• DNDi logo
  • Our work
    • Diseases
      • Sleeping sickness
      • Visceral leishmaniasis
      • Cutaneous leishmaniasis
      • Chagas disease
      • Filaria: river blindness
      • Mycetoma
      • Paediatric HIV
      • Cryptococcal meningitis
      • Hepatitis C
      • Dengue
      • COVID-19
      • Antimicrobial resistance
    • Research & development
      • R&D portfolio & list of projects
      • Drug discovery
      • Translational research
      • Clinical trials
      • Registration & access
      • Treatments delivered
    • Advocacy
      • Open and collaborative R&D
      • Transparency of R&D costs
      • Pro-access policies
  • Networks & partners
    • Partnerships
      • Our partners
      • Partnering with us
    • Global networks
      • Chagas Platform
      • HAT Platform
      • HELP Helminth Elimination Platform
      • LEAP Platform
      • redeLEISH Network
    • DNDi worldwide
      • DNDi Global Headquarters
      • DNDi DRC
      • DNDi East Africa
      • DNDi Japan
      • DNDi Latin America
      • DNDi North America
      • DNDi South Asia
      • DNDi South-East Asia
      • DNDi Southern Africa
  • News & resources
    • News & stories
      • News
      • Stories
      • Statements
      • Viewpoints
      • Social media
      • eNews Newsletter
    • Press
      • Press releases
      • In the media
    • Resources
      • Scientific articles
      • Our publications
      • Videos
    • Events
  • About us
    • About
      • Who we are
      • How we work
      • Our strategy
      • Our donors
      • Annual reports
    • Our people
      • Our leadership
      • Our governance
      • Contact us
    • Work with us
      • Working at DNDi
      • Job opportunities
      • Requests for proposal
  • Donate
DNDi logo
  • DNDi logo
  • Our work
    • Diseases
      • Sleeping sickness
      • Visceral leishmaniasis
      • Cutaneous leishmaniasis
      • Chagas disease
      • Filaria: river blindness
      • Mycetoma
      • Paediatric HIV
      • Cryptococcal meningitis
      • Hepatitis C
      • Dengue
      • COVID-19
      • Antimicrobial resistance
    • Research & development
      • R&D portfolio & list of projects
      • Drug discovery
      • Translational research
      • Clinical trials
      • Registration & access
      • Treatments delivered
    • Advocacy
      • Open and collaborative R&D
      • Transparency of R&D costs
      • Pro-access policies
  • Networks & partners
    • Partnerships
      • Our partners
      • Partnering with us
    • Global networks
      • Chagas Platform
      • HAT Platform
      • HELP Helminth Elimination Platform
      • LEAP Platform
      • redeLEISH Network
    • DNDi worldwide
      • DNDi Global Headquarters
      • DNDi DRC
      • DNDi East Africa
      • DNDi Japan
      • DNDi Latin America
      • DNDi North America
      • DNDi South Asia
      • DNDi South-East Asia
      • DNDi Southern Africa
  • News & resources
    • News & stories
      • News
      • Stories
      • Statements
      • Viewpoints
      • Social media
      • eNews Newsletter
    • Press
      • Press releases
      • In the media
    • Resources
      • Scientific articles
      • Our publications
      • Videos
    • Events
  • About us
    • About
      • Who we are
      • How we work
      • Our strategy
      • Our donors
      • Annual reports
    • Our people
      • Our leadership
      • Our governance
      • Contact us
    • Work with us
      • Working at DNDi
      • Job opportunities
      • Requests for proposal
  • Donate
Home > Scientific articles
Jan 2021
Share on twitter
Share on facebook
Share on linkedin
Share on email
Share on print

Novel linker variants of antileishmanial/antitubercular 7-substituted 2-nitroimidazooxazines offer enhanced solubility

ACS Medicinal Chemistry Letters

by Thompson AM, O’Connor PD, Yardley V, Maes L, Launay D, Braillard S, Chatelain E, Wan B, Franzblau SG, Ma Z, Cooper CB, Denny WA. ACS Medicinal Chemistry Letters 2021, 12, 2, 275–281. doi: 10.1021/acsmedchemlett.0c00649

Summary: Antitubercular 7-substituted 2-nitroimidazo[2,1-b][1,3]oxazines were previously shown to exhibit potent antileishmanial and antitrypanosomal activities, and lead optimization culminated in a new clinical investigational drug for visceral leishmaniasis: DNDI-0690. Given the high attrition rate for small molecules in clinical development, this study aimed to discover novel backup candidates with divergent candidate profiles, especially analogues possessing greater aqueous solubility. 32 analogues were prepared, including an O-carbamate which had the best balance of increased solubility, suitable metabolic stability, excellent oral bioavailability (100%), and strong in vivo efficacy in a visceral leishmaniasis mouse model (97% parasite load reduction at 25 mg/kg).

access the article
Visceral leishmaniasis

Latest scientific articles

Loading...
Scientific articles
14 Apr 2022

Understanding individual motivations among members of online communities

Les Cahiers du Numérique
Scientific articles
15 Mar 2022

Development and introduction of fexinidazole into the Global Human African Trypanosomiasis Program

The American Journal of Tropical Medicine and Hygiene
Scientific articles
14 Mar 2022

The pandemic response box ─ accelerating drug discovery efforts after disease outbreaks

ACS Infectious Diseases
Scientific articles
10 Mar 2022

Drug development for the treatment of onchocerciasis: Population pharmacokinetic and adverse events modeling of emodepside

PLOS Neglected Tropical Diseases
VIEW ALL

Stay connected

Get our latest news, personal stories, research articles, and job opportunities. 

DNDi logo
Facebook-f
Twitter
Instagram
Linkedin-in
Youtube
International non-profit developing safe, effective, and affordable treatments for the most neglected patients.

Learn more

  • Diseases
  • R&D portfolio
  • Policy advocacy

Get in touch

  • Our offices
  • Contact us
  • Integrity Line

Support us

  • Donate
  • Subscribe to eNews

Work with us

  • Join research networks
  • Jobs
  • RFPs
  • Terms of Use   
  •   Acceptable Use Policy   
  •   Privacy Policy   
  •   Cookie Policy   
  •   Our policies   

  • Except for images, films and trademarks which are subject to DNDi’s Terms of Use, content on this site is licensed under a Creative Commons Attribution-NonCommercial-Share Alike 3.0 Switzerland License