## 7 Potential Inhibitors of Squalene Synthas
In another experiment, a series of 4,1-benzoxazepine derivatives [1-[[(3R,5S)-7-chloro-5-(2,3-dimethoxyphenyl)]-1-(3-hydroxy-2,2-dimethylpropyl)]-2-oxo-1,2,3-5-tetrahydro-4,1-benzoxazepine-3-ylacetyl]piperidine-4-acetic acid (9); 1-[[(3R,5S)-1-(3-acetoxy-2,2-dimethylpropyl)]-7-chloro5-(2,3-dimethoxyphenyl)]-2-oxo-1,2,3,5-tetrahydro-4,1-benzoxazepine-3-yl]acetyl]piperidine-4-acetic acid (10); 1-[[(3R,5S)-7-chloro-5-(2,3-dimethoxyphenyl)-1-[2,2-dimethyl-3-(propyloxy)]-2-oxo-1,2,3,5-tetrahydro-4,1-benzoxazepine-3-yl]acetyl]]piperidine-4-acetic acid (11); 1-[[(3R,5S)-1-[3-(butyryloxy)-2,2-dimethylpropyl]-7-chloro-5-(2,3-dimethoxyphenyl)-2-oxo-1,2,3,5-tetrahydro4,1-benzoxazepine-3-yl]acetyl]]piperidine-4-acetic acid (12); 1-[[(3R,5S)-1-[3-(butyryloxy)-2,2-dimethylpropyl]-7-chloro-5-(2,3-dimethoxyphenyl)-2-oxo-1,2,3,5-tetrahydro4,1-benzoxazepine-3-yl]acetyl]]piperidine-4-acetic acid (13); 1-[[(3R,5S)-7-chloro-5-(2,3-dimethoxyphenyl)-1-[2,2-dimethyl-3-(isobutyrylov)propyl]-2-oxo-1,2,3,5-tetrahydro-4,1-benzoxazepinein-3-yl]acetyl]]piperidine-4-acetic acid (14)); 1-[[(3R,5S)-7-chloro-5-(2,3-dimethoxyphenyl)-1-[2,2-dimethyl-3-(isobutyrylov)propyl]-2-oxo-1,2,3,5-tetrahydro-4,1-benzoxazepinein-3-yl]acetyl]]piperidine-4-acetic acid (14)); 1-[[(3R,5S)-7-chloro-5-(2,3-dimethoxyphenyl)-1-[2,2-dimethyl-3-(pivaloyloxymethyl)propyl]-2-oxo-1,2,3,5-tetrahydro-4,1-benzoxazepinein-3-yl]acetyl]]piperidine-4-acetic acid (14)) were synthesized and evaluated for inhibition of squalene synthase and sterol synthesis in rat liver by [PERSON] et al. [50]. Under in vitro conditions, compounds 9-14 inhibited squalene synthase with IC\({}_{50}\) values of 45, 76, 87, 93, 89 and 471 nM, respectively. Under in vivo conditions, the single oral administration of 10 mg/kg compounds 9-14 to [14C]acetate (50 uCi/kg)-induced Wistar rats inhibited sterol synthesis by 64, 81, 40, 30, 34, and 43%, respectively [50]. Although the exact mechanism of action of benzoxazepine derivatives has not yet been fully elucidated, they are believed to interact with multiple receptors, including serotonin, dopamine, and norepinephrine receptors [51], modulate the activity of certain enzymes, such as monoamine oxidase [52], or interact with certain ion channels, such as calcium and potassium channels [51,53]. Furthermore, [PERSON] et al. [10] verified and confirmed the _T. cruzi_ epimastigote squalene synthase inhibitory (noncompetitive inhibitor) potential of 3-(biphenyl-4-yl)-3-hydroxyquinuclidine (3-biphenyl-4-yl-1-aza-bicyclo [2.2.2]-octan-3-ol; BPQ-OH) (3) with a Ki value of 48 nM. Furthermore, in vitro anti-_T. cruzi_ (amostigote forms) (IC\({}_{50}\): 3 nM; SI: 33.33, Vero cells) and anti-_L. mexicana_ (promastigotes) (IC\({}_{50}\): 12 uM) experiments revealed low IC\({}_{50}\) values. Although appropriate controls were not used for the assessment, the results of this study clearly indicated the selective antiparasitic activity of the quinuclidine derivative BPQ-OH. A year later, [PERSON] et al. [54] reported a series of five 3-ethylidenequinuclidine derivatives (compounds 15-19) [(Z)-3-[2-(9H-Fluoren-2-yloxy)ethylidene]quinuclidine hydrochloride (15); (E)-3-[2-(9H-fluoren-2-yloxy)ethylidene]quinuclidine hydrochloride (16); 3-[2-(9H-fluoren-2-yloxy)ethyl]quinuclidine hydrochloride (17); (Z)-3-[2-(9H-fluoren-2-yloxy)ethylidene]quinuclidine hydrochloride (18); 3-[2-(9H-fluoren-2-yloxy)ethylidene]quinuclidine hydrochloride (19); (Z)-3-[2-(9H-fluoren-2-ylamino)ethylidene]quinuclidine hydrochloride (19); and (Z)-3-[2-[N-(9H-fluoren-2-yl)-N-methylamino)ethylidene]quinuclidine fumarate (10)] that inhibits squalene synthase from the hamster liver with IC\({}_{50}\) values of 0.076, 0.15, 0.25, 0.27 and 0.56 uM, respectively. Compound (15), which was the most potent inhibitor, also demonstrated effective inhibition against human hepatoma cells (IC\({}_{50}\): 48 nM).