Benzimidazole pharmacophore

Utilizing the same aryl fluoride linker on conventional MeOPEG polymer, these authors also presented a microwave-accelerated liquid-phase synthesis of benzimidazoles (Scheme 7.70) [79]. This bicydic pharmacophore is an important and valuable structural element in medicinal chemistry, showing a broad spectrum of pharmacological activities, such as antihistaminic, antiparasitic, and antiviral effects. 

Several patent applications have been filed claiming CXCR4 antagonists, where the cyclam structure has been replaced with a N-(lH-benzimidazol-2-ylmethyl)-5,6,7,8-tetrahydro-8-quinolineamine pharmacophore, like compounds 39 and 40 (Figure 12) [120-124], Salt forms suitable for development have been described for 41 (AMD070) in a recent patent application [125]. These filings describe a novel tetrahydroquinolineamine pharmacophore. 

A possible relationship between benzimidazole and fentanyl-like analgesics is discussed on p. 485 the high potencies seen in both series may be related to the presence of a nonbasic N-Ar pharmacophore. 

These studies indicated that replacement of the methoxycarbonylamino group at 2-position of benzimidazoles by acylamino or urea pharmacophores may help to retain the biological activity, although they are weaker than the benzimidazole-2-car-bamates. Thus, it may be concluded that the presence of a methoxycarbonylamino function at 2-position of a 5(6)-substituted benzimidazole is usually essential for optimal anthelmintic activity. 

The presence of a pharmacophore at 5(6)-position of 2-substituted benzimidazole is an important factor for determining the biological profile of the compounds of this class. The substituents at this position not only prevent the molecule to undergo facile 5-hydroxylation to form weakly active or inactive metabolites, but also helps in segregating the therapeutic response against enteric and tissue-dwelling helminths. The major structural changes carried out at this site are discussed below. 

Also the more recently designed 5-HTa receptor antagonists fit the S-HTg receptor antagonist pharmacophore. Some examples (figure 2) are the naphthahmide derivative (compound 1) [218] the 3-methyl-l-indolizine derivative (compoiind 2) [219], the pjnrrolo[2,l-c][l,4]benzoxazine-6-carboxamide derivative (compound 3) [220], the benzopyrano[3,4-c]quinoline derivative (compoimd 4) [221] and the benzimidazole-4-carboxylic acid derivative (compound 5) [222]. 

A detailed study revealed that introduction of 1-alkyl-1, 3-dihydro-2H-benzimidazol-2-ones on known pharmacophores is compatible with neuroleptic (milenperone), antiemetic (domperidone, 7) and also with antihistaminic-antiallergic activity (oxatomide). 

Monocyclic and Bicyclic aromatic heterocycles such as imidazoles, thiazoles, thiadiazoles, oxazoles, oxadiazoles quinazolines, indoles, benzimidazoles, purines pyrido[43-d]pyri-midines, thiazolo[5,4-d]pyrimidines, thiazolo[4,5-d]pyrimidines, oxazolo[5,4-d]pyrimi-dines and thieno[2,3-d]pyrimidines are renowned pharmacophores in drug discovery. These special structures are well explained and exemplified in chemical compound libraries. In this chapter, several types of thiazole based heterocyclic scaffolds such as mono-cyclic or bicyclic systems synthesis and their biological activities studies are presented, which are not frequently present in books and reviews. We mention the first importance of synthetic route of various thiazole based compounds and their applications in medicinal chemistry in this chapter. 

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