Antipsoriatic agent

The free acid analogue of the antipsoriatic agent etretinate (103) is prepared in substantially the same way as the parent compound. Thus, the aldehyde group in 98 is converted finally to the pho.sphonate (101) by sequential reduction (99), conversion to the chloride (100), and finally reaction with triethyl phosphite. Condensation of the ylide from 101 with the benzaldehyde 102 gives etretinate (103) saponification affords acitretin (104) [25]. 

Topical corticosteroids (Table 16-1) may halt synthesis and mitosis of DNA in epidermal cells and appear to inhibit phospholipase A, lowering the amounts of arachidonic acid, prostaglandins, and leukotrienes in the skin. These effects, coupled with local vasoconstriction, reduce erythema, pruritus, and scaling. As antipsoriatic agents, they are best used adjunc-tively with a product that specifically functions to normalize epidermal hyperproliferation. 

The 4-substituted glutarimide derivative cycloheximide 121 is an antipsoriatic agent . 

A number of simple analogs of the antipsoriatic agent anthralin (dithranol) were prepared by K. Muller and co-workers by changing the positions of the hydroxyl groups as well as adding new functional groups into various positions of the anthracenone nucleus. The benzyl bromide functionality was converted to the corresponding aldehyde by the Kornblum oxidation in fair yield. 

Antipsoriatic agents are used to treat psoriasis, a serious chronic skin condition characterized by scaly pink patches. A number of agents may be used in treatment, but there is no cure. KERATOLYTic (desquamating) AGENTS are used extensively, including coal tar, dithranol, etretinate, ichthammol and salicylic acid also retinoids (see below) and corticosteroids. 

Trade name Dovonex (Leo Pharma) (Galderma) Indications Psoriasis Category Antipsoriatic agent Half-life 30 minutes... 

Hydroxyurea inactivates the enzyme ribonucleotide reductase, inhibiting ceU synthesis in the S-phase of the DNA cycle. An antimetabolite that is primarily used to treat hematologic mahgnan-cies, it has been used for the treatment of psoriasis for more than 3 decades. It is selectively used, particularly in those with hver disease who would be at risk of adverse effects with other antipsoriatic agents. However, hydroxyurea is less effective than methotrexate. ... 

Calcipotriene is an antipsoriatic agent. It is a synthetic vitamin Dj analog. In a manner similar to vitamin D, calcipotriene regulates skin cell production and development, thereby modifying the abnormal growth and production of kerati-nocytes, responsible for the scaly red patches characteristic of psoriasis (see Figure 105). Calcipotriene is indicated in the treatment of plaque psoriasis. Scalp solution topical treatment of chronic, moderately severe psoriasis of the scalp. 

In the naphthoquinone group, a number of lapacho compounds, the most common naphthoquinonic constituents of the inner bark of Tabebuia impetiginosa (Mart ex D C.) Standi were evaluated in vitro against the growth of the human keratinocyte cell line HaCaT. All compounds inhibited keratinocyte growth and appear to be promising as effective antipsoriatic agent [147],... 

C4H5N4O3, Mr 158.12. A. is widely distributed as adeg-radation product from purine metabolism. The Ry form has mp. 226- 229°C (decomp.), (0)0 -92.4° (H2O), pKg 8.5 (25 °C), and is moderately soluble in water. The (5)-form is isolated from Platanus orien-talis. The racemate forms monoclinic prisms with mp. 238-240°C (decomp.) it is less soluble in water than the enantiomer. A. is used for wound healing and as an antipsoriatic agent. 

L-threo-form. Safingoi, INN. SPC 100270 Widespread as a component of cerebrosides, in admixture with smaller amts, of homologues. Antipsoriatic agent. Inhibitor of protein kinase C. When used in combination with chemotherapy agents, increases their antitumour effects. Mp 108°. [a] —14.1 (CHCI3). 

Achievement of efficacy by any therapeutic regimen requires days to weeks. Initial dramatic response may be achieved with some agents such as corticosteroids. However, sustained benefit with pharmacologically specific antipsoriatic therapy may require 2 to 8 weeks or longer for clinically meaningful response. 

Mechanism of Action A topical agent that binds DNA, inhibiting synthesis of nucleic protein, and reduces mitotic activity. Therapeutic Effect Results in damage to DNA sugar and enhances membrane lipid peroxidation, which may play a critical role in the antipsoriatic action. 

A second indication for keratolytical and some moisturizing agents (e.g., urea) is the penetration enhancement of topically applied antipsoriatic drugs (e.g., salicylic acid in the dithranol and coal tar treatment or corticosteroids). This may result in an economical benefit.11... 

Immunomodulator. Antiviral and antiinflammatory agent. Exhibits antipsoriatic activity. Also used against other autoimmune diseases such as arthritis, eczema and systemic lupus erythematosus. Viscous oil. [a]o -12 (neat). 1.4687. Log P -1.31 (calc). Low toxicity and no serious side effects, but requires large therapeutic dosage. 

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