Method of treating disorders and conditions using peripherally-restricted antagonists and inhibitors
First Claim
1. A method for treating, preventing or reducing one or more 5-HT3 mediated disorders in a subject in need thereof comprising administering to said subject a therapeutically effective amount of a compound selected from the group consisting of:
- (a) a quaternary ammonium derivative of MCI-225 (MCI-225-QUAT);
(b) a quaternary ammonium derivative of MCI-225 (MCI-225-QUAT) possessing an enhanced therapeutic profile;
(c) a peripherally-restricted 5-HT3 receptor antagonist together with an additional agent for treating, preventing or reducing the one or more 5-HT3 mediated disorders in the subject;
(d) a peripherally-restricted 5-HT3 receptor antagonist possessing an enhanced therapeutic profile together with an additional agent for treating, preventing or reducing the one or more 5-HT3 mediated disorders in the subject; and
(e) a peripherally-restricted 5-HT3 receptor antagonist together with an additional agent for treating, preventing or reducing the one or more 5-HT3 mediated disorders in the subject, wherein the peripherally-restricted 5-HT3 receptor antagonist possesses an enhanced therapeutic profile resulting from the combination of the peripherally-restricted 5-HT3 receptor antagonist with the additional agent.
2 Assignments
0 Petitions
Accused Products
Abstract
The instant invention features compounds, for example, 5-HT3 receptor antagonists, having a peripherally restricted mode of action such that the compounds affect 5-HT3 receptors of the peripheral nervous system with diminished or reduced effects in the central nervous system. The compounds are particularly useful in treating disorders or conditions ameliorated by antagonism of peripheral 5-HT3 receptors. Moreover, side-effects attributable to antagonism of central 5-HT3 receptors can be lessened or reduced using the peripherally restricted compounds of the invention.
81 Citations
210 Claims
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1. A method for treating, preventing or reducing one or more 5-HT3 mediated disorders in a subject in need thereof comprising administering to said subject a therapeutically effective amount of a compound selected from the group consisting of:
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(a) a quaternary ammonium derivative of MCI-225 (MCI-225-QUAT);
(b) a quaternary ammonium derivative of MCI-225 (MCI-225-QUAT) possessing an enhanced therapeutic profile;
(c) a peripherally-restricted 5-HT3 receptor antagonist together with an additional agent for treating, preventing or reducing the one or more 5-HT3 mediated disorders in the subject;
(d) a peripherally-restricted 5-HT3 receptor antagonist possessing an enhanced therapeutic profile together with an additional agent for treating, preventing or reducing the one or more 5-HT3 mediated disorders in the subject; and
(e) a peripherally-restricted 5-HT3 receptor antagonist together with an additional agent for treating, preventing or reducing the one or more 5-HT3 mediated disorders in the subject, wherein the peripherally-restricted 5-HT3 receptor antagonist possesses an enhanced therapeutic profile resulting from the combination of the peripherally-restricted 5-HT3 receptor antagonist with the additional agent. - View Dependent Claims (2)
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3-18. -18. (canceled)
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19. A method for treating one or more 5-HT3 mediated disorders in a subject in need thereof comprising administering to said subject a therapeutically effective amount of a compound selected from the group consisting of
(a) a compound of Formula I: - or a pharmaceutically acceptable salt thereof;
(b) a compound of Formula II;
or a pharmaceutically acceptable salt thereof; and
(c) a compound of Formula III;
or a pharmaceutically acceptable salt thereof. - View Dependent Claims (20, 21, 22, 23, 24, 25, 26)
- or a pharmaceutically acceptable salt thereof;
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27-30. -30. (canceled)
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31. A packaged pharmaceutical composition for treating one or more 5-HT3 mediated disorders in a subject, comprising a container holding a therapeutically effective amount of a peripherally-restricted 5-HT3 receptor antagonist;
- and instructions for using the composition for treating the one or more 5-HT3 mediated disorders in the subject.
- View Dependent Claims (32, 33)
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34. A pharmaceutical composition for treating one or more 5-HT3 mediated disorders in a subject, comprising a compound selected from the group consisting of:
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(a) a peripherally-restricted 5-HT3 receptor antagonist selected based on its peripheral restriction, (b) an MCI-225-QUAT;
(c) an MCI-225-QUAT possessing an enhanced therapeutic profile; and
(d) a peripherally-restricted 5-HT3 receptor antagonist together with an additional agent for treating the one or more 5-HT3 mediated disorders in the subject;
and a pharmaceutically acceptable carrier. - View Dependent Claims (38)
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35-37. -37. (canceled)
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39. A method for treating a functional bowel disorder in a subject in need thereof comprising administering to said subject a therapeutically effective amount of a compound selected from the group consisting of:
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(a) a quaternary ammonium derivative of MCI-225 (MCI-225-QUAT);
(b) a peripherally-restricted 5-HT3 receptor antagonist together with an additional agent for treating the functional bowel disorder in the subject; and
(c) a peripherally-restricted 5-HT3 receptor antagonist together with a noradrenaline reuptake inhibitor. - View Dependent Claims (40)
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41-59. -59. (canceled)
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60. A method for treating a functional bowel disorder in a subject in need thereof comprising administering to said subject a therapeutically effective amount of a compound selected from the group consisting of
(a) a compound of Formula I: - or a pharmaceutically acceptable salt thereof;
(b) a compound of Formula II;
or a pharmaceutically acceptable salt thereof; and
(c) a compound of Formula III;
or a pharmaceutically acceptable salt thereof. - View Dependent Claims (61, 62, 63, 64, 65, 66)
- or a pharmaceutically acceptable salt thereof;
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67. A method of treating at least one symptom of a lower urinary tract disorder in a subject in need thereof comprising administering to said subject a therapeutically effective amount of a quaternary ammonium derivative of MCI-225 (MCI-225-QUAT).
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68-82. -82. (canceled)
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83. A method of treating at least one symptom of a lower urinary tract disorder in a subject in need thereof comprising administering to said subject a therapeutically effective amount of a compound selected from the group consisting of
(a) a compound of Formula I: - or a pharmaceutically acceptable salt thereof,
(b) a compound of Formula II;
or a pharmaceutically acceptable salt thereof, and(c) a compound of Formula III;
or a pharmaceutically acceptable salt thereof. - View Dependent Claims (84, 85, 86, 87, 88, 89)
- or a pharmaceutically acceptable salt thereof,
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90. A method for treating urinary incontinence in a subject in need thereof comprising administering to said subject a therapeutically effective amount of a compound selected from the group consisting of:
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(a) a quaternary ammonium derivative of MCI-225 (MCI-225-QUAT);
(b) a quaternary ammonium derivative of MCI-225 (MCI-225-QUAT) possessing an enhanced therapeutic profile;
(c) a peripherally-restricted 5-HT3 receptor antagonist together with an additional agent for treating the urinary incontinence in the subject; and
(d) a peripherally-restricted 5-HT3 receptor antagonist together with a noradrenaline reuptake inhibitor. - View Dependent Claims (138)
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91. (canceled)
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92. A method for treating nausea, vomiting, retching or any combination thereof in a subject in need thereof comprising administering to said subject a therapeutically effective amount of (a) a quaternary ammonium derivative of MCI-225 (MCI-225-QUAT);
- or (b) a quaternary ammonium derivative of MCI-225 (MCI-225-QUAT) possessing an enhanced therapeutic profile.
- View Dependent Claims (94, 95, 96, 100)
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93. (canceled)
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97-99. -99. (canceled)
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101-115. -115. (canceled)
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116. A method for treating nausea, vomiting, retching or any combination thereof in a subject in need thereof comprising administering to said subject a t therapeutically effective amount of a compound selected from the group consisting of
(a) a compound of Formula I: - or a pharmaceutically acceptable salt thereof;
(b) a compound of Formula II;
or a pharmaceutically acceptable salt thereof; and
(c) a compound of Formula III;
or a pharmaceutically acceptable salt thereof. - View Dependent Claims (117, 118, 119, 120, 121, 122)
- or a pharmaceutically acceptable salt thereof;
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123-129. -129. (canceled)
- 130. A method of treating at least one symptom of a lower urinary tract disorder in a subject in need of treatment, wherein the symptom is selected from the group consisting of urinary frequency, urinary urgency, nocturia and enuresis, comprising coadministering to said subject a peripherally-restricted 5-HT3 receptor antagonist with an additional agent.
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133-137. -137. (canceled)
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139. (canceled)
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140. A method for treating nausea, vomiting, retching or any combination thereof in a subject in need thereof comprising administering to said subject a compound selected from the group consisting of:
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(a) a peripherally-restricted 5-HT3 receptor antagonist together with an additional agent for treating the nausea, vomiting, retching or any combination thereof in the subject;
(b) a peripherally-restricted 5-HT3 receptor antagonist together with a noradrenaline reuptake inhibitor;
(c) a peripherally-restricted 5-HT3 receptor antagonist selected based on its peripheral restriction; and
(d) a peripherally-restricted 5-HT3 receptor antagonist together with an additional agent, wherein the additional agent is selected based on its effect in combination with the peripherally-restricted 5-HT3 receptor antagonist for treating the nausea, vomiting, retching or any combination thereof in the subject. - View Dependent Claims (144)
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141-143. -143. (canceled)
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145-159. -159. (canceled)
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160. A compound selected from the group consisting of
(a) Formula I: - or a pharmaceutically acceptable salt thereof;
(b) Formula II;
or a pharmaceutically acceptable salt thereof; and
(c) Formula III;
or a pharmaceutically acceptable salt thereof. - View Dependent Claims (161, 162, 163, 164, 165, 166)
- or a pharmaceutically acceptable salt thereof;
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167. A packaged pharmaceutical composition for treating a functional bowel disorder in a subject, comprising a container holding a therapeutically effective amount of a peripherally-restricted 5-HT3 receptor antagonist;
- and instructions for using the composition for treating the functional bowel disorder in the subject.
- View Dependent Claims (168)
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169. A pharmaceutical composition for treating a functional bowel disorder in a subject, comprising a compound selected from the group consisting of:
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(a) a peripherally-restricted 5-HT3 receptor antagonist selected based on its peripheral restriction;
(b) an MCI-225-QUAT;
(c) an MCI-225-QUAT possessing an enhanced therapeutic profile; and
(d) a peripherally-restricted 5-HT3 receptor antagonist together with an additional agent for treating the functional bowel disorder in the subject;
and a pharmaceutically acceptable carrier. - View Dependent Claims (173)
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170-172. -172. (canceled)
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174-176. -176. (canceled)
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177. (canceled)
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178. A packaged pharmaceutical composition for treating at least one symptom of a lower urinary tract disorder in a subject, comprising a container holding a therapeutically effective amount of a peripherally-restricted 5-HT3 receptor antagonist;
- and instructions for using the composition for treating the at least one symptom of a lower urinary tract disorder in the subject.
- View Dependent Claims (179)
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180. A pharmaceutical composition for treating at least one symptom of a lower urinary tract disorder in a subject in need of treatment, comprising a compound selected from the group consisting of:
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(a) a peripherally-restricted 5-HT3 receptor antagonist selected based on its peripheral restriction;
(b) an MCI-225-QUAT;
(c) an MCI-225-QUAT possessing an enhanced therapeutic profile; and
(d) a peripherally-restricted 5-HT3 receptor antagonist together with an additional agent for treating the at least one symptom of a lower urinary tract disorder in the subject;
and a pharmacuetically acceptable carrier, wherein the symptom is selected from the group consisting of urinary frequency, urinary urgency, nocturia and enuresis. - View Dependent Claims (184)
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181-183. -183. (canceled)
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185-187. -187. (canceled)
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188. A packaged pharmaceutical composition for treating urinary incontinence in a subject, comprising a container holding a therapeutically effective amount of a peripherally-restricted 5-HT3 receptor antagonist;
- and instructions for using the composition for treating urinary incontinence in a subject.
- View Dependent Claims (189)
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190. A pharmaceutical composition for treating urinary incontinence in a subject in need thereof, comprising a compound selected from the group consisting of:
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(a) a peripherally-restricted 5-HT3 receptor antagonist selected based on its peripheral restriction;
(b) an MCI-225-QUAT;
(c) an MCI-225-QUAT possessing an enhanced therapeutic profile;
(d) a peripherally-restricted 5-HT3 receptor antagonist together with an additional agent for treating the urinary incontinence in the subject;
and a pharmaceutically acceptable carrier. - View Dependent Claims (194)
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191-193. -193. (canceled)
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195. (canceled)
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196. A packaged pharmaceutical composition for treating nausea, vomiting, retching or any combination thereof in a subject, comprising a container holding a therapeutically effective amount of a peripherally-restricted 5-HT3 receptor antagonist;
- and instructions for using the composition for treating the nausea, vomiting, retching or any combination thereof in the subject.
- View Dependent Claims (197)
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198. A pharmaceutical composition for treating nausea, vomiting, retching or any combination thereof in a subject, comprising a compound selected from the group consisting of:
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(a) a peripherally-restricted 5-HT3 receptor antagonist selected based on its peripheral restriction;
(b) an MCI-225-QUAT;
(c) an MCI-225-QUAT possessing an enhanced therapeutic profile;
(d) a peripherally-restricted 5-HT3 receptor antagonist together with an additional agent for treating the nausea, vomiting, retching or any combination thereof in the subject;
(e) a peripherally-restricted 5-HT3 receptor antagonist selected based on its peripheral restriction together with an additional agent for treating the nausea, vomiting, retching or any combination thereof in the subject; and
(f) a peripherally-restricted 5-HT3 receptor antagonist selected based on its peripheral restriction together with an additional agent for treating the nausea, vomiting, retching or any combination thereof in the subject, wherein the additional agent is selected based on its effect in combination with the peripherally-restricted 5-HT3 receptor antagonist;
and a pharmaceutically acceptable carrier. - View Dependent Claims (204, 205, 206, 209)
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199-203. -203. (canceled)
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207-208. -208. (canceled)
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210. (canceled)
Specification