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Your search keyword '"Monzon, Katina"' showing total 8 results
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8 results on '"Monzon, Katina"'

1. Discovery of adamantane ethers as inhibitors of 11β-HSD-1: Synthesis and biological evaluation

Author

Patel, Jyoti R., Shuai, Qi, Dinges, Jurgen, Winn, Marty, Pliushchev, Marina, Fung, Steven, Monzon, Katina, Chiou, William, Wang, Jiahong, Pan, Liping, Wagaw, Seble, Engstrom, Kenneth, Kerdesky, Francis A., Longenecker, Kenton, Judge, Russell, Qin, Wenying, Imade, Hovis M., Stolarik, DeAnne, Beno, David W.A., Brune, Michael, Chovan, Linda E., Sham, Hing L., Jacobson, Peer, and Link, J.T.

Published
2007
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2. Adamantane sulfone and sulfonamide 11-β-HSD1 Inhibitors

Author

Sorensen, Bryan, Winn, Martin, Rohde, Jeff, Shuai, Qi, Wang, Jiahong, Fung, Steven, Monzon, Katina, Chiou, William, Stolarik, DeAnne, Imade, Hovis, Pan, Liping, Deng, Xiaoqing, Chovan, Linda, Longenecker, Kenton, Judge, Russell, Qin, Wenying, Brune, Michael, Camp, Heidi, Frevert, Ernst U., Jacobson, Peer, and Link, J.T.

Published
2007
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8. Discovery and metabolic stabilization of potent and selective 2-amino-N-(adamant-2-yl) acetamide 11beta-hydroxysteroid dehydrogenase type 1 inhibitors.

Author

Rohde JJ, Pliushchev MA, Sorensen BK, Wodka D, Shuai Q, Wang J, Fung S, Monzon KM, Chiou WJ, Pan L, Deng X, Chovan LE, Ramaiya A, Mullally M, Henry RF, Stolarik DF, Imade HM, Marsh KC, Beno DW, Fey TA, Droz BA, Brune ME, Camp HS, Sham HL, Frevert EU, Jacobson PB, and Link JT

Subjects
11-beta-Hydroxysteroid Dehydrogenase Type 1 genetics, Adamantane pharmacokinetics, Animals, Cell Line, Humans, In Vitro Techniques, Mice, Microsomes, Liver metabolism, Piperazines pharmacokinetics, Rats, Stereoisomerism, Structure-Activity Relationship, Tissue Distribution, 11-beta-Hydroxysteroid Dehydrogenase Type 1 antagonists & inhibitors, Adamantane analogs & derivatives, Adamantane chemical synthesis, Piperazines chemical synthesis
Abstract

Starting from a rapidly metabolized adamantane 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) inhibitor 22a, a series of E-5-hydroxy-2-adamantamine inhibitors, exemplified by 22d and (+/-)-22f, was discovered. Many of these compounds are potent inhibitors of 11beta-HSD1 and are selective over 11beta-HSD2 for multiple species (human, mouse, and rat), unlike other reported species-selective series. These compounds have good cellular potency and improved microsomal stability. Pharmacokinetic profiling in rodents indicated moderate to large volumes of distribution, short half-lives, and a pharmacokinetic species difference with the greatest exposure measured in rat with 22d. One hour postdose liver, adipose, and brain tissue 11beta-HSD1 inhibition was confirmed with (+/-)-22f in a murine ex vivo assay. Although 5,7-disubstitued-2-adamantamines provided greater stability, a single, E-5-position, polar functional group afforded inhibitors with the best combination of stability, potency, and selectivity. These results indicate that adamantane metabolic stabilization sufficient to obtain short-acting, potent, and selective 11beta-HSD1 inhibitors has been discovered.

Published
2007
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