Claims
- 1. The compounds having the formula (Ic): ##STR27## wherein: R.sup.2 and R.sup.3 are the same or different and each represents a hydrogen atom or hydroxy-protecting group;
- R.sup.5 represents a hydroxymethyl group, a protected hydroxymethyl group, a formyl group, a protected formyl group, a carboxy group, a protected carboxy group or a group of formula --CONR.sub.2 in which each R represents a hydrogen atom; a C.sub.1 -C.sub.6 alkyl group; a phenyl group which is unsubstituted or has at least one substituent selected from a C.sub.1 -C.sub.6 alkyl group, a C.sub.1 -C.sub.6 haloalkyl group, a halogen atom and a C.sub.1 -C.sub.6 alkoxy group; a C.sub.1 -C.sub.6 aliphatic carboxylic acyl group or a sulfonyl group and the two groups or atoms represented by R may be the same or different;
- A represents the --O--CH.sub.2 --or , --S--CH.sub.2 -- group;
- m represents 0 or an integer from 1 to 4;
- n' represents an integer from 2 to 4;
- B.sup.c represents the --CH.sub.2 CH.sub.2 --, trans--CH.dbd.CH-- or --C.tbd.C-- group;
- R.sup.4c represents a C.sub.3 -C.sub.12 alkenyl group;
- a C.sub.3 -C.sub.12 alkynyl group, said alkenyl and alkynyl groups being unsubstituted or having one or more substituents selected from halogen atoms, C.sub.1 -C.sub.6 alkoxy groups, hydroxy, and C.sub.1 -C.sub.6 aliphatic carboxylic acyl groups; a C.sub.3 -C.sub.7 cycloalkyl group, said cycloalkyl group being unsubstituted or having at least one substituent selected from C.sub.1 -C.sub.6 alkyl groups, C.sub.1 -C.sub.6 haloalkyl groups, halogen atoms, C.sub.1 -C.sub.6 alkoxyl groups, hydroxy and C.sub.1 -C.sub.6 aliphatic carboxylic acyl groups; or a group of formula --CH.sub.2 --Q.sub.p --R.sup.6 wherein p represents 0 or 1; Q represents an oxygen atom, a sulphur atom or a --CH.sub.2 -- group; and R.sup.6 represents a C.sub.3 -C.sub.7 cycloalkyl group which is unsubstituted or has at least one substituent selected from C.sub.1 -C.sub.6 alkyl groups, C.sub.1 14 C.sub.6 haloalkyl groups, halogen atoms, C.sub.1 -C.sub.6 alkoxy groups, hydroxy and C.sub.1 -C.sub.6 aliphatic carboxylic acyl group; or a phenyl group which is unsubstituted or has at least one substituent selected from C.sub.1 -C.sub.6 alkyl groups, C.sub.1 -C.sub.6 haloalkyl groups, halogen atoms and C.sub.1 -C.sub.6 alkoxy groups; the dotted line represents a double bond between the 2- and 3-positions or between the 3- and 4- positions and a single bond between the other of said positions; and
- said hydroxy-protecting group and the protecting group of said protected hydroxymethyl group represents a C.sub.1 -C.sub.6 aliphatic carboxylic acyl group, benzoyl group, toluoyl group, naphthoyl group, a phenyl-(C.sub.1 -C.sub.2 alkyl) group, a naphthyl-(C.sub.1 -C.sub.2 alkyl) group, a C.sub.1 -C.sub.3 alkoxymethyl group, benzoylmethyl group, a 1-(C.sub.1 -C.sub.3 alkoxy)ethyl group, a tri-(C.sub.1 -C.sub.6 alkyl)silyl group, a diphenyl-(C.sub.1 -C.sub.6 alkyl)silyl group, or a 5- or 6-membered heterocyclic group containing only at least one of oxygen and sulphur as the heteroatoms and containing 1 to 3 atoms as heteroatoms and optionally having a C.sub.1 -C.sub.6 alkoxy group as a substituent;
- and pharmaceutically acceptable salts thereof.
- 2. The compounds as claimed in claim 1, wherein:
- R.sup.5 represents a hydroxymethyl group, a protected hydroxymethyl group, a carboxy group, a protected carboxy group or the group of formula --CO.NR.sub.2 ; R.sup.2 and R.sup.3 both represent hydrogen atoms; R.sup.4c represents a C.sub.3 -C.sub.12 alkenyl group, a C.sub.4 -C.sub.7 alkynyl group, an optionally substituted 5- or 6- membered cycloalkyl group or a group of formula --CH.sub.2 --Q.sub.p --R.sup.6c in which p is 0 or p is 1 and Q represents an oxygen atom or a methylene group and R.sup.6c represents a 5- or 6- membered cycloalkyl group or a phenyl group (said cycloalkyl or phenyl group optionally having one or more C.sub.1 -C.sub.6 alkyl, halogen or C.sub.1 -C.sub.6 alkoxy substituents; A represents an oxymethylene group or a thiomethylene group.
- 3. The compounds as claimed in claim 1, wherein: R.sup.5 represents a hydroxymethyl group, a carboxy group, a protected carboxy group or an N-methanesulfonyl-carbamoyl group; R.sup.2 and R.sup.3 both represent hydrogen atoms; R.sup.4c represents a C.sub.3 -C.sub.12 alkenyl group, a C.sub.4 -C.sub.7 alkynyl group, an optionally substituted 5- or 6- membered cycloalkyl group or a group of formula --CH.sub.2 --Q.sub.p --R.sup.6c (in which p is 0 or p is 1 and Q represents an oxygen atom or a methylene group, and R.sup.6c represents a 5- or 6- membered cycloalkyl or phenyl group, said cycloalkyl or phenyl group optionally having one or more C.sub.1 -C.sub.6 alkyl, halogen or C.sub.1 -C.sub.6 alkoxy substituents); A represents an oxymethylene group, a thiomethylene group or a vinylene group and B.sup.c represents a trans-vinylene group.
- 4. The compounds as claimed in claim 1, wherein: R.sup.5 represents a hydroxymethyl group, a carboxy group or a protected carboxy group; R.sup.2 and R.sup.3 both represent hydrogen atoms; R.sup.4c represents a C.sub.3 -C.sub.12 alkenyl group, a C.sub.4 -C.sub.7 alkynyl group, an optionally substituted 5- or 6- membered cycloalkyl group or a group of formula --CH.sub.2 --Q.sub.p R.sup.6c (in which p is 0 or p is 1 and Q represents an oxygen atom, and R.sup.6c represents a 5- or 6- membered cycloalkyl group or a phenyl group, said cycloalkyl or phenyl group optionally having one or more methyl, fluorine, chlorine or methoxy substituents); A represents an oxymethylene group or a thiomethylene group; B.sup.c represents a trans-vinylene group,
- 5. The compounds as claimed in claim 1, wherein:
- R.sup.5 represents a hydroxymethyl group, a carboxy group or a methoxycarbonyl group; R.sup.2 and R.sup.3 both represent hydrogen atoms; R.sup.4c represents a C.sub.3 -C.sub.12 alkenyl group, a C.sub.4 -C.sub.7 alkynyl group, a cyclopentyl group, a cyclohexyl group or a group of formula --CH.sub.2 --Q.sub.p --R.sup.6c (which in p is 0, or p is 1 and Q represents an oxygen atom, and R.sup.6c represents a cyclopentyl group, a cyclohexyl group or a phenyl group); A represents an oxymethylene group or a thiomethylene group; B.sup.c represents a trans- vinylene group; and n' is 2.
- 6. The compounds as claimed in claim 1, wherein m is 0.
- 7. The compounds as claimed in claim 1, wherein the double bond is at the 2- position.
- 8. The compounds as claimed in claim 1, selected from the group consisting of:
- 3-[2-(Carboxymethoxy)ethyl]-6.beta.-(3.alpha.-hydroxyoct-5-en-1-ynyl)7.alpha.-hydroxy-cis-bicyclo[3,3,0]oct-2/3-ene
- 3-[2-(Carboxymethoxy)ethyl]-6.beta.-(3.alpha.-hydroxy-5-methyl- nona-1[-dienyl)-7.alpha.-hydroxy-cis-bicyclo[3,3,0]oct-2/3-ene
- 3-[2-(Carboxymethoxy)ethyl]-6.beta.-(3.alpha.-hydroxy-4,7- dimethylocta-1,6-dienyl )-7.alpha.-hydroxy-cis-bicyclo[3,3.0]-oct-2/3-ene
- 3-[2-(Carboxymethoxy)ethyl]-6.beta.-(3.alpha.-hydroxy-9-methyl-deca-1,8-dienyl)-7.alpha.-hydroxy-cis-bicyclo[3,3,0oct-2/3ene
- 3-[2-(Carboxymethoxy)ethyl]-6.beta.-(3.alpha.-hydroxy-5,9-dimethyldeca-1.8-dienyl)-7.alpha.-hydroxy-cis-bicyclo[3,3,0]-oct-2/3-ene
- 3-[2-(Carboxymethoxy)ethyl]-6.beta.-(3.alpha.-hydroxy4-methyloct-1-en-6-ynyl)-7.alpha.-hydroxy-cis-bicyclo[3,3,0]oct-2/3-ene
- 3-[2-(Carboxymethoxy)ethyl]-6.beta.-(3.alpha.-hydroxy4,4-dimethyloct-1-en-6-ynyl)-7.alpha.-hydroxy-cis-bicyclo[3,3,0]oct-2/3-ene
- 3-[2-(Carboxymethoxy)ethyl]-6.beta.-(3.alpha.-hydroxy3-cyclopentylprop-1-enyl)-7.alpha.-hydroxy-cis-bicyclo[3,3,0]oct-2/3-ene
- 3-[2-(Carboxymethoxy)ethyl]-6.beta.-(3.alpha.-hydroxy3-cyclohexylprop-1-enyl)-7.alpha.-hydroxy-cis-bicyclo[3,3,0]oct-2/3-ene
- 3-[2-(Carboxymethoxy)ethyl]-6.beta.-(3.alpha.-hydroxy4-cyclopentylbut-1-enyl)-7.alpha.-hydroxy-cis-bicyclo[3,3,0]oct-2/3-ene
- 3-[2-(Carboxymethoxy)ethyl]-6.beta.-(3.alpha.-hydroxy-4-phenoxybut-1-enyl)-7.alpha.-hydroxy-cis-bicyclo-3,3,0]oct-2/3-ene
- 3-[2-(Methanesulfonylcarbamoylmethoxy)ethyl]-6.beta.-(3.alpha.-hydroxy-5,9-dimethyldeca-1,8-dienyl)-7.alpha.- hydroxy-cis-bicyclo[3,3,0]oct-2/3-ene (wherein "oct-2/3-ene" means oct-2-ene, oct-3-ene or a mixture of oct-2-ene and oct-3-ene) and pharmaceutically acceptable salts and esters thereof.
- 9. The compounds as claimed in claim 6, wherein the double bond is at the 2- position.
- 10. The compound of claim 1, wherein A is --O--CH.sub.2 --.
- 11. The compounds of claim 1 wherein R.sup.4c is 1-methyl-5-hexenyl, 1-methyl-3-pentynyl, cyclopentyl and cyclohexyl and A is --O--CH.sub.2.
- 12. The compound of claim 1 wherein R.sup.4c is C.sub.3 -C.sub.12 is alkenyl or C.sub.3 -C.sub.12 alkynyl.
- 13. The compound as claimed in claim 1, selected from the group consisting of 3-[2-Carboxymethoxy)ethyl]-6.beta.(3.alpha.-hydroxyoct-5-en-1-ynyl)-7.alpha.-hydroxy-cis-bicyclo[3,3,0]oct-2/3-ene (wherein "oct-2/3-ene" means oct-2-ene, oct-3-ene or a mixture of oct-2-ene and oct-3-ene) and pharmaceutically acceptable salts and esters thereof.
- 14. The compound as claimed in claim 1, selected from the group consisting of 3-[2-(Carboxymethoxy)ethyl]-6.beta.-(3.alpha.-hydroxy-4-methyl-nona-1,8-dienyl)-7.beta.-hydroxy-cis-bicyclo[3,3,0]oct-2/3-ene (wherein "oct-2/3-ene" means oct-2-ene, oct-3-ene or a mixture of oct-2-ene and oct-3-ene) and pharmaceutically acceptable salts and esters thereof.
- 15. The compound as claimed in claim 1, selected from the group consisting of 3-[2-Carboxymethoxy)ethyl]-6.beta.-(3.alpha.-hydroxy-4,7-dimethylocta-1,6-dienyl)-7.alpha.-hydroxy-cis-bicyclo[3,3,0]-oct-2/3-ene (wherein "oct-2/3-ene" means oct-2-ene, oct-3-ene or a mixture of oct-2-ene and oct-3-ene) and pharmaceutically acceptable salts and esters thereof.
- 16. The compounds as claimed in claim 1, selected from the group consisting of 3-[2-(Carboxymethoxy)ethyl]-6.beta.-(3.alpha.-hydroxy-9-methyl-deca-1,8-dienyl)-7.beta.-hydroxy-cis-bicyclo[3,3,0]oct-2/3-ene (wherein "oct-2/3-ene" means oct-2-ene, oct-3-ene or a mixture of oct-2-ene and oct-3-ene) and pharmaceutically acceptable salts and esters thereof.
- 17. The compound as claimed in claim 1, selected from the group consisting of 3-[2-(Carboxymethoxy)ethyl]-6.beta.(3.alpha.-hydroxy-5,9-dimethyldeca-1,8-dienyl)-7.alpha.-hydroxy-cis-bicyclo[3,3,0]-oct-2/3-ene (wherein "oct-2/3-ene" means oct-2-ene, oct-3-ene or a mixture of oct-2-ene and oct-3-ene) and pharmaceutically acceptable salts and esters thereof.
- 18. The compound as claimed in claim 1, selected from the group consisting of 3-[2-(Carboxymethoxy)ethyl]-6.beta.-(3.alpha.-hydroxy-4-methyloct-1-en-6-ynyl)-7.alpha.-hydroxy-cis-bicyclo-[3,3,0]oct-2/3-ene (wherein "oct-2/3-ene" means oct-2-ene, oct-3-ene or a mixture of oct-2-ene and oct-3-ene) and pharmaceutically acceptable salts and esters thereof.
- 19. The compound as claimed in claim 1, selected from the group consisting of 3-[2-(Carboxymethoxy)ethyl]-6.beta.-(3.alpha.-hydoxy-4,4-dimethyloct-1-en-6-ynyl)-7.alpha.-hydroxy-cis-bicyclo-[3,3,0]oct-2/3-ene (wherein "oct-2/3-ene" means oct-2-ene, oct-3-ene or a mixture of oct-2-ene and oct-3-ene)and pharmaceutically acceptable salts and esters thereof.
- 20. The compound as claimed in claim 1, selected from the group consisting of 3-[2-(Carboxymethoxy)ethyl]-6.beta.-(3.alpha.-hydroxy-3-cyclopentylprop-1-enyl)-7.alpha.-hydroxy-cis-bicyclo-[3,3,0]-oct-2/3-ene (wherein "oct-2/3-ene" means oct-2-ene, oct-3-ene or a mixture of oct-2-ene and oct-3-ene) and phrarmaceutically acceptable salts and esters thereof.
- 21. The compound as claimed in claim 1, selected from the group consisting of 3-[2-(Carboxymethoxy)ethyl]-6.beta.-(3.alpha.-hydroxy-3-cyclohexylprop-1-enyl)-7.alpha.-hydroxy-cis-bicyclo-[3,3,0]oct-2/3-ene (wherein "oct-2/3-ene" means oct-2-ene, oct-3-ene or a mixture of oct-2-ene and oct-3-ene) and pharmaceutically acceptable salts and esters thereof.
- 22. The compound as claimed in claim 1, selected from the group consisting of 3-[2-(Carboxymethoxy)ethyl]-6.beta.-(3.alpha.-hydroxy-4-cyclopentylbut-1-enyl)-7.alpha.-hydroxy-cis-bicyclo-[3,3,0]-oct-2/3-ene (wherein "oct-2/3-ene" means oct-2-ene, oct-3-ene or a mixture of oct-2-ene and oct-3-ene) and pharmaceutically acceptable salts and esters thereof.
- 23. The compound as claimed in claim 1, selected from the group consisting of 3-[2-(Carboxymethoxy)ethyl]-6.beta.-(3.alpha.-hydroxy-4-phenoxybut-1-enyl)-7.alpha.-hydroxy-cis-bicyclo-[3,3,0]oct-2/3-ene (wherein "oct-2/3-ene" means oct-2-ene, oct-3-ene or a mixture of oct-2-ene and oct-3-ene) and pharmaceutically acceptable salts and esters thereof.
- 24. The compound as claimed in claim 1, selected from the group consisting of 3-[2-(Methanesulfonylcarbamoylmethoxy)ethyl]-6.beta.-(3.alpha.-hydroxy-5,9-dimethyldeca-1,8-dienyl)-7.alpha.-hydroxy-cis-bicyclo[3,3,0]oct-2/3-ene (wherein "oct-2/3-ene" means oct-2-ene, oct-3-ene or a mixture of oct-2-ene and oct-3-ene) and pharmaceutically acceptable salts and esters thereof.
- 25. A pharmaceutical composition comprising at least one therapeutic compound in admixture with a pharmaceutically acceptable carrier or diluent wherein said compound is selected from the group consistent of compounds of the formula (Ic): ##STR28## wherein: R.sup.2 and R.sup.3 are the same or different and each represents a hydrogen atom or hydroxy-protecting group;
- R.sup.5 represents a hydroxymethyl group, a protected hydroxymethyl group, a formyl group, a protected formyl group, a carboxy group, a protected carboxy group or a group of formula --CONR.sub.2 in which each R represents a hydrogen atom; a C.sub.1 -C.sub.6 alkyl group; a phenyl group which is unsubstituted or has at least one substituent selected from a C.sub.1 -C.sub.6 alkyl group, a C.sub.1 -C.sub.6 haloalkyl group, a halogen atom and a C.sub.1 -C.sub.6 alkoxy group; a C.sub.1 -C.sub.6 aliphatic carboxylic acyl group or a sulfonyl group and the two groups or atoms represented by R may be the same or different;
- A represents the --O--CH.sub.2 --, or --S--CH.sub.2 -- group;
- m represents 0 or an integer from 1 to 4;
- n' represents an integer from 2 to 4;
- B.sup.c represents the --CH.sub.2 CH.sub.2 --, trans--CH.dbd.CH-- or --C.tbd.C-- group;
- R.sup.4c represents a C.sub.3 -C.sub.12 alkenyl group;
- a C.sub.3 -C.sub.12 alkynyl group, alkenyl and alkynyl groups being unsubstituted or having one or more substituents selected from halogen atoms, C.sub.1 -C.sub.6 alkoxy groups, hydroxy, and
- C.sub.1 -C.sub.6 aliphatic carboxylic acyl groups, a C.sub.3 -C.sub.7 cycloalkyl group, said cycloalkyl group being unsubstituted or having at least one substituent selected from C.sub.1 -C.sub.6 alkyl groups, C.sub.1 -C.sub.6 haloalkyl groups, halogen atoms, C.sub.1 -C.sub.6 alkoxyl groups, hydroxy and C.sub.1 -C.sub.6 aliphatic carboxylic acyl groups; or a group of formula --CH.sub.2 --Q.sub.p --R.sup.6 wherein p represents 0 or 1; Q represents an oxygen atom, a sulphur atom or a -CH.sub.2 -- group; and R.sup.6 represents a C.sub.3 -C.sub.7 cycloalkyl group which is unsubstituted or has at least one substituent selected from C.sub.1 -C.sub.6 alkyl groups, C.sub.1 -C.sub.6 haloalkyl groups, halogen atoms, C.sub.1 -C.sub.6 alkoxy groups, hydroxy and C.sub.1 -C.sub.6 aliphatic carboxylic acyl groups; or a phenyl group which is unsubstituted or has at least one substituent selected from C.sub.1 -C.sub.6 alkyl groups, C.sub.1 -C.sub.6 haloalkyl groups, halogen atoms and C.sub.1 -C.sub.6 alkoxy groups; the dotted line represents a double bond between the 2- and 3positions or between the 3- and 4- positions and a single bond between the other of said positions; and
- said hydroxy-protectinq group and the protectinq group of said protected hydroxymethyl group represents a C.sub.1 -C.sub.6 aliphatic carboxylic acyl group, benzoyl group, toluoyl group, naphthoyl group, a phenyl-(C.sub.1 -C.sub.2 alkyl) group, a naphthyl-(C.sub.1 -C.sub.2 alkyl) group, a C.sub.1 -C.sub.3 alkoxymethyl group, benzoylmethyl group, a 1-(C.sub.1 -C.sub.3 alkoxy)ethyl group, a tri-(C.sub.1 -C.sub.6 alkyl)silyl group, a diphenyl-(C.sub.1 -C.sub.6 alkyl)silyl group, or a 5- or 6-membered heterocyclic group containing only at least one of oxygen and sulphur as the heteroatoms and containing 1 to 3 atoms as heteroatoms and optionally having a C.sub.1 -C.sub.6 alkoxy group as a substituent;
- and pharmaceutically acceptable salts thereof.
- 26. The composition as claimed in claim 25, wherein:
- R.sup.5 represents a hydroxymethyl group, a protected hydroxymethyl group, a carboxy group, a protected carboxy group or the group of formula --CO.NR.sub.2 ; R.sup.2 and R.sup.3 both represent hydrogen atoms; R.sup.4c represents a C.sub.3 -C.sub.12 alkenyl group, a C.sub.4 -C.sub.7 alkynyl group, an optionally substituted 5- or 6- membered cycloalkyl group or a group of formula --CH.sub.2 --Q.sub.p --R.sup.6c in which p is 0 or p is 1 and Q represents an oxygen atom or a methylene group and R.sup.6c represents a 5- or 6- membered cycloalkyl group or a phenyl group (said cycloalkyl or phenyl group optionally having one or more C.sub.1 -C.sub.6 alkyl, halogen or C.sub.1 -C.sub.6 alkoxy substituents); A represents an oxymethylene group or a thiomethylene group.
- 27. The composition as claimed in claim 25, wherein:
- R.sup.5 represents a hydroxymethyl group, a carboxy group, a protected carboxy group or an N-methanesulfonylcarbamoyl group; 2 and R.sup.3 both represent hydrogen atoms; R.sup.4c represents a C.sub.3 -C.sub.12 alkenyl group, a C.sub.4 -C.sub.7 alkynyl group, an optionally substituted 5- or 6- membered cycloalkyl group or a group of formula --CH.sub.2 --Q.sub.p --R.sup.6c (in which p is 0 or p is 1 and Q represents an oxygen atom or a methylene group, and
- R.sup.6c represents a 5- or 6- membered cycloalkyl or phenyl group, said cycloalkyl or phenyl group optionally having one or more C.sub.1 -C.sub.6 alkyl, halogen or C.sub.1 -C.sub.6 alkoxy substituents); A represents an oxymethylene group, a thiomethylene group or a vinylene group; and
- B.sup.c represents a trans-vinylene group.
- 28. The composition as claimed in claim 25, wherein:
- R.sup.5 represents a hydroxymethyl group, a carboxy group or a protected carboxy group; R.sup.2 and R.sup.3 both represent hydrogen atoms; R.sup.4c represents a C.sub.3 -C.sub.12 alkenyl group, a C.sub.4 -C.sub.7 alkynyl group, an optionally substituted 5- or 6- membered cycloalkyl group or a group of formula --CH.sub.2 --Q.sub.p --R.sup.6c (in which p is 0 or p is 1 and Q represents an oxygen atom, and R.sup.6c represents a 5- or 6- membered cycloalkyl group or a phenyl group, said cycloalkyl or phenyl group optionally having one or more methyl, fluorine, chlorine or methoxy substituents): A represents an oxymethylene group or a thiomethylene group; B.sup.c represents a trans-vinylene group.
- 29. The composition as claimed in claim 25, wherein:
- R.sup.5 represents a hydroxymethyl group, a carboxy group or a methoxycarbonyl group; R.sup.2 and R.sup.3 both represent hydrogen atoms; R.sup.4c represents a C.sub.3 -C.sub.12 alkenyl group, a C.sub.4 -C.sub.7 alkynyl group, a cyclopentyl group, a cyclohexyl group or a group of formula --CH.sub.2 --Q.sub.p --R.sup.6c (in which p is 0, or p is 1 and Q represents an oxygen atom, and R.sup.6c represents a cyclopentyl group, a cyclohexyl group or a phenyl group); A represents an oxymethylene group or a thiomethylene group; B.sup.c represents a trans- vinylene group; and n is 2.
- 30. The composition as claimed in any one of claims 25 to wherein m is 0.
- 31. The composition as claimed in claim 30, wherein the double bond is at the 2-position.
- 32. The composition as claimed in claim 25 wherein the double bond is at the 2-position.
- 33. The composition as claimed in claim 25, wherein said compound is selected from the group consisting of:
- 3-[2-(Carboxymethoxy)ethyl]-6.beta.-(3.alpha.-hydroxy-oct-5-en-1-ynyl)-7.alpha.-hydroxy-cis-bicyclo[3,3,0]-oct-2/3-ene
- 3-[2-(Carboxymethoxy)ethyl]-6.beta.-(3.alpha.-hydroxy-4-methylnona-1,8-dienyl)-7.alpha.-hydroxy-cis-bicyclo[3,3,0]- oct-2/3-ene
- 3-[2-(Carboxymethoxy)ethyl]-6.beta.-(3.alpha.-hydroxy-4,7-dimethylocta-1,6-dienyl)-7.alpha.-hydroxy-cis-bicyclo[3,3,0]oct-2/3-ene
- 3-[2-(Carboxymethoxy)ethyl]-6.beta.-(3.alpha.-hydroxy-9-methyldeca-1,8-dienyl)-7.alpha.-hydroxy-cis-bicyclo[3,3,0]-oct-2/3-ene
- 3-[2-(Carboxymethoxy)ethyl]-6.beta.-(3.alpha.-hydroxy-5,9-dimethyldeca-1,8-dienyl)-7.alpha.-hydroxy-cis-bicyclo[3,3,0]oct-2/3-ene
- 3-[2-(Carboxymethoxy)ethyl]-6.beta.-(3.alpha.-hydroxy-4-methyloct-1-en-6-ynyl)-7.alpha.-hydroxy-cis-bicyclo[3,3.0]oct-2/3-ene
- 3-[2-(Carboxymethoxy)ethyl]-6.beta.-(3.alpha.-hydroxy-4,4-dimethyloct-1-en-6-ynyl)-7.alpha.-hydroxy-cis-bicyclo[3,3,0]oct-2/3-ene
- 3- [2- (Carboxymethoxy)ethyl]-62 - (3.alpha.-hydroxy-3-cyclopentylprop-1-enyl )-7.alpha.-hydroxy-cis-bicyclo[3,3,0]oct-2/3-ene
- 3-[2-(Carboxymethoxy)ethyl]-6.beta.-(3.alpha.-hydroxy-3-cyclohexylprop-1-enyl)-7.alpha.-hydroxy-cis-bicyclo[3,3,0]oct-2/3-ene
- 3-[2-(Carboxymethoxy)ethyl]-6.beta.-(3.alpha.-hydroxy-4-cyclopentylbut-1-enyl)-7.alpha.-hydroxy-cis-bicyclo[3,3,0]oct-2/3-ene
- 3-[2-(Carboxymethoxy)ethyl]-6.beta.-(3.alpha.-hydroxy-4-phenoxybut-1-enyl)-7.alpha.-hydroxy-cis-bicyclo[3,3,0]oct-2/3-ene
- 3-[2-(Methanesulfonylcarbamoylmethoxy)ethyl]6.beta.-(3.alpha.-hydroxy-5,9-dimethyldeca-1,8-dienyl)-7.alpha.-hydroxy-cis-bicyclo[3,3,0]oct-2/3-ene
- (wherein "oct-2/3-ene" means oct-2-ene, oct-3-ene or a mixture of oct-2-ene and oct-3-ene) and pharmaceutically acceptable salts and esters thereof.
- 34. A method of treating a mammal for the treatment off prophylaxis of thrombosis by administering thereto an effective amount of at least one compound selected from the group consisting of compounds having the formula (Ic): ##STR29## wherein: R.sup.2 and R.sup.3 are the same or different and each represents a hydrogen atom or hydroxy-protecting group;
- R.sup.5 represents a hydroxymethyl group, a protected hydroxymethyl group, a formyl group, a protected formyl group, a carboxy group, a protected carboxy group or a group of formula --CONR.sub.2 in which each R represents a hydrogen atom; a C.sub.1 -C.sub.6 alkyl group; a phenyl group which is unsubstituted or has at least one substituent selected from a C.sub.1 -C.sub.6 alkyl group, a C.sub.1 -C.sub.6 haloalkyl group, a halogen atom and a C.sub.1 -C.sub.6 alkoxy group; a C.sub.1 -C.sub.6 aliphatic carboxylic acyl group or a sulfonyl group and the two groups or atoms represented by R may be the same or different;
- A represents the --O--CH.sub.2 --, or --S--CH.sub.2 -- group;
- m represents 0 or an integer from 1 to 4;
- n' represents an integer from 2 to 4;
- B.sup.C represents the --CH.sub.2 CH.sub.2 --, trans--CH.dbd.CH-- or --C.tbd.C-- group;
- R.sup.4C represents a C.sub.3 -C.sub.12 alkenyl group;
- a C.sub.3 -C.sub.12 alkynyl group, alkenyl and alkynyl groups being unsubstittuted or having one or more substituents selected from halogen atoms, C.sub.1 -C.sub.6 alkoxy groups, hydroxy, and C.sub.1 -C.sub.6 aliphatic carboxylic acyl groups; a C.sub.3 -C.sub.7 cycloalkyl group, said cycloalkyl group being unsubstituted or having at least one substituent selected from C.sub.1 -C.sub.6 alkyl groups, C.sub.1 -C.sub.6 haloalkyl groups, halogen atoms, C.sub.1 -C.sub.6 alkoxyl groups, hydroxy and C.sub.1 -C.sub.6 aliphatic carboxylic acyl groups; or a group of formula --CH.sub.2 --Q.sub.p --R.sup.6 wherein p represents 0 or 1; Q represents an oxygen atom, a sulphur atom or a --CH.sub.2 -- group; and R.sup.6 represents a C.sub.3 -C.sub.7 cycloalkyl group which is unsubstituted or has at least one substituent selected from C.sub.1 -C.sub.6 alkyl groups, C.sub.1 -C.sub.6 haloalkyl groups, halogen atoms, C.sub.1 -C.sub.6 alkoxy groups, hydroxy and C.sub.1 -C.sub.6 aliphatic carboxylic acyl groups; or a phenyl group which is unsubstituted or has at least one substituent selected from C.sub.1 -C.sub.6 alkyl groups, C.sub.1 -C.sub.6 haloalkyl groups, halogen atoms and C.sub.1 -C.sub.6 alkoxy groups; the dotted line represents a double bond between the 2- and 3-positions or between the 3- and 4- positions and a single bond between the other of said positions; and
- said hydroxy-protcting group and the protecting group of said protected hydroxymethyl group represents a C.sub.1 -C.sub.6 aliphatic carboxylic acyl group, benzoyl group, toluoyl group, naphthoyl group, a phenyl-(C.sub.1 -C.sub.2 alkyl) group, a naphthyl-(C.sub.1 -C.sub.2 alkyl) group, a C.sub.1 -C.sub.3 alkoxymethyl group, benzoylmethyl group, a 1-(C.sub.1 -C.sub.3 alkoxy)ethyl group, a tri-(C.sub.1 -C.sub.6 alkyl)silyl group, a diphenyl-(C.sub.1 -C.sub.6 alkyl)silyl group, or a 5- or 6-membered heterocyclic group containing only at least one of oxygen and sulphur as the heteroatoms and containing 1 to 3 atoms as heteroatoms and optionally having a C.sub.1 -C.sub.6 alkoxy group as a substituent;
- and pharmaceutically acceptable salts thereof.
- 35. The method as claimed in claim 32 wherein:
- R.sup.5 represents a hydroxymethyl group, a protected hydroxymethyl group, a carboxy group, a protected carboxy group or the group of formula --CO.NR.sup.2 ; R.sup.2 and R.sup.3 both represent hydrogen atoms; R.sup.4c represents a C.sub.3 -C.sub.12 alkenyl group, a C.sub.4 -C.sub.7 alkynyl group, an optionally substituted 5- or 6- membered cycloalkyl group or a group of formula --CH.sub.2 --Q.sub.p --R.sup.6c in which p is 0 or p is 1 and Q represents an oxygen atom or a methylene group and R.sup.6c represents a 5- or 6- membered cycloalkyl group or a phenyl group (said cycloalkyl or phenyl group optionally having one or more C.sub.1 -C.sub.6 alkyl, halogen or C.sub.1 -C.sub.6 alkoxy substituents); A represents an oxymethylene group or a thiomethylene group.
- 36. The method as claimed in claim 32, wherein:
- R.sup.5 represents a hydroxymethyl group, a carboxy group, a protected carboxy group or an N-methanesulfonylcarbamoyl group; R.sup.2 and R.sup.3 both represent hydrogen atoms; R.sup.4c represents a C.sub.3 -C.sub.12 alkenyl group, a C.sub.4 -C.sub.7 alkynyl group, an optionally substituted 5- or 6- membered cycloalkyl group or a group of formula --CH.sub.2 --Q.sub.p --R.sup.6c (in which p is 0 or p is 1 and Q represents an oxygen atom or a methylene group, and
- R.sup.6c represents a 5- or 6- membered cycloalkyl or phenyl group, said cycloalkyl or phenyl group optionally having one or more C.sub.1 -C.sub.6 alkyl, halogen or C.sub.1 -C.sub.6 alkoxy substituents); A represents an oxymethylene group, a thiomethylene group or a vinylene group; and B.sup.c represents a trans-vinylene group.
- 37. The method as claimed in claim 32, wherein:
- R.sup.5 represents a hydroxymethyl group, a carboxy group or a protected carboxy group; R.sup.2 and R.sup.3 both represent hydrogen atoms; R.sup.4c represents a C.sub.3 -C.sub.12 alkenyl group, a C.sub.4 -C.sub.7 alkynyl group, an optionally substituted 5- or 6- membered cycloalkyl group or a group of formula -CH.sub.2 --Q.sub.p --R.sup.6c (in which p is 0 or p is 1 and Q represents an oxygen atom, and R.sup.6c represents a 5- or 6- membered cycloalkyl group or a phenyl group, said cycloalkyl or phenyl group optionally having one or more methyl, fluorine, chlorine or methoxy substituenta); A represents an oxymethylene group or a thiomethylene group; B.sup.c represents a trans-vinylene group,
- 38. The method as claimed in claim 32, wherein:
- R.sup.5 represents a hydroxymethyl group, a carboxy group or a methoxycarbonyl group; R.sup.2 and R.sup.3 both represent hydrogen atoms; R.sup.4c represents a C.sub.3 -C.sub.12 alkenyl group, a C.sub.4 -C.sub.7 alkynyl group, a cyclopentyl group, a cyclohexyl group or a group of formula --CH.sub.2 --Q.sub.p --R.sup.6c (in which p is 0, or p is 1 and Q represents an oxygen atom, and R.sup.6c represents a cyclopentyl group, a cyclohexyl group or a phenyl group); A represents an oxymethylene group or a thiomethylene group; B.sup.c represents a trans- vinylene group; and n' is 2.
- 39. The method as claimed in claim 36, wherein m is 0.
- 40. The method as claimed in claim 39, wherein the double bond is at the 2-position.
- 41. The method as claimed in claim 35 wherein the double bond is at the 2-position.
- 42. The method as claimed in claim 35, wherein said compound is selected from the group consisting of:
- 3-[2-(Carboxymethoxy)ethyl]-6.beta.-(3.alpha.-hydroxy- oct-5-en-1-ynyl)-7.alpha.-hydroxy-cis-bicyclo[3,3,0]- oct-2/3-ene
- 3-[2-(Carboxymethoxy)ethyl]-6.beta.- (3.alpha.-hydroxy-4-methylnona-1,8-dienyl ) -7.alpha.-hydroxy-cis-bicyclo[3,3,0 ]-oct-2/3-ene
- 3-[2-(Carboxymethoxy)ethyl]-68-(3.alpha.-hydroxy-4,7-dimethylocta-1,6-dienyl)-7.alpha.-hydroxy-cis-bicyclo[3,3,0]oct-2/3-ene
- 3-[2-(Carboxymethoxy)ethyl]-6.beta.-(3.alpha.-hydroxy-9-methyldeca-1,8-dienyl)-7.alpha.-hydroxy-cis-bicyclo[3,3,0]oct-2/3-ene
- 3-[2-(Carboxymethoxy)ethyl]-6.beta.-(3.alpha.-hydroxy-5,9-dimethyldeca-1,8-dienyl)-7.alpha.-hydroxy-cis-bicyclo[3,3,0]oct-2/3-ene
- 3-[2-(Carboxymethoxy)ethyl]-6.beta.-(3.alpha.-hydroxy-4-methyloct-1-en-6-ynyl)-7.alpha.-hydroxy-cis-bicyclo[3.3,0]oct-2/3-ene
- 3-[2-(Carboxymethoxy)ethyl]-6.beta.-(3.alpha.-hydroxy-4,4-dimethyloct-1-en-6-ynyl)-7.alpha.-hydroxy-ciebicyclo[3,3,0]oct-2/3-ene
- 3-[2-(Carboxymethoxy)ethyl]-6.beta.-(3.alpha.-hydroxy-3-cyclopentylprop-1-enyl)-7.alpha.-hydroxy-cis-bicyclo[3,3,0]oct-2/3-ene
- 3-[2-(Carboxymethoxy)ethyl]-6.beta.-(3.alpha.-hydroxy-3-cyclohexylprop-1-enyl)-7.alpha.-hydroxy-cis-bicyclo[3,3,0]oct-2/3-ene
- 3-[2-(Carboxymethoxy)ethyl]-6.beta.-(3.alpha.-hydroxy-4-cyclopentylbut-1-enyl)-7.alpha.-hydroxy-cis-bicyclo[3,3,0]oct-2/3-ene
- 3-[2-(Carboxymethoxy)ethyl]-6.beta.-(3.alpha.-hydroxy-4-phenoxybut-1-enyl)-7.alpha.-hydroxy-cis-bicyclo[3,3,0]oct-2/3-ene
- 3-[2-(Methanesulfonylcarbamoylmethoxy)ethyl]6.beta.-(3.alpha.-hydroxy-5,9-dimethyldeca-1,8-dienyl)-7.alpha.- hydroxy-cis-bicyclo[3,3,0]oct-2/3-ene
- (wherein "oct-2/3-ene" means oct-2-ene, oct-3-ene or a mixture of oct-2-ene and oct-3-ene) and pharmaceutically acceptable salts and esters thereof.
Priority Claims (3)
Number |
Date |
Country |
Kind |
58-136625 |
Jul 1983 |
JPX |
|
59-27810 |
Feb 1984 |
JPX |
|
59-38151 |
Feb 1984 |
JPX |
|
Parent Case Info
This application is a continuation of application Ser. No. 07/955,248, filed Oct. 1, 1992 (abandoned); which is a continuation of application Ser. No. 07/758,272 filed Aug. 27, 1991 (abandoned); which is a continuation of application Ser. No. 07/587,578 filed Sep. 21, 1990 (abandoned); which is a continuation of application Ser. No. 07/473,094 filed Jan. 31, 1990 (abandoned); which is a continuation of application Ser. No. 07/296,317 filed Jan. 9, 1989 (abandoned); which is a continuation of application Ser. No. 06/872,284 filed Aug. 11, 1986 (abandoned); which is a division of application Ser. No. 06/634,351 filed Jul. 25, 1984 (abandoned).
Foreign Referenced Citations (3)
Number |
Date |
Country |
0011591 |
May 1980 |
EPX |
0055208 |
Jun 1982 |
EPX |
8402902 |
Aug 1984 |
WOX |
Non-Patent Literature Citations (4)
Entry |
Chem. Pharm. Bull. 35, pp. 4000-4015 (1987). |
Torisawa, Chem. Letters, 1984 pp. 1069-1072. |
Shibasaki, Tet. Letters, 1983, pp. 3493-3496. |
Iseki et al, Synthesis of dl-9(O)-Methano-.DELTA..sup.6 -prostaglandin I.sub.1, Chem. Pharm. Bull. vol. 31 (1983) pp. 4448-4455. |
Divisions (1)
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Number |
Date |
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Parent |
634351 |
Jul 1984 |
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Continuations (6)
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Date |
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955248 |
Oct 1992 |
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Parent |
758272 |
Aug 1991 |
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Parent |
587578 |
Sep 1990 |
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Parent |
473094 |
Jan 1990 |
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Parent |
296317 |
Jan 1989 |
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Parent |
872284 |
Aug 1986 |
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