Sunday, May 22, 2016

Morinidazole | Treatment of Amoebiasis | Treatment of Anaerobic Bacterial Infections | Treatment of Trichomoniasis | 5-nitroimidazole Antimicrobial

Morinidazole [R,S-1-(2-methyl-5-nitro-1H-imidazol-1-yl)-3-morpholinopropan-2-ol] is a 5-nitroimidazole antimicrobial injection with potent activities against anaerobic Gram-negative sporeless bacilli and Gram-positive cocciMorinidazole is a novel third generation 5-nitroimidazole-class antimicrobial agent indicated for the treatment of amoebiasis and anaerobic bacterial infections including appendicitis and pelvic inflammatory disease [1].
Its efficacy against Clostridium perfringens, Bacteroides fragilis, Veillonella parvula, Bacteroides distasonis, Bacteroides ovatus, Bacteroides vulgatus, and Bacteroides melaninogenicus is equal to that of ornidazole and superior to those of metronidazole and tinidazole.
Morinidazole has been approved for the treatment of amoebiasis, trichomoniasis, and anaerobic bacterial infections in China.

Morinidazole: 2D and 3D Structure

Mechanism of Action

5-Nitroimidazole antimicrobial drugs act via nitroreduction of the molecules in the pathogens [2].

Dosages and Approvals
Morinidazole, discovered and developed by Jiangsu Hansoh Pharmaceutical, was approved by the CFDA in February 2014. The recommended dose is 500 mg (100 mL injection) twice daily every 6-8 hours continuously for 5-7 days.

Common name: Morinidazole
Trademarks: -
Molecular Formula: C11H18N4O4
CAS Registry Number: 92478-27-8
CAS Name:R,S-1-(2-methyl-5-nitro-1H-imidazol-1-yl)-3-morpholinopropan-2-ol
Molecular Weight: 270.29
InChI: InChI=1S/C11H18N4O4/c1-9-12-6-11(15(17)18)14(9)8-10(16)7-13-2-4-19-5-3-13/h6,10,16H,2-5,7-8H2,1H3C
Mechanism of Action: Antimicrobial Activity via Nitroreduction
Activity: Treatment of Amoebiasis; Treatment of Trichomoniasis; Treatment of Anaerobic Bacterial Infections; Antimicrobial Agents
Status: Launched 2014 (China)
Chemical Class: 5-Nitroimidazole; Small-molecules; Imidazoles; Nitro containing; Hydroxyl containing; Morpholine containing
Originator: Jiangsu Hansoh Pharmaceutical

Morinidazole Synthesis
WO2006058457A1: It appears to be the industrial process.

1H NMR (Estimated) for Morinidazole

Experimental: 1H NMR (CD3Cl) δ 2.57 (3H, S) δ 4.25~4.35 (2H, m) δ 4.84~4.71 (3H, m) δ 7.92 (1H, S)

1. Gao, R.; et. al. Metabolism and pharmacokinetics of morinidazole in humans: identification of diastereoisomeric morpholine N+-glucuronides catalyzed by UDP glucuronosyltransferase 1A9. Drug Metab Dispos 2012, 40(3), 556-67. (free copy)
2. Kedderis, G. L.; et. al. Covalent interaction of 5-nitroimidazoles with DNA and protein in vitro: mechanism of reductive activation. Chem Res Toxicol 1989, 2(3), 146-9. (FMO only)
3. Cen, J.; et. al. Alpha-substituted 2-methyl-5-nitroimidazol-1-ethanol derivatives. WO2006058457