🔬 Introduction

Tipranavir is a non-peptidic HIV-1 protease inhibitor (PI), developed by Boehringer Ingelheim in the 1990s–2000s.
It was unique among PIs because it could remain active against many multi-drug–resistant HIV strains.

During preclinical development, several Tipranavir analogues were synthesized to explore:

• Better oral bioavailability
• Reduced liver toxicity
• Improved pharmacokinetics compared to parent Tipranavir

However, most analogues never advanced beyond early lab or preclinical stages, so detailed open-source information is very limited.

⚗️ Composition

• Chemical class: Diarylpyrone derivatives (non-peptidic)
• Core structure: Similar to Tipranavir, analogues carried modifications on:
  • Hydroxyl groups (to change binding affinity)
  • Aromatic rings (to alter resistance profile)
  • Side-chain substitutions (to tweak solubility and bioavailability)
• Exact analogue formulas are mostly reported in patents and chemistry journals, not public databases.

💊 Uses (Intended / Investigational)

• Primary purpose: Treatment of HIV-1 infection in patients resistant to multiple protease inhibitors.
• Goal of analogues:
  • Maintain or improve antiviral activity against resistant HIV strains.
  • Reduce hepatic toxicity and improve tolerability (Tipranavir itself had significant liver risk).
  • Possibly combine better with ritonavir boosting.

Most analogues were research-only and never entered clinical use.

⚠️ Side Effects (Expected / Observed in Related Compounds)

Since detailed human trials weren’t done for most analogues, side-effect data are extrapolated from Tipranavir itself:

Common (Tipranavir):

• Nausea, vomiting, diarrhea
• Headache, fatigue
• Abdominal pain

Serious:

• Hepatotoxicity (boxed warning)
• Intracranial hemorrhage (rare but reported)
• Drug–drug interactions via CYP3A4 metabolism

For analogues:

• Animal studies suggested less hepatotoxicity for some, but no robust human data exist.
• None progressed to market, so clinical safety profiles remain unknown.

✅ In short:
Tipranavir analogues were experimental protease inhibitors designed to overcome HIV drug resistance with fewer side effects, but they largely remained in preclinical research. Information is scarce because they never reached approval or widespread clinical testing.