Claims
- 1. A compound of the formula: ##STR43## wherein R.sup.1 is C.sub.10-30 alkyl or a group of the formula R.sup.5 NHCO-- in which R.sup.5 is C.sub.10-30 alkyl;
- R.sup.2 is hydrogen, hydroxy, C.sub.1-5 alkoxy, phenyl-C.sub.1-5 alkoxy, C.sub.1-5 alkanoyloxy, benzoyloxy, phenoxycarbonyloxy, C.sub.1-5 alkoxycarbonyloxy, a group of the formula ##STR44## (in which W is oxygen or sulfur, and R.sup.6 and R.sup.7 are independently hydrogen or C.sub.1-5 alkyl or both, taken together with the adjacent nitrogen atom, form a 3- to 7-membered hetero ring selected from the class consisting of 1-aziridinyl, 1-azetidinyl, 1-pyrrolidinyl, piperidino, 1-perhydroazepinyl, 1-piperazinyl, morpholino, thiomorpholino, 1-perhydrodiazepinyl, 4-perhydrooxazepinyl and 4-perhydrothiazepinyl), amino, C.sub.1-5 alkanoylamino, benzoylamino, optionally oxo-substituted 3- to 7-membered monocyclic amino selected from the class consisting of 1-aziridinyl, 1-azetidinyl, 1-pyrrolidinyl, piperidino, 1-perhydroazepinyl, 1-piperazinyl, morpholino, thiomorpholino, 1-perhydroazepinyl, 1-piperazinyl, morpholino, thiomorpholino, 1-perhydrodiazepinyl, 4-perhydrooxazepinyl and 4-perhydrothiazepinyl, or optionally oxo-substituted 2-isoindolinyl;
- R.sup.3 is C.sub.1-8 alkylene;
- R.sup.4 is hydrogen, C.sub.1-6 alkyl or phenyl-C.sub.1-6 alkyl;
- X is O, S or a group of the formula: ##STR45## (in which R.sup.8 is hydrogen, optionally carboxy or C.sub.1-5 alkoxycarbonyl substituted C.sub.1-5 alkyl, C.sub.1-5 alkanoyl, benzoyl, phenoxycarbonyl, C.sub.1-5 alkoxycarbonyl, carbamoyl, mono- or di-C.sub.1-5 alkylcarbamoyl or 3- or 7-membered cyclic aminocarbonyl selected from the class consisting of (aziridin-1-yl)carbonyl, (azetidin-1-yl)carbonyl, (pyrrolidin-1-yl)carbonyl, piperidino-carbonyl, (perhydroazepin-1-yl)carbonyl, (piperazin-1-yl)carbonyl, morpholinocarbonyl and thiomorpholinocarbonyl);
- Y is O, S or a group of the formula ##STR46## (in which R.sup.9 is hydrogen, optionally carboxy or C.sub.1-5 alkoxycarbonyl substituted C.sub.1-5 alkyl, C.sub.1-5 alkanoyl, benzoyl, phenoxycarbonyl, C.sub.1-5 alkoxycarbonyl, carbamoyl, mono- or di-C.sub.1-5 alkylcarbamoyl or 3- to 7-membered cyclic aminocarbonyl selected from the class consisting of (aziridin-1-yl)carbonyl, (azetidin-1-yl)carbonyl, (pyrrolidin-1-yl)carbonyl, piperidino-carbonyl, (perhydroazepin-1-yl)carbonyl, (piperazin-1-yl)-carbonyl, morpholinocarbonyl and thiomorpholinocarbonyl); and R.sup.8 and R.sup.9 or R.sup.4 and R.sup.9 may form C.sub.1-4 alkenylene or alkylene unsubstituted or substituted by oxo; and
- Z is a nitrogen-containing heterocyclic group selected from the class consisting of azetidinyl, pyrrolidinyl, piperidinyl, perhydroazepinyl, pyrrolinyl, pyrazolinyl, pyrrolyl, pyridyl, oxazolyl, thiazolyl, pyridazinyl, pyrimidyl, pyrazinyl, imidazolyl, morpholinyl, thiomorpholinyl, piperazinyl, pyrazolidinyl, indolyl, isoindolyl, 1H-indazolyl, purinyl, quinolinyl, isoquinolinyl, 1,2,3,4-tetrahydroquinolinyl, perhydroindolyl and perhydroisoquinolinyl, each of said groups being unsubstituted or substituted by optionally hydroxy- or amino-substituted C.sub.1-4 alkyl, hydroxy, amino, imino, mono-or di-C.sub.1-4 alkylamino, carbamoyl, ureido, carboxy, carboxylato or C.sub.1-4 alkoxycarbonyl, wherein a nitrogen atom in said nitrogen-containing heterocyclic group may be converted into a quaternary salt with R.sup.4, wherein R.sup.3 is bound to Z at a position adjacent to the nitrogen atom contained in said nitrogen-containing heterocyclic group represented by Z or a pharmaceutically acceptable salt thereof.
- 2. A compound according to claim 1, wherein R.sup.1 is C.sub.14-20 alkyl or C.sub.14-20 alkyl--NHCO--.
- 3. A compound according to claim 1, wherein R.sup.1 is C.sub.14-18 alkyl or C.sub.14-18 alkyl--NHCO--.
- 4. A compound according to claim 1, wherein R.sup.1 is C.sub.15-18 alkyl or C.sub.15-18 alkyl--NHCO--.
- 5. A compound according to claim 1, wherein R.sup.1 is C.sub.16-18 alkyl or C.sub.16-18 alkyl--NHCO--.
- 6. A compound according to claim 1, wherein R.sup.1 is octadecyl or octadecylcarbamoyl.
- 7. A compound according to claim 1, wherein R.sup.1 is octadecylcarbamoyl.
- 8. A compound according to claim 1, wherein R.sup.2 is C.sub.1-5 alkoxy.
- 9. A compound according to claim 1, wherein R.sup.2 is methoxy.
- 10. A compound according to claim 1, wherein R.sup.3 is methylene, ethylene or trimethylene.
- 11. A compound according to claim 1, wherein R.sup.3 is methylene or ethylene.
- 12. A compound according to claim 1, wherein R.sup.4 is hydrogen or C.sub.1-6 alkyl.
- 13. A compound according to claim 1, wherein R.sup.4 is hydrogen, methyl or ethyl.
- 14. A compound according to claim 1, wherein X is O, imino or C.sub.1-5 alkanoylimino.
- 15. A compound according to claim 1, wherein X is O.
- 16. A compound according to claim 1, wherein Y is C.sub.1-5 alkanoylimino.
- 17. A compound according to claim 1, wherein Y is acetylimino.
- 18. A compound according to claim 1, wherein ##STR47## is a group of the formula: ##STR48##
- 19. A compound according to claim 1, wherein Z--R.sup.4 is an optionally C.sub.1-6 alkyl, C.sub.1-4 alkoxycarbonyl-C.sub.1-6 alkyl, carboxylato-C.sub.1-6 alkyl or phenyl-C.sub.1-6 alkyl substituted azetidinyl, pyrrolidinyl, piperidinyl, perhydroazepinyl, pyrrolinyl, pyrazolinyl, pyrrolyl, pyridyl, oxazolyl, thiazolyl, pyridazinyl, pyrimidyl, pyradinyl, imidazolyl, morpholinyl, thiomorpholinyl, piperazinyl, pyrazolidinyl, indolyl, isoindolyl, 1H-indazolyl, purinyl, quinolinyl, isoquinolinyl, perhydroindolyl or perhydroisoquinolinyl group being unsubstituted or substituted by optionally hydroxy or amino substituted C.sub.1-4 alkyl, hydroxy, amino, imino, mono- or di-C.sub.1-4 alkylamino, carbamoyl, ureido, carboxy, carboxylato or C.sub.1-4 alkoxycarbonyl.
- 20. A compound according to claim 1, wherein Z--R.sup.4 is an optionally C.sub.1-6 alkyl, C.sub.1-4 alkoxycarbonyl-C.sub.1-6 alkyl, carboxylato-C.sub.1-6 alkyl or phenyl-C.sub.1-6 alkyl substituted morpholinyl, pyrrolidinyl, piperidinyl, imidazolyl, pyridyl or thiazolyl group being unsubstituted or substituted by optionally hydroxy or amino substituted C.sub.1-4 alkyl, hydroxy, amino, imino, mono- or di-C.sub.1-4 alkylamino, carbamoyl, ureido, carboxy, carboxylato or C.sub.1-4 alkoxycarbonyl.
- 21. A compound according to claim 1, wherein Z--R.sup.4 is an optionally C.sub.1-6 alkyl, C.sub.1-4 alkoxycarbonyl-C.sub.1-6 alkyl, carboxylato-C.sub.1-6 alkyl or phenyl-C.sub.1-6 alkyl substituted pyridyl or thiazolyl group being unsubstituted or substituted by optionally hydroxy or amino substituted C.sub.1-4 alkyl, hydroxy, amino, imino, mono- or di-C.sub.1-4 alkylamino, carbamoyl, ureido, carboxyl, carboxylato or C.sub.1-4 alkoxycarbonyl.
- 22. A compound according to claim 1, wherein Z--R.sup.4 is pyridyl or thiazolyl.
- 23. A compound according to claim 1, wherein Z--R.sup.4 is 2-pyridyl, thiazol-2-yl or thiazol-4-yl.
- 24. A compound according to claim 1, wherein Z--R.sup.4 is an optionally C.sub.1-6 alkyl, C.sub.1-4 alkoxycarbonyl-C.sub.1-6 alkyl, carboxylato-C.sub.1-6 alkyl or phenyl-C.sub.1-6 alkyl substituted imidazolio, pyridinio, oxazolio, thiazolio, pyridazinio, pyrimidinio, pyradinio, quinolinio, isoquinolinio, morpholinio, piperidinio, piperazinio or pyrrolidinio group being unsubstituted or substituted by optionally hydroxy or amino substituted C.sub.1-4 alkyl, hydroxy, amino, imino, mono- or di-C.sub.1-4 alkylamino, carbamoyl, ureido, carboxy, carboxylato or C.sub.1-4 alkoxycarbonyl.
- 25. A compound according to claim 1, wherein Z--R.sup.4 is an optionally C.sub.1-6 alkyl, C.sub.1-4 alkoxycarbonyl-C.sub.1-6 alkyl, carboxylato-C.sub.1-6 alkyl or phenyl-C.sub.1-6 alkyl substituted morpholinio, pyrrolidinio, piperidinio, imidazolio, pyridinio or thiazolio group being unsubstituted or substituted by optionally hydroxy or amino substituted C.sub.1-4 alkyl, hydroxy, amino, imino, mono- or di-C.sub.1-4 alkylamino, carbamoyl, ureido, carboxy, carboxylato or C.sub.1-4 alkoxycarbonyl.
- 26. A compound according to claim 1, wherein Z--R.sup.4 is an optionally, C.sub.1-6 alkyl, C.sub.1-4 alkoxycarbonyl-C.sub.1-6 alkyl, carboxylato-C.sub.1-6 alkyl or phenyl-C.sub.1-6 alkyl substituted pyridinio or thiazolio group being unsubstituted or substituted by optionally hydroxy or amino substituted C.sub.1-4 alkyl, hydroxy, amino, imino, mono- or di-C.sub.1-4 alkylamino, carbamoyl, ureido, carboxy, carboxylato or C.sub.1-4 alkoxycarbonyl.
- 27. A compound according to claim 1, wherein Z--R.sup.4 is 1-(C.sub.1-6 alkyl)pyridinio-2-yl.
- 28. A compound according to claim 1, wherein Z--R.sup.4 is 1-ethylpyridinio-2-yl.
- 29. A compound according to claim 1, wherein Z--R.sup.4 is 3-(C.sub.1-6 alkyl)thiazolio-2-yl.
- 30. A compound according to claim 1, wherein Z--R.sup.4 is 3-ethylthiazolio-2-yl.
- 31. A compound according to claim 1, wherein Z--R.sup.4 is 3-(C.sub.1-6 alkyl)thiazolio-4-yl.
- 32. A compound according to claim 1, wherein Z--R.sup.4 is 3-ethylthiazolio-4-yl.
- 33. A compound according to claim 1, wherein R.sup.2 is C.sub.1-5 alkoxy, phenyl-C.sub.1-5 alkoxy, C.sub.1-5 alkanoyloxy, C.sub.1-5 alkoxycarbonyloxy, mono- to di-C.sub.1-5 alkylcarbamoyloxy, C.sub.1-5 alkanoylamino, 1-aziridinyl, 1-azetidinyl, 1-pyrrolidinyl, piperidino, 1-perhydroazepinyl, 1-piperazinyl, morpholino, thiomorpholino, 1-perhydrodiazepinyl, 4-perhydrooxazepinyl, 4-perhydrothiazepinyl or phthalimido.
- 34. A compound according to claim 1, wherein Y is O or a group of the formula: ##STR49## in which R.sup.9 is hydrogen, C.sub.1-5 alkyl, C.sub.1-5 alkanoyl, C.sub.1-5 alkoxycarbonyl, carbamoyl, mono- or di-C.sub.1-5 alkylcarbamoyl, (aziridin-1-yl)carbonyl, (azetidin-1-yl)carbonyl, (pyrrolidin-1-yl)carbonyl, piperidinocarbonyl, (perhydroazepin-1-yl)-carbonyl, (piperazin-1-yl)carbonyl, morpholinocarbonyl or thiomorpholinocarbonyl.
- 35. A pharmaceutical composition suitable for inhibiting activities of platelet activating factor which comprises as an active ingredient, an effective amount of a compound as claimed in claim 1 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, excipient or diluent therefor.
- 36. A pharmaceutically acceptable salt according to claim 1 of 3-O-[N-acetyl-N-(N-methylpyridinio-2-yl)methyl]-carbamoyl-2-O-methyl-1-O-octadecylcarbamoylglycerol with an anion.
- 37. A pharmaceutically acceptable salt according to claim 1 of 1-ethyl-2-[N-acetyl-N-(3-octadecylcarbamoyloxy-2-methoxypropyloxy)carbonylamino]methylpyridinium with an anion.
- 38. A pharmaceutically acceptable salt according to claim 1 of 2-[N-acetyl-N-(3-octadecylcarbamoyloxy-2-methoxypropoxycarbonyl)amino]methyl-3-methylthiazolium with an anion.
- 39. A pharmaceutically acceptable salt according to claim 1 of 2-[N-acetyl-N-(3-octadecylcarbamoyloxy-2-methoxypropoxycarbonyl)amino]methyl-3-ethylthiazolium with an anion.
- 40. A pharmaceutically acceptable salt according to claim 1 of 2-[N-(3-octadecylcarbamoyloxy-2-ethoxypropyloxycarbonyl)amino]methyl-N-ethylpyridinium with an anion.
- 41. A pharmaceutically acceptable salt according to claim 1 of 4-[N-acetyl-N-(3-octadecylcarbamoyloxy-2-methoxypropoxycarbonyl)amino]methyl-3-ethylthiazolium with an anion.
Priority Claims (4)
Number |
Date |
Country |
Kind |
PCT/JP84/00163 |
Apr 1984 |
WOX |
|
PCT/JP84/00476 |
Oct 1984 |
WOX |
|
PCT/JP85/00062 |
Feb 1985 |
WOX |
|
60-219874 |
Oct 1985 |
JPX |
|
Parent Case Info
This application is a continuation of U.S. application Ser. No. 07/141,276, filed Jan. 6, 1988, now abandoned, which is a divisional of U.S. application Ser. No. 06/906,310, filed Sept. 12, 1986, now U.S. Pat. No. 4,737,518, which is a continuation-in-part of U.S. application Ser. No. 06/719,579, filed Apr. 3, 1985, abandoned.
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Number |
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Date |
Kind |
4408052 |
Hozumi et al. |
Oct 1983 |
|
4426525 |
Hozumi et al. |
Jan 1984 |
|
4582824 |
Nishikawa et al. |
Apr 1986 |
|
4731373 |
Barner |
Mar 1988 |
|
Foreign Referenced Citations (3)
Number |
Date |
Country |
94856 |
Sep 1983 |
EPX |
109255 |
May 1984 |
EPX |
59-31728 |
Feb 1984 |
JPX |
Non-Patent Literature Citations (1)
Entry |
Central Patents Index Basic Abstracts Journal Section B: Week K14 (1 Jun. 83) 33708 K/14 J58035-116. |
Divisions (1)
|
Number |
Date |
Country |
Parent |
906310 |
Sep 1986 |
|
Continuations (1)
|
Number |
Date |
Country |
Parent |
141276 |
Jan 1988 |
|
Continuation in Parts (1)
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Number |
Date |
Country |
Parent |
719579 |
Apr 1985 |
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