Patent
Morpholine and thiomorpholine tachykinin receptor antagonists
| العنوان: | Morpholine and thiomorpholine tachykinin receptor antagonists |
|---|---|
| Patent Number: | 6,235,735 |
| تاريخ النشر: | May 22, 2001 |
| Appl. No: | 09/526,843 |
| Application Filed: | March 16, 2000 |
| مستخلص: | Substituted heterocycles of the general structural formula: ##STR1## are tachykinin receptor antagonists useful in the treatment of inflammatory diseases, pain or migraine, asthma and emesis, and calcium channel blockers useful in the treatment of cardiovascular conditions such as angina, hypertension or ischemia. |
| Inventors: | Dorn, Conrad P. (Plainfield, NJ); Hale, Jeffrey J (Westfield, NJ); Finke, Paul E. (Milltown, NJ); Maccoss, Malcolm (Freehold, NJ); Mills, Sander G. (Woodbridge, NJ); Shah, Shrenik K. (Metuchen, NJ); Chambers, Mark Stuart (Watford, GBX); Ladduwahetty, Tamara (Buckhurst Hill, GBX); Harrison, Timothy (Great Dunmow, GBX); Williams, Brian John (Great Dunnow, GBX) |
| Assignees: | Merck & Co., Inc. (Rahway, NJ) |
| Claim: | What is claimed is |
| Claim: | 1. A method for the prevention or treatment of nausea or emesis induced by radiation or by a cancer chemotherapeutic agent in a mammal in need thereof which comprises the administration to the mammal of an effective amount of a compound which is 2-(R)-(1-(R)-3,5-bis(trifluoromethyl)phenyl)ethoxy)-3-(S)-(4-fluoro)phenyl -4-(3-(5-oxo-1H,4H-1,2,4-triazolo)methylmorpholine, or a pharmaceutically acceptable salt thereof. |
| Claim: | 2. The method of claim 1 wherein the mammal is a human. |
| Claim: | 3. The method of claim 1 wherein the nausea or emesis is induced by radiation. |
| Claim: | 4. The method of claim 1 wherein the nausea or emesis is induced by a cancer chemotherapeutic agent which is cisplatin. |
| Claim: | 5. The method of claim 1 wherein the nausea or emesis is induced by a cancer chemotherapeutic agent which is cyclophosphamide. |
| Claim: | 6. The method of claim 1 wherein the nausea or emesis is induced by a cancer chemotherapeutic agent which is doxorubicin. |
| Claim: | 7. The method of claim 1 wherein the nausea or emesis is induced by a cancer chemotherapeutic agent which is daunorubicin. |
| Claim: | 8. The method of claim 1 wherein the nausea or emesis is induced by a cancer chemotherapeutic agent which is etoposide. |
| Claim: | 9. A method for the prevention or treatment of nausea or emesis induced by radiation or by a cancer chemotherapeutic agent in a mammal in need thereof which comprises the administration to the mammal of an effective amount of: a compound which is ##STR28## |
| Claim: | or a pharmaceutically acceptable salt thereof. |
| Claim: | 10. The method of claim 9 wherein the mammal is a human. |
| Claim: | 11. The method of claim 9 wherein the nausea or emesis is induced by radiation. |
| Claim: | 12. The method of claim 9 wherein the nausea or emesis is induced by a cancer chemotherapeutic agent which is cisplatin. |
| Claim: | 13. The method of claim 9 wherein the nausea or emesis is induced by a cancer chemotherapeutic agent which is cyclophosphamide. |
| Claim: | 14. The method of claim 9 wherein the nausea or emesis is induced by a cancer chemotherapeutic agent which is doxorubicin. |
| Claim: | 15. The method of claim 9 wherein the nausea or emesis is induced by a cancer chemotherapeutic agent which is daunorubicin. |
| Claim: | 16. The method of claim 9 wherein the nausea or emesis is induced by a cancer chemotherapeutic agent which is etoposide. |
| Claim: | 17. A method for the prevention or treatment of post-operative nausea and vomiting in a mammal in need thereof which comprises the administration to the mammal of an effective amount of a compound which is 2-(R)-(1-(R)3,5-bis(trifluoromethyl)phenyl)ethoxy)-3-(S)-(4-fluoro)phenyl- 4-(3-(5-oxo-1H,4H-1,2,4-triazolo)methylmorpholine, or a pharmaceutically acceptable salt thereof. |
| Claim: | 18. A method for the prevention or treatment of post-operative nausea and vomiting in a mammal in need thereof which comprises the administration to the mammal of an effective amount of a compound which is: ##STR29## |
| Current U.S. Class: | 5142/362; 514/872 |
| Current International Class: | A61K 315355; A61P 108 |
| Patent References Cited: | 2943022 June 1960 Siemer et al. 3005818 October 1961 Siemer et al. 3458509 July 1969 Levine et al. 3506673 April 1970 Warawa et al. 3541090 November 1970 Herlinger et al. 4010266 March 1977 McLoughlin et al. 4360519 November 1982 White et al. 4476311 October 1984 Shetty et al. 4705553 November 1987 Bushmenn et al. 4782054 November 1988 Regnier et al. 4943578 July 1990 Naylor et al. 5064838 November 1991 Carr et al. 5095021 March 1992 Zipplies et al. 5130310 July 1992 Weidman et al. 5360820 November 1994 Hagan et al. 5393762 February 1995 Desai et al. 5420158 May 1995 Yous et al. 5538982 July 1996 Hagan et al. 5547964 August 1996 Hagan et al. 5576317 November 1996 Gonsalves 5593983 January 1997 Campbell 5637699 June 1997 Dorn et al. 5719147 February 1998 Dorn et al. |
| Other References: | Advenier. et al., "Neurokinin A (NK2) Receptor Revisited With SR48968 . . . ", Biochem. and Biophys., Res. Comm.; 184(3), pp.1418-1424 (1992). Edmonds-Alt. et al., A Potent and Selective Non-Peptide Antagonist of the Neurokinin A (NK2) Receptor, Life Sci., 50, pp. PL101-PL106 (1992). Frossard, et al. "Tachykinin Receptors and the Airways" Life Sci, 49, pp. 1491-1953. (1991). Guthrie, et al., "The Use of Penodate-Oxidized Glycosides in the Robinson-Schopf . . . ", J. Chem. Society, vol. C(1), pp.62-66 (1967). Howson, et al., "An SAR Study for the Non-Peptide Substance P Receptor . . . ", Borg. & Med Chem. Lett., vol. 2(6), pp. 559-564 (1992). G. Rucker, et al., Arch. Pharm., (Weinheim, Ger.) 315(10), 839-846 (1982), "Stabilitasuntersuchungen and Phenylethylaminsubstitutuierten Pyrazolonein". Chem. Abstracts, 73 (3) p. 361, No. 14777c (Jul. 20, 1970), "Diastereoisomeric Configuration of Morpholine Derivatives". I.V. Bozhko, et al., Kinet. Katal., 31 (3), 737-738 (1990) (Russ.). Lowe, et al. "The Discovery of (2S,3S)-cis-2(Diphenylmethyl)-N-(2-methoxyphenyl)methyl . . .", J. Med. Chem., vol. 35, pp. 2591-2600 (1992). McCormick, "Properties of Penodate-Oxidised Polysaccharides", J. Chem. Society. vol. C(23). pp. 2121-27 (1966). Montgomery, et al., "2-Fluoropurine Ribonucleosides", J. of Med. Chem., vol. 13(3), pp. 421-7 (1970). Payan, et al., "Substance P. Recognition by a Subset of Human T Lymphocytes", J. Clin. Invest., 74, 1532-1539 (1984). Peyronel, et al., "Synthesis of RP-67,580, a New Potent Nonpeptide Substance P Antagonist", Biorg. and Med. Chem. Lett., vol. 2(6), pp. 559-564 (1992). Siemer, et al., "Analgesic 1-phenyl-2,3-dimethyl-4-morpholinomethyl-3-pyrazolin-5-ones . . . " Chem. Abstracts, 56, No. 6 No. 5977e (1962). Chem. Astracts, 113 (20) p. 123, No. 17441m (Nov. 12, 1990), "Amine Hydrochlorides--Catalysts for Hydrochlorination". |
| Primary Examiner: | Ramsuer, Robert |
| Attorney, Agent or Firm: | Thies, J. Eric Rose, David L. |
| رقم الانضمام: | edspgr.06235735 |
| قاعدة البيانات: | USPTO Patent Grants |
| الوصف غير متاح. |