Patent CA-1246594-A (CA)
Inventor: JONES ROBERT L
IPC: C07D493/08
Filed: 1981-06-30
Granted: 1988-12-13
Abstract: ABSTRACT                    PROSTAGLANDINS A process for the preparation of a compound of formula (I)                           (I) wherein    represents one of the divalent cyclic groups   the letters a and b indicating in each case the points of attachment of the substituents R1 and C(R2)=NR, respectively;  R1 is a 6-carboxyhex-2-enyl group or a modification thereof in which the group is altered by one, or an appropriate combination of two or more of the following:  (a) reduction of the double bond optionally accompanied by replacement of a carbon atom at the 1, 2 or 3 position by a sulphur or oxygen atom, (b) alteration of the position of the double bond, (c) shortening or lengthening of the carbon chain by one or two methylene groups, and (d) formation of an amide, ester or salt derivative of the carboxy group;  R2 is hydrogen, a C1-10 aliphatic hydrocarbon group or a C1-10 aliphatic hydrocarbon group substituted directly or through an oxygen or sulphur atom by an aromatic group Ar, where Ar is a phenyl, napthyl, fluorenyl, dibenzocyclohexyl, dibenzo-cycloheptyl, pyridyl, benzthiazolyl, dihydrobenzthiazolyl, N-methyl-dihydrobenzthiazolyl, benzoxazolyl, dihydrobenzoxazolyl or N-methyl-dihydrobenzoxazolyl group or such a group substituted by one or more substituents selected from C1-10 alkoxy, halogen, C1-10 halogen-substituted alkyl, sulphamoyl, amino, hydroxyl, nitro and C1-10 alkyl groups, and R is a group -OR3, -OR4, -A-R3 or -N=R5 in which A is -NH-, -NH.CO-, -NH.CO.CH2N(R6)-, -NH.SO2-, -NH.CO.NH- or -NH.CS.NH- and wherein R3 is a C1-10 aliphatic hydrocarbon group, an aromatic group Ar or an aliphatic hydrocarbon group substituted by one or more groups Ar directly or through an oxygen or sulphur atom, R4 is a C1-10 aliphatic hydrocarbon group which is substituted through an oxygen atom by a C1-10 aliphatic hydrocarbon group which is itself substituted directly by one or more aromatic groups Ar, R5 is a C1-10 aliphatic hydrocarbon group, an aromatic group Ar', where Ar' is a fluorenylidene, dibenzo-cyclohexylidene, dibenzocycloheptylidene, dihydrobenzthiazolylidene, N-methyldihydrobenzthiazolylidene, dihydrobenzoxazolylidene or N-methyldihydrobenzoxazolylidene group or such a group Ar' substituted on a benzene ring or rings thereof by one or more substituents selected from C1-10 alkoxy, halogen, C1-10 halogen-substituted alkyl, sulphamoyl, amino  hydroxyl, nitro and C1-10 groups, or a C1-10 aliphatic hydrocarbon group substituted by one or more aromatic groups Ar directly or through an oxygen or sulphur atom, and R6 is hydrogen, a C1-10 aliphatic hydrocarbon group, an aromatic group Ar or a C1-10 aliphatic hydrocarbon group substituted by one or more groups Ar directly or through an oxygen or sulphur atom;  with the proviso that when R is a group -OR3, -NH.COR3 or -NH.CO.NHR3 then                 excludes the divalent cyclic groups                  and                    comprises reacting a compound of formula (II)   with a reagent ZNH2, Y being either R1 as defined above for compound (I) or a precursor for R1, Z being either R as defined above for compound (I) or a precursor for R, and the other symbols being as defined for compound (I), and where appropriate converting the group Y and/or the group Z in the resultant product into the groups R2 and R, respectively, of the compound (I).  The compounds are of value for use in pharmaceutical compositions particularly in the context of the inhibition of thromboxane activity.