| 摘要 |
Prepn. of cpds. (I) and their acid-addn. salts comprises reaction of (II) or (III) with R1R2NH, NH3 or (IV). (R1 and R2 are H, or 1-10C alkyl, 3-8C cycloalkyl or 4-14C cycloalkylalkyl, all 3 gps. being opt. substd. ; or R2 is H and R1 is R4-E-W-; W is 2-6C n-alkylene opt. substd. by 1 or 2 1-4C alkyls; E is O, S, SO, SO2 or, when R4 is alkyl, NR5; R5 is 1-6C alkyl; R4 is H or 1-6C n-alkyl opt. substd. by 1 or 2 1-4C alkyls; or NR4R5 is a pyrrolidine, piperidine, morpholine, piperazine or N-methylpiperazine ring; in ring X the broken line represents a double bond on one side of the N and Z is C or N such that ring X is an opt. substd. 5- or 6-membered aromatic heterocyclic ring contg. at least 1 N and opt. also contg. 1 or 2 N, S or O; A is phenylene, 5-7C cycloalkylene or 1-8C alkylene opt. substd. by 1 or 2 1-3C alkyls and with 1 or 2 S, O, NH, N-(1-6C)alkyl, cis- or trans-vinylene, ethynylene, phenylene or 5-7C cycloalkylene opt. inserted into the backbone of the chain, . ; R3 is CONR6R7 or C(:NR8)NHR9; R6 is e.g. H, OH, 1-6C alkanoylamino, 1-6C alkyl, 3-8C cycloalkyl, 4-12C cycloalkylalkyl, 2-6C alkenyl, or 2-6C alkynyl, opt. substd. 6-10C aryl, opt. substd. heteroaryl or heteroaralkyl; or R6+R7 complete a 5- to 7-membered satd. ring opt. contg. a double bond or an additional O or 1-6C N-alkyl; R8+R9 form, e.g. with the N.C:N hain to which they are attached, a mono- or bi-cyclic heterocyclic ring system composed of 5- and/or 6-membered rings, the system being opt. partly or fully unsatd., and opt. including additional N, O or S and being opt. substd.; and R8+R9, when joined, is e.g. substd. by heteroarylalkyl, and the heteroaryl is a 5- or 6-membered heterocyclic ring contg. 1-4 heteroatoms selected from O, N or S, and the ring is opt. substd. by 1 or 2 Me; R14 is opt. substd. aryl; and R15 is H or a R1 substit. (other than H)). (20pp Dwg.No.0/0) EPAB- EP-105590 B A process for the manufacture of a guanidine derivative of the formula (I) in which R1 and R2, which may be the same or different, are hydrogen or branched or unbranched 1-10C alkyl, 3-8C cycloalkyl or 4-14C cycloalkylalkyl, each alkyl, cycloalkyl or cycloalkylalkyl being optionally substituted by one or more halogens selected from fluorine, chlorine and bromine, provided that at least one of R1 and R2 is halogen-substituted alkyl, cycloalkyl or cycloalkylalkyl and provided there is no halogen substituent on the carbon of the alkyl, cycloalkyl or cycloalkylalkyl which is directly attached to the nitrogen, or -R2 is hydrogen and -R1 is of the formula R4-E-W- in which W is an unbranched 2-6C alkylene chain which is optionally substituted by one or two 1-4C alkyls, E is oxygen, sulphur, sulphinyl, sulphonyl or, when R4 is alkyl, of the formula NR5 in which R5 is 1-6C alkyl, R4 is hydrogen or an unbranched 1-6C alkyl which is optionally substituted by one or two 1-4C alkyls, or R4 and R5 are joined to form, together with the nitrogen to which they are attached, a pyrrolidine, piperidine, morpholine, piperazine or N-methylpiperazine ring; in ring X the dotted line is a double bond on one side of the nitrogen and Z is carbon or nitrogen such that ring X is a 5- or 6-membered aromatic heterocyclic ring which contains at least one nitrogen and may optionally contain one or two additional hetero atoms selected from oxygen, nitrogen and sulphur, which heterocyclic ring may, where possible, carry one or two optional substitutents, the optional substituents on ring X being selected from fluorine, chlorine, bromine, 1-6C alkyl, 1-6C alkoxy, trifluoromethyl and hydroxy; A is phenylene or 5-7C cycloalkylene or a 1-8C alkylene chain which is optionally substituted by one or two 1-3C alkyls and into which is optionally inserted, as part of the backbone of the chain, one or two groups selected from oxygen, sulphur, NH, 1-6C N-alkyl, cis and trans vinylene, ethynylene, phenylene and 5 - EP-105590 B A process for the manufacture of a guanidine derivative of the formula (I) in which R1 and R2, which may be the same or different, are hydrogen or branched or unbranched 1-10C alkyl, 3-8C cycloalkyl or 4-14C cycloalkylalkyl, each alkyl, cycloalkyl or cycloalkylalkyl being optionally substituted by one or more halogens selected from fluorine, chlorine and bromine, provided that at least one of R1 and R2 is halogen-substituted alkyl, cycloalkyl or cycloalkylalkyl and provided there is no halogen substituent on the carbon of the alkyl, cycloalkyl or cycloalkylalkyl which is directly attached to the nitrogen, or -R2 is hydrogen and -R1 is of the formula R4-E-W- in which W is an unbranched 2-6C alkylene chain which is optionally substituted by one or two 1-4C alkyls, E is oxygen, sulphur, sulphinyl, sulphonyl or, when R4 is alkyl, of the formula NR5 in which R5 is 1-6C alkyl, R4 is hydrogen or an unbranched 1-6C alkyl which is optionally substituted by one or two 1-4C alkyls, or R4 and R5 are joined to form, together with the nitrogen to which they are attached, a pyrrolidine, piperidine, morpholine, piperazine or N-methylpiperazine ring; in ring X the dotted line is a double bond on one side of the nitrogen and Z is carbon or nitrogen such that ring X is a 5- or 6-membered aromatic heterocyclic ring which contains at least one nitrogen and may optionally contain one or two additional hetero atoms selected from oxygen, nitrogen and sulphur, which heterocyclic ring may, where possible, carry one or two optional substitutents, the optional substituents on ring X being selected from fluorine, chlorine, bromine, 1-6C alkyl, 1-6C alkoxy, trifluoromethyl and hydroxy; A is phenylene or 5-7C cycloalkylene or a 1-8C alkylene chain which is optionally substituted by one or two 1-3C alkyls and into which is optionally inserted, as part of the backbone of the chain, one or two groups selected from oxygen, sulphur, NH, 1-6C N-alkyl, cis and trans vinylene, ethynylene, phenylene and 5
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