9, 10-secopregnane derivative and pharmaceutical

#This application is a U.S. national phase application under 35. U.S.C. §371of International Patent Application No. PCT/JP2007/061221, filed Jun. 1, 2007, and claims the benefit of Japanese Patent Application No. 2006-155465, filed Jun. 2, 2006. The International Application was published in Japanese on Dec. 13, 2007 as WO 2007/142158. The disclosures of all the prior applications are hereby incorporated by reference in their entireties.

#The present invention relates to a 9,10-secopregnane derivative (vitamin D3derivative) and a pharmaceutical composition containing it as an active ingredient.

#Psoriasis vulgaris, ichthyosis syndrome, keratosis of palm and sole, pustulosis of palm and sole and lichen pilaris are dyskeratosis in a broad sense showing various characteristic skin signs such as erythema, wetting, hypertrophy, keratinization and scale. This disease is an intractable chronic disease and causes a big obstacle to comfortableness of daily life of patients. With regard to its pathological background, it has been believed to be based on disorder of growth and differentiation of both inflammatory cells and skin cells.

#The compound of the invention may be produced from a known compound or from an easily synthesizable intermediate, for example, according to the method mentioned below. In production of the compound of the invention, in case where the starting material has a substituent having an influence on the reaction, in general, the starting material is previously protected with a suitable protective group according to a known method and then reacted. The protective group may be removed after the reaction according to a known method.

#[In the formula, Y, Z, R1, R2, R3, Ra, Rb, Rc. and Rdhave the same meanings as above. Y1represents (1) a single bond, (2) an alkylene having 1to 5carbon atoms and optionally substituted with 1to 3. substituents selected from a group consisting of halogen, protected hydroxy and oxo, (3) an alkenylene having 1to 5carbon atoms, or (4) phenylene. R5and R6each represent a protective group for hydroxy. Z1, Z2and Z3are the same or different, each represents halogen, nitro or cyano. Z4represents (1) hydrogen, (2) a protected hydroxy, or (3) —NR13R14R13represents a hydrogen, or an alkyl having 1. to 6carbon atoms; R14 represents (1) an alkyl having 1. to 6and optionally substituted with a protected hydroxy, or (2) an alkylsulfonyl having 1. to 6carbon atoms.]

#This reaction is condensation of a compound (alcohol) of the general formula [2] and a compound (carboxylic acid) of the general formula [3] followed by deprotection, and therefore it may be accomplished according to a method per se as condensation and deprotection. For example, the above alcohol is reacted with the above carboxylic acid and then deprotected, thereby producing a compound of the invention.