TETRAZOLE-SUBSTITUTED ARYLAMIDES AS P2X3 AND P2X2/3 ANTAGONISTS
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Abstract
Compounds of the formula I:
or a pharmaceutically acceptable salt thereof, wherein, R1 is optionally substituted tetrazolyl, R2 is optionally substituted phenyl, optionally substituted pyridinyl or optionally substituted thienyl, and R3, R4, R5 and R6 are as defined herein. Also provided are methods of using the compounds for treating diseases associated with the P2X3 and/or a P2X2/3 receptor antagonist and methods of making the compounds.
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Citations
135 Claims
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1-109. -109. (canceled)
- 110. A compound of formula IIc:
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117-1. The compound of claim 110, wherein R5 is:
- methoxymethyl;
hydroxymethyl;
or pyridazin-2-yl.
- methoxymethyl;
- 120. A compound of formula IIIc:
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130. The compound 2′
- -fluoro-5-(5-isopropyl-tetrazol-1-yl)-4′
-methyl-biphenyl-3-carboxylic acid ((S)-2-hydroxy-1-methyl-ethyl)-amide, or a pharmaceutically acceptable salt thereof.
- -fluoro-5-(5-isopropyl-tetrazol-1-yl)-4′
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131. The compound 2′
- -fluoro-5-(5-isopropyl-tetrazol-1-yl)-4′
-methyl-biphenyl-3-carboxylic acid (5-methyl-pyrazin-2-ylmethyl)-amide, or a pharmaceutically acceptable salt thereof.
- -fluoro-5-(5-isopropyl-tetrazol-1-yl)-4′
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132. The compound 2′
- -fluoro-5-(5-isopropyl-tetrazol-1-yl)-4′
-methyl-biphenyl-3-carboxylic acid (2-methoxy-1-methyl-ethyl)-amide, or a pharmaceutically acceptable salt thereof.
- -fluoro-5-(5-isopropyl-tetrazol-1-yl)-4′
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133. The compound 5-(5-isopropyl-tetrazol-1-yl)-4′
- -methyl-biphenyl-3-carboxylic acid (2-hydroxy-1-methyl-ethyl)-amide, or a pharmaceutically acceptable salt thereof.
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134. The compound 2′
- -fluoro-5-(5-isopropyl-tetrazol-1-yl)-4′
-methyl-biphenyl-3-carboxylic acid (1-pyrazin-2-yl-ethyl)-amide, or a pharmaceutically acceptable salt thereof.
- -fluoro-5-(5-isopropyl-tetrazol-1-yl)-4′
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135. A compound of formula IVc:
Specification