SUBSTITUTED MORPHOLINES OR THEIR PHARMACEUTICALLY ACCEPTABLE SALTS, METHOD OF THEIR SYNTHESIS, PHARMACEUTICAL COMPOSITION AND METHOD OF COUNTERACTION TO SUBSTANCE P OR INHIBITION OF NEUROKININ-1 RECEPTORS Russian patent published in 2001 - IPC

FIELD: organic chemistry, pharmacy. SUBSTANCE: invention proposes substituted morpholines of the formula (I) or their pharmaceutically acceptable salts where each of R² and R³ means hydrogen atom; R⁶, R⁷ and R⁸ are taken among hydrogen, fluorine atom or CF₃; each of R¹¹, R¹² and R¹³ means independently hydrogen or halogen atom; A means unsubstituted C_1-6- alkylene; B means heterocycle taken among 1,2,4-triazolyl, 5-oxo-1,2,4-triazolyl, 2-oxo-1,3-imidazolyl or imidazolyl substituted with X where X means residue of phosphoryl -PO(O^-)₂•2M⁺ salt and M is pharmaceutically acceptable monovalent counterion; Y means -O-; Z is hydrogen atom or C_1-6- -alkyl; p = 0. Compounds of the formula (I) are synthesized by phosphorylation of corresponding parent morpholine derivatives with phosphoryl-transferring reagent. New synthesized compounds are antagonists of substance P and neurokinin-1 that are prodrugs and exhibit increased solubility in aqueous solutions as compared with the parent drugs. Invention proposes also pharmaceutical composition eliciting activity inhibiting neurokinin-1 receptors and containing compounds of the formula (I) taken in the effective amount. Also, invention proposes method of counteraction to substance P near site of its receptors or inhibition of neurokinin-1 receptors. EFFECT: new compounds indicated above, improved method of synthesis, valuable pharmacological properties. 22 cl, 97 ex