Claims
- 1. A process for the preparation of a 5-�(2H-pyrrol-2-ylidene)methyl!-2,2'-bi-1H-pyrrole compound of formula (I): ##STR11## wherein R1 represents hydrogen, phenyl, C.sub.1 -C.sub.20 alkyl or C.sub.2 -C.sub.20 alkenyl, wherein the alkyl and alkenyl groups are unsubstituted or substituted by 1 to 3 substituents chosen independently from halogen, C.sub.1 -C.sub.6 alkoxy, hydroxy, aryl and aryloxy;
- R2 represents hydrogen, C.sub.1 -C.sub.6 alkyl, cyano, carboxy or (C.sub.1 -C.sub.6 alkoxy)carbonyl;
- R3 represents halogen, hydroxy or C.sub.1 -C.sub.11 alkoxy unsubstituted or substituted by phenyl;
- R4 represent hydrogen, C.sub.1 -C.sub.6 alkyl or phenyl;
- each of R5 and R6 independently represents hydrogen, C.sub.2 -C.sub.20 alkanoyl, C.sub.3 -C.sub.20 alkenoyl, phenyl, C.sub.1 -C.sub.20 alkyl or C.sub.2 -C.sub.20 alkenyl, wherein the alkanoyl, alkenoyl, alkyl and the alkenyl groups are unsubstituted or substituted by 1 to 3 substituents chosen independently from halogen, C.sub.1 -C.sub.6 alkoxy, hydroxy, aryl, aryloxy, cyano, carboxy, (C.sub.1 -C.sub.6 alkoxy) carbonyl, (C.sub.3 -C.sub.4 alkenyl) carbamoyl, aralkylcarbamoyl, arylcarbamoyl and -CONRcRd in which each of Rc and Rd independently is hydrogen or C.sub.1 -C.sub.6 alkyl or Rc and Rd, taken together with the nitrogen atom to which they are linked, form a morpholino or piperidino ring;
- or two of R4, R5 and R6 taken together form a C.sub.4 -C.sub.12 polymethylene chain, which are unsubstituted or substituted by a C.sub.1 -C.sub.12 alkyl, by a C.sub.2 -C.sub.12 alkenyl or by a C.sub.1 -C.sub.12 alkylidene group, wherein the alkyl, alkenyl and alkylidene groups are in turn unsubstituted or substituted by a substituent chosen from halogen, C.sub.1 -C.sub.6 alkoxy, hydroxy, cyano, carboxy, (C.sub.1 -C.sub.6 alkoxy)carbonyl, aryloxy and aryl; the remaining one being hydrogen or C.sub.1 -C.sub.12 alkyl; and the pharmaceutically acceptable salts thereof;
- the process comprising reacting a compound of formula (VIII) ##STR12## wherein R2, R3, R4, R5, R6 are as defined above and X is a leaving group, with a compound of formula (IX) ##STR13## wherein R1 is as defined above and R7 is hydrogen or a lower alkyl chain;
- and, if desired, converting a compound of formula (I) into another compound of formula (I) and/or, if desired, salifying a compound of formula (I) and/or, if desired, converting a salt of a compound of formula (I) into a free compound and/or, if desired, separating a mixture of isomers of a compound of formula (I) into the single isomers.
- 2. A process according to claim 1, wherein in a compound of formula (VIII) the leaving group X is halogen or a trifluoromethanesulphonate group, in a compound of formula (IX) R7 is hydrogen or a C.sub.1 -C.sub.4 alkyl chain, and the reaction is carried out in an organic solvent, in the presence of a palladium (O) catalyst and of a basic agent.
- 3. A process according to claim 2, wherein in a compound of formula (VIII) the leaving group X is trifluoromethanesulphonate and the reaction is carried out in dioxane or toluene, in the presence of a Pd(PPh.sub.3).sub.4 and sodium or potassium carbonate.
- 4. A process according to claim 1, wherein in the compound of formula (I):
- R1 represents hydrogen, C.sub.1 -C.sub.12 alkyl or C.sub.2 -C.sub.12 alkenyl, wherein the alkyl and the alkenyl groups are unsubstituted or substituted by aryl or aryloxy;
- R2 represents hydrogen, cyano, carboxy or (C.sub.1 -C.sub.4 alkoxy) carbonyl;
- R3 represents hydroxy or C.sub.1 -C.sub.11 alkoxy unsubstituted or substituted by phenyl;
- R4 represents hydrogen or C.sub.1 -C.sub.4 alkyl;
- each of R5 and R6 independently represents hydrogen, C.sub.3 -C.sub.14 alkyl or C.sub.3 -C.sub.14 alkenyl, wherein the alkyl and the alkenyl groups are unsubstituted or substituted by a substituent chosen from halogen, C.sub.1 -C.sub.4 alkoxy, hydroxy, aryl, aryloxy, cyano, carboxy, (C.sub.1 -C.sub.4 alkoxy)carbonyl, aralkylcarbamoyl, arylcarbamoyl and -CONRcRd in which each of Rc and Rd independently is hydrogen or C.sub.1 -C.sub.4 alkyl or Rc and Rd, taken together with the nitrogen atom to which they are linked, form a morpholino or piperidino ring; or two of R4, R5 and R6 taken together form a C.sub.4 -C.sub.9 polymethylene chain, which are unsubstituted or substituted by a C.sub.1 -C.sub.6 alkyl, by a C.sub.3 -C.sub.6 alkenyl or by a C.sub.1 -C.sub.8 alkylidene group, wherein the alkyl, alkenyl and alkylidene groups are in turn unsubstituted or substituted by a substituent chosen from halogen, C.sub.1 -C.sub.4 alkoxy, hydroxy, cyano, carboxy, (C.sub.1 -C.sub.4 alkoxy)carbonyl, aryloxy and aryl; the remaining one being hydrogen or C.sub.1 -C.sub.6 alkyl.
- 5. A process according to claim 1, wherein the compound of formula (I) is selected from:
- 4-methoxy-5-�(5-undecyl-2H-pyrrol-2-ylidene)methyl!-2,2'-bi-1H-pyrrole;
- 4-ethoxy-5-��5-(undec-10-en-1-yl)-2H-pyrrol-2-ylidene! methyl!-2,2'-bi-1H-pyrrole;
- 4-ethoxy-5-�(5-decyl-2H-pyrrol-2-ylidene)methyl!-2,2'-bi-1H-pyrrole;
- 4-ethoxy-5-�(5-dodecyl-2H-pyrrol-2-ylidene)methyl!-2,2'-bi-1H-pyrrole;
- 4-ethoxy-5-�(5-phenethyl-2H-pyrrol-2-ylidene)methyl!-2,2'-bi-1H-pyrrole;
- 4-ethoxy-5-��5-(5-phenoxy-pent-1-yl)-2H-pyrrol-2-ylidene! methyl!-2,2'-bi-1H-pyrrole;
- 4-ethoxy-5-�(5-tridecyl-2H-pyrrol-2-ylidene)methyl!-2,2'-bi-1H-pyrrole;
- 4-ethoxy-5-�(5-methyl-2H-pyrrol-2-ylidene)methyl!-2,2'-bis-1H-pyrrole;
- 4-amyloxy-5-�(5-undecyl-2H-pyrrol-2-ylidene)methyl!-2,2'-bi-1H-pyrrole;
- 4-undecyloxy-5-�(5-undecyl-2H-pyrrol-2-ylidene)methyl!-2,2'-bi-1H-pyrrole;
- 4-undecyloxy-5-�(2H-pyrrol-2-ylidene)methyl!-2,2'-bi-1H-pyrrole;
- 4-buthoxy-5-�(5-tridecyl-2H-pyrrol-2-ylidene)methyl!-2,2'-bi-1H-pyrrole;
- 4-benzyloxy-5-�(5-tridecyl-2H-pyrrol-2-ylidene)methyl!-2,2'-bi-1H-pyrrole;
- 4-buthoxy-5-��5-(5-phenoxy-pent-1-yl)-2H-pyrrol-2-ylidene! methyl)-2,2'-bi-1H-pyrrole;
- 4-benzyloxy-5-��5-(5-phenoxy-pent-1-yl)-2H-pyrrol-2-ylidene! methyl!-2,2'-bi-1H-pyrrole;
- 4-propoxy-5-�(5-undecyl-2H-pyrrol-2-ylidene)methyl!-2,2'-bi-1H-pyrrole;
- 4-butoxy-5-�(5-undecyl-2H-pyrrol-2-ylidene)methyl!-2,2'-bi-1H-pyrrole;
- 4-isopropoxy-5-�(5-undecyl-2H-pyrrol-2-ylidene)methyl!-2,2'-bi-1H-pyrrole;
- 5 4-propoxy-5-�(5-decyl-2H-pyrrol-2-ylidene)methyl!-2,2'-bi-1H-pyrrole;
- 4-propoxy-5-�(5-dodecyl-2H-pyrrol-2-ylidene)methyll-2,2'-bi-1H-pyrrole;
- 4-propoxy-5-��5-(undec-10-en-1-yl)-2H-pyrrol-2-ylidene! methyl!-2,2'-bi-1H-pyrrole;
- 4-propoxy-5-��5-(5-phenoxy-pent-1-yl)-2H-pyrrol-2-ylidene! methyl!-2,2'-bi-1H-pyrrole;
- 4-benzyloxy-5-�(5-undecyl-2H-pyrrol-2-ylidene)methyl!2,2'-bi-1H-pyrrole;
- 4-benzyloxy-5-�(2H-pyrrol-2-ylidene)methyl!-2,2'-bi-1H-pyrrole;
- 4-methoxy-5-��5-(7-cyano-hept-1-yl)-2H-pyrrol-2-ylidene! methyl!-2,2'-bi-1H-pyrrole;
- 4-methoxy-5-��5-(undec-10-en-1-yl)-2H-pyrrol-2-ylidene! 30 methyl!-2,2'-bi-1H-pyrrole;
- 4-methoxy-5-�(5-decyl-2H-pyrrol-2-ylidene)methyl!-2,2'-bi-1H-pyrrole;
- 4-methoxy-5-�(5-dodecyl-2H-pyrrol-2-ylidene)methyl!-2,2'-bi-1H-pyrrole;
- 4-methoxy-5-�(5-tridecyl-2H-pyrrol-2-ylidene)methyl!-2,2'-bi-1H-pyrrole;
- 4-methoxy-5-�(5-pentadecyl-2H-pyrrol-2-ylidene)methyl!-2,2'-bi-1H-pyrrole;
- 4-methoxy-5-�(5-propyl-2H-pyrrol-2-ylidene)methyl!-2.2'-bi-1H-pyrrole;
- 4-methoxy-5-�(5-heptyl-2H-pyrrol-2-ylidene)methyl!-2,2'-bi-1H-pyrrole;
- 4-methoxy-5-�(5-phenethyl-2H-pyrrol-2-ylidene)methyll-2,2'-bi-1H-pyrrole;
- 4-methoxy-5-�(5-methyl-4-undecyl-2H-pyrrol-2-ylidene)methyl!-2,2'-bi-1H-pyrrole;
- 4-methoxy-5-�(5-propyl-4-undecyl-2H-pyrrol-2-ylidene)methyl!-2,2'-bi-1H-pyrrole;
- 4-methoxy-5-��5-(5-phenoxy-pent-1-yl)-2H-pyrrol-2-ylidene! methyl!-2,2'-bi-1H-pyrrole;
- 4-methoxy-5-�(4-ethyl-3,5-dimethyl-2H-pyrrol-2-ylidene) methyl!-2,2'-bi-1H-pyrrole;
- 4-methoxy-5-�(4-hexyl-5-methyl-2H-pyrrol-2-ylidene)methyl!-2,2'-bi-1H-pyrrole;
- 4-methoxy-5-�(5-nonyl-2H-pyrrol-2-ylidene)methyl!-2,2'-bi-1H-pyrrole;
- 4-methoxy-5-�(5-methyl-4-pentyl-2H-pyrrol-2-ylidene)methyl!-2,2'-bi-1H-pyrrole;
- 4-methoxy-5-��5-(5-carboxy-pent-1-yl)-2H-pyrrol-2-ylidene! methyl!-2,2'-bi-1H-pyrrole;
- 4-methoxy-5-��5-(5-carboxy-pent-1-yl)-2H-pyrrol-2-ylidene! methyl!-2,2'-bi-1H-pyrrole, methyl ester;
- 4-methoxy-5-��5-(6-hydoxy-hex-1-yl)-2H-pyrrol-2-ylidene! methyl!-2,2'-bi-1H-pyrrole;
- 4-methoxy-5-��5-(6-fluoro-hex-1-yl)-2H-pyrrol-2-ylidene! methyl!-2,2'-bi-1H-pyrrole;
- 4-methoxy-5-��5-(5-morpholinecarboxamido-pent-1-yl)-2H-pyrrol-2-ylidene!methyl!-2,2'-bi-1H-pyrrole;
- 4-ethoxy-5-�(5-ethyl-4-pentyl-2H-pyrrol-2-ylidene)methyl!-2,2'-bi-1H-pyrrole;
- 4-ethoxy-5-�(5-methyl-4-pentyl-2H-pyrrol-2-ylidene)methyl!-2,2'-bi-1H-pyrrole;
- 4-ethoxy-5-�(5-ethyl-4-undecyl-2H-pyrrol-2-ylidene)methyl!-2,2'-bi-1H-pyrrole;
- 4-ethoxy-5-�(5-methyl-4-undecyl-2H-pyrrol-2-ylidene)methyl!-2,2'-bi-1H-pyrrole;
- 4-ethoxy-5-�(5-heptyl-4-undecyl-2H-pyrrol-2-ylidene)methyl!-2,2'-bi-1H-pyrrole;
- 4-propoxy-5-�(5-ethyl-4-undecyl-2H-pyrrol-2-ylidene)methyl)-2,2'-bi-1H-pyrrole;
- 4-ethoxy-5-�(4-ethyl-3,5-dimethyl-2H-pyrrol-2-ylidene) methyl!-2,2'-bi-1H-pyrrole;
- 4-ethoxy-5-��5-(5-carboxy-pent-1-yl)-2H-pyrrol-2-ylidene! methyl!-2,2'-bi-1H-pyrrole;
- 4-propoxy-5-��5-(5-carboxy-pent-1-yl)-2H-pyrrol-2-ylidene! methyl!-2,2'-bi-1H-pyrrole;
- 4-ethoxy-5-��5-(6-hydroxy-hex-1-yl)-2H-pyrrol-2-ylidene! methyl!-2,2'-bi-1H-pyrrole;
- 4-propoxy-5-��5-(6-hydroxy-hex-1-yl)-2H-pyrrol-2-ylidene! methyl!-2,2'-bi-1H-pyrrole;
- 4-propoxy-5-��5-(11-carboxy-undec-1-yl)-2H-pyrrol-2-ylidene! methyl!-2,2'-bi-1H-pyrrole;
- 4-propoxy-5-��5-(12-carboxy-dodec-1-yl)-2H-pyrrol-2-ylidene! methyl!-2,2'-bi-1H-pyrrole;
- 4-propoxy-5-��5-(12-hydroxy-dodec-1-yl)-2H-pyrrol-2-ylidene! methyl!-2,2'-bi-1H-pyrrole;
- 4-propoxy-5-��5-(13-hydroxy-tridec-1-yl)-2H-pyrrol-2-ylidene! methyl!-2,2'-bi-1H-pyrrole;
- 4-propoxy-5-��5-(11-cyano-undec-1-yl)-2H-pyrrol-2-ylidene! methyl!-2,2'-bi-1H-pyrrole;
- 4-propoxy-5-��5-(11-carbamoyl-undec-1-yl)-2H-pyrrol-2-ylidene!methyl!-2,2'-bi-1H-pyrrole;
- 4-propoxy-5-��5-(11-ethoxycarbonyl-undec-1-yl)-2H-pyrrol-2-ylidene!methyl!-2,2'-bi-1H-pyrrole;
- 4-ethoxy-5-�(5-undecanoyl-2H-pyrrol-2-ylidene)methyl!-2,2'-bi-1H-pyrrole;
- 4-ethoxy-5-��5-(11-carboxy-undec-1-yl)-2H-pyrrol-2-ylidene! methyl)-2,2'-bi-1H-pyrrole;
- 4-ethoxy-5-��5-(12-carboxy-dodec-1-yl)-2H-pyrrol-2-ylidene! methyl!-2,2'-bi-1H-pyrrole;
- 5 4-ethoxy-5-��5-(12-hydroxy-dodec-1--yl)-2H-pyrrol-2-ylidene! methyl!-2,2'-bi-1H-pyrrole;
- 4-ethoxy-5-��5-(13-hydroxy-tridec-1-yl)-2H-pyrrol-2-ylidene! methyl!-2,2'-bi-1H-pyrrole;
- 4-ethoxy-5-��5-(11-cyano-undec-1-yl)-2H-pyrrol-2-ylidene! methyl!-2,2'-bi-1H-pyrrole;
- 4-ethoxy-5-��5-(11-carbamoyl-undec-1-yl)-2H-pyrrol-2-ylidene! methyl!-2,2'-bi-iH-pyrrole;
- 4-ethoxy-5-��5-(11-ethoxycarbonyl-undec-1-yl)-2H-pyrrol-2-ylidene!methyl!-2,2'-bi-1H-pyrrole;
- 4-methoxy-5-�(4,5,6,7-tetrahydro-2H-indol-2-ylidene)methyl!-2,2'-bi-1H-pyrrole;
- 4-methoxy-5-�(4-hexyl-4,5,6,7-tetrahydro-2H-indol-2-ylidene) methyl!-2,2'-bi-1H-pyrrole;
- 4-ethoxy-5-�(4-hexyl-4,5,6,7-tetrahydro-2H-indol-2-ylidene) methyl!-2,2'-bi-1H-pyrrole;
- 4-propoxy-5-�(4-hexyl-4,5,6,7-tetrahydro-2H-indol-2-ylidene) methyl!-2,2'-bi-1H-pyrrole;
- 4-ethoxy-5-��4-(4-carboxy-but-1-yl)-4,5,6,7-tetrahydro-2H-indol-2-ylidene!methyl!-2,2'-bi-1H-pyrrole;
- 4-ethoxy-5-�(3,5-nonamethylene-2H-pyrrol-2-ylidene)methyl!-2,2'-bi-1H-pyrrole;
- 4-propoxy-5-1(3,5-nonamethylene-2H-pyrrol-2-ylidene)methyl!-2,2'-bi-1H-pyrrole;
- 4-ethoxy-5-��4-(4-ethoxycarbonyl-but-1-yl)-4,5,6,7-tetrahydro-2H-indol-2-ylidene!methyl!-2,2'-bi-1H-pyrrole;
- 4-ethoxy-5'-methyl-5-�(5-methyl-2H-pyrrol-2-ylidene)methyl-2,2'-bi-1H-pyrrole;
- 4-propoxy-5'-methyl-5-�(5-undecyl-2H-pyrrol-2-ylidene) methyl!-2,2'-bi-1H-pyrrole;
- 4-ethoxy-5'-methyl-5-��5-(undec-10-en-1-yl)-2H-pyrrol-2-ylidene!methyl!-2,2'-bi-1H-pyrrole;
- 4-ethoxy-5'-methyl-5-�(5-decyl-2H-pyrrol-2-ylidene)methyl!-2,2'-bi-1H-pyrrole;
- 4-ethoxy-5'-methyl-5-�(5-dodecyl-2H-pyrrol-2-ylidene)methyl!-2,2'-bi-1H-pyrrole;
- 4-ethoxy-5'-methyl-5-�(3,5-nonamethylene-2H-pyrrol-2-ylidene) methyl!-2,2'-bi-1H-pyrrole;
- 4-ethoxy-5'-heptyl-5-�(5-undecyl-2H-pyrrol-2-ylidene)methyl)-2,2'-bi-1H-pyrrole;
- 4-ethoxy-5-methyl-5-�(5-undecyl-2H-pyrrol-2-ylidene)methyl!-2,2'-bi-1H-pyrrole;
- 3-cyano-4-propoxy-5-�(5-undecyl-2H-pyrrol-2-ylidene)methyl!-2,2'-bi-1H-pyrrole;
- 3-cyano-4-ethoxy-5-�(5-undecyl-2H-pyrrol-2-ylidene)methyl!-2,2'-bi-1H-pyrrole;
- 3-cyano-4-ethoxy-5-��5-(undec-10-en-1-yl)-2H-pyrrol-2-ylidene!methyl!-2,2'-bi-1H-pyrrole;
- 3-cyano-4-ethoxy-5'-methyl-5-�(5-undecyl-2H-pyrrol-2-ylidene)methyl!-2,2'-bi-1H-pyrrole;
- 3-ethoxycarbonyl-4-propoxy-5'-methyl-5-�(5-undecyl-2H-pyrrol-2-ylidene)methyl!-2,2'-bi-1H-pyrrole;
- 4-ethoxycarbonyl-4-ethoxy-5'-methyl-5-�(5-undecyl-2H-pyrrol-2-ylidene)methyl!-2,2'-bi-1H-pyrrole;
- 3-ethoxycarbonyl-4-ethoxy-5'-methyl-5-��(5-undec-10-en-1-yl-2H-pyrrol-2-ylidene!methyl!-2,2'-bi-1H-pyrrole;
- 3-methoxycarbonyl-4-methoxy-5'-methyl-5-�(5-undecyl-2H-pyrrol-2-ylidene)methyl!-2,2'-bi-1H-pyrrole;
- 3-ethoxycarbonyl-4-ethoxy-5'-methyl-5-�(3,5-nona-methylene-2H-pyrrol-2-ylidene)methyl!-2,2'-bi-1H-pyrrole;
- 3-ethoxycarbonyl-4-ethoxy-5'-propyl-5-�(5-undecyl-2H-pyrrol-2-ylidene)methyl!-2,2'-bi-1H-pyrrole;
- 3-ethoxycarbonyl-4-propoxy-5'-methyl-5-��5-(undec-10-en-1-yl)-2H-pyrrol-2-ylidene!methyl!-2,2'-bi-1H-pyrrole;
- 3-carboxy-4-propoxy-5'-methyl-5-�(5-undecyl-2H-pyrrol-2-ylidene)methyl!-2,2'-bi-1H-pyrrole;
- 3-carboxy-4-ethoxy-5'-methyl-5-�(5-undecyl-2H-pyrrol-2-ylidene)methyl!-2,2'-bi-1H-pyrrole;
- 3-carboxy-4-ethoxy-5'-methyl-5-��5-(undec-10-en-1-yl)-2H-pyrrol-2-ylidene!methyl!-2,2'-bi-1H-pyrrole; and
- 3-carboxy-4-ethoxy-5'-propyl-5-�(5-undecyl-2H-pyrrol-2-ylidene)methyl!-2,2'-bi-1H-pyrrole; or a pharmaceutically acceptable salt thereof.
- 6. A compound of formula (VIII) ##STR14## wherein R2, R3, R4, R5, R6 are as defined in claim 1 and X is a trifluoromethanesulphonate group.
Priority Claims (1)
Number |
Date |
Country |
Kind |
9603212 |
Feb 1996 |
GBX |
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Parent Case Info
This application is a 371 of PCT/EP97/00368 filed Jan. 22, 1997.
PCT Information
Filing Document |
Filing Date |
Country |
Kind |
102e Date |
371c Date |
PCT/EP97/00368 |
1/22/1997 |
|
|
10/15/1997 |
10/15/1997 |
Publishing Document |
Publishing Date |
Country |
Kind |
WO97/30029 |
8/21/1997 |
|
|
Foreign Referenced Citations (1)
Number |
Date |
Country |
9517381 |
Jun 1995 |
WOX |
Non-Patent Literature Citations (2)
Entry |
CA 13265-13268: Porphyrins. III. Preliminary studies on the synthesis of porphyrin a. Badger et al, 1964. |
Journal of the Chemical Society. Porphyrins. Part I. Intramolecular Hydrogen Bonding in Pyrromethenes and Porphyrins. Badger et al, 1962. |