US2022002275A1PendingUtilityA1
Enzyme inhibitors

Assignee: KALVISTA PHARMACEUTICALS LTDPriority: May 31, 2016Filed: Sep 21, 2021Published: Jan 6, 2022
Est. expiryMay 31, 2036(~9.9 yrs left)· nominal 20-yr term from priority
Inventors:Rebecca Louise Davie Hannah Joy Edwards David Michael Evans Simon Teanby Hodgson Stephen John Pethen David Philip Rooker
C07D 403/14C07D 401/10A61P 27/02A61P 7/10A61K 31/506A61K 31/4439C07D 401/14C07D 403/10C07D 403/06A61P 9/00A61P 7/08A61P 7/04A61P 9/02A61P 3/10A61P 35/00A61P 11/00A61P 19/02A61P 1/18A61P 31/00A61P 25/00A61P 1/00A61P 29/00A61P 13/12A61K 31/4155A61K 31/444A61K 31/501
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Claims
Abstract

The present invention provides a selection of compounds of formula (I): compositions comprising such compounds; the use of such compounds in therapy (for example in the treatment or prevention of a disease or condition in which plasma kallikrein activity is implicated); and methods of treating patients with such compounds; wherein R5, R6, R7, A, B, W, X, Y and Z are as defined herein.
Claims

exact text as granted — not AI-modified
What is claimed is: 
     
         1 . A compound selected from the group consisting of:
 N-[(3-fluoro-4-methoxypyridin-2-yl)methyl]-3-(methoxymethyl)-1-({4-[(4-methylpyrazol-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide;   N-[(4-fluoro-5-methoxypyridazin-3-yl)methyl]-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide;   3-(methoxymethyl)-N-[(5-methoxypyridazin-3-yl)methyl]-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide;   3-(methoxymethyl)-N-[(6-methoxypyrimidin-4-yl)methyl]-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide;   3-amino-N-[(3-fluoro-4-methoxypyridin-2-yl)methyl]-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide;   N-[(3-fluoro-4-methoxypyridin-2-yl)methyl]-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)-3-(trifluoromethyl)pyrazole-4-carboxamide;   3-(dimethylamino)-N-[(3-fluoro-4-methoxypyridin-2-yl)methyl]-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide;   N-[(5-cyano-2-methoxypyridin-4-yl)methyl]-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide;   N-[(5-cyano-3-fluoro-2-methoxypyridin-4-yl)methyl]-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide;   3-(methoxymethyl)-N-[(4-methoxypyrimidin-2-yl)methyl]-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide;   N-[(4-methoxy-3,5-dimethylpyridin-2-yl)methyl]-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide;   N-[(3-cyano-4-methoxypyridin-2-yl)methyl]-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide;   N-[(3-cyanopyridin-2-yl)methyl]-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide;   N-{[3-(difluoromethyl)-4-methoxypyridin-2-yl]methyl}-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide;   N-[(5-chloro-4-methoxypyridin-2-yl)methyl]-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide;   N-[(5-chloro-3-cyanopyridin-2-yl)methyl]-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide;   N-[(5-chloro-3-fluoropyridin-2-yl)methyl]-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide;   N-[(4-chloro-3-fluoropyridin-2-yl)methyl]-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide;   N-[(3-fluoro-5-methylpyridin-2-yl)methyl]-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide;   N-[(4-methoxy-5-methylpyridin-2-yl)methyl]-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide;   N-[(3-cyano-5-methylpyridin-2-yl)methyl]-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide;   N-[(4-methoxy-3-methylpyridin-2-yl)methyl]-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide;   N-[(3-cyano-6-methoxypyridin-2-yl)methyl]-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide;   N-{[6-(difluoromethyl)-3-fluoro-4-methoxypyridin-2-yl]methyl}-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide;   N-{[5-(difluoromethyl)-3-fluoro-4-methoxypyridin-2-yl]methyl}-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide;   N-[(3,5-difluoropyridin-2-yl)methyl]-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide;   N-[(3-fluoro-6-methylpyridin-2-yl)methyl]-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide;   N-[(3-fluoro-4-methylpyridin-2-yl)methyl]-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide;   N-[(3-chloro-4-methylpyridin-2-yl)methyl]-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide;   1-({4-[(5-fluoro-2-oxopyridin-1-yl)methyl]phenyl}methyl)-N-[(3-fluoro-4-methoxypyridin-2-yl)methyl]-3-(methoxymethyl)pyrazole-4-carboxamide;   N-[(5-methoxy-1-methylpyrazol-3-yl)methyl]-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide;   N-[(4-chloro-5-methoxy-1-methylpyrazol-3-yl)methyl]-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide;   N-[(5-methoxy-1,4-dimethylpyrazol-3-yl)methyl]-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide;   N-[(4-chloro-1-methylpyrazol-3-yl)methyl]-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide;   3-amino-N-[(2,6-difluoro-3-methoxyphenyl)methyl]-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide;   N-[(2,6-difluoro-3,5-dimethoxyphenyl)methyl]-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide;   N-[(2-cyano-5-methoxyphenyl)methyl]-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide;   N-[(2-cyano-3-methoxyphenyl)methyl]-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide;   N-{[2-fluoro-3-methoxy-6-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide;   N-{[5-methoxy-2-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide;   N-[(5-methoxy-2-methylphenyl)methyl]-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide;   N-[(6-carbamoyl-2-fluoro-3-methoxyphenyl)methyl]-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide;   3-amino-N-[(6-cyano-2-fluoro-3-methoxyphenyl)methyl]-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide;   N-[(6-cyano-2-fluoro-3-methoxyphenyl)methyl]-3-(dimethylamino)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide;   3-amino-N-[(2-cyano-5-methoxyphenyl)methyl]-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide;   N-[(2-cyano-5-methoxyphenyl)methyl]-3-(dimethylamino)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide;   3-amino-N-{[5-methoxy-2-(trifluoromethyl)phenyl]methyl}-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide;   3-amino-N-{[2-(difluoromethyl)-5-methoxyphenyl]methyl}-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide;   N-{[5-fluoro-2-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide;   N-[(2,6-difluoro-3-methoxyphenyl)methyl]-3-(dimethylamino)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide;   N-[(6-cyano-2-fluoro-3-methoxyphenyl)methyl]-3-(methoxymethyl)-1-({5-[(2-oxopyridin-1-yl)methyl]pyridin-2-yl}methyl)pyrazole-4-carboxamide;   N-[(6-cyano-2-fluoro-3-methoxyphenyl)methyl]-3-(methoxymethyl)-1-({6-[(2-oxopyridin-1-yl)methyl]pyridin-3-yl}methyl)pyrazole-4-carboxamide;   N-[(6-cyano-2-fluoro-3-methoxyphenyl)methyl]-1-({4-[(5-fluoro-2-oxopyridin-1-yl)methyl]phenyl}methyl)-3-(methoxymethyl)pyrazole-4-carboxamide;   N-[(2-cyano-5-methoxyphenyl)methyl]-3-(methoxymethyl)-1-({5-[(2-oxopyridin-1-yl)methyl]pyridin-2-yl}methyl)pyrazole-4-carboxamide;   N-[(2-cyano-5-methoxyphenyl)methyl]-3-(methoxymethyl)-1-({6-[(2-oxopyridin-1-yl)methyl]pyridin-3-yl}methyl)pyrazole-4-carboxamide;   N-[(2-cyano-5-methoxyphenyl)methyl]-1-({4-[(5-fluoro-2-oxopyridin-1-yl)methyl]phenyl}methyl)-3-(methoxymethyl)pyrazole-4-carboxamide;   N-[(6-cyano-2-fluoro-3-methoxyphenyl)methyl]-3-(methoxymethyl)-1-({4-[(2-oxopiperidin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide;   N-[(6-cyano-2-fluoro-3-methoxyphenyl)methyl]-3-(methoxymethyl)-1-{[2-(pyrrolidin-1-yl)pyrimidin-5-yl]methyl}pyrazole-4-carboxamide;   N-[(6-cyano-2-fluoro-3-methoxyphenyl)methyl]-1-{[2-(pyrrolidin-1-yl)pyrimidin-5-yl]methyl}-3-(trifluoromethyl)pyrazole-4-carboxamide;   N-{[2-fluoro-3-methoxy-6-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-3-(methoxymethyl)-1-({4-[(4-methylpyrazol-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide;   N-{[5-methoxy-2-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-3-(methoxymethyl)-1-({4-[(4-methylpyrazol-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide;   N-{[2-fluoro-6-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-3-(methoxymethyl)-1-({4-[(4-methylpyrazol-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide;   N-{[5-methoxy-2-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)-3-(trifluoromethyl)pyrazole-4-carboxamide;   N-{[2-fluoro-6-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)-3-(trifluoromethyl)pyrazole-4-carboxamide;   3-amino-N-{[2-fluoro-3-methoxy-6-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide;   3-amino-N-{[5-methoxy-2-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide;   3-amino-N-{[2-fluoro-6-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide;   3-(dimethylamino)-N-{[2-fluoro-3-methoxy-6-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide;   3-(dimethylamino)-N-{[5-methoxy-2-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide;   3-(dimethylamino)-N-{[2-fluoro-6-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide;   3-amino-N-{[5-chloro-2-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide;   N-{[5-chloro-2-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide;   N-{[2-chloro-6-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide;   3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)-N-{[2-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}pyrazole-4-carboxamide;   3-(methoxymethyl)-N-{[2-methyl-6-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide;   N-[(2-cyano-6-fluorophenyl)methyl]-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide;   N-{[2-fluoro-3-methoxy-6-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-3-(methoxymethyl)-1-{[6-(pyrrolidin-1-yl)pyridin-3-yl]methyl}pyrazole-4-carboxamide;   N-{[5-methoxy-2-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-3-(methoxymethyl)-1-{[6-(pyrrolidin-1-yl)pyridin-3-yl]methyl}pyrazole-4-carboxamide;   N-{[2-fluoro-3-methoxy-6-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-3-(methoxymethyl)-1-{[2-(pyrrolidin-1-yl)pyrimidin-5-yl]methyl}pyrazole-4-carboxamide;   N-{[5-methoxy-2-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-3-(methoxymethyl)-1-{[2-(pyrrolidin-1-yl)pyrimidin-5-yl]methyl}pyrazole-4-carboxamide;   N-{[2-fluoro-6-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-3-(methoxymethyl)-1-{[6-(pyrrolidin-1-yl)pyridin-3-yl]methyl}pyrazole-4-carboxamide;   N-{[2-fluoro-6-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-3-(methoxymethyl)-1-{[2-(pyrrolidin-1-yl)pyrimidin-5-yl]methyl}pyrazole-4-carboxamide;   N-{[2-fluoro-3-methoxy-6-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-1-{[6-(pyrrolidin-1-yl)pyridin-3-yl]methyl}-3-(trifluoromethyl)pyrazole-4-carboxamide;   N-{[5-methoxy-2-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-1-{[6-(pyrrolidin-1-yl)pyridin-3-yl]methyl}-3-(trifluoromethyl)pyrazole-4-carboxamide;   N-{[2-fluoro-6-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-1-{[6-(pyrrolidin-1-yl)pyridin-3-yl]methyl}-3-(trifluoromethyl)pyrazole-4-carboxamide;   1-{[2-(3,3-difluoropyrrolidin-1-yl)pyrimidin-5-yl]methyl}-N-{[2-fluoro-3-methoxy-6-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-3-(methoxymethyl)pyrazole-4-carboxamide;   1-{[6-(3,3-difluoropyrrolidin-1-yl)pyridin-3-yl]methyl}-N-{[2-fluoro-3-methoxy-6-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-3-(methoxymethyl)pyrazole-4-carboxamide;   1-{[2-(3,3-difluoropyrrolidin-1-yl)pyrimidin-5-yl]methyl}-N-{[5-methoxy-2-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-3-(methoxymethyl)pyrazole-4-carboxamide;   1-{[6-(3,3-difluoropyrrolidin-1-yl)pyridin-3-yl]methyl}-N-{[5-methoxy-2-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-3-(methoxymethyl)pyrazole-4-carboxamide;   and a pharmaceutically acceptable salt or solvate thereof.   
     
     
         2 . The compound of  claim 1  that is selected from the group consisting of:
 N-[(3-fluoro-4-methoxypyridin-2-yl)methyl]-3-(methoxymethyl)-1-({4-[(4-methylpyrazol-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 3-(methoxymethyl)-N-[(4-methoxypyrimidin-2-yl)methyl]-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-[(5-chloro-3-cyanopyridin-2-yl)methyl]-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-[(5-chloro-3-fluoropyridin-2-yl)methyl]-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-[(3,5-difluoropyridin-2-yl)methyl]-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-[(3-fluoro-6-methylpyridin-2-yl)methyl]-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-[(3-fluoro-4-methylpyridin-2-yl)methyl]-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-[(3-chloro-4-methylpyridin-2-yl)methyl]-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-[(4-chloro-1-methylpyrazol-3-yl)methyl]-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-[(2-cyano-5-methoxyphenyl)methyl]-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 and a pharmaceutically acceptable salt or solvate thereof. 
 
     
     
         3 . The compound of  claim 1  that is selected from the group consisting of:
 N-[(3-fluoro-4-methoxypyridin-2-yl)methyl]-3-(methoxymethyl)-1-({4-[(4-methylpyrazol-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 3-amino-N-[(3-fluoro-4-methoxypyridin-2-yl)methyl]-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-[(3-fluoro-4-methoxypyridin-2-yl)methyl]-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)-3-(trifluoromethyl)pyrazole-4-carboxamide; 
 N-[(3-cyano-4-methoxypyridin-2-yl)methyl]-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-[(3-cyanopyridin-2-yl)methyl]-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-{[3-(difluoromethyl)-4-methoxypyridin-2-yl]methyl}-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-[(4-methoxy-5-methylpyridin-2-yl)methyl]-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-[(4-methoxy-3-methylpyridin-2-yl)methyl]-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-[(3-cyano-6-methoxypyridin-2-yl)methyl]-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-{[6-(difluoromethyl)-3-fluoro-4-methoxypyridin-2-yl]methyl}-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 1-({4-[(5-fluoro-2-oxopyridin-1-yl)methyl]phenyl}methyl)-N-[(3-fluoro-4-methoxypyridin-2-yl)methyl]-3-(methoxymethyl)pyrazole-4-carboxamide; 
 3-amino-N-[(2,6-difluoro-3-methoxyphenyl)methyl]-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-[(2-cyano-5-methoxyphenyl)methyl]-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-[(2-cyano-3-methoxyphenyl)methyl]-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-{[2-fluoro-3-methoxy-6-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-{[5-methoxy-2-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-[(5-methoxy-2-methylphenyl)methyl]-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-[(6-carbamoyl-2-fluoro-3-methoxyphenyl)methyl]-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 3-amino-N-[(6-cyano-2-fluoro-3-methoxyphenyl)methyl]-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-[(6-cyano-2-fluoro-3-methoxyphenyl)methyl]-3-(dimethylamino)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 3-amino-N-[(2-cyano-5-methoxyphenyl)methyl]-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-{[5-fluoro-2-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-[(6-cyano-2-fluoro-3-methoxyphenyl)methyl]-3-(methoxymethyl)-1-({5-[(2-oxopyridin-1-yl)methyl]pyridin-2-yl}methyl)pyrazole-4-carboxamide; 
 N-[(6-cyano-2-fluoro-3-methoxyphenyl)methyl]-3-(methoxymethyl)-1-({6-[(2-oxopyridin-1-yl)methyl]pyridin-3-yl}methyl)pyrazole-4-carboxamide; 
 N-[(6-cyano-2-fluoro-3-methoxyphenyl)methyl]-1-({4-[(5-fluoro-2-oxopyridin-1-yl)methyl]phenyl}methyl)-3-(methoxymethyl)pyrazole-4-carboxamide; 
 N-[(2-cyano-5-methoxyphenyl)methyl]-3-(methoxymethyl)-1-({5-[(2-oxopyridin-1-yl)methyl]pyridin-2-yl}methyl)pyrazole-4-carboxamide; 
 N-[(2-cyano-5-methoxyphenyl)methyl]-3-(methoxymethyl)-1-({6-[(2-oxopyridin-1-yl)methyl]pyridin-3-yl}methyl)pyrazole-4-carboxamide; 
 N-[(2-cyano-5-methoxyphenyl)methyl]-1-({4-[(5-fluoro-2-oxopyridin-1-yl)methyl]phenyl}methyl)-3-(methoxymethyl)pyrazole-4-carboxamide; 
 N-[(6-cyano-2-fluoro-3-methoxyphenyl)methyl]-3-(methoxymethyl)-1-{[2-(pyrrolidin-1-yl)pyrimidin-5-yl]methyl}pyrazole-4-carboxamide; 
 N-[(6-cyano-2-fluoro-3-methoxyphenyl)methyl]-1-{[2-(pyrrolidin-1-yl)pyrimidin-5-yl]methyl}-3-(trifluoromethyl)pyrazole-4-carboxamide; 
 N-{[2-fluoro-6-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)-3-(trifluoromethyl)pyrazole-4-carboxamide; 
 N-[(2-cyano-6-fluorophenyl)methyl]-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-{[2-fluoro-3-methoxy-6-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-3-(methoxymethyl)-1-{[6-(pyrrolidin-1-yl)pyridin-3-yl]methyl}pyrazole-4-carboxamide; 
 N-{[2-fluoro-3-methoxy-6-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-3-(methoxymethyl)-1-{[2-(pyrrolidin-1-yl)pyrimidin-5-yl]methyl}pyrazole-4-carboxamide; 
 and a pharmaceutically acceptable salt or solvate thereof. 
 
     
     
         4 . The compound of  claim 1  that is selected from the group consisting of:
 N-[(3-fluoro-4-methoxypyridin-2-yl)methyl]-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)-3-(trifluoromethyl)pyrazole-4-carboxamide; 
 N-[(6-cyano-2-fluoro-3-methoxyphenyl)methyl]-3-(methoxymethyl)-1-({5-[(2-oxopyridin-1-yl)methyl]pyridin-2-yl}methyl)pyrazole-4-carboxamide; 
 N-[(6-cyano-2-fluoro-3-methoxyphenyl)methyl]-3-(methoxymethyl)-1-({6-[(2-oxopyridin-1-yl)methyl]pyridin-3-yl}methyl)pyrazole-4-carboxamide; 
 N-[(2-cyano-5-methoxyphenyl)methyl]-3-(methoxymethyl)-1-({5-[(2-oxopyridin-1-yl)methyl]pyridin-2-yl}methyl)pyrazole-4-carboxamide; 
 N-[(2-cyano-5-methoxyphenyl)methyl]-3-(methoxymethyl)-1-({6-[(2-oxopyridin-1-yl)methyl]pyridin-3-yl}methyl)pyrazole-4-carboxamide; 
 and a pharmaceutically acceptable salt or solvate thereof. 
 
     
     
         5 . The compound of  claim 1  that is selected from the group consisting of:
 N-[(3-fluoro-4-methoxypyridin-2-yl)methyl]-3-(methoxymethyl)-1-({4-[(4-methylpyrazol-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 3-(methoxymethyl)-N-[(6-methoxypyrimidin-4-yl)methyl]-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 3-amino-N-[(3-fluoro-4-methoxypyridin-2-yl)methyl]-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-[(3-fluoro-4-methoxypyridin-2-yl)methyl]-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)-3-(trifluoromethyl)pyrazole-4-carboxamide; 
 3-(dimethylamino)-N-[(3-fluoro-4-methoxypyridin-2-yl)methyl]-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-[(5-cyano-2-methoxypyridin-4-yl)methyl]-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 3-(methoxymethyl)-N-[(4-methoxypyrimidin-2-yl)methyl]-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-[(4-methoxy-3,5-dimethylpyridin-2-yl)methyl]-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-[(3-cyanopyridin-2-yl)methyl]-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-[(5-chloro-3-cyanopyridin-2-yl)methyl]-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-[(5-chloro-3-fluoropyridin-2-yl)methyl]-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-[(4-methoxy-5-methylpyridin-2-yl)methyl]-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-[(4-methoxy-3-methylpyridin-2-yl)methyl]-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-[(3,5-difluoropyridin-2-yl)methyl]-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-[(3-fluoro-6-methylpyridin-2-yl)methyl]-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-[(3-fluoro-4-methylpyridin-2-yl)methyl]-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-[(3-chloro-4-methylpyridin-2-yl)methyl]-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 1-({4-[(5-fluoro-2-oxopyridin-1-yl)methyl]phenyl}methyl)-N-[(3-fluoro-4-methoxypyridin-2-yl)methyl]-3-(methoxymethyl)pyrazole-4-carboxamide; 
 N-[(5-methoxy-1-methylpyrazol-3-yl)methyl]-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-[(4-chloro-1-methylpyrazol-3-yl)methyl]-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 3-amino-N-[(2,6-difluoro-3-methoxyphenyl)methyl]-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-[(2-cyano-5-methoxyphenyl)methyl]-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-[(2-cyano-3-methoxyphenyl)methyl]-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-{[2-fluoro-3-methoxy-6-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-{[5-methoxy-2-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-[(5-methoxy-2-methylphenyl)methyl]-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-[(6-carbamoyl-2-fluoro-3-methoxyphenyl)methyl]-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 3-amino-N-[(6-cyano-2-fluoro-3-methoxyphenyl)methyl]-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-[(6-cyano-2-fluoro-3-methoxyphenyl)methyl]-3-(dimethylamino)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-{[5-fluoro-2-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-[(6-cyano-2-fluoro-3-methoxyphenyl)methyl]-3-(methoxymethyl)-1-({5-[(2-oxopyridin-1-yl)methyl]pyridin-2-yl}methyl)pyrazole-4-carboxamide; 
 N-[(6-cyano-2-fluoro-3-methoxyphenyl)methyl]-3-(methoxymethyl)-1-({6-[(2-oxopyridin-1-yl)methyl]pyridin-3-yl}methyl)pyrazole-4-carboxamide; 
 N-[(6-cyano-2-fluoro-3-methoxyphenyl)methyl]-1-({4-[(5-fluoro-2-oxopyridin-1-yl)methyl]phenyl}methyl)-3-(methoxymethyl)pyrazole-4-carboxamide; 
 N-[(6-cyano-2-fluoro-3-methoxyphenyl)methyl]-3-(methoxymethyl)-1-{[2-(pyrrolidin-1-yl)pyrimidin-5-yl]methyl}pyrazole-4-carboxamide; 
 N-{[2-fluoro-3-methoxy-6-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-3-(methoxymethyl)-1-({4-[(4-methylpyrazol-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-{[5-methoxy-2-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-3-(methoxymethyl)-1-({4-[(4-methylpyrazol-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-{[2-fluoro-6-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)-3-(trifluoromethyl)pyrazole-4-carboxamide; 
 3-amino-N-{[5-chloro-2-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-{[5-chloro-2-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-{[2-chloro-6-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)-N-{[2-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}pyrazole-4-carboxamide; 
 N-{[2-fluoro-3-methoxy-6-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-3-(methoxymethyl)-1-{[6-(pyrrolidin-1-yl)pyridin-3-yl]methyl}pyrazole-4-carboxamide; 
 N-{[2-fluoro-3-methoxy-6-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-3-(methoxymethyl)-1-{[2-(pyrrolidin-1-yl)pyrimidin-5-yl]methyl}pyrazole-4-carboxamide; 
 N-{[5-methoxy-2-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-3-(methoxymethyl)-1-{[2-(pyrrolidin-1-yl)pyrimidin-5-yl]methyl}pyrazole-4-carboxamide; 
 1-{[2-(3,3-difluoropyrrolidin-1-yl)pyrimidin-5-yl]methyl}-N-{[2-fluoro-3-methoxy-6-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-3-(methoxymethyl)pyrazole-4-carboxamide; 
 and a pharmaceutically acceptable salt or solvate thereof. 
 
     
     
         6 . The compound of  claim 1  that is selected from the group consisting of:
 3-amino-N-[(3-fluoro-4-methoxypyridin-2-yl)methyl]-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-[(3-fluoro-4-methoxypyridin-2-yl)methyl]-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)-3-(trifluoromethyl)pyrazole-4-carboxamide; 
 3-(dimethylamino)-N-[(3-fluoro-4-methoxypyridin-2-yl)methyl]-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-[(5-cyano-2-methoxypyridin-4-yl)methyl]-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-[(4-methoxy-3,5-dimethylpyridin-2-yl)methyl]-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-[(5-chloro-3-cyanopyridin-2-yl)methyl]-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-[(5-chloro-3-fluoropyridin-2-yl)methyl]-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-[(4-methoxy-3-methylpyridin-2-yl)methyl]-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-[(3-fluoro-4-methylpyridin-2-yl)methyl]-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-[(3-chloro-4-methylpyridin-2-yl)methyl]-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 1-({4-[(5-fluoro-2-oxopyridin-1-yl)methyl]phenyl}methyl)-N-[(3-fluoro-4-methoxypyridin-2-yl)methyl]-3-(methoxymethyl)pyrazole-4-carboxamide; 
 3-amino-N-[(2,6-difluoro-3-methoxyphenyl)methyl]-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-[(2-cyano-5-methoxyphenyl)methyl]-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-{[2-fluoro-3-methoxy-6-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-{[5-methoxy-2-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-[(5-methoxy-2-methylphenyl)methyl]-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-[(6-carbamoyl-2-fluoro-3-methoxyphenyl)methyl]-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 3-amino-N-[(6-cyano-2-fluoro-3-methoxyphenyl)methyl]-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-[(6-cyano-2-fluoro-3-methoxyphenyl)methyl]-3-(dimethylamino)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-{[5-fluoro-2-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-[(6-cyano-2-fluoro-3-methoxyphenyl)methyl]-3-(methoxymethyl)-1-({5-[(2-oxopyridin-1-yl)methyl]pyridin-2-yl}methyl)pyrazole-4-carboxamide; 
 N-[(6-cyano-2-fluoro-3-methoxyphenyl)methyl]-3-(methoxymethyl)-1-({6-[(2-oxopyridin-1-yl)methyl]pyridin-3-yl}methyl)pyrazole-4-carboxamide; 
 N-[(6-cyano-2-fluoro-3-methoxyphenyl)methyl]-1-({4-[(5-fluoro-2-oxopyridin-1-yl)methyl]phenyl}methyl)-3-(methoxymethyl)pyrazole-4-carboxamide; 
 N-[(6-cyano-2-fluoro-3-methoxyphenyl)methyl]-3-(methoxymethyl)-1-{[2-(pyrrolidin-1-yl)pyrimidin-5-yl]methyl}pyrazole-4-carboxamide; 
 N-{[2-fluoro-3-methoxy-6-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-3-(methoxymethyl)-1-({4-[(4-methylpyrazol-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-{[5-methoxy-2-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-3-(methoxymethyl)-1-({4-[(4-methylpyrazol-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-{[2-fluoro-6-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)-3-(trifluoromethyl)pyrazole-4-carboxamide; 
 3-amino-N-{[5-chloro-2-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-{[5-chloro-2-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-{[2-chloro-6-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)-N-{[2-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}pyrazole-4-carboxamide; 
 N-{[2-fluoro-3-methoxy-6-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-3-(methoxymethyl)-1-{[6-(pyrrolidin-1-yl)pyridin-3-yl]methyl}pyrazole-4-carboxamide; 
 N-{[2-fluoro-3-methoxy-6-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-3-(methoxymethyl)-1-{[2-(pyrrolidin-1-yl)pyrimidin-5-yl]methyl}pyrazole-4-carboxamide; 
 N-{[5-methoxy-2-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-3-(methoxymethyl)-1-{[2-(pyrrolidin-1-yl)pyrimidin-5-yl]methyl}pyrazole-4-carboxamide; 
 1-{[2-(3,3-difluoropyrrolidin-1-yl)pyrimidin-5-yl]methyl}-N-{[2-fluoro-3-methoxy-6-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-3-(methoxymethyl)pyrazole-4-carboxamide; 
 and a pharmaceutically acceptable salt or solvate thereof. 
 
     
     
         7 . The compound of  claim 1  that is selected from the group consisting of:
 3-amino-N-[(3-fluoro-4-methoxypyridin-2-yl)methyl]-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-[(3-fluoro-4-methoxypyridin-2-yl)methyl]-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)-3-(trifluoromethyl)pyrazole-4-carboxamide; 
 N-[(4-methoxy-3-methylpyridin-2-yl)methyl]-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 1-({4-[(5-fluoro-2-oxopyridin-1-yl)methyl]phenyl}methyl)-N-[(3-fluoro-4-methoxypyridin-2-yl)methyl]-3-(methoxymethyl)pyrazole-4-carboxamide; 
 3-amino-N-[(2,6-difluoro-3-methoxyphenyl)methyl]-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-{[2-fluoro-3-methoxy-6-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-{[5-methoxy-2-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-[(6-carbamoyl-2-fluoro-3-methoxyphenyl)methyl]-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 3-amino-N-[(6-cyano-2-fluoro-3-methoxyphenyl)methyl]-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-[(6-cyano-2-fluoro-3-methoxyphenyl)methyl]-3-(dimethylamino)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-[(6-cyano-2-fluoro-3-methoxyphenyl)methyl]-3-(methoxymethyl)-1-({6-[(2-oxopyridin-1-yl)methyl]pyridin-3-yl}methyl)pyrazole-4-carboxamide; 
 N-[(6-cyano-2-fluoro-3-methoxyphenyl)methyl]-1-({4-[(5-fluoro-2-oxopyridin-1-yl)methyl]phenyl}methyl)-3-(methoxymethyl)pyrazole-4-carboxamide; 
 N-{[2-fluoro-3-methoxy-6-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-3-(methoxymethyl)-1-({4-[(4-methylpyrazol-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-{[5-methoxy-2-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-3-(methoxymethyl)-1-({4-[(4-methylpyrazol-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-{[2-fluoro-6-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)-3-(trifluoromethyl)pyrazole-4-carboxamide; 
 3-amino-N-{[5-chloro-2-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-{[5-chloro-2-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-{[2-fluoro-3-methoxy-6-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-3-(methoxymethyl)-1-{[6-(pyrrolidin-1-yl)pyridin-3-yl]methyl}pyrazole-4-carboxamide; 
 N-{[2-fluoro-3-methoxy-6-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-3-(methoxymethyl)-1-{[2-(pyrrolidin-1-yl)pyrimidin-5-yl]methyl}pyrazole-4-carboxamide; 
 1-{[2-(3,3-difluoropyrrolidin-1-yl)pyrimidin-5-yl]methyl}-N-{[2-fluoro-3-methoxy-6-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-3-(methoxymethyl)pyrazole-4-carboxamide; 
 and a pharmaceutically acceptable salt or solvate thereof. 
 
     
     
         8 . The compound of  claim 1  that is selected from the group consisting of:
 N-[(6-cyano-2-fluoro-3-methoxyphenyl)methyl]-3-(methoxymethyl)-1-{[2-(pyrrolidin-1-yl)pyrimidin-5-yl]methyl}pyrazole-4-carboxamide; 
 N-[(6-cyano-2-fluoro-3-methoxyphenyl)methyl]-1-{[2-(pyrrolidin-1-yl)pyrimidin-5-yl]methyl}-3-(trifluoromethyl)pyrazole-4-carboxamide; 
 N-{[2-fluoro-3-methoxy-6-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-3-(methoxymethyl)-1-{[6-(pyrrolidin-1-yl)pyridin-3-yl]methyl}pyrazole-4-carboxamide; 
 N-{[5-methoxy-2-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-3-(methoxymethyl)-1-{[6-(pyrrolidin-1-yl)pyridin-3-yl]methyl}pyrazole-4-carboxamide; 
 N-{[2-fluoro-3-methoxy-6-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-3-(methoxymethyl)-1-{[2-(pyrrolidin-1-yl)pyrimidin-5-yl]methyl}pyrazole-4-carboxamide; 
 N-{[5-methoxy-2-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-3-(methoxymethyl)-1-{[2-(pyrrolidin-1-yl)pyrimidin-5-yl]methyl}pyrazole-4-carboxamide; 
 N-{[2-fluoro-6-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-3-(methoxymethyl)-1-{[6-(pyrrolidin-1-yl)pyridin-3-yl]methyl}pyrazole-4-carboxamide; 
 N-{[2-fluoro-6-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-3-(methoxymethyl)-1-{[2-(pyrrolidin-1-yl)pyrimidin-5-yl]methyl}pyrazole-4-carboxamide; 
 N-{[2-fluoro-3-methoxy-6-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-1-{[6-(pyrrolidin-1-yl)pyridin-3-yl]methyl}-3-(trifluoromethyl)pyrazole-4-carboxamide; 
 N-{[5-methoxy-2-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-1-{[6-(pyrrolidin-1-yl)pyridin-3-yl]methyl}-3-(trifluoromethyl)pyrazole-4-carboxamide; 
 N-{[2-fluoro-6-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-1-{[6-(pyrrolidin-1-yl)pyridin-3-yl]methyl}-3-(trifluoromethyl)pyrazole-4-carboxamide; 
 1-{[2-(3,3-difluoropyrrolidin-1-yl)pyrimidin-5-yl]methyl}-N-{[2-fluoro-3-methoxy-6-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-3-(methoxymethyl)pyrazole-4-carboxamide; 
 1-{[6-(3,3-difluoropyrrolidin-1-yl)pyridin-3-yl]methyl}-N-{[2-fluoro-3-methoxy-6-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-3-(methoxymethyl)pyrazole-4-carboxamide; 
 1-{[2-(3,3-difluoropyrrolidin-1-yl)pyrimidin-5-yl]methyl}-N-{[5-methoxy-2-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-3-(methoxymethyl)pyrazole-4-carboxamide; 
 1-{[6-(3,3-difluoropyrrolidin-1-yl)pyridin-3-yl]methyl}-N-{[5-methoxy-2-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-3-(methoxymethyl)pyrazole-4-carboxamide; 
 and a pharmaceutically acceptable salt or solvate thereof. 
 
     
     
         9 . The compound of  claim 1  that is selected from the group consisting of:
 N-[(6-cyano-2-fluoro-3-methoxyphenyl)methyl]-3-(methoxymethyl)-1-{[2-(pyrrolidin-1-yl)pyrimidin-5-yl]methyl}pyrazole-4-carboxamide; 
 N-{[2-fluoro-3-methoxy-6-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-3-(methoxymethyl)-1-{[6-(pyrrolidin-1-yl)pyridin-3-yl]methyl}pyrazole-4-carboxamide; 
 N-{[2-fluoro-3-methoxy-6-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-3-(methoxymethyl)-1-{[2-(pyrrolidin-1-yl)pyrimidin-5-yl]methyl}pyrazole-4-carboxamide; 
 N-{[5-methoxy-2-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-3-(methoxymethyl)-1-{[2-(pyrrolidin-1-yl)pyrimidin-5-yl]methyl}pyrazole-4-carboxamide; 
 1-{[2-(3,3-difluoropyrrolidin-1-yl)pyrimidin-5-yl]methyl}-N-{[2-fluoro-3-methoxy-6-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-3-(methoxymethyl)pyrazole-4-carboxamide; 
 1-{[6-(3,3-difluoropyrrolidin-1-yl)pyridin-3-yl]methyl}-N-{[2-fluoro-3-methoxy-6-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-3-(methoxymethyl)pyrazole-4-carboxamide; 
 N-{[5-methoxy-2-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-3-(methoxymethyl)-1-{[2-(pyrrolidin-1-yl)pyrimidin-5-yl]methyl}pyrazole-4-carboxamide; 
 N-{[2-fluoro-3-methoxy-6-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-1-{[6-(pyrrolidin-1-yl)pyridin-3-yl]methyl}-3-(trifluoromethyl)pyrazole-4-carboxamide; 
 1-{[2-(3,3-difluoropyrrolidin-1-yl)pyrimidin-5-yl]methyl}-N-{[5-methoxy-2-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-3-(methoxymethyl)pyrazole-4-carboxamide; 
 and a pharmaceutically acceptable salt or solvate thereof. 
 
     
     
         10 . The compound of  claim 1 , wherein the compound is
 N-[(6-cyano-2-fluoro-3-methoxyphenyl)methyl]-3-(methoxymethyl)-1-{[2-(pyrrolidin-1-yl)pyrimidin-5-yl]methyl}pyrazole-4-carboxamide;   or a pharmaceutically acceptable salt or solvate thereof.   
     
     
         11 . The compound of  claim 1 , wherein the compound is
 N-{[2-fluoro-3-methoxy-6-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-3-(methoxymethyl)-1-{[6-(pyrrolidin-1-yl)pyridin-3-yl]methyl}pyrazole-4-carboxamide;   or a pharmaceutically acceptable salt or solvate thereof.   
     
     
         12 . The compound of  claim 1 , wherein the compound is
 N-{[2-fluoro-3-methoxy-6-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-3-(methoxymethyl)-1-{[2-(pyrrolidin-1-yl)pyrimidin-5-yl]methyl}pyrazole-4-carboxamide;   or a pharmaceutically acceptable salt or solvate thereof.   
     
     
         13 . The compound of  claim 1 , wherein the compound is
 N-{[5-methoxy-2-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-3-(methoxymethyl)-1-{[2-(pyrrolidin-1-yl)pyrimidin-5-yl]methyl}pyrazole-4-carboxamide;   or a pharmaceutically acceptable salt or solvate thereof.   
     
     
         14 . The compound of  claim 1 , wherein the compound is
 1-{[2-(3,3-difluoropyrrolidin-1-yl)pyrimidin-5-yl]methyl}-N-{[2-fluoro-3-methoxy-6-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-3-(methoxymethyl)pyrazole-4-carboxamide;   or a pharmaceutically acceptable salt or solvate thereof.   
     
     
         15 . The compound of  claim 1 , wherein the compound is
 1-{[6-(3,3-difluoropyrrolidin-1-yl)pyridin-3-yl]methyl}-N-{[2-fluoro-3-methoxy-6-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-3-(methoxymethyl)pyrazole-4-carboxamide;   or a pharmaceutically acceptable salt or solvate thereof.   A compound of  claim 1 , wherein the compound is N-{[5-methoxy-2-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-3-(methoxymethyl)-1-{[2-(pyrrolidin-1-yl)pyrimidin-5-yl]methyl}pyrazole-4-carboxamide;   or a pharmaceutically acceptable salt or solvate thereof.   
     
     
         16 . The compound of  claim 1 , wherein the compound is
 N-{[2-fluoro-3-methoxy-6-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-1-{[6-(pyrrolidin-1-yl)pyridin-3-yl]methyl}-3-(trifluoromethyl)pyrazole-4-carboxamide;   or a pharmaceutically acceptable salt or solvate thereof.   
     
     
         17 . The compound of  claim 1 , wherein the compound is
 1-{[2-(3,3-difluoropyrrolidin-1-yl)pyrimidin-5-yl]methyl}-N-{[5-methoxy-2-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-3-(methoxymethyl)pyrazole-4-carboxamide;   or a pharmaceutically acceptable salt of solvate thereof.   
     
     
         18 . The compound of  claim 1 , wherein the compound is
 N-[(3-fluoro-4-methoxypyridin-2-yl)methyl]-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)-3-(trifluoromethyl)pyrazole-4-carboxamide;   or a pharmaceutically acceptable salt or solvate thereof.   
     
     
         19 . The compound of  claim 1 , wherein the compound is
 N-[(6-cyano-2-fluoro-3-methoxyphenyl)methyl]-3-(methoxymethyl)-1-({5-[(2-oxopyridin-1-yl)methyl]pyridin-2-yl}methyl)pyrazole-4-carboxamide;   or a pharmaceutically acceptable salt or solvate thereof.   
     
     
         20 . The compound of  claim 1 , wherein the compound is
 N-[(6-cyano-2-fluoro-3-methoxyphenyl)methyl]-3-(methoxymethyl)-1-({6-[(2-oxopyridin-1-yl)methyl]pyridin-3-yl}methyl)pyrazole-4-carboxamide;   or a pharmaceutically acceptable salt or solvate thereof.   
     
     
         21 . The compound of  claim 1  that is selected from the group consisting of:
 N-[(3-fluoro-4-methoxypyridin-2-yl)methyl]-3-(methoxymethyl)-1-({4-[(4-methylpyrazol-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-[(4-fluoro-5-methoxypyridazin-3-yl)methyl]-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 3-(methoxymethyl)-N-[(5-methoxypyridazin-3-yl)methyl]-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 3-(methoxymethyl)-N-[(6-methoxypyrimidin-4-yl)methyl]-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-[(5-cyano-2-methoxypyridin-4-yl)methyl]-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-[(5-cyano-3-fluoro-2-methoxypyridin-4-yl)methyl]-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 3-(methoxymethyl)-N-[(4-methoxypyrimidin-2-yl)methyl]-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-[(4-methoxy-3,5-dimethylpyridin-2-yl)methyl]-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-[(3-cyano-4-methoxypyridin-2-yl)methyl]-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-[(3-cyanopyridin-2-yl)methyl]-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-{[3-(difluoromethyl)-4-methoxypyridin-2-yl]methyl}-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-[(5-chloro-4-methoxypyridin-2-yl)methyl]-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-[(5-chloro-3-cyanopyridin-2-yl)methyl]-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-[(5-chloro-3-fluoropyridin-2-yl)methyl]-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-[(4-chloro-3-fluoropyridin-2-yl)methyl]-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-[(3-fluoro-5-methylpyridin-2-yl)methyl]-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-[(4-methoxy-5-methylpyridin-2-yl)methyl]-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-[(3-cyano-5-methylpyridin-2-yl)methyl]-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-[(4-methoxy-3-methylpyridin-2-yl)methyl]-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-[(3-cyano-6-methoxypyridin-2-yl)methyl]-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-{[6-(difluoromethyl)-3-fluoro-4-methoxypyridin-2-yl]methyl}-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-{[5-(difluoromethyl)-3-fluoro-4-methoxypyridin-2-yl]methyl}-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-[(3,5-difluoropyridin-2-yl)methyl]-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-[(3-fluoro-6-methylpyridin-2-yl)methyl]-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-[(3-fluoro-4-methylpyridin-2-yl)methyl]-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-[(3-chloro-4-methylpyridin-2-yl)methyl]-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 1-({4-[(5-fluoro-2-oxopyridin-1-yl)methyl]phenyl}methyl)-N-[(3-fluoro-4-methoxypyridin-2-yl)methyl]-3-(methoxymethyl)pyrazole-4-carboxamide; 
 N-[(5-methoxy-1-methylpyrazol-3-yl)methyl]-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-[(4-chloro-5-methoxy-1-methylpyrazol-3-yl)methyl]-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-[(5-methoxy-1,4-dimethylpyrazol-3-yl)methyl]-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-[(4-chloro-1-methylpyrazol-3-yl)methyl]-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-[(2,6-difluoro-3,5-dimethoxyphenyl)methyl]-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-[(2-cyano-5-methoxyphenyl)methyl]-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-[(2-cyano-3-methoxyphenyl)methyl]-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-{[2-fluoro-3-methoxy-6-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-{[5-methoxy-2-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-[(5-methoxy-2-methylphenyl)methyl]-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-[(6-carbamoyl-2-fluoro-3-methoxyphenyl)methyl]-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-{[5-fluoro-2-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-[(6-cyano-2-fluoro-3-methoxyphenyl)methyl]-3-(methoxymethyl)-1-({5-[(2-oxopyridin-1-yl)methyl]pyridin-2-yl}methyl)pyrazole-4-carboxamide; 
 N-[(6-cyano-2-fluoro-3-methoxyphenyl)methyl]-3-(methoxymethyl)-1-({6-[(2-oxopyridin-1-yl)methyl]pyridin-3-yl}methyl)pyrazole-4-carboxamide; 
 N-[(6-cyano-2-fluoro-3-methoxyphenyl)methyl]-1-({4-[(5-fluoro-2-oxopyridin-1-yl)methyl]phenyl}methyl)-3-(methoxymethyl)pyrazole-4-carboxamide; 
 N-[(2-cyano-5-methoxyphenyl)methyl]-3-(methoxymethyl)-1-({5-[(2-oxopyridin-1-yl)methyl]pyridin-2-yl}methyl)pyrazole-4-carboxamide; 
 N-[(2-cyano-5-methoxyphenyl)methyl]-3-(methoxymethyl)-1-({6-[(2-oxopyridin-1-yl)methyl]pyridin-3-yl}methyl)pyrazole-4-carboxamide; 
 N-[(2-cyano-5-methoxyphenyl)methyl]-1-({4-[(5-fluoro-2-oxopyridin-1-yl)methyl]phenyl}methyl)-3-(methoxymethyl)pyrazole-4-carboxamide; 
 N-[(6-cyano-2-fluoro-3-methoxyphenyl)methyl]-3-(methoxymethyl)-1-({4-[(2-oxopiperidin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-[(6-cyano-2-fluoro-3-methoxyphenyl)methyl]-3-(methoxymethyl)-1-{[2-(pyrrolidin-1-yl)pyrimidin-5-yl]methyl}pyrazole-4-carboxamide; 
 N-{[2-fluoro-3-methoxy-6-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-3-(methoxymethyl)-1-({4-[(4-methylpyrazol-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-{[5-methoxy-2-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-3-(methoxymethyl)-1-({4-[(4-methylpyrazol-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-{[2-fluoro-6-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-3-(methoxymethyl)-1-({4-[(4-methylpyrazol-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-{[5-chloro-2-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-{[2-chloro-6-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)-N-{[2-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}pyrazole-4-carboxamide; 
 3-(methoxymethyl)-N-{[2-methyl-6-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-[(2-cyano-6-fluorophenyl)methyl]-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-{[2-fluoro-3-methoxy-6-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-3-(methoxymethyl)-1-{[6-(pyrrolidin-1-yl)pyridin-3-yl]methyl}pyrazole-4-carboxamide; 
 N-{[5-methoxy-2-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-3-(methoxymethyl)-1-{[6-(pyrrolidin-1-yl)pyridin-3-yl]methyl}pyrazole-4-carboxamide; 
 N-{[2-fluoro-3-methoxy-6-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-3-(methoxymethyl)-1-{[2-(pyrrolidin-1-yl)pyrimidin-5-yl]methyl}pyrazole-4-carboxamide; 
 N-{[5-methoxy-2-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-3-(methoxymethyl)-1-{[2-(pyrrolidin-1-yl)pyrimidin-5-yl]methyl}pyrazole-4-carboxamide; 
 N-{[2-fluoro-6-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-3-(methoxymethyl)-1-{[6-(pyrrolidin-1-yl)pyridin-3-yl]methyl}pyrazole-4-carboxamide; 
 N-{[2-fluoro-6-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-3-(methoxymethyl)-1-{[2-(pyrrolidin-1-yl)pyrimidin-5-yl]methyl}pyrazole-4-carboxamide; 
 1-{[2-(3,3-difluoropyrrolidin-1-yl)pyrimidin-5-yl]methyl}-N-{[2-fluoro-3-methoxy-6-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-3-(methoxymethyl)pyrazole-4-carboxamide; 
 1-{[6-(3,3-difluoropyrrolidin-1-yl)pyridin-3-yl]methyl}-N-{[2-fluoro-3-methoxy-6-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-3-(methoxymethyl)pyrazole-4-carboxamide; 
 1-{[2-(3,3-difluoropyrrolidin-1-yl)pyrimidin-5-yl]methyl}-N-{[5-methoxy-2-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-3-(methoxymethyl)pyrazole-4-carboxamide; 
 1-{[6-(3,3-difluoropyrrolidin-1-yl)pyridin-3-yl]methyl}-N-{[5-methoxy-2-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-3-(methoxymethyl)pyrazole-4-carboxamide; 
 and a pharmaceutically acceptable salt or solvate thereof. 
 
     
     
         22 . The compound of  claim 1  that is selected from the group consisting of:
 N-{[2-fluoro-3-methoxy-6-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-{[5-methoxy-2-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-{[2-fluoro-3-methoxy-6-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-3-(methoxymethyl)-1-({4-[(4-methylpyrazol-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-{[5-methoxy-2-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-3-(methoxymethyl)-1-({4-[(4-methylpyrazol-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-{[5-methoxy-2-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)-3-(trifluoromethyl)pyrazole-4-carboxamide; 
 3-amino-N-{[2-fluoro-3-methoxy-6-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 3-amino-N-{[5-methoxy-2-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 3-(dimethylamino)-N-{[2-fluoro-3-methoxy-6-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 3-(dimethylamino)-N-{[5-methoxy-2-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide; 
 N-{[2-fluoro-3-methoxy-6-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-3-(methoxymethyl)-1-{[6-(pyrrolidin-1-yl)pyridin-3-yl]methyl}pyrazole-4-carboxamide; 
 N-{[5-methoxy-2-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-3-(methoxymethyl)-1-{[6-(pyrrolidin-1-yl)pyridin-3-yl]methyl}pyrazole-4-carboxamide; 
 N-{[2-fluoro-3-methoxy-6-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-3-(methoxymethyl)-1-{[2-(pyrrolidin-1-yl)pyrimidin-5-yl]methyl}pyrazole-4-carboxamide; 
 N-{[5-methoxy-2-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-3-(methoxymethyl)-1-{[2-(pyrrolidin-1-yl)pyrimidin-5-yl]methyl}pyrazole-4-carboxamide; 
 N-{[2-fluoro-3-methoxy-6-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-1-{[6-(pyrrolidin-1-yl)pyridin-3-yl]methyl}-3-(trifluoromethyl)pyrazole-4-carboxamide; 
 N-{[5-methoxy-2-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-1-{[6-(pyrrolidin-1-yl)pyridin-3-yl]methyl}-3-(trifluoromethyl)pyrazole-4-carboxamide; 
 1-{[2-(3,3-difluoropyrrolidin-1-yl)pyrimidin-5-yl]methyl}-N-{[2-fluoro-3-methoxy-6-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-3-(methoxymethyl)pyrazole-4-carboxamide; 
 1-{[6-(3,3-difluoropyrrolidin-1-yl)pyridin-3-yl]methyl}-N-{[2-fluoro-3-methoxy-6-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-3-(methoxymethyl)pyrazole-4-carboxamide; 
 1-{[2-(3,3-difluoropyrrolidin-1-yl)pyrimidin-5-yl]methyl}-N-{[5-methoxy-2-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-3-(methoxymethyl)pyrazole-4-carboxamide; 
 1-{[6-(3,3-difluoropyrrolidin-1-yl)pyridin-3-yl]methyl}-N-{[5-methoxy-2-(1,2,3,4-tetrazol-1-yl)phenyl]methyl}-3-(methoxymethyl)pyrazole-4-carboxamide; 
 and a pharmaceutically acceptable salt or solvate thereof. 
 
     
     
         23 . A pharmaceutical composition comprising a compound or pharmaceutically acceptable salt or solvate thereof of  claim 1  and a pharmaceutically acceptable carrier, diluent or excipient. 
     
     
         24 . A method of treating a disease or condition in which plasma kallikrein activity is implicated comprising administering to a subject in need thereof a therapeutically effective amount of a compound or pharmaceutically acceptable salt or solvate thereof of  claim 1 . 
     
     
         25 . The method of  claim 24 , wherein the disease or condition in which plasma kallikrein activity is implicated is impaired visual acuity, diabetic retinopathy, diabetic macular edema, hereditary angioedema, diabetes, pancreatitis, cerebral haemorrhage, nephropathy, cardiomyopathy, neuropathy, inflammatory bowel disease, arthritis, inflammation, septic shock, hypotension, cancer, adult respiratory distress syndrome, disseminated intravascular coagulation, blood coagulation during cardiopulmonary bypass surgery or bleeding from post operative surgery. 
     
     
         26 . The method of  claim 24 , wherein the disease or condition in which plasma kallikrein activity is implicated is retinal vascular permeability associated with diabetic retinopathy and diabetic macular edema. 
     
     
         27 . The method of  claim 24 , wherein the disease or condition mediated by plasma kallikrein is hereditary angioedema. 
     
     
         28 . The method of  claim 24 , wherein the disease or condition in which plasma kallikrein activity is implicated is diabetic macular edema. 
     
     
         29 . The method of  claim 24 , wherein the disease or condition in which plasma kallikrein activity is implicated is retinal vein occlusion.
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