Tipranavir uses and side effects
Table of Contents
🔬 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.
| # | Compound / Code | Structural Modification | Activity (Ki or IC₉₀) | Source |
|---|---|---|---|---|
| 1 | Compound I–VI (from J. Med. Chem. SAR series) | Variants of dihydropyrone scaffold with different sulfonamide and aryl substitutions | Compound VI (Tipranavir itself): Ki = 8 pM; IC₉₀ = 100 nM | Turner et al., J. Med. Chem. 1998 (ACS Publications) |
| 2 | Cycloalkylpyranones / Cycloalkyldihydropyrones | Ring-size modifications on the pyrone core (e.g., different cycloalkyl sizes) | Activity explored in SAR but exact numbers vary | Romines et al., J. Med. Chem. 1996 (PMC) |
| 3 | Tetronic-acid analogues (3-sulfonylanilido-tetronic acids) | Dihydropyrone core replaced with tetronic acid; varied substituents on sulfonylanilide | Structure-dependent anti-HIV activity reported (no specific values in summary) | Schobert et al., Tetrahedron 2008 (Wikipedia, Google Patents) |
| 4 | 1,3-Cyclohexanedione analogue | Core swapped to 1,3-cyclohexanedione ring; synthesized via Michael addition strategy | Ki ≈ 12 nM—“excellent HIV protease inhibition” | Ding et al., Letters in Organic Chemistry 2009 (EurekaSelect) |
| 5 | Boronic acid-containing analogues | Incorporate phenylboronate, benzoxaborole, or borono-pyridyl moieties in place of aryl sulfonamide headgroups | Specified as enhanced inhibitors; exact activity data not provided | US patent application on boronic acid inhibitors (2017) (Justia Patents) |
| 6 | Cycloalkyl-modified pyranones | Also noted in early SAR exploration alongside pyrone variants | SAR explored but detailed potencies not excerpted | Romines et al., J. Med. Chem. 1996 (PMC) |
Related Articles
Daruhaldi Sumbloo ke Tibbi Fawaid aur Istemaal
روایتی طور پر، سنبلو کو ہاضمے کے مسائل، جگر کے امراض، جلدی بیماریوں، بخار، سانس کے مسائل اور جسمانی توانائی بڑھانے کے لیے استعمال کیا جاتا ہے۔ اس کی جڑ اور چھال سب سے زیادہ کارآمد مانی جاتی ہیں۔ آیوروید میں اس کے ذائقے کو کڑوا، قابض اور گرم قرار دیا گیا ہے، اور اسے اکثر دیگر جڑی بوٹیوں کے ساتھ ملا کر استعمال کیا جاتا ہے۔
Sehat GuideBerberis aristata Benefits and Side Effects
Traditional use of B. aristata for liver disorders has some support from experimental models showing protective effects of berberine against chemically induced liver toxicity, improvement in markers of liver function, and reductions in oxidative stress and inflammation in hepatic tissue
Sehat Guide
Carbidopa kaam kaise karti hai
کاربی ڈوپا مونوہائیڈریٹ ایک اہم دوا ہے جو لیوو ڈوپا (Levodopa) کے ساتھ ملا کر پارکنسن کی بیماری اور دیگر پارکنسونی عوارض کے علاج کے لیے استعمال ہوتی ہے۔ یہ ایک خاص انزائم کو روکتی ہے جو دماغ تک پہنچنے سے پہلے لیوو ڈوپا کو ڈوپامین میں تبدیل کر دیتا ہے۔ یوں زیادہ مقدار میں لیوو ڈوپا دماغ میں پہنچتی ہے اور علامات بہتر ہوتی ہیں، ساتھ ہی متلی اور دیگر ضمنی اثرات بھی کم ہو جاتے ہیں۔ کاربی ڈوپا اکیلی استعمال نہیں کی جاتی کیونکہ یہ دماغ میں داخل نہیں ہو سکتی؛ اس کی اصل اہمیت لیوو ڈوپا کے اثر کو بڑھانے میں ہے۔
Sehat Guide