Coupling of acceptor-substituted diazo compounds and tertiary thioamides: synthesis of enamino carbonyl compounds and their pharmacological evaluation

Jim Secka; Arpan Pal; Francis A. Acquah; Blaine H. M. Mooers; Anand B. Karki; Dania Mahjoub; Mohamed K. Fakhr; David R. Wallace; Takuya Okada; Naoki Toyooka; Adama Kuta; Naga Koduri; Deacon Herndon; Kenneth P. Roberts; Zhiguo Wang; Bethany Hileman; Nisha Rajagopal; Syed R. Hussaini

doi:10.1039/D2RA02415B

Coupling of acceptor-substituted diazo compounds and tertiary thioamides: synthesis of enamino carbonyl compounds and their pharmacological evaluation†

Jim Secka,^a Arpan Pal,^a Francis A. Acquah,

^bcd Blaine H. M. Mooers,

^bcd Anand B. Karki,^e Dania Mahjoub,^e Mohamed K. Fakhr,^e David R. Wallace,^f Takuya Okada,^g Naoki Toyooka,^g Adama Kuta,^a Naga Koduri,^a Deacon Herndon,^a Kenneth P. Roberts,^a Zhiguo Wang,^a Bethany Hileman,^a Nisha Rajagopal^a and Syed R. Hussaini

^a

Author affiliations

^a Department of Chemistry and Biochemistry, The University of Tulsa, 800 S. Tucker Drive, Tulsa, Oklahoma 74104, USA
E-mail: syed-hussaini@utulsa.edu

^b Department of Biochemistry and Molecular Biology, University of Oklahoma of Health Sciences Center, Oklahoma City, OK 73104, Unites States

^c Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA

^d Laboratory of Biomolecular Structure and Function, University of Oklahoma of Health Sciences Center, Oklahoma City, OK 73104, USA

^e Department of Biological Science, The University of Tulsa, 800 S. Tucker Drive, Tulsa, Oklahoma 74104, USA

^f Department of Pharmacology and Physiology, Oklahoma State University Center for Health Sciences, Tulsa, Oklahoma 74107, USA

^g Faculty of Engineering, University of Toyama, 3190 Gofuku, Toyama, Japan

Abstract

This paper describes the synthesis of enamino carbonyl compounds by the copper(I)-catalyzed coupling of acceptor-substituted diazo compounds and tertiary thioamides. We plan to use this method to synthesize indolizidine (−)-237D analogs to find α6-selective antismoking agents. Therefore, we also performed in silico α6-nAchRs binding studies of selected products. Compounds with low root-mean-square deviation values showed more favorable binding free energies. We also report preliminary pharmacokinetic data on indolizidine (−)-237D and found it to have weak activity at CYP3A4. In addition, as enamino carbonyl compounds are also known for antimicrobial properties, we screened previously reported and new enamino carbonyl compounds for antibacterial, antimicrobial, and antifungal properties. Eleven compounds showed significant antimicrobial activities.

RSC Advances

Coupling of acceptor-substituted diazo compounds and tertiary thioamides: synthesis of enamino carbonyl compounds and their pharmacological evaluation†

Abstract

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Coupling of acceptor-substituted diazo compounds and tertiary thioamides: synthesis of enamino carbonyl compounds and their pharmacological evaluation

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