suzuki–Miyaura Cross-Coupling Reaction. Eur. J. Org. Chem. 2016:2013–2023. doi: 10.1002/ejoc.201600072. PubMed DOI
Zou M.F., Cao J., Rodriguez A.L., Conn P.J., Newman A.H. Design and synthesis of substituted N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamides as positive allosteric modulators of the metabotropic glutamate receptor subtype 5. Bioorg. Med. Chem. Lett. 2011;21:2650–2654. doi: 10.1016/j.bmcl.2010.12.110. PubMed DOI PMC
Martin R., Buchwald S.L. Palladium-Catalyzed Suzuki-Miyaura Cross-Coupling Reactions Employing Dialkylbiaryl Phosphine Ligands. Acc. Chem. Res. 2008;41:1461–1473. doi: 10.1021/ar800036s. PubMed DOI PMC
Bruneau A., Roche M., Alami M., Messaoudi S. 2-Aminobiphenyl Palladacycles: The “Most Powerful” Precatalysts in C−C and C−Heteroatom Cross-Couplings. ACS Catal. 2015;5:1386–1396. doi: 10.1021/cs502011x. DOI
Shi S., Meng G., Szostak M. Synthesis of Biaryls through Nickel-Catalyzed Suzuki–Miyaura Coupling of Amides by Carbon–Nitrogen Bond Cleavage. Angew. Chem. Int. Ed. 2016;55:6959–6963. doi: 10.1002/anie.201601914. PubMed DOI
Tomanová M., Jedinák L., Košař J., Kvapil L., Hradil P., Cankař P. Synthesis of 4-substituted pyrazole-3,5-diamines via Suzuki–Miyaura coupling and iron-catalyzed reduction. Org. Biomol. Chem. 2017;15:10200–10211. doi: 10.1039/C7OB02373A. PubMed DOI
Jorda R., Schütznerová E., Cankař P., Brychtová V., Navrátilová J., Kryštof V. Novel arylazopyrazole inhibitors of cyclin-dependent kinases. Bioorg. Med. Chem. 2015;23:1975–1981. doi: 10.1016/j.bmc.2015.03.025. PubMed DOI
Jorda R., Navrátilová J., Hušková Z., Schütznerová E., Cankař P., Strnad M., Kryštof V. Arylazopyrazole AAP1742 Inhibits CDKs and Induces Apoptosis in Multiple Myeloma Cells via Mcl-1 Downregulation. Chem. Biol. Drug Des. 2014;84:402–408. doi: 10.1111/cbdd.12330. PubMed DOI
Kryštof V., Rárová L., Liebl J., Zahler S., Jorda R., Voller J., Cankař P. The selective P-TEFb inhibitor CAN508 targets angiogenesis. Eur. J. Med. Chem. 2011;46:4289–4294. doi: 10.1016/j.ejmech.2011.06.035. PubMed DOI
Dufert M.A., Billingsley K.L., Buchwald S.L. Suzuki-Miyaura Cross-Coupling of Unprotected, Nitrogen-Rich Heterocycles: Substrate Scope and Mechanistic Investigation. J. Am. Chem. Soc. 2013;135:12877–12885. doi: 10.1021/ja4064469. PubMed DOI PMC