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- DOI 10.18231/j.ctppc.2024.008
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Medicinal chemistry of benzimidazole, a versatile pharmacophore
Introduction
Benzimidazole6 shows ine-imine tautomerism and has been used for in variety of the medicines as the active constituent. In this review article the Benzimidazole and the marketed medicines have been illustrated and exemplified. A typical allopathic medicinal chemistry review of medicines containing Benzimidazole moiety. Benzimidazole is a heterocyclic aromatic organic compound. This bicyclic compound may be viewed as fused rings of the aromatic compounds benzene and imidazole. It is a white solid that appears in form of tabular crystals.[1], [2], [3], [4], [5]
IUPAC:1H-1,3-Benzimidazole
The properties of Benzimidazole moiety can be studied by the following table.
|
Properties |
|
|
Chemical formula |
C7H6N2 |
|
Molar mass |
118.139 g·mol−1 |
|
Melting point |
170 to 172 °C (338 to 342 °F; 443 to 445 K) |
|
Acidity (pKa) |
12.8 (for benzimidazole) and 5.6 (for the conjugate acid) |
Review
Benzimidazole is a versatile moiety. In this review the marketed benzimidazoles are being discussed thus following classes of drugs have been exemplified. Drugs containing benzimidazole ring /derivatives are as follows and can be divided into following categories:
Anti ulcer
Omeprazole [6]
It is proton pump inhibitor ,used in ulcer ,to reduce acidity.
IUPAC: (R)-omeprazole is a 5-methoxy-2-{[(4-methoxy-3,5-dimethylpyridin-2- yl)methyl]sulfinyl}-1H-benzimidazole that has R configuration at the sulfur atom.
Marketed Preparation
Omeprazole inj: 40 mg& capsules are available.
Anti-helminthic
Thiabendazole [7]
Thiabendazole is a member of the class of benzimidazoles carrying a 1,3-thiazol-4-yl substituent at position 2. It belong to anthelmintic class of drug.
In market thaibendazole ointment & tablets are available.
Anti bacterial
Albendazole [8]
It is a broad-spectrum anthelmintic and antiprotozoal agent of the benzimidazole type. [3] It is used for the treatment of a variety of intestinal parasite infections, including ascariasis, pinworm infection, hookworninfection, trichuriasis, strongyloidiasis, taeniasis, clonorchiasis, opisthorchias is, cutaneous larva migrans, giardiasis, and gnathostomiasis, among other diseases.
IUPAC: methyl-[5-(propylthio)-1H-benzoimidazol-2-yl]carbamate (38.1.18), is also made by the heterocyclization of a derivative of phenylenediamine to a derivative of benzimidazole.
Marketed Preparation
Albendazole is available in chewable tab &suspension formulation.
Anti hypertensive
Telmisartan [9]
Telmisartan is used alone or together with other medicines to treat high blood pressure (hypertension).
IUPAC : 2-(4-{[4-methyl-6-(1-methyl-1H-1, 3-benzodiazol-2-yl)-2-propyl-1H-1, 3- benzodiazol-1-yl]methyl} phenyl) benzoic acid.
Marketed Preparation
Telmisartan is available in tablet form, individual or with combination of other drug.
Anti viral
Maribavir [10]
Benzimidazole ring is present in modified form.
Maribavir, sold under the brand name Livtencity, is an antiviral medication that is used to treat post-transplant cytomegalovirus. Maribavir is a cytomegalovirus pUL97 kinase inhibitor that works by preventing the activity of human cytomegalovirus enzyme pUL97, thus blocking virus replication.
IUPAC: l-ribofuranosyl benzimidazole (5,6-dichloro-2-isopropylamino-1-[β-l-ribofuranosyl]- 1H-benzimadazole).
Marketed Preparation
Antihistaminic
Bilastine[11]
It is a second-generation antihistamine and takes effect by selectively inhibiting the histamine H₁ receptor, preventing these allergic reactions.
IUPAC: 2-[4-[2-[4-[1-(2-ethoxyethyl) benzimidazol-2-yl] piperidin-1-yl] ethyl] phenyl]-2- methylpropionic acid, is a novel molecule with a molecular weight of 463.6 daltons and a chemical structure similar to piperidinyl-benzimidazole.
Marketed Preparation
Bilastine is available in tablet& oral solution formulation.
Anti cancer
Niraparib [12]
Niraparib, sold is an anti-cancer medication used for the treatment of epithelial ovarian, fallopian tube, or primary peritoneal cancer. It is taken by mouth. It is a PARP inhibitor.
IUPAC: 2-[4-(piperidin-3-yl)phenyl]-2H-indazole-7-carboxamide that has S-configuration.
Its is approved as a first-line maintenance treatment for women with advanced ovarian cancer after responding to platinum-based chemotherapy.
Marketed Preparation
Available in capsule form.
Analgesic Benzitramide
Bezitramide in 2004 the drug was with drawn from the market. Bezitramideisapro drug which rapid hydrolysis of apropri onyl-group to form the major metabolite, R-4618.It was manufactured by Janssen (sub company of johnson & johnson).
Marketed Preparation
Burgodin [13]
Anti-psychotic
Benperidol [14]
Benperidol is a first generation antipsychotic. It is also known by the trade name Anquil.
It has ketone modification in benzimidazole ring structure.
Marketed Preparation
Benperidol-nuraxpharm tablet available in 2, 4 &10mg preparation in market.
Conclusion
Several marketed preparations containing benzimidazole functional groups have been reviewed in this paper. Some benzimidazole containing drugs being discovered over a century ago and still widely used today. Also, its use is not limited to human allopathic medicine purpose only and some of them also used in veterinary allopathic medicine. Thus, it is concluded that benzimidazole is a versatile moiety.
Source of Funding
None.
Conflict of Interest
None.
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