Finasteride structure

Cosmeceuticals are substances that are applied to skin or hair but do not modify its structure and function. One aspect that differentiates cosmeceuticals from cosmetics is that most, if not all, of them originate from bona fide medicinal chemistry programs. In this chapter, four representative cosmeceuticals are discussed isotretinoin (1) and tazarotene (2) for acne and minoxidil (3) and finasteride (4) for hair growth, respectively. Ironically, in spite of their market successes, neither minoxidil nor... 

The single-crystal structures of both Forms I and II are known (Wenslow et al. 2000), but no complete single-crystal data exist for the solvates. Minimized force field calculations based upon the crystal structures indicate a lower total energy for Form I than for Form II of finasteride, which is consistent with the thermodynamic conclusions from melting and solubility data. 

Figure 22 Proposed chemical structure of the NADP-finasteride adduct. PADPR, phosphoadenosine diphosphoribose.

The design of enzyme inhibitors has included random screening of synthetic chemical agents, natural products, and combinatorial libraries followed by molecular optimization or structure-activity relationships of so-called lead structures as well as bio-isosteric analogues of the enzyme substrates themselves. Drugs (e.g., finasteride) also have been developed for one indication but, based on observed side effects, have lead to other uses. 

Finasteride is a clinically useful agent in the treatment of prostate hyperplasia and male pattern baldness. It is a potent inhibitor of human steroid-5a-reductase, the enzyme responsible for the reduction of testosterone to dihydrotestosterone (Fig. 5.19). (see Chapter 45) The inhibitory action of finasteride has been attributed both to its similarity in structure to testosterone, which allows it to bind to the enzyme and be reduced to dihydrofinasteride in place of testosterone, as well as to its ability to act as a mechanism-based inhibitor, during which it can tie up the cofactor, NADPH, by forming a covalent NADP-dihydrofinasteride adduct (Fig. 5.19) (see Chapter 45). This adduct very slowly releases dihydrofinasteride with a half-life of one month (37). 

Figure 1-15. Chemical structures of the active androgens, testosterone and DHT, some examples of antiandrogens, an estrogen, and finasteride.

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