Prostaglandins analogues

During recent years, cross metathesis has found a wide range of applications in total synthesis. CM has been the key step in the syntheses of (-)-lasubine 11 [134], (+)-7a-ept-7-deoxycasuarine [135], and melithiazole C [136] to name just a few examples. It has been used for the modification of tetrapyrrolic macrocycles [137] as well as erythromycin derivatives [138], the dimerisation of steroids [139] and the synthesis of prostaglandin analogues [140]. 

Dithioacetal monoxides undergo Michael addition to acrylonitrile. The addition products are easily converted into y-ketonitriles 382 (equation 221). Benzenesulphinyl allylic carbanions 383 derived from the corresponding allylic sulphoxides react selectively at the y-position with a variety of cycloalkenones to give the l,4-adducts " (equation 222). Recently, Nokami and coworkers have synthesized some prostaglandin analogues via a three-component coupling process involving 1,4-addition of phenylsul-phinyl allylic carbanion (equation 223) . ... 

Drugs that target other sites of platelet action include thromboxane synthetase inhibitors, serotonin or 5-hydroxytryptamine (5-HT2) receptor blockers, and thromboxane A2 receptor blockers, in addition to cyclooxygenase inhibitors and prostaglandin analogues. 

A synthesis of the prostaglandin analogue TEI-9826 is presented in Scheme 9.40 as an example of the use of an Ir-catalyzed aUyUc alkylation [44]. The allylic alkylation with a malonic amide of the Weinreb type as pronucleophile gave the substi-... 

Scheme 9.40 Synthesis of the prostaglandin analogue TEI-9826 via Ir-catalyzed allylic alkylation.

Cytotec containing misoprostol (prostaglandin analogue) may cause abnormal vaginal bleeding. 

Xalatan drops is a proprietary preparation of latanoprost (prostaglandin analogue), indicated in glaucoma. 

Xalatan (latanoprost) is a prostaglandin analogue, which increases the uvoscleral outflow, thereby decreasing the intraocular pressure. The drops, which are applied once daily, preferably in the evening, may cause eye discoloration especially in patients with mixed colour irides. 

Adverse reactions to the prostaglandin analogue carboprost tromethamine include all of the following EXCEPT... 

T. Ota, M. Aihara, S. Narumiya, M. Araie, The effects of prostaglandin analogues on lOP in prostanoid FP-receptor-deficient mice. Invest. Ophthalmol. Vis. Sci. 46 (2005) 4159. 

B. Resul, J. Stjernschantz, Structure-activity relationships of prostaglandin analogues as ocular hypotensive agents, Curr. Opin. Then Pat. 3 (1993) 781. 

B.J. Whittle, S. Moncada, K. Mullane, J.R. Vane, Platelet and cardiovascular activity of the hydantoin BW245C, a potent prostaglandin analogue. Prostaglandins 25 (1983) 205. 

Lubipmstone has emerged as a novel agent for the treatment of constipation. This prostaglandin analogue potently activates intestinal CP channels, without altering Na" " and K" " balance. This difluoromethyl ketone is in equilibrium with the bicychc hemiketalic form, which is predominant in the absence of water (Figure 8.72). ... 

The answer is a. (Hardman, p 914.) Misoprostol is a prostaglandin analogue of PGE with an affinity for the gastric mucosa. It stimulates the secretion of mucus and bicarbonate, enhances cell proliferation, preserves the microcirculation, and stabilizes tissue lysosomes. Misoprostol is approved by the FDA for protection against the ulcerogenic action of NSAIDs (not because it antagonizes NSAIDs). 

The important use of prostaglandin analogues is in the arthritic patients who are on chronic use of NSAID s and are not responding to receptor antagonists. 

Cystoid macular edema, iritis, Herpes simplex keratitis, periocular skin darkening, and headaches have been described in patients treated with prostaglandin analogues. These adverse effects occur rarely, and cystoid macular edema, iritis and H. simplex keratitis occur in eyes with risk factors. Repeated rechallenge with masked controls is required to establish a causal relation. However, even without firm establishment of a causal relation, caution is advised with the use of prostaglandin analogues in the eyes of patients with risk factors for macular edema, iritis, and H. simplex keratitis (76). 

Schumer RA, Camras CB, Mandahl AK. Putative side effects of prostaglandin analogues. Surv Ophthalmol 2002 47(Suppl 1) S219. 

Linden C. Therapeutic potential of prostaglandin analogues in glaucoma. Expert Opin Investig Drugs 2001 10(4) 679-94. 

Fliers E, Duren DR, van Zwieten PA. A prostaglandin analogue as a probable cause of myocardial infarction in a young woman. BMJ 1991 302(6773) 416. 

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