also, the cyano benzyl moiety is significant because it partly imitates the steroid backbone of the natural hormone androstenedione. the cyano groups are at the para position of the benzonitrile, they are electron-withdrawing and that is important for the activity as it acts as carbonyl group of androstenedione. two aryl groups also play an important role in the inhibition. quantitative structure activity relationship (qsar) qsar models have been made to figure out the most-valuable structural and physicochemical parameters for nsais inhibitory activity. these models demonstrate a precise understanding of nsais effectiveness. dipole moment and molar refractivity are considered to be the most meaningful physicochemical properties that affect the inhibition of aromatase. this implies that bulky, complex, flexible and steric characteristic of molecules is important. also, often the hydrophobic properties matter. thereby, nsais activity is mostly dependent on the size and shape of the drug structure along with steric characteristics and interaction of the azole group to the heme prosthetic group. history independent work leading to initial discovery classification of aromatase inhibitors inhibitors generation type i (steroidal) type ii (non-steroidal) first testololactone aminoglutethimide second formestane fadrozole third exemestane anastrozole letrozole in the 1920s the initial discovery of estrogens and the bioactivity in urinary extracts contributed the momentum for greater understanding of the structure, biosynthesis, secretion, and the function of the various estrogens. this was mainly due to the independent work of edward doisy and adolf butenandt who isolated estriol, estrone, and estradiol from urine of pregnant women. by blocking biosynthesis using drugs, it has been seen that employing agents that specifically affect estrogen production has shown the highest promise. thus, by creating an aromatic ring in the steroid molecule the final step in the pathway of estrogen biosynthesis is inhibited, and this gave rise to the trivial name of aromatase for the enzyme catalyzing this reaction. in 1960 aminoglutethimide was marketed as an anticonvulsant. later in 1963, a doctor at the sinai hospital in detroit proclaimed that it produced increased symptoms of addison's disease. with more lab work it was discovered that it had a blocking effect on steroidal biosynthesis. later on, in the 1970s it was used in women with breast cancer. subdivision of aromatase inhibitors aromatase inhibitors have been distinctively sub-divided into two main groups due to their difference in mechanism of action and structure. type i inhibitors that are steroidal aromatase inhibitors and type ii inhibitors that are non-steroidal aromatase inhibitors. the evolution of aromatase inhibitors has progressively increased in potency and specificity with each generation from discovery. the progression has been necessary as the first-generation of drug-induced inhibitors of the enzyme were not particularly potent and lacked specificity that would often produce side effects unrelated to estrogen deprivation. thus, development from first-generation to third-generation has given remarkable specificity and potency. drug development for specific treatment initial studies on estrogen and its enzymatic activity and function was a component of the birth control pill. investigations showed that inhibition of the enzyme might have extensive practical application for treatment of hormone-dependent breast cancer, alterations of ovarian and endometrial function, and treatment of benign disorders such as gynecomastia. the unraveling of aromatase enzyme varied function has thus shown an extensive success in the field of endocrinology concerning breast cancer therapy. they have provided one of the first molecular targets for rational drug development in the treatment of cancer.