Claims for Patent: 6,329,392

Summary for Patent: 6,329,392

Title:	Substituted piperidines useful for the treatment of allergic diseases
Abstract:	The present invention relates to novel substituted piperidine derivatives of the formula ##STR1## stereoisomers thereof, and pharmaceutically acceptable salts thereof which are useful as histamine receptor antagonists and tachykinin receptor antagonist. Such antagonists are useful in the treatment of allergic diseases including: seasonal rhinitis, allergic rhinitis, and sinusitis.
Inventor(s):	Burkholder; Timothy P. (Carmel, IN), Bratton; Larry D. (Whitmore Lake, MI), Kudlacz; Elizabeth M. (Groton, CT), Maynard; George P. (Westbrook, CT), Kane; John M. (Cincinnati, OH), Santiago; Braulio (San Juan, PR)
Assignee:	Aventis Pharmaceuticals, Inc. (Bridgewater, NJ)
Application Number:	09/079,924
Patent Claims:	1. A compound of the formula ##STR120## wherein G.sub.1 is --CH.sub.2 -- or --C(O)--; G.sub.2 is --CH.sub.2 -- or --C(O)--; G.sub.3 is --CH.sub.2 -- or --C(O)--; m is 2 or 3; n is 0 or 1; q is 1 or 2; r is 0 or 1; Ar.sub.1 is a radical chosen from the group consisting of ##STR121## wherein R.sub.1 is from 1 to 3 substituents each independently chosen from the group consisting of hydrogen, halogen, hydroxy, CF.sub.3, C.sub.1 -C.sub.6 alkyl, and C.sub.1 -C.sub.6 alkoxy; R.sub.2 is from 1 to 2 substituents each independently chosen from the group consisting of hydrogen, halogen, C.sub.1 -C.sub.6 alkyl, and C.sub.1 -C.sub.6 alkoxy; Ar.sub.2 is a radical chosen from the group consisting of ##STR122## wherein R.sub.3 is from 1 to 3 substituents each independently chosen from the group consisting of hydrogen, halogen, C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy, and --OCH.sub.2 CO.sub.2 R.sub.21 wherein R.sub.21 is chosen from the group consisting of hydrogen and C.sub.1 -C.sub.4 alkyl; R.sub.4 is from 1 to 2 substituents each independently chosen from the group consisting of hydrogen, halogen, C.sub.1 -C.sub.6 alkyl, and C.sub.1 -C.sub.6 alkoxy; and X.sub.1 and X.sub.2 are as defined in one of parts A), B), or C): A) X.sub.1 is hydrogen; X.sub.2 is a radical chosen from the group consisting of ##STR123## wherein p is 1 or 2 R.sub.5 is from 1 to 3 substituents each independently chosen from the group consisting of hydrogen, halogen, CF.sub.3, C.sub.1 -C.sub.6 alkyl, and C.sub.1 -C.sub.6 alkoxy; R.sub.6 is from 1 to 3 substituents each independently chosen from the group consisting of hydrogen, halogen, CF.sub.3, C.sub.1 -C.sub.6 alkyl, and C.sub.1 -C.sub.6 alkoxy, R.sub.7 is hydrogen or hydroxy; Ar.sub.3 is a radical chosen from the group consisting of ##STR124## wherein R.sub.8 is from 1 to 3 substituents each independently chosen from the group consisting of hydrogen, halogen, CF.sub.3, C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy, and --CO.sub.2 R.sub.19 wherein R.sub.19 is chosen from the group consisting of hydrogen and C.sub.1 -C.sub.4 alkyl; R.sub.9 is from 1 to 2 substituents each independently chosen from the group consisting of hydrogen, halogen, C.sub.1 -C.sub.6 alkyl, and C.sub.1 -C.sub.6 alkoxy; R.sub.10 is chosen from the group consisting of hydrogen, --CH.sub.3, and --CH.sub.2 OH; R.sub.20 is chosen from the group consisting of hydrogen, C.sub.1 -C.sub.4 alkyl, and benzyl; Z is chosen from the group consisting of hydrogen, C.sub.1 -C.sub.4 alkyl, --(CH.sub.2).sub.w --O-- (CH.sub.2).sub.t --(CH.sub.2).sub.f A, --(CH.sub.2).sub.u CO.sub.2 R.sub.11, --(CH.sub.2).sub.u C(O)NR.sub.12 R.sub.13, --(CH.sub.2).sub.g C(O)(CH.sub.2).sub.h CH.sub.3, --(CH.sub.2).sub.w --O--Ar.sub.4, and --CH.sub.2 OCH.sub.2 CH.sub.2 Si(CH.sub.3).sub.3 wherein w is an integer from 2 to 5; t is an integer from 1 to 3; f is 2 or 3; u is an integer from 1 to 4; g is an integer from 1 to 3; h is an integer from 0 to 3; w is an integer from 2 to 4; Y is chosen from the group consisting of hydrogen, --CH.dbd.CH.sub.2, --CH.dbd.C(CH.sub.3).sub.2, and --CO.sub.2 R.sub.14 wherein R.sub.14 is chosen from the group consisting of hydrogen and C.sub.1 -C.sub.4 alkyl; A is chosen from the group consisting of --NR.sub.17 R.sub.18, acetylamino, and morpholino wherein R.sub.17 is chosen from the group consisting of hydrogen and C.sub.1 -C.sub.4 alkyl and R.sub.18 is C.sub.1 -C.sub.4 alkyl; R.sub.11 is chosen from the group consisting of hydrogen and C.sub.1 -C.sub.4 alkyl; R.sub.12 is chosen from the group consisting of hydrogen, C.sub.1 -C.sub.4 alkyl, and benzyl; R.sub.13 is chosen from the group consisting of hydrogen and C.sub.1 -C.sub.4 alkyl; Ar.sub.4 is a radical chosen from the group consisting of ##STR125## wherein v is an integer from 1 to 3; R.sub.15 is chosen from the group consisting of hydrogen and --CO.sub.2 R.sub.16 wherein R.sub.16 is chosen from the group consisting of hydrogen and C.sub.1 -C.sub.4 alkyl; B) X.sub.1 is hydroxy; and X.sub.2 is a radical chosen from the group consisting of ##STR126## wherein p, R.sub.5, Z, and Ar.sub.3 are as previously defined; C) X.sub.2 is a radical of the formula; ##STR127## wherein R.sub.5 and R.sub.6 are as previously defined; and X.sub.1 and Z.sub.1 taken together form a second bond between the carbon atoms bearing X.sub.1 and Z.sub.1 ; provided that when G.sub.1 is --C(O)-- then G.sub.2 and G.sub.3 are --CH.sub.2 --; further provided that when G.sub.2 is --C(O)-- then G.sub.1 and G.sub.3 are --CH.sub.2 --; still further provided that when G.sub.3 is --C(O)-- then G.sub.1 and G.sub.2 are --CH.sub.2 --; or stereoisomers, or pharmaceutically acceptable salt thereof. 2. A compound of claim 1 wherein m is 2. 3. A compound of claim 2 wherein G.sub.2 is --C(O)--. 4. A compound of claim 3 wherein X.sub.1 is hydrogen. 5. A compound of claim 4 wherein X.sub.2 is a radical of the formula ##STR128## 6. A compound of claim 5 wherein R.sub.5 is hydrogen, p is 1, and Ar.sub.3 is 4-fluoro-phenyl. 7. A compound of claim 5 wherein R.sub.5 is hydrogen, p is 1, and Ar.sub.3 is pyrid-2-yl. 8. A compound of claim 5 wherein R.sub.5 is hydrogen, p is 1, and Ar.sub.3 is fur-2-yl. 9. A compound of claim 4 wherein X.sub.2 is a radical of the formula ##STR129## 10. A compound of claim 9 wherein Z is 2-ethoxy-ethyl. 11. A compound of claim 9 wherein Z is 2-fur-2-ylmethoxy-ethyl. 12. A compound of claim 3 wherein X.sub.1 is hydroxy. 13. A compound of claim 12 wherein X.sub.2 is a radical of the formula ##STR130## 14. A compound of claim 13 wherein R.sub.5 is hydrogen, p is 1, and Ar.sub.3 is 4-fluoro-phenyl. 15. A compound of claim 1 wherein the compound is (+)- or (-)-1-(3,4,5-Trimethoxy-benzoyl)-3-[2-[4-[1-(4-fluoro-benzyl)-1H-benzoimid azole-2-carbonyl]-piperidin-1-yl]-ethyl]-3-(3,4-dimethoxy-phenyl)-pyrrolidi ne or a mixture thereof. 16. A compound of claim 1 wherein the compound is (+)- or (-)-1-Benzoyl-3-[2-[4-[1-(4-fluoro-benzyl)-1H-benzoimidazole-2-carbonyl]-p iperidin-1-yl]-ethyl]-3-(3,4-dimethoxy-phenyl)-pyrrolidine or a mixture thereof. 17. A compound of claim 1 wherein the compound is (+)- or (-)-1-Benzoyl-3-[2-[4-[1-(4-fluoro-benzyl)-1H-benzoimidazol-2-yl]-4-hydrox y-piperidin-1-yl]-ethyl]-3-(3,4-dimethoxy-phenyl)-pyrrolidine or a mixture thereof. 18. A compound of claim 1 wherein the compound is (+)- or (-)-1-Benzoyl-3-[2-[4-(benzothiazol-2-yl)-piperidin-1-yl]-ethyl]-3-(3,4-di methoxy-phenyl)-pyrrolidine or a mixture thereof. 19. A compound of claim 1 wherein the compound is (+)- or (-)-1-(3,4,5-Trimethoxybenzoyl)-3-[2-[4-[1-(4-fluoro-benzyl)-1H-benzoimida zol-2-yl]-4-hydroxy-piperidin-1-yl]-ethyl]-3-(3,4-dimethoxy-phenyl)-pyrroli dine or a mixture thereof. 20. A compound of claim 1 wherein the compound is (+)- or (-)-1-(3,4,5-Trimethoxy-benzoyl)-3-[2-[4-[1-(4-fluoro-benzyl)-1H-benzoimid azole-2-carbonyl]-piperidin-1-yl]-ethyl]-3-(3,4-dichloro-phenyl)-pyrrolidin e or a mixture thereof. 21. A compound of claim 1 wherein the compound is (+)- or (-)-1-(3,4,5-Trimethoxy-benzoyl)-3-[2-[4-[1-(4-fluoro-benzyl)-1H-benzoimid azol-2-yl(3-4-hydroxy-piperidin-1-yl]-ethyl]-3-(3,4-dichloro-phenyl)-pyrrol idine or a mixture thereof. 22. A compound of claim 1 wherein the compound is (+)- or (-)-1-Benzoyl-3-[2-[4-(benzothiazole-2-carbonyl)-piperidin-1-yl]-ethyl]-3- (3,4-dimethoxy-phenyl)-pyrrolidine or a mixture thereof. 23. A compound of claim 1 wherein the compound is (+)- or (-)-1-(3,4,5-Trimethoxybenzoyl)-3-[2-[4-(hydroxy-diphenyl-methyl)-piperidi n-1-yl]-ethyl]-3-(3,4-dimethoxy-phenyl)-pyrrolidine or a mixture thereof. 24. A compound of claim 1 wherein the compound is (+)- or (-)-1-(3,4,5-Trimethoxy-benzoyl)-3-[2-[4-[1-(4-fluoro-benzyl)-1H-benzoimid azole-2-carbonyl]-piperidin-1-yl]-ethyl]-3-(benzo[1,3]dioxol-5-yl)-pyrrolid ine or a mixture thereof. 25. A compound of claim 1 wherein the compound is (+)- or (-)-1-(3,4,5-Trimethoxy-benzoyl)-3-[2-[4-[1-(4-fluoro-benzyl)-1H-benzoimid azole-2-carbonyl]-piperidin-1-yl]-ethyl]-3-phenyl-pyrrolidine or a mixture thereof. 26. A compound of claim 1 wherein the compound is (+)- or (-)-1-(3,4,5-Trimethoxy-benzoyl)-3-[2-[4-[1-(4-fluoro-benzyl)-1H-benzoimid azole-2-carbonyl]-piperidin-1-yl]-ethyl]-3-(4-trifluoromethyl-phenyl)-pyrro lidine or a mixture thereof. 27. A compound of claim 1 wherein the compound is (+)- or (-)-1-(3,4,5-Trimethoxy-benzoyl)-3-[2-[4-[1-(4-fluoro-benzyl)-1H-benzoimid azole-2-carbonyl]-piperidin-1-yl]-ethyl]-3-(2,4-difluoro-phenyl)-pyrrolidin e or a mixture thereof. 28. A compound of claim 1 wherein the compound is (+)- or (-)-1-(3-Isopropoxy-phenyl-acetyl)-3-[2-[4-[1-(4-fluoro-benzyl)-1H-benzoim idazole-2-carbonyl]-piperidin-1-yl]-ethyl]-3-(benzo[1,3]dioxol-5-yl)-pyrrol idine or a mixture thereof. 29. A compound of claim 1 wherein the compound is (+)- or (-)-1-(2,3,4-Trimethoxy-benzoyl)-3-[2-[4-[1-(4-fluoro-benzyl)-1H-benzoimid azole-2-carbonyl]-piperidin-1-yl]-ethyl]-3-(benzo[1,3]dioxol-5-yl)-pyrrolid ine or a mixture thereof. 30. A compound of claim 1 wherein the compound is (+)- or (-)-1-(3,4,5-Triethoxy-benzoyl)-3-[2-[4-[1-(4-fluoro-benzyl)-1H-benzoimida zole-2-carbonyl]-piperidin-1-yl]-ethyl]-3-(3,4-dimethoxy-phenyl)-pyrrolidin e or a mixture thereof. 31. A compound of claim 1 wherein the compound is (+)- or (-)-1-(3,4,5-Trimethoxy-benzoyl)-3-[2-[4-benzhydrylidene-piperidin-1-yl]-e thyl]-3-(3,4-dichloro-phenyl)-pyrrolidine or a mixture thereof. 32. A compound of claim 1 wherein the compound is (+)- or (-)-1-(3,4,5-Trimethoxy-benzoyl)-3-[2-[4-[1H-benzoimidazole-2-carbonyl]-pi peridin-1-yl]-ethyl]-3-(3,4-dichloro-phenyl)-pyrrolidine or a mixture thereof. 33. A compound of claim 1 wherein the compound is (+)- or (-)-1-(3,4,5-Trimethoxy-benzoyl)-3-[2-[4-[1-(2-(morpholin-4-yl)-ethyl)-1H- benzoimidazole-2-carbonyl]-piperidin-1-yl]-ethyl]-3-(3,4-dichloro-phenyl)-p yrrolidine or a mixture thereof. 34. A compound of claim 1 wherein the compound is (+)- or (-)-1-(3,4,5-Trimethoxy-benzoyl)-3-[2-[4-[1-(pyrid-2-ylmethyl)-1H-benzoimi dazole-2-carbonyl]-piperidin-1-yl]-ethyl]-3-(3,4-dichloro-phenyl)-pyrrolidi ne or a mixture thereof. 35. A compound of claim 1 wherein the compound is (+)- or (-)-1-(3,4,5-Trimethoxy-benzoyl)-3-[2-[4-[1-(3-ethoxycarbonyl-propyl)-1H-b enzoimidazole-2-carbonyl]-piperidin-1-yl]-ethyl]-3-(3,4-dichloro-phenyl)-py rrolidine or a mixture thereof. 36. A compound of claim 1 wherein the compound is (+)- or (-)-1-(3,4,5-Trimethoxy-benzoyl)-3-[2-[4-[1-(3-carboxy-propyl)-1H-benzoimi dazole-2-carbonyl]-piperidin-1-yl]-ethyl]-3-(3,4-dichloro-phenyl)-pyrrolidi ne or a mixture thereof. 37. A compound of claim 1 wherein the compound is (+)- or (-)-1-(3,4,5-Trimethoxy-benzoyl)-3-[2-[4-[1H-benzoimidazole-2-carbonyl]-pi peridin-1-yl]-ethyl]-3-phenyl-pyrrolidine or a mixture thereof. 38. A compound of claim 1 wherein the compound is (+)- or (-)-1-(3,4,5-Trimethoxy-benzoyl)-3-[2-[4-[1-(pyrid-2-ylmethyl)-1H-benzoimi dazole-2-carbonyl]-piperidin-1-yl]-ethyl]-3-phenyl-pyrrolidine or a mixture thereof. 39. A compound of claim 1 wherein the compound is (+)- or (-)-1-(3,4,5-Trimethoxy-benzoyl)-3-[2-[4-[1-(4-methoxycarbonyl-benzyl)-1H- benzoimidazole-2-carbonyl]-piperidin-1-yl]-ethyl]-3-phenyl-pyrrolidine or a mixture thereof. 40. A compound of claim 1 wherein the compound is (+)- or (-)-1-(3,4,5-Trimethoxy-benzoyl)-3-[2-[4-[1-(4-carboxy-benzyl)-1H-benzoimi dazole-2-carbonyl]-piperidin-1-yl]-ethyl]-3-phenyl-pyrrolidine or a mixture thereof. 41. A compound of claim 1 wherein the compound is (+)- or (-)-1-(3,4,5-Trimethoxy-benzoyl)-3-[2-[4-[1-(2-ethoxy-ethyl)-1H-benzoimida zole-2-carbonyl]-piperidin-1-yl]-ethyl]-3-phenyl-pyrrolidine or a mixture thereof. 42. A compound of claim 1 wherein the compound is (+)- or (-)-1-(3,4,5-Trimethoxy-benzoyl)-3-[2-[4-[1H-benzoimidazole-2-carbonyl]-pi peridin-1-yl]-ethyl]-3-phenyl-pyrrolidine or a mixture thereof. 43. A compound of claim 1 wherein the compound is (+)- or (-)-1-(3,4,5-Trimethoxy-benzoyl)-3-[2-[4-[1H-benzoimidazole-2-carbonyl]-pi peridin-1-yl]-ethyl]-3-(3,4-dimethoxy-phenyl)-pyrrolidine or a mixture thereof. 44. A compound of claim 1 wherein the compound is (+)- or (-)-1-(3,4,5-Trimethoxy-benzoyl)-3-[2-[4-[1-(4-carbomethoxy-phenylmethyl)- 1H-benzoimidazole-2-carbonyl]-piperidin-1-yl]-ethyl]-3-(3,4-dimethoxy-pheny l)-pyrrolidine or a mixture thereof. 45. A compound of claim 1 wherein the compound is (+)- or -)-1-(3,4,5-Trimethoxy-benzoyl)-3-[2-[4-[1-(4-carboxy-phenylmethyl)-1H-ben zoimidazole-2-carbonyl]-piperidin-1-yl]-ethyl]-3-(3,4-dimethoxy-phenyl)-pyr rolidine or a mixture thereof. 46. A compound of claim 1 wherein the compound is (+)- or (-)-1-(3,4,5-Trimethoxy-benzoyl)-3-[2-[4-[1-(fur-2-ylmethyl)-1H-benzoimida zole-2-carbonyl]-piperidin-1-yl]-ethyl]-3-phenyl-pyrrolidine or a mixture thereof. 47. A compound of claim 1 wherein the compound is (+)- or (-)-1-(3,4,5-Trimethoxy-benzoyl)-3-[2-[4-[1-(2-fur-2-ylmethoxy-ethyl)-1H-b enzoimidazole-2-carbonyl]-piperidin-1-yl]-ethyl]-3-phenyl-pyrrolidine or a mixture thereof. 48. A compound of claim 1 wherein the compound is (+)- or (-)-1-(3,4,5-Trimethoxy-benzoyl)-3-[2-[4-[1-(2-allyloxy-ethyl)-1H-benzoimi dazole-2-carbonyl]-piperidin-1-yl]-ethyl]-3-phenyl-pyrrolidine or a mixture thereof. 49. A compound of claim 1 wherein the compound is (+)- or (-)-1-(3,4,5-Trimethoxy-benzoyl)-3-[2-[4-[1-(2-(3,3-dimethylallyloxy)-ethy l)-1H-benzoimidazole-2-carbonyl]-piperidin-1-yl]-ethyl]-3-phenyl-pyrrolidin e or a mixture thereof. 50. A compound of claim 1 wherein the compound is (+)- or (-)-1-(2,4-Dichloro-benzoyl)-3-[2-[4-[1-(4-fluoro-benzyl)-1H-benzoimidazol e-2-carbonyl]-piperidin-1-yl]-ethyl]-3-(benzo[1,3]dioxol-5-yl)-pyrrolidine or a mixture thereof. 51. A compound of claim 1 wherein the compound is (+)- or (-)-1-(3-Isopropoxy-phenyl-acetyl)-3-[2-[4-[1-(2-ethoxy-ethyl)-1H-benzoimi dazole-2-carbonyl]-piperidin-1-yl]-ethyl]-3-(3,4-dichloro-phenyl)-piperidin e or a mixture thereof. 52. A compound of claim 1 wherein the compound is (+)- or (-)-1-(3,4,5-Trimethoxy-benzyl)-3-[2-[4-[1-(4-fluoro-benzyl)-1H-benzoimida zol-2-yl]-4-hydroxy-piperidin-1-yl]-ethyl]-3-(phenylmethyl)-2-oxo-pyrrolidi ne or a mixture thereof. 53. A compound of claim 1 wherein the compound is (+)- or (-)-1-(3,4,5-Trimethoxy-benzyl)-3-[2-[4-[1-(4-fluoro-benzyl)-1H-benzoimida zol-2-yl]-4-hydroxy-piperidin-1-yl]-ethyl]-3-(3,4-dichloro-phenylmethyl)-2- oxo-pyrrolidine or a mixture thereof. 54. A compound of claim 1 wherein the compound is (+)- or (-)-1-(3,4,5-Trimethoxy-benzyl)-3-[2-[4-[1-(4-fluoro-benzyl)-1H-benzoimida zol-2-yl]-4-hydroxy-piperidin-1-yl]-ethyl]-3-(3,4-dimethoxy-phenylmethyl)-2 -oxo-pyrrolidine or a mixture thereof. 55. A compound of claim 1 wherein the compound is (+)- or (-)-1-(3,4,5-Trimethoxy-benzyl)-3-[2-[4-[1-(4-fluoro-benzyl)-1H-benzoimida zol-2-yl]-4-hydroxy-piperidin-1-yl]-ethyl]-3-(4-fluoro-phenylmethyl)-2-oxo- pyrrolidine or a mixture thereon. 56. A compound of claim 1 wherein the compound is (+)- or (-)-1-(3,4,5-Trimethoxy-benzyl)-3-[2-[4-[1-(4-fluoro-benzyl)-1H-benzoimida zol-2-yl]-4-hydroxy-piperidin-1-yl]-ethyl]-3-(2,4-difluoro-phenylmethyl)-2- oxo-pyrrolidine or a mixture thereof. 57. A compound of claim 1 wherein the compound is (+)- or (-)-1-Benzyl-3-[2-[4-[1-(4-fluoro-benzyl)-1H-benzoimidazol-2-yl]-4-hydroxy -piperidin-1-yl]-ethyl]-3-(phenylmethyl)-2-oxo-pyrrolidine or a mixture thereof. 58. A compound of claim 1 wherein the compound is (+)- or (-)-1-(3-Isopropoxy-phenyl-acetyl)-3-[2-[4-[1-(4-fluoro-benzyl)-1H-benzoim idazole-2-carbonyl]-piperidin-1-yl]-ethyl]-3-(3,4-dichloro-phenyl)-piperidi ne or a mixture thereof. 59. A compound of claim 1 wherein the compound is (+)- or (-)-1-(3,4,5-Trimethoxy-benzoyl)-3-[2-[4-[1-(3-(2-carbomethoxy-phenoxy)-pr opyl)-1H-benzoimidazole-2-carbonyl]-piperidin-1-yl]-ethyl]-3-phenyl-pyrroli dine or a mixture thereof. 60. A compound of claim 1 wherein the compound is (+)- or (-)-1-(3,4,5-Trimethoxy-benzoyl)-3-[2-[4-[1-(3-(2-carboxy-phenoxy)-propyl) -1H-benzoimidazole-2-carbonyl]-piperidin-1-yl]-ethyl]-3-phenyl-pyrrolidine or a mixture thereof. 61. A compound of claim 1 wherein the compound is (+)- or (-)-1-(3,4,5-Trimethoxy-benzoyl)-3-[2-[4-[1-(pyrid-2-ylmethyl)-1H-benzoimi dazole-2-carbonyl]-piperidin-1-yl]-ethyl]-3-(4-methoxy-phenyl)-pyrrolidine or a mixture thereof. 62. A compound of claim 1 wherein the compound is (+)- or (-)-1-(3,4,5-Trimethoxy-benzyl)-3-[3-[4-[1-(2-ethoxy-ethyl)-1H-benzoimidaz ole-2-carbonyl]-piperidin-1-yl]-propyl]-3-(4-fluoro-phenylmethyl)-2-oxo-pyr rolidine or a mixture thereof. 63. A compound of claim 1 wherein the compound is (+)- or (-)-1-(3,4,5-Trimethoxy-benzoyl)-3-[2-[4-[1-(2-ethoxy-ethyl)-1H-benzoimida zole-2-carbonyl]-piperidin-1-yl]-ethyl]-3-(3,4-difluoro-phenyl)-pyrrolidine or a mixture thereof. 64. A compound of claim 1 wherein the compound is (+)- or (-)-1-(3,4,5-Trimethoxy-benzoyl)-3-[2-[4-[1-(2-ethoxy-ethyl)-1H-benzoimida zole]-4-hydroxy-piperidin-1-yl]-ethyl]-3-(3,4-dichloro-phenyl)-pyrrolidine or a mixture thereof. 65. A compound of claim 1 wherein the compound is (+)- or (-)-1-(3,4,5-Trimethoxy-benzoyl)-3-[2-[4-[1-(4-fluoro-benzyl)-1H-benzoimid azole-2-carbonyl]-piperidin-1-yl]-ethyl]-3-(3,4-dichloro-phenyl)-piperidine or a mixture thereof. 66. A compound of claim 1 wherein the compound is (+)- or (-)-1-(3,4,5-Trimethoxy-benzyl)-3-[2-[4-[1-(pryid-2-ylmethyl)-1H-benzoimid azole-2-carbonyl]-piperidin-1-yl]-ethyl]-3-(4-fluoro-phenylmethyl)-2-oxo-py rrolidine or a mixture thereof. 67. A compound of claim 1 wherein the compound is (+)- or (-)-1-(3,4,5-Trimethoxy-benzoyl)-3-[2-[4-(l-(2-ethoxy-ethyl)-1H-benzoimida zole-2-carbonyl]-piperidin-1-yl]-ethyl]-3-(3,4-dichloro-phenyl)-pyrrolidine or a mixture thereof. 68. A compound of claim 1 wherein the compound is (+)- or (-)-1-(3,4,5-Trimethoxy-benzoyl)-3-[2-[4-[1H-benzoimidazole-2-carbonyl]-pi peridin-1-yl]-ethyl]-3-(4-methoxy-phenyl)-pyrrolidine or a mixture thereof. 69. A pharmaceutical composition comprising a histamic receptor inhibitory effective amount or a tachykinin receptor antagonistic effective amount of a compound of claim 1. 70. A pharmaceutical composition comprising a histamic receptor inhibitory effective amount or a tachykinin receptor antagonistic effective amount of a compound of claim 1 and one or more pharmaceutically acceptable inert carriers. 71. A method of treating allergic response or inflammatory response in a patient in need thereof, comprising administering to said patient a histamine receptor inhibitory effective amount or a tachykinin receptor antagonistic effective amount of a compound of claim 1. 72. The method of claim 71 wherein said allergic or inflammatory response is in allergic rhinitis. 73. The method of claim 71 wherein said allergic or inflammatory response is in asthma. 74. The method of claim 71 wherein said allergic or inflammatory response is in opthalmic allergies. 75. The method of claim 71 wherein said allergic or inflammatory response is in inflammatory bowel disease. 76. The method of claim 71 wherein said allergic or inflammatory response is in uveitis. 77. A method of treating emesis in a patient in need thereof comprising administering to said patient an antiemetic effective amount of a compound of claim 1.

Details for Patent 6,329,392

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Jubilant Hollisterstier Llc	N/A	positive skin test control-histamine	Injection	103891	March 13, 1924	6,329,392	2018-05-15