Aromatase Inhibitors Better Than Tamoxifen
Major thought leaders have agreed that Aromatase Inhibitors such as Arimidex (from Astra Zenaca) are superior to Tamoxifen as an adjunct to early breast cancer treatment.
Read the article for more information. I want to comment on the molecules themselves.
Here is the description from the prescribing information (pdf) for Arimidex:
ARIMIDEX®(anastrozole) tablets for oral administration contain 1 mg of anastrozole, a non-steroidal aromatase inhibitor. It is chemically described as 1,3-Benzenediacetonitrile, α, α, α’, α’-tetramethyl-5-(1H-1,2,4-triazol-1-ylmethyl). Its molecular formula is C17H19N5and its structural formula is:
Anastrozole is an off-white powder with a molecular weight of 293.4. Anastrozole has moderate aqueous solubility (0.5 mg/mL at 25°C); solubility is independent of pH in the physiological range. Anastrozole is freely soluble in methanol, acetone, ethanol, and tetrahydrofuran, and very soluble in acetonitrile. Each tablet contains as inactive ingredients: lactose, magnesium stearate, hydroxypropylmethylcellulose, polyethylene glycol, povidone, sodium starch glycolate, and titanium dioxide.
I can’t help but make an observation based on my process development background. The molecule is symmetrical which makes synthesis easier. It also is achiral; it doesn’t have any chiral centers. In my days of process development, I’d love to have a project such as the synthesis of this molecule land on my desk.
Let’s compare Arimidex to tamoxifen. Here’s the description from the prescribing for Nolvadex:
NOLVADEX (tamoxifen) tablets, a nonsteroidal antiestrogen, are for oral administration. Chemically, NOLVADEX is the trans-isomer of a triphenylethylene derivative. The chemical name is (Z)2-[4-(1,2-diphenyl-1-butenyl) phenoxy]-N,N-dimethylethanamine 2 hydroxy-1,2,3-peopanetricarboxylate (1:1). The structural and empirical formulas are:
Tamoxifen citrate has a molecular weight of 563.62, the pKa’ is 8.85, the equilibrium solubility in water at 37 ªC is 0.5 mg/mL and in 0.02 N HCl at 37 ªC, it is 0.2 mg/mL.
I should also mention that Astra Zenaca use to manufacture tamoxifen under the brand name Nolvadex but has discontinued the commercial manufacturing and distribution of it. There are other sources for generic tamoxifen.
Back to the synthesis of tamoxifen; I can remember being in graduate school and first seeing this molecule and coming up with routes to he molecule. First, since it is only the trans isomer it has to be either sperated from the cis isomer or made in a sterospecific manner. Both of these are more difficult than the synthesis of anastrozole.
Other Resources
• ARIMIDEX - Postmenopausal Women with Hormone Receptor-Positive Early Breast Cancer
• Nolvadex Online, Description, Chemistry, Ingredients - Tamoxifen Citrate - RxList Monographs
• Arimidex Online, Description, Chemistry, Ingredients - Anastrozole - RxList Monographs
• Tamoxifen (3Dchem.com; chemical information)
Technorati Tags: anastrozole, Arimidex, breast cancer, Tamoxifen
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