Product Number: P109000
English Name: Pretomanid
English Alias: (S)-2-nitro-6-((4-(trifluoromethoxy)benzyl)oxy)-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine
CAS Number: 187235-37-6
Molecular Formula: C₁₄H₁₂F₃N₃O₅
Molecular Weight: 359.26
Product Advantages：
High purity and controllable crystal form：HPLC purity ≥99.5%, with crystal form consistency confirmed by XRD (X-ray diffraction), meeting the strict quality requirements of WHO and FDA for new drug APIs.
Outstanding stability：Purity decrease <1% after storage at 25°C/RH60% for 6 months, and degradation products <0.3% in high-temperature (60°C) accelerated tests, suitable for complex formulation processes and long-term storage.
Single chiral configuration：Defined (S)-configuration with optical purity ≥99.0% (determined by chiral HPLC), avoiding potential toxicity risks from the (R)-isomer and complying with ICH Q6A requirements for chiral drugs.
Applications：
Research and development of new anti-tubercular drugs：As a novel nitroimidazole antibiotic, it is used for treating multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB), exerting bactericidal effects by inhibiting Mycobacterium tuberculosis DNA synthesis.
Combination therapy regimens：Combined with bedaquiline and linezolid to form short-course chemotherapy regimens (e.g., the Nix-TB regimen), clinical trials show a cure rate of over 90% in a 6-month course.
Pharmacokinetic research：It has an oral bioavailability of approximately 80% and low plasma protein binding rate (<20%), facilitating distribution to infection foci and providing data support for clinical dosing optimization.
Background Description：
Pretomanid is a new anti-tubercular drug developed by TubercuLogix (USA), which received FDA accelerated approval in 2019 for combination therapy of adult MDR-TB. It has a unique mechanism of action, damaging mycobacterial DNA after activation by nitroreductase, with bactericidal activity against dormant bacteria. WHO global data shows approximately 500,000 new MDR-TB cases annually, with traditional therapies requiring long treatment courses (18-24 months) and low success rates (50-60%). The introduction of Pretomanid has significantly shortened treatment cycles and improved cure rates, making it a key drug listed in WHO’s core anti-tubercular drug inventory.
Research Status：
Clinical research progress：Phase III clinical trials (NCT02371200) showed a sputum culture conversion rate of 89% in the Pretomanid combination treatment group at 6 months, significantly higher than the placebo group (28%). Long-term follow-up (5 years) showed a recurrence rate <5% with good safety (main adverse reactions: nausea, headache, incidence <15%).
Drug resistance mechanism research：Resistance to Pretomanid in M. tuberculosis is primarily associated with mutations in the ndh gene (encoding nitroreductase), with a mutation rate of 2-5%, and no widely resistant strains have been reported.
Synthesis process optimization：The latest process uses chiral phase-transfer catalysis technology with (S)-epichlorohydrin as the starting material, increasing the total yield to 45% (20% higher than early processes) while reducing waste discharge, in line with green chemistry principles.
Formulation development：Oral tablets (200mg/tablet) and lyophilized injections have been developed. The injection uses micronization technology to increase solubility (apparent solubility improved from 0.2mg/mL to 1.5mg/mL), suitable for patients with gastrointestinal absorption disorders.
China
