Prostaglandin Derivatives, Methods for their preparation, Pharmaceutical compositions containing them and their use in the treatment of glaucoma and ocular hypertension.

摘要

Enhance the pharmacological activity of prostate nitric acid derivatives and greater tolerance. They can be used to treat glaucoma and high blood pressure in the eyes. 1: A general formula compound (1): r-x-y-ono2 (1) or an acceptable salt or stereoisomer for drug use, wherein R is the residue of prostaglandin (2), and its symbol represents a simple or double link; L is selected from the compounds in the preparation group (3),X is -O.-S-O-NHThis is a bivalent radical substance with the following meanings: (a) C1-20 linear or separator chain tar, optionally replaced by one or more substitutes selected from the following groups: halogenated atom, hydroxyl compound, ONO2 or T, where t is - OC (o) (C1-10 tar) - ONO2 or O (C1-10 tar) - on2; cyclopropene with 5 to 7 atoms. C in a ring, in which the ring is replaced by an optional T1 transverse chain, where T1 is a linear or branched C1-10 tar group; (b) a formula compound (4),(c) A formula compound (5), wherein n is an integer from 0 to 20 and N1 is an integer from 0 to 20; (d) a formula compound (6), wherein X1 = - oco-o-coo - and R2 are h or CH3; Z is - (c h) N1 or bivalent radical as defined in (B) above,N1 as defined above, N2 is an integer from 0 to 2; (E) a formula compound (7), wherein Y1 is - ch2-ch2 - (CH2) N2; or - CH = ch - (CH2) N2 -;Z is the bivalent radical as defined in - (CH) N1 - or (b) above,N1, N2, R2 and X1 are previously defined; (f) a formula compound (8), wherein N1 and R2 are previously defined and R3 is h-o-coch3, provided that, in the bivalent radicals mentioned in (b) - (f), once and are selected,2. Group 2 and - (CH2) N1; g) a compound selected from the preparation group (9), wherein X2 is - (O-O-S),N3 is an integer between 1 and 6 and R2; (H) a formula compound (10), wherein N4 is an integer between 0 and 10; N5 is an integer between 1 and 10, R4, R5, R6, R7, equal to or different, and is a linear or branched chain of H or C1-4 oil layer; Among them, group A2 is connected with other formula (11), N5 is defined above; Y2 is a saturated, unsaturated or aromatic heterocyclic ring composed of 5 or 6 members, containing one or more heteroatoms selected from n, O, S,And select (12) from the compounds of the preparation group. ILO Convention No. 11: a process for the preparation of a general (1) formulated compound, defined in ILO Convention No. 1, which includes: (I) reaction to a formulated compound (13), wherein L is defined in ILO Convention No. 1, P is h, or a protective hydroxyl compound and W is - oh, Cl, O-oc (o) R1, R1 is a linear or separator chain C1-5 tar group; contains a z-y-q formulation compound, where and in claim 1, Z is HX or Z1; X is defined in claim 1, Z1 is selected from the following groups: CL, Br, I, mesilo, tosilo; q is - on2 or Z1 and (II), if q is Z1,Conversion of (I) the compound obtained from Paso (I) into a nitrate derivative and (III) the compound obtained from (I) or (II) step is optionally unprotected.