Claims
- 1. A 9-chloroprostane of the formula ##STR5## wherein the 9-chlorine atom can be in the .alpha.- or .beta.-position,
- R.sub.1 is OR.sub.2 wherein,
- R.sub.2 is H; C.sub.1-10 -alkyl; C.sub.1-10 -alkyl substituted by halogen, C.sub.1-4 -alkoxy, C.sub.6-10 -aryl or -aroyl, C.sub.6-10 -aryl or -aroyl substituted by the substituents defined below for the R.sub.2 aryl groups, di-C.sub.1-4 -alkylamino, or tri-C.sub.1-4 -alkylammonium; C.sub.4-10 -cycloalkyl; C.sub.4-10 -cycloalkyl-substituted by C.sub.1-4 -alkyl; C.sub.6-10 -aryl; C.sub.6-10 -aryl substituted by 1-3 halogen atoms, phenyl, 1-3 C.sub.1-4 -alkyl groups, or a chloromethyl, fluoromethyl, trifluoromethyl, carboxy, hydroxy or C.sub.1-4 -alkoxy group; or an aromatic heterocycle of 5- or 6-total ring atoms and 1-2 hetero N, O or S atoms, the remainder being carbon atoms;
- A is cis--CH.dbd.CH--,
- B is --CH.sub.2 --CH.sub.2 --, trans--CH.dbd.CH-- or --C.dbd.C--,
- W is hydroxymethylene or ##STR6## wherein the OH-group in each case can be in the .alpha.- or .beta.-position, and can be etherified or esterified by tetrahydropyranyl, tetrahydrofuranyl, .alpha.-ethoxyethyl, trimethylsilyl, dimethyl-tert-butylsilyl, tribenzylsilyl, acetyl, propionyl, butyryl or benzoyl;
- D and E together represent a direct bond or
- D is a straight-chain or branched alkylene group of 1-10 carbon atoms, optionally substituted by fluorine, and
- E is a direct bond, and
- R.sub.4 is hydroxy or hydroxy etherified or esterified as defined for W above;
- R.sub.5 is a C.sub.1-10 -hydrocarbon aliphatic group substituted by halogen;
- or a physiologically acceptable salt thereof with a base when R.sub.1 is OH.
- 2. A 9-chloroprostane of the formula ##STR7## wherein the 9-chlorine atom can be in the .alpha.- or .beta.-position
- R.sub.1 is OR.sub.2 wherein,
- R.sub.2 is H; C.sub.1-10 -alkyl; C.sub.1-10 -alkyl substituted by halogen, C.sub.1-4 -alkoxy, C.sub.6-10 -aryl or -aroyl, C.sub.6-10 -aryl or -aroyl substituted by the substituents defined below for the R.sub.2 aryl groups, di-C.sub.1-4 -alkylamino, or tri-C.sub.1-4 -alkylammonium; C.sub.4-10 -cycloalkyl; C.sub.4-10 -cycloalkyl-substituted by C.sub.1-4 -alkyl; C.sub.6-10 -aryl; C.sub.6-10 -aryl substituted by 1-3 halogen atoms, phenyl, 1-3 C.sub.1-4 -alkyl groups, or a chloromethyl, fluoromethyl, trifluoromethyl, carboxy, hydroxy or C.sub.1-4 -alkoxy group; or an aromatic heterocycle of 5- or 6-total ring atoms and 1-2 hetero N, O or S atoms, the remainder being carbon atoms;
- A is cis--CH.dbd.CH--,
- B is --CH.sub.2 --CH.sub.2 --, trans--CH.dbd.CH-- or --C.tbd.C--,
- W is hydroxymethylene or ##STR8## wherein the OH-group in each case can be in the .alpha.- or .beta.-position, and can be etherified or esterified by tetrahydropyranyl, tetrahydrofuranyl, .alpha.-ethoxyethyl, trimethylsilyl, dimethyl-tert-butylsilyl, tribenzylsilyl, acetyl, propionyl, butyryl or benzoyl;
- D and E together represent a direct bond or
- D is a straight-chain or branched alkylene group of 1-10 carbon atoms, optionally substituted by fluorine, and
- E is a direct bond, and
- R.sub.4 is hydroxy or hydroxy etherified or esterified as defined for W above;
- R.sub.5 is unsaturated and is a C.sub.1-10 hydrocarbon aliphatic group; or a C.sub.1-10 -hydrocarbon aliphatic group substituted by halogen;
- or a physiologically acceptable salt thereof with a base when R.sub.1 is OH.
- 3. A 9-chloroprostane of the formula ##STR9## wherein the 9-chlorine atom can be in the .alpha.- or .beta.-position
- R.sub.1 is OR.sub.2 wherein,
- R.sub.2 is H; C.sub.1-10 -alkyl; C.sub.1-10 -alkyl substituted by halogen, C.sub.1-4 -alkoxy, C.sub.6-10 -aryl or -aroyl, C.sub.6-10 -aryl or -aroyl substituted by the substituents defined below for the R.sub.2 aryl groups, di-C.sub.1-4 -alkylamino, or tri-C.sub.1-4 -alkylammonium; C.sub.4-10 -cycloalkyl; C.sub.4-10 -cycloalkyl substituted by C.sub.1-4 -alkyl; C.sub.6-10 -aryl; C.sub.6-10 -aryl substituted by 1-3 halogen atoms, phenyl, 1-3 C.sub.1-4 -alkyl groups, or a chloromethyl, fluoromethyl, trifluoromethyl, carboxy, hydroxy or C.sub.1-4 -alkoxy group; or an aromatic heterocycle of 5- or 6-total ring atoms and 1-2 hetero N, O or S atoms, the remainder being carbon atoms;
- A is cis--CH.dbd.CH--,
- B is --CH.sub.2 --CH.sub.2 -- or --C.tbd.C--,
- W is hydroxymethylene or ##STR10## wherein the OH-group in each case can be in the .alpha.-or .beta.-position, and can be etherified or esterified by tetrahydropyranyl, tetrahydrofuranyl, .alpha.-ethoxyethyl, trimethylsilyl, dimethyl-tert-butylsilyl, tribenzylsilyl, acetyl, propionyl, butyryl or benzoyl;
- D and E together represent a direct bond or
- D is a straight-chain or branched alkylene group of 1-10 carbon atoms, optionally substituted by fluorine, and
- E is a direct bond, and
- R.sub.4 is hydroxy or hydroxy etherified or esterified as defined for W above;
- R.sub.5 is a C.sub.1-10 hydrocarbon aliphatic group; or a C.sub.1-10 -hydrocarbon aliphatic group substituted by halogen;
- or a physiologically acceptable salt thereof with a base when R.sub.1 is OH.
- 4. (5Z,13E)-(8R,9R,11R,12R,15R)-9-Chloro-11,15-dihydroxy-16,16,19-trimethyl-5,13,18-prostatrienoic acid, a compound of claim 2.
- 5. (5Z,13E)-(8R,9R,11R,12R,15R)-9-Chloro-11,15-dihydroxy-16,16,19-trimethyl-5,13,18-prostatrienoic acid methyl ester, a compound of claim 2.
- 6. (5Z,13E,18Z)-(8R,9R,11R,12R,15S,16RS)-9,19-Dichloro-11,15-dihydroxy-16-methyl-5,13,18-prostatrienoic acid, a compound of claim 2.
- 7. A compound of claim 2, wherein R.sub.5 is selected such that the 18-position of the resultant compound contains a double bond.
- 8. A method of achieving a cytoprotective effect in a patient comprising administering a cytoprotectively effective amount of a compound of claim 4.
- 9. A method of achieving a cytoprotective effect in a patient comprising administering a cytoprotectively effective amount of a compound of claim 3.
- 10. A method of achieving a cytoprotective effect in a patient comprising administering a cytoprotectively effective amount of a compound of claim 2.
- 11. A method of achieving a cytoprotective effect in a patient comprising administering a cytoprotectively effective amount of a compound of claim 1.
- 12. A pharmaceutical composition comprising a cytoprotective amount of a compound of claim 3 and a pharmaceutically acceptable carrier.
- 13. A pharmaceutical composition comprising a cytoprotective amount of a compound of claim 2 and a pharmaceutically acceptable carrier.
- 14. A pharmaceutical composition comprising a cytoprotective amount of a compound of claim 1 and a pharmaceutically acceptable carrier.
- 15. (5Z,13E)-(9R,11R,15R,16RS)-9-Chloro-11,15-dihydroxy-16-fluoro-5,13-prostadienoic acid methyl ester, a compound of claim 1.
- 16. (5Z,13E)-(9R,11R,15R,16RS)-9-Chloro-11,15-dihydroxy-16-fluoro-5,13-prostadienoic acid, a compound of claim 1.
- 17. (5Z,13E)-8R,9R,11R,12R,15S,16RS)-9-Chloro-11,15-dihydroxy-16,19-dimethyl-5,13,18-prostatrienoic acid, a compound of claim 2.
- 18. (5Z,13E)-(8R,9S,11R,12R,15S,16RS)-9-Chloro-11,15-dihydroxy-16,19-dimethyl-5,13,18-prostatrienoic acid, a compound of claim 2.
Priority Claims (1)
Number |
Date |
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2950027 |
Dec 1979 |
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CROSS REFERENCE TO RELATED APPLICATIONS
This application is a divisional of U.S. Ser. No. 07/096,232 filed Sep. 8, 1987 now U.S. Pat. No. 5,079,259, which is a continuation of 06/754,702 now abandoned filed Jul. 15, 1985, which is a continuation of 06/581,741 now abandoned filed Feb. 16, 1984, which was a divisional of 06/387,140 filed Jun. 10, 1982, now U.S. Pat. No. 4,444,788, which is a continuation-in-part of U.S. application Ser. No. 215,762, filed on Dec. 10, 1980 now abandoned, whose disclosures are incorporated by reference herein.
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4192799 |
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Mar 1988 |
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4444788 |
Skuballa et al. |
Apr 1984 |
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Foreign Referenced Citations (1)
Number |
Date |
Country |
0000207 |
Jan 1979 |
EPX |
Non-Patent Literature Citations (4)
Entry |
Muchowski, "Synthesis and Bronchial Dilator Activity," Chemistry, Biochemistry & Pharmacological Activity of Prostanoids, Pergamon Press (Jul. 10-14, 1978). |
Binder et al., "16-Aryloxprostaglandins: A New Class of Ptent Luteolytic Agent," Prostaglandins, vol. 6, No. 1, pp. 87-91 (Apr. 10, 1974). |
Corey et al., "Total Synthesis of Prostaglandins F.sub.2 and E.sub.2 as the Naturally Occurring Forms," J. of the Amer. Chem. Soc., 92:2, pp. 397-398 (Jan. 28, 1970). |
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Divisions (2)
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Date |
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96232 |
Sep 1987 |
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Parent |
387140 |
Jun 1982 |
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Continuations (2)
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Parent |
754702 |
Jul 1985 |
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Parent |
581741 |
Feb 1984 |
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Continuation in Parts (1)
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215762 |
Dec 1980 |
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