Macozinone: Revised synthesis and crystal structure of a promising new drug for treating drug-sensitive and drug-resistant tuberculosis

Gang Zhang, Courtney Aldrich

Research output: Contribution to journalArticle

Abstract

Mycobacterium tuberculosis (Mtb), the principal etiological agent of tuberculosis (TB), infects over one-quarter of humanity and is now the leading cause of infectious disease mortality by a single pathogen. Macozinone {2-[4-(cyclohexylmethyl)piperazin-1-yl]-8-nitro-6-(trifluorometh yl)-4H-1,3-benzo thia zin-4-one, C20H23F3N4O3S} is a promising new drug for treating drug-sensitive and drug-resistant TB that has successfully completed phase I clinical trials. We report the complete spectroscopic and structural characterization by 1H NMR, 13C NMR, HRMS, IR, and X-ray crystallography. The cyclo hexyl moiety is observed to be nearly perpendicular to the core formed by the 1,3-benzo thia zin-4-one and piperazine groups. The central piperazine ring adopts a slightly distorted chair conformation caused by sp 2-hybridization of the nitro N atom, which donates into the electron-deficient 1,3-benzo thia zin-4-one group.

Original languageEnglish (US)
Pages (from-to)1031-1035
Number of pages5
JournalActa Crystallographica Section C: Structural Chemistry
Volume75
DOIs
StatePublished - Aug 1 2019

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tuberculosis
drugs
Crystal structure
Nuclear magnetic resonance
crystal structure
X ray crystallography
Pathogens
synthesis
Pharmaceutical Preparations
Conformations
nuclear magnetic resonance
pathogens
mortality
infectious diseases
Atoms
seats
crystallography
Electrons
causes
rings

Keywords

  • Crystal structure
  • Drug resistant
  • Drug sensitive
  • Macozinone
  • Synthesis
  • Tuberculosis.

PubMed: MeSH publication types

  • Journal Article
  • Research Support, Non-U.S. Gov't
  • Video-Audio Media

Cite this

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abstract = "Mycobacterium tuberculosis (Mtb), the principal etiological agent of tuberculosis (TB), infects over one-quarter of humanity and is now the leading cause of infectious disease mortality by a single pathogen. Macozinone {2-[4-(cyclohexylmethyl)piperazin-1-yl]-8-nitro-6-(trifluorometh yl)-4H-1,3-benzo thia zin-4-one, C20H23F3N4O3S} is a promising new drug for treating drug-sensitive and drug-resistant TB that has successfully completed phase I clinical trials. We report the complete spectroscopic and structural characterization by 1H NMR, 13C NMR, HRMS, IR, and X-ray crystallography. The cyclo hexyl moiety is observed to be nearly perpendicular to the core formed by the 1,3-benzo thia zin-4-one and piperazine groups. The central piperazine ring adopts a slightly distorted chair conformation caused by sp 2-hybridization of the nitro N atom, which donates into the electron-deficient 1,3-benzo thia zin-4-one group.",
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AU - Aldrich, Courtney

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N2 - Mycobacterium tuberculosis (Mtb), the principal etiological agent of tuberculosis (TB), infects over one-quarter of humanity and is now the leading cause of infectious disease mortality by a single pathogen. Macozinone {2-[4-(cyclohexylmethyl)piperazin-1-yl]-8-nitro-6-(trifluorometh yl)-4H-1,3-benzo thia zin-4-one, C20H23F3N4O3S} is a promising new drug for treating drug-sensitive and drug-resistant TB that has successfully completed phase I clinical trials. We report the complete spectroscopic and structural characterization by 1H NMR, 13C NMR, HRMS, IR, and X-ray crystallography. The cyclo hexyl moiety is observed to be nearly perpendicular to the core formed by the 1,3-benzo thia zin-4-one and piperazine groups. The central piperazine ring adopts a slightly distorted chair conformation caused by sp 2-hybridization of the nitro N atom, which donates into the electron-deficient 1,3-benzo thia zin-4-one group.

AB - Mycobacterium tuberculosis (Mtb), the principal etiological agent of tuberculosis (TB), infects over one-quarter of humanity and is now the leading cause of infectious disease mortality by a single pathogen. Macozinone {2-[4-(cyclohexylmethyl)piperazin-1-yl]-8-nitro-6-(trifluorometh yl)-4H-1,3-benzo thia zin-4-one, C20H23F3N4O3S} is a promising new drug for treating drug-sensitive and drug-resistant TB that has successfully completed phase I clinical trials. We report the complete spectroscopic and structural characterization by 1H NMR, 13C NMR, HRMS, IR, and X-ray crystallography. The cyclo hexyl moiety is observed to be nearly perpendicular to the core formed by the 1,3-benzo thia zin-4-one and piperazine groups. The central piperazine ring adopts a slightly distorted chair conformation caused by sp 2-hybridization of the nitro N atom, which donates into the electron-deficient 1,3-benzo thia zin-4-one group.

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