Claims
- 1. A method of treating a condition which is susceptible to treatment by agonism of the mu opioid receptor which comprises administering to a subject in need thereof an amount of a compound effective to treat the condition wherein the compound has the formula: ##STR24## wherein X is selected from N--R.sup.1 or O;
- R.sup.1 is selected from the group consisting of hydrogen, C.sub.3-6 cycloalkyl, unsubstituted or substituted C.sub.1-6 alkyl where the substituent on the alkyl is selected from mono-, di- or tri-halogen, C.sub.1-4 alkoxy, carboxy, CONH.sub.2, SO.sub.2 NH.sub.2, a heterocyclic ring or aryl, and unsubstituted or substituted C.sub.2-6 alkenyl where the substituent on the alkenyl is selected from mono-, di- or tri-halogen, C.sub.1-4 alkoxy, carboxy, CONH.sub.2, SO.sub.2 NH.sub.2,
- R.sup.2 is independently one or more of hydrogen, halogen, C.sub.1-4 alkoxy, mono-, di- or tri-halogenated C.sub.1-4 alkoxy or unsubstituted or substituted C.sub.1-6 alkyl where the substituent on the alkyl is selected from mono-, di- or tri-halogen, C.sub.1-4 alkoxy, carboxy, CONH.sub.2, SO.sub.2 NH.sub.2,
- R.sup.3 is selected from hydrogen, cyano, CO.sub.2 R.sup.1, CONH.sub.2, CONHR.sup.1, CON(R.sup.1 ).sub.2, C.sub.3-6 cycloalkyl, C.sub.3-6 cycloalkyl wherein one of the carbon atoms is replaced with a heteroatom selected from O or NH, or unsubstituted or substituted mono- or di-C.sub.1-6 alkyl wherein the substituent on the mono- or di-alkyl is selected from hydroxy, C.sub.1-4 alkoxy, amino or mono-, di- or tri-halogen;
- R.sup.4 is independently one or more of hydrogen, C.sub.1-6 alkyl, halogen, C.sub.1-4 alkoxy, mono-, di- or tri-halogenated C.sub.1-4 alkoxy, nitro, amino, mono-, di- or tri-halogenated C.sub.1-6 alkyl, C.sub.1-6 alkylsulfonyl, C.sub.1-4 alkylenedioxy, unsubstituted or substituted aryl where the substituent on the aryl is selected from halogen, unsubstituted C.sub.1-3 alkyl, mono-, di- or tri-halogenated C.sub.1-3 alkyl or C.sub.1-4 alkoxy-C.sub.1-3 alkyl, or unsubstituted or substituted heterocyclic ring where the substituent on the heterocyclic ring is selected from halogen, unsubstituted C.sub.1-3 alkyl, mono-, di- or tri-halogenated C.sub.1-3 alkyl or C.sub.1-4 alkoxy-C.sub.1-3 alkyl;
- R.sup.5 is independently one or more of hydrogen, cyano, C.sub.1-6 alkyl, CO.sub.2 R.sup.1, CONH.sub.2, CONHR.sup.1, CON(R.sup.1).sub.2 ; and
- n is an integer of from 2 to 4;
- and the pharmaceutically acceptable salts thereof.
- 2. A method of alleviating pain in a subject in need thereof which comprises administering to the subject a therapeutically effective amount of the compound of claim 1.
- 3. The method of alleviating pain of claim 2, wherein
- R.sup.3 is selected from cyano, CO.sub.2 R.sup.1, CONH.sub.2, CONHR.sup.1, CON(R.sup.1).sub.2, C.sub.3-6 cycloalkyl, C.sub.3-6 cycloalkyl wherein one of the carbon atoms is replaced with a heteroatom selected from O or NH, or unsubstituted or substituted mono- or di-C.sub.1-6 alkyl wherein the substituent on the mono- or di-alkyl is selected from hydroxy, C.sub.1-4 alkoxy, amino or mono-, di- or tri-halogen; and
- R.sup.4 is independently one or more of hydrogen, C.sub.1-6 alkyl, halogen, C.sub.1-4 alkoxy, mono-, di- or tri-halogenated C.sub.1-4 alkoxy, nitro or C.sub.1-4 alkylenedioxy;
- and the pharmaceutically acceptable salts thereof.
- 4. The method of alleviating pain of claim 3, wherein
- R.sup.1 is selected from the group consisting of hydrogen, unsubstituted or substituted C.sub.1-6 alkyl where the substituent on the alkyl is selected from mono-, di- or tri-halogen, C.sub.1-4 alkoxy, carboxy, CONH.sub.2, a heterocyclic ring or phenyl, and unsubstituted or substituted C.sub.2-6 alkenyl where the substituent on the alkenyl is mono-, di- or tri-halogen;
- R.sup.2 is independently one or more of hydrogen, halogen or C.sub.1-6 alkyl;
- R.sup.3 is selected from cyano, C.sub.1-4 alkoxycarbonyl, CONH.sub.2 or unsubstituted or substituted mono- or di-C.sub.1-6 alkyl wherein the substituent on the mono- or di-alkyl is mono-, di- or tri-halogen;
- R.sup.4 is independently one or more of hydrogen or halogen; and
- R.sup.5 is independently one or more of hydrogen, cyano, C.sub.1-6 alkyl or CO.sub.2 R.sup.1 ;
- and the pharmaceutically acceptable salts thereof.
- 5. The method of alleviating pain of claim 4, wherein
- R.sup.1 is selected from hydrogen, C.sub.1-6 alkyl, mono-, di- or tri-halogenated C.sub.1-6 alkyl, benzyl, C.sub.2-6 alkenyl or mono-, di- or tri-halogenated C.sub.2-6 alkenyl;
- R.sup.3 is selected from cyano or mono- or di-C.sub.1-6 alkyl; and
- R.sup.4 is independently one or more of hydrogen or chlorine;
- and the pharmaceutically acceptable salts thereof.
- 6. The method of alleviating pain of claim 5, wherein the compound has the formula ##STR25## wherein R.sup.1 is selected from hydrogen, C.sub.1-4 alkyl, C.sub.2-6 alkenyl, benzyl, trifluoroethyl or fluoroethyl;
- R.sup.2 is independently one or more of hydrogen, chlorine, fluorine or methyl; and
- R.sup.3 is selected from hydrogen, methyl or dimethyl; and
- R.sup.5 is independently one or more of hydrogen, cyano, methyl or methoxycarbonyl;
- and the pharmaceutically acceptable salts thereof.
- 7. The method of alleviating pain of claim 6, wherein the compound has the formula ##STR26## and the pharmaceutically acceptable salts thereof.
- 8. The method of alleviating pain of claim 7, wherein the compound is selected from the group consisting of
- 1,1-dioxido-2-(4-(4-(3-propyl -2-oxo-1-benzinidazolinyl)piperidin-1-yl)butyl)-5-chloro-1,2-benzisothiazol-3-(2H)-one;
- 1,1-dioxido-2-(4-(4-(3-ethyl-2-oxo-1-benzimidazolinyl)piperidin-1-yl)pentyl)-1,2-benzisothiazol-3(2H)-one;
- 1,1-dioxido-2-(4-(4-(3-ethyl-2-oxo-1-benzimidazolinyl)piperidin-1-yl)4-methylpentyl)-1,2-benzisothiazol-3(2H)-one;
- 1,1-dioxido-2-(4-(4-(3-ethyl-2-oxo-1-benzimidazolinyl)piperidin-1-yl)butyl)-1,2-benzisothiazol-3(2H)-one;
- 1,1-dioxido-2-(4-(4-(3-(2,2,2-trifluoroethyl)-2-oxo-1-benzimidazolinyl)piperidin-1-yl)butyl)-1,2-benzisothiazol-3(2H)-one;
- 1,1-dioxido-2-(4-(4-(3-n-propyl-2-oxo-1-benzimidazolinyl)piperidin-1-yl)butyl)-1,2-benzisothiazol-3(2H)-one;
- 1,1-dioxido-2-(4-(4-(3-benzyl-2-oxo-1-benzimidazolinyl)piperidin-1-yl)butyl)-1,2-benzisothiazol-3(2H)-one;
- 1,1-dioxido-2-(4-(4-(3-ethyl-2-oxo-1-benzimidazolinyl)piperidin-1-yl)butyl-5-chloro-1,2-benzisothiazol-3(2H)-one;
- 1,1-dioxido-2-(4-(4-(3-(2-fluoroethyl)-2-oxo-1-benzimidazolinyl)piperidin-1-yl)butyl-5-chloro-1,2-benzisothiazol-3(2H)-one;
- 1,1-dioxido-2-(4-(4-(3-ethyl-2-oxo-1-benzimidazolinyl)piperidin-1-yl)butyl)-4,5-ethylenedioxy-1,2-benzisothiazol-3(2H)-one;
- 1,1-dioxido-2-(4-(4-(5-methyl-3-ethyl-2-oxo-1-benzimidazolinyl)piperidin-1-yl)butyl)-5-chloro-1,2-benzisothiazol-3(2H)-one;
- 1,1-dioxido-2-(4-(4-(2-oxo-1-benzimidazolinyl)piperidin-1-yl)-4-methylpentyl)-1,2-benzisothiazol-3(2H)-one;
- 1. 1-dioxido-2-(4-(4-(2-oxo-1-benzimidazolinyl)piperidin-1-yl)pentyl)-1,2-benzisothiazol-3(2H)-one;
- 1,1-dioxido-2-(4-(4-(3-isopropyl-2-oxo-1-benzimidazolinyl)piperidin-1-yl)butyl)-5-chloro-1,2-benzisothiazol-3(2H)-one;
- 1,1-dioxido-2-(4-(4-(3-butyl-2-oxo-1-benzimidazolinyl)piperidin-1-yl)butyl)-5-chloro-1,2-benzisothiazol-3(2H)-one;
- 1,1-dioxido-2-(4-(4-(3-(2,2,2-trifluoroethyl)-2-oxo-1-benzimidazolinyl)piperidin-1-yl)butyl)-5-chloro-1,2-benzisothiazol-3(2H)-one;
- 1,1-dioxido-2-(4-(4-(2-oxo-3-benzoxazolinyl)piperidin-1-yl)pentyl)-1,2-benzisothiazol-3(2H)-one;
- 1,1-dioxido-2-(4-(4-(6-methyl-2-oxo-3-benzoxazolinyl)piperidin-1-yl)pentyl)-1,2-benzisothiazol-3(2H)-one;
- 1,1-dioxido-2-(4-(4-(-2-oxo-3-benzoxazolinyl)-2-methylpiperidin-1-yl)butyl)-1,2-benzisothiazol-3(2H)-one;
- 1,1-dioxido-2-(4-(4-(2-oxo-1-benzimidazolinyl)-3-methoxycarbonylpiperidin-1-yl)butyl)-5-chloro-1,2-benzisothiazol-3(2H)-one;
- 1,1-dioxido-2-(4-(4-(5-fluoro-3-ethyl-2-oxo-1-benzimidazolinyl)piperidin-1-yl)butyl)-5-chloro-1,2-benzisothiazol-3(2H)-one;
- 1,1-dioxido-2-(4-(2-cyano-4-(3-propyl-2-oxo-1-benzimidazolinyl) piperidin-1-yl)butyl)-5-chloro-1,2-benzisothiazol-3(2H)-one; and
- 1,1-dioxido-2-(4-(4-(3-n-propyl-2-oxo-1-benzimidazolinyl)piperidin-1-yl)pentyl)-5-chloro-1,2-benzisothiazol-3(2H)-one;
- and the pharmaceutically acceptable salts thereof.
- 9. The method of alleviating pain of claim 8, wherein the compound is selected from
- 1,1-dioxido-2-(4-(4-(2-oxo-1-benzimidazolinyl)piperidin-1-yl)pentyl)-1,2-benzisothiazol-3(2H)-one;
- 1,1-dioxido-2-(4-(4-(3-ethyl-2-oxo-1-benzimidazolinyl)piperidin-1-yl)pentyl)-1,2-benzisothiazol-3(2H)-one;
- 1,1-dioxido-2-(4-(4-(3-n-propyl-2-oxo-1-benzimidazolinyl)piperidin-1-yl)pentyl)-5-chloro-1,2-benzisothiazol-3(2H)-one;
- 1,1-dioxido-2-(4-(4-(3-ethyl-2-oxo-1-benzimidazolinyl)piperidin-1-yl)4-methylpentyl)-1,2-benzisothiazol-3(2H)-one; or
- 1. 1-dioxido-2-(4-(4-(2-oxo-1-benzimidazolinyl)piperidin-1-yl)-4-methylpentyl)-1,2-benzisothiazol-3(2H)-one;
- and the pharmaceutically acceptable salts thereof.
- 10. The method of alleviating pain of claim 9, wherein the compound is selected from
- 1,1-dioxido-2-(4-(4-(3-ethyl-2-oxo-1-benzimidazolinyl)piperidin-1-yl)4-methylpentyl)-1,2-benzisothiazol-3(2H)-one;
- 1,1-dioxido-2-(4-(4-(2-oxo-1-benzimidazolinyl)piperidin-1-yl)-4-methylpentyl)-1,2-benzisothiazol-3(2H)-one; or
- 1,1-dioxido-2-(4-(4-(3-ethyl-2-oxo-1-benzimidazolinyl)piperidin-1-yl)pentyl)-1,2-benzisothiazol-3(2H)-one;
- and the pharmaceutically acceptable salts thereof.
- 11. A method of inducing analgesia in a subject in need thereof which comprises administering to the subject a therapeutically effective amount of the compound of claim 1.
- 12. The method of inducing analgesia of claim 11, wherein
- R.sup.3 is selected from cyano, CO.sub.2 R.sup.1, CONH.sub.2, CONHR.sup.1, CON(R.sup.1).sub.2, C.sub.3-6 cycloalkyl, C.sub.3-6 cycloalkyl wherein one of the carbon atoms is replaced with a heteroatom selected from O or NH, or unsubstituted or substituted mono- or di-C.sub.1-6 alkyl wherein the substituent on the mono- or di-alkyl is selected from hydroxy, C.sub.1-4 alkoxy, amino or mono-, di- or tri-halogen; and
- R.sup.4 is independently one or more of hydrogen, C.sub.1-6 alkyl, halogen, C.sub.1-4 alkoxy, mono-, di- or tri-halogenated C.sub.1-4 alkoxy, nitro or C.sub.1-4 alkylenedioxy.
- 13. The method of inducing analgesia of claim 12, wherein
- R.sup.1 is selected from the group consisting of hydrogen, unsubstituted or substituted C.sub.1-6 alkyl where the substituent on the alkyl is selected from mono-, di- or tri-halogen, C.sub.1-4 alkoxy, carboxy, CONH.sub.2, a heterocyclic ring or phenyl, and unsubstituted or substituted C.sub.2-6 alkenyl where the substituent on the alkenyl is mono-, di- or tri-halogen;
- R.sup.2 is independently one or more of hydrogen, halogen or C.sub.1-6 alkyl;
- R.sup.3 is selected from cyano, C.sub.1-4 alkoxycarbonyl, CONH.sub.2 or unsubstituted or substituted mono- or di-C.sub.1-6 alkyl wherein the substituent on the mono- or di-alkyl is mono-, di- or tri-halogen;
- R.sup.4 is independently one or more of hydrogen or halogen; and
- R.sup.5 is independently one or more of hydrogen, cyano, C.sub.1-6 alkyl or CO.sub.2 R.sup.1 ;
- and the pharmaceutically acceptable salts thereof.
- 14. The method of inducing analgesia of claim 13, wherein
- R.sup.1 is selected from hydrogen, C.sub.1-6 alkyl, mono-, di- or tri-halogenated C.sub.1-6 alkyl, benzyl, C.sub.2-6 alkenyl or mono-, di- or tri-halogenated C.sub.2-6 alkenyl;
- R.sup.3 is selected from cyano or mono- or di-C.sub.1-6 alkyl; and
- R.sup.4 is independently one or more of hydrogen or chlorine;
- and the pharmaceutically acceptable salts thereof.
- 15. The method of inducing analgesia of claim 14, wherein the compound has the formula ##STR27## wherein R.sup.1 is selected from hydrogen, C.sub.1-4 alkyl, C.sub.2-6 alkenyl, benzyl, trifluoroethyl or fluoroethyl;
- R.sup.2 is independently one or more of hydrogen, chlorine, fluorine or methyl; and
- R.sup.3 is selected from hydrogen, methyl or dimethyl; and
- R.sup.5 is independently one or more of hydrogen, cyano, methyl or methoxycarbonyl;
- and the pharmaceutically acceptable salts thereof.
- 16. The method of inducing analgesia of claim 15, wherein the compound has the formula ##STR28## and the pharmaceutically acceptable salts thereof.
- 17. The method of inducing analgesia of claim 16, wherein the compound is selected from the group consisting of
- 1. 1-dioxido-2-(4-(4-(3-propyl-2-oxo-1-benzimidazolinyl)piperidin-1-yl)butyl)-5-chloro-1,2-benzisothiazol-3-(2H)-one;
- 1,1-dioxido-2-(4-(4-(3-ethyl-2-oxo-1-benzimidazolinyl)piperidin-1-yl)pentyl)-1,2-benzisothiazol-3(2H)-one;
- 1,1-dioxido-2-(4-(4-(3-ethyl-2-oxo-1-benzimidazolinyl)piperidin-1-yl)4-methylpentyl)-1,2-benzisothiazol-3(2H)-one;
- 1,1-dioxido-2-(4-(4-(3-ethyl-2-oxo-1-benzimidazolinyl)piperidin-1-yl)butyl)-1,2-benzisothiazol-3(2H)-one;
- 1,1-dioxido-2-(4-(4-(3-(2,2,2-trifluoroethyl)-2-oxo-1-benzimidazolinyl)piperidin-1-yl)butyl)-1,2-benzisothiazol-3(2H)-one;
- 1,1-dioxido-2-(4-(4-(3-n-propyl-2-oxo-1-benzimidazolinyl)piperidin-1-yl)butyl)-1,2-benzisothiazol-3(2H)-one;
- 1,1-dioxido-2-(4-(4-(3-benzyl-2-oxo-1-benzimidazolinyl)piperidin-1-yl)butyl)-1,2-benzisothiazol-3(2H)-one;
- 1,1-dioxido-2-(4-(4-(3-ethyl-2-oxo-1-benzimidazolinyl)piperidin-1-yl)butyl-5-chloro-1,2-benzisothiazol-3(2H)-one;
- 1,1-dioxido-2-(4-(4-(3-(2-fluoroethyl)-2-oxo-1-benzimidazolinyl)piperidin-1-yl)butyl-5-chloro-1,2-benzisothiazol-3(2H)-one;
- 1,1-dioxido-2-(4-(4-(3-ethyl-2-oxo-1-benzimidazolinyl)piperidin-1-yl)butyl)-4,5-ethylenedioxy-1,2-benzisothiazol-3(2H)-one;
- 1,1-dioxido-2-(4-(4-(5-methyl-3-ethyl-2-oxo-1-benzimidazolinyl)piperidin-1-yl)butyl)-5-chloro-1,2-benzisothiazol-3(2H)-one;
- 1,1-dioxido-2-(4-(4-(2-oxo-1-benzimidazolinyl)piperidin-1-yl)-4-methylpentyl)-1,2-benzisothiazol-3(2H)-one;
- 1,1-dioxido-2-(4-(4-(2-oxo-1-benzimidazolinyl)piperidin-1-yl)pentyl)-1,2-benzisothiazol-3(2H)-one;
- 1,1-dioxido-2-(4-(4-(3-isopropyl-2-oxo-1-benzimidazolinyl)piperidin-1-yl)butyl)-5-chloro-1,2-benzisothiazol-3(2H)-one;
- 1,1-dioxido-2-(4-(4-(3-butyl-2-oxo-1-benzimidazolinyl)piperidin-1-yl)butyl)-5-chloro-1,2-benzisothiazol-3(2H)-one;
- 1,1-dioxido-2-(4-(4-(3-(2,2,2-trifluoroethyl)-2-oxo-1-benzimidazolinyl)piperidin-1-yl)butyl)-5-chloro-1,2-benzisothiazol-3(2H)-one;
- 1,1-dioxido-2-(4-(4-(2-oxo-3-benzoxazolinyl)piperidin-1-yl)pentyl)-1,2-benzisothiazol-3(2H)-one;
- 1. 1-dioxido-2-(4-(4-(6-methyl-2-oxo-3-benzoxazolinyl)piperidin-1-yl)pentyl)-1,2-benzisothiazol-3(2H)-one;
- 1,1-dioxido-2-(4-(4-(-2-oxo-3-benzoxazolinyl)-2-methylpiperidin-1-yl)butyl)-1,2-benzisothiazol-3(2H)-one;
- 1,1-dioxido-2-(4-(4-(2-oxo-1-benzimidazolinyl)-3-methoxycarbonylpiperidin-1-yl)butyl)-5-chloro-1,2-benzisothiazol-3(2H)-one;
- 1,1-dioxido-2-(4-(4-(5-fluoro-3-ethyl-2-oxo-1-benzimidazolinyl)piperidin-1-yl)butyl)-5-chloro-1,2-benzisothiazol-3(2H)-one;
- 1,1-dioxido-2-(4-(2-cyano-4-(3-propyl-2-oxo-1-benzimidazolinyl) piperidin-1-yl)butyl)-5-chloro-1,2-benzisothiazol-3(2H)-one; and
- 1,1-dioxido-2-(4-(4-(3-n-propyl-2-oxo-1-benzimidazolinyl)piperidin-1-yl)pentyl)-5-chloro-1,2-benzisothiazol-3(2H)-one;
- and the pharmaceutically acceptable salts thereof.
- 18. The method of inducing analgesia of claim 17, wherein the compound is selected from
- 1,1-dioxido-2-(4-(4-(2-oxo-1-benzimidazolinyl)piperidin-1-yl)pentyl)-1,2-benzisothiazol-3(2H)-one;
- 1,1-dioxido-2-(4-(4-(3-ethyl-2-oxo-1-benzimidazolinyl)piperidin-1-yl)pentyl)-1,2-benzisothiazol-3(2H)-one;
- 1,1-dioxido-2-(4-(4-(3-n-propyl-2-oxo-1-benzimidazolinyl)piperidin-1-yl)pentyl)-5-chloro-1,2-benzisothiazol-3(2H)-one;
- 1,1-dioxido-2-(4-(4-(3-ethyl-2-oxo-1-benzimidazolinyl)piperidin-1-yl)4-methylpentyl)-1,2-benzisothiazol-3(2H)-one; or
- 1,1-dioxido-2-(4-(4-(2-oxo-1-benzimidazolinyl)piperidin-1-yl)-4-methylpentyl)-1,2-benzisothiazol-3(2H)-one;
- and the pharmaceutically acceptable salts thereof.
- 19. The method of inducing analgesia of claim 18, wherein the compound is selected from
- 1,1-dioxido-2-(4-(4-(3-ethyl-2-oxo-1-benzimidazolinyl)piperidin-1-yl)4-methylpentyl)-1,2-benzisothiazol-3(2H)-one;
- 1,1-dioxido-2-(4-(4-(2-oxo-1-benzimidazolinyl)piperidin-1-yl)-4-methylpentyl)-1,2-benzisothiazol-3(2H)-one; or
- 1,1-dioxido-2-(4-(4-(3-ethyl-2-oxo-1-benzimidazolinyl)piperidin-1-yl)pentyl)-1,2-benzisothiazol-3(2H)-one;
- and the pharmaceutically acceptable salts thereof.
Parent Case Info
This application is a divisional of U.S. Ser. No. 08/860,314, filed Aug. 13, 1997, U.S. Pat. No. 5,952,351, which is the national stage of International Application No. PCT/US 96/02534, filed Feb. 23, 1996, which is a continuation-in-part of prior applications U.S. Ser. Nos. 08/392,699, filed Feb. 23, 1995, abandoned, and 60/002,534, filed Aug. 18, 1995, abandoned, the contents of both of which are hereby incorporated by reference.
US Referenced Citations (17)
Foreign Referenced Citations (7)
Number |
Date |
Country |
2 621 588 |
Apr 1989 |
FRX |
WO 9216213 |
Oct 1992 |
WOX |
WO 9408040 |
Apr 1994 |
WOX |
WO 9410989 |
May 1994 |
WOX |
WO 9421660 |
Sep 1994 |
WOX |
WO 9528397 |
Oct 1995 |
WOX |
WO 9625934 |
Aug 1996 |
WOX |
Non-Patent Literature Citations (5)
Entry |
Elde et al. "Distribution of neuropeptide receptors . . . " Medline 95336119, 1995. |
A. F. Casey, "Opioid Receptors and their Ligands: Recents Developments", Advances in Drug Research, vol. 18, pp. 179-285, (1989). |
J. M. Wetzel et al., "Discovery of Alpha 1a Adrenergic Receptor Antagonists based on the L-Type . . . ", Journal of Medicinal Chemistry, vol. 38, No. 10, pp. 1579-1581, (1995). |
C. Chapple, "Medical treatment for benign prostatic hyperplasia: surgery still gives the best results", British Medical Journal, vol. 304, No. 6836, p. 1198(2), May 9, 1992. |
T. Resine et al., "Opioid Analgesics and Antagonists", Goodman and Gilman's The Pharmaceutical Basis of Therapeutics, pp. 521-555, (1995). |
Divisions (1)
|
Number |
Date |
Country |
Parent |
860314 |
|
|