AZABICYCLES MODULATING INHIBITION OF CELLULAR ADHESION, PHARMACEUTICAL COMPOSITION BASED ON THEREOF AND METHOD FOR TREATMENT

摘要

FIELD: organic chemistry, medicine, pharmacy. SUBSTANCE: invention relates to compound of the formula (I): wherein R¹ represents: (i) R³-Z³- or: (ii) R³-L³-Ar¹-L⁴-Z³-; R² represents hydrogen atom; R³ represents alkyl, aryl optionally substituted with one or two substituents taken among halogen atom and C_1-4-alkyl, arylalkyl; R⁵ represents hydrogen atom; R⁷ and R^7a represent hydrogen atom; R⁸ represents hydrogen atom; R⁹ represents alkyl optionally substituted with halogen atom, aryl, heteroaryl comprising up to 2 heteroatoms taken among nitrogen and oxygen atoms, or alkyl substituted with aryl or heteroaryl; A¹ represents unsubstituted C_1-3-alkylene bond with linear chain; Ar¹ represents arylene that can be substituted optionally with C_1-4-alkoxy-group or heteroaryldiyl comprising up to 2 heteroatoms taken among nitrogen and oxygen atoms; L¹ represents alkylene bond that is substituted optionally with ; L³ represents -NR⁵-C(=Z)-NR⁵-, -Z-, -NR⁵-, -NR⁵-C(= O)-O-, or O- C(=O)-NR⁵- L⁴ represents alkylene bond; Z represents oxygen atom; Z¹ represents C(R⁷)(R^7a); Z³ represents C(=O) or SO₂; Y represents carboxy-group under condition that when R¹ represents R³ or R³-C(=O) then R³ can't represent alkyl; or its corresponding N-oxide or ester that can be converted to the primary molecule in vivo by metabolism, or pharmaceutically acceptable salt of such compound, or its N-oxide, or its ester. Invention relates also to pharmaceutical composition eliciting inhibitory effect on cellular adhesion and comprising effective amount of compound of the formula (I) and pharmaceutically acceptable carrier or excipient. Invention relates also to the application of compound of the general formula (I): wherein R¹ represents R³ or R³--C(=O) wherein R³ represents alkyl; , Z, Z¹, Z³ and Y are given above; or its corresponding N-oxide or ester that can be converted to the primary molecule in vivo by metabolism; or pharmaceutically acceptable salt of such compound or its N-oxide or ester used for preparing a medicinal agent used for treatment of patient suffering with states or subjected for states that can be relieved by administration of inhibitor of α4β1-mediated cellular adhesion. Invention relates also to method for treatment of patient suffering with states or subjected for states that can be relieved by administration of inhibitor of α4β1-mediated cellular adhesion involving administration to the indicated patient the effective dose of compound of the formula (I). Invention provides preparing new compounds eliciting inhibitory effect on cellular adhesion. EFFECT: improved treatment method, valuable medicinal properties of compounds. 65 cl, 3 tbl, 40 ex