109523-16-2Relevant academic research and scientific papers
SUBSTITUTED 2-AZA-BICYCLO[2.2.2]OCTANE-3-CARBOXYLIC ACID (BENZYL-CYANO-METHYL)-AMIDES INHIBITORS OF CATHEPSIN C
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Paragraph 0318; 0320, (2014/09/30)
This invention relates to 2-Aza-bicyclo[2.2.2]octane-3-carboxylic acid (benzyl-cyano-methyl)-amides of formula 1 and their use as inhibitors of Cathepsin C, pharmaceutical compositions containing the same, and methods of using the same as agents for treatment and/or prevention of diseases connected with dipeptidyl peptidase I activity, e.g. respiratory diseases.
SUBSTITUTED 2-AZA-BICYCLO[2.2.2]OCTANE-3-CARBOXYLIC ACID (BENZYL-CYANO-METHYL)-AMIDES INHIBITORS OF CATHEPSIN C
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Page/Page column 71; 72, (2014/09/29)
This invention relates to 2-Aza-bicyclo[2.2.2]octane-3-carboxylic acid (benzyl-cyano-methyl)-amides of formula 1 and their use as inhibitors of Cathepsin C, pharmaceutical compositions containing the same, and methods of using the same as agents for treatment and/or prevention of diseases connected with dipeptidyl peptidase I activity, e.g. asthma and allergic diseases, gastrointestinal inflammatory diseases, eosinophilic diseases, chronic obstructive pulmonary disease, infection by pathogenic microbes, rheumatoid arthritis or atherosclerosis.
Selection of a 2-azabicyclo[2.2.2]octane-based α4β1 integrin antagonist as an inhaled anti-asthmatic agent
Lawson, Edward C.,Santulli, Rosemary J.,Dyatkin, Alexey B.,Ballentine, Scott A.,Abraham, William M.,Rudman, Sandra,Page, Clive P.,de Garavilla, Lawrence,Damiano, Bruce P.,Kinney, William A.,Maryanoff, Bruce E.
, p. 4208 - 4216 (2007/10/03)
The α4β1 integrin, expressed on eosinophils and neutrophils, induces inflammation in the lung by facilitating cellular infiltration and activation. From a number of potent α4β1 antagonists that we evaluated for
2-CYANOPYRROLIDINECARBOXAMIDE COMPOUND
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Page/Page column 125, (2008/06/13)
A compound of the formula (I) or a pharmaceutically acceptable salt thereof: [wherein X1 and X2 each is independently lower alkylene; X3 is =CH2, =CHF or =CF2; R1 is substituent, R2 and R3 each is independently H or lower alkyl; n is 0, 1, 2, 3 or 4.] having the activity inhibiting DPP-IV activity. They are therefore useful in the treatment of conditions mediated by DPP-IV, such as NIDDM.
New prolyl endopeptidase inhibitors: In vitro and in vivo activities of azabicyclo[2.2.2]octane, azabicyclo[2.2.1]heptane, and perhydroindole derivatives
Portevin, Bernard,Benoist, Alain,Rémond, Georges,Hervé, Yolande,Vincent, Michel,Lepagnol, Jean,De Nanteuil, Guillaume
, p. 2379 - 2391 (2007/10/03)
A series of potent and selective prolylendopeptidase (PEP) inhibitors of the α-keto heterocyclic type has been obtained by replacing the classical central proline of 1-[1-(4-phenylbutanoyl)-L-prolyl]pyrrolidine (SUAM 1221, 3) by non-natural amino acids PHI, ABO, and ABH. These 4-phenylbutanoyl side- chain-containing inhibitors exhibited potent in vitro inhibitory potencies with IC50 around 30 nM (compounds 24 and 25). Modulation of the side chain by replacement of the terminal phenyl ring by the dicyclopropyl moiety afforded derivatives 30 and 32 with improved potencies (IC50 between 10 and 20 nM). Furthermore, replacing the linear 4-phenylbutanoyl side chain by the (2-phenylcyclopropyl)carbonyl entity provided potent inhibitors with IC50 culminating at 0.9 nM on a rat cortex enzymatic preparation (compound 70). The configuration of the cyclopropyl ring had to be R,R in order to obtain not only a strong PEP inhibition in vitro but also a good activity in vivo, exemplified by inhibitor 68, which gave ID50 ip and po of 0.3 and 1 mg/kg, respectively. Finally, demonstration of the cognition-enhancing properties of compound 54 was given in the passive avoidance test using scopolamine- induced amnesia in the rat, where it dose dependently inhibited the scopolamine-induced decrease in avoidance response.
