Clomiphene, structure

Figure 1.4. Structure of clomiphene and tamoxifen, two non-steroidal synthetic anti-oestrogens that have found medical application...

In one large study, some adverse reactions in treated women were due to its ovulatory effects and others were direct reactions to the substance itself (2). The most common problem was ovarian enlargement (14%), followed by hot flushes (11%), abdominal and pelvic discomfort (7.0%), and nausea and vomiting (2.1%). Incidental symptoms were breast discomfort, vaginal changes, psychological symptoms, headache, heavier menses, and increased urinary frequency. Sporadic case-reports on clomiphene in the literature relate to fetal ovarian dysplasia or maternal psychosis (SEDA-7, 391), either of which may have been coincidental. However, it must be borne in mind that the substance is related structurally to tripar-anol, an obsolete drug that produced a series of disastrous adverse effects some 40 years ago. 

The first ER modulators studied clinically were clomiphene (4) and tamoxifen (5), which exemplify the triphenylethylene (TPE) structural class. TPEs were originally investigated as contraceptives, but molecules such as tamoxifen (5) and toremifene (6) were found to display strong antagonism of estrogen in mammary tissue, leading to their development for the treatment of breast cancer. A more recent member of this structural class, afimoxifene (7) is currently under development as a transdermal gel formulation for the treatment of cyclical mastalgia.1 13... 

Structures of the txans-isomer of tamoxifen, raloxifene, tians-clomiphene (enclomiphene), andful-... 

Human chorionic gonadotropin mimics LH both in structure and in function. It is produced by the placenta during pregnancy and is isolated from the urine of pregnant women. In the protocols for lUI or IVF, exogenous hCG must be administered to stimulate a scheduled ovulation. Between 36 and 72 hours after intramuscular administration, the dominant follicle ruptures and releases its egg. At that point, the scheduled lUI or IVF occurs. The hCG can be given in combination with clomiphene citrate to enhance ovulation (95). (For an in-depth discussion of hCG, see Chapter 7.)... 

Tamoxifen, a drug used in the treatment of breast cancer, and clomiphene, a drug used as a fertility treatment, have similar structures but very different effects. Assign or Z configuration to the double bonds in both compounds. 

A compound similar to clomiphene was separated into its cis (I.C.I. 47,699) and trans (I.C.I. 46,474) structures (23 and 24 respectively) which were shown to have markedly different biological activities.21... 

---