- PENICILLIN-BINDING PROTEIN INHIBITORS
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Described herein are certain boron-containing compounds, compositions, preparations and their use as modulators of the transpeptidase function of bacterial penicillin-binding proteins and as antibacterial agents. In some embodiments, the compounds describ
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Paragraph 00452
(2019/12/15)
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- BRIDGED BICYCLIC KALLIKREIN INHIBITORS
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Provided herein are kallikrein modulating compounds, pharmaceutical compositions comprising the same, and uses thereof.
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Page/Page column 206
(2016/12/26)
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- Enhancement of hydrophobic interactions and hydrogen bond strength by cooperativity: Synthesis, modeling, and molecular dynamics simulations of a congeneric series of thrombin inhibitors
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Accurately predicting the binding affinity of ligands to their receptors by computational methods is one of the major challenges in structure-based drug design. One of the potentially significant errors in these predictions is the common assumption that the ligand binding affinity contributions of noncovalent interactions are additive. Herein we present data obtained from two separate series of thrombin inhibitors containing hydrophobic side chains of increasing size that bind in the S3 pocket and with, or without, an adjacent amine that engages in a hydrogen bond with Gly 216. The first series of inhibitors has a m-chlorobenzyl moiety binding in the S1 pocket, and the second has a benzamidine moiety. When the adjacent hydrogen bond is present, the enhanced binding affinity per ?2 of hydrophobic contact surface in the S3 pocket improves by 75% and 59%, respectively, over the inhibitors lacking this hydrogen bond. This improvement of the binding affinity per ?2 demonstrates cooperativity between the hydrophobic interaction and the hydrogen bond.
- Muley, Laveena,Baum, Bernhard,Smolinski, Michael,Freindorf, Marek,Heine, Andreas,Klebe, Gerhard,Hangauer, David G.
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supporting information; experimental part
p. 2126 - 2135
(2010/08/19)
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- Novel pyrazolopyrimidines as cyclin dependent kinase inhibitors
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In its many embodiments, the present invention provides a novel class of pyrazolo[1,5-a]pyrimidine compounds as inhibitors of cyclin dependent kinases, methods of preparing such compounds, pharmaceutical compositions containing one or more such compounds, methods of preparing pharmaceutical formulations comprising one or more such compounds, and methods of treatment, prevention, inhibition, or amelioration of one or more diseases associated with the CDKs using such compounds or pharmaceutical compositions.
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- PYRAZOLOPYRIMIDINES AS CYCLIN-DEPENDENT KINASE INHIBITORS
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In its many embodiments, the present invention provides a novel class of pyrazolo[1,5-a]pyrimidine compounds as inhibitors of cyclin dependent kinases, methods of preparing such compounds, pharmaceutical compositions containing one or more such compounds, methods of preparing pharmaceutical formulations comprising one or more such compounds, and methods of treatment, prevention, inhibition, or amelioration of one or more diseases associated with the CDKs using such compounds or pharmaceutical compositions.
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- Noncovalent tripeptidic thrombin inhibitors incorporating amidrazone, amine and amidine functions at P1
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A series of noncovalent tripeptidic thrombin inhibitors incorporating amidrazone, amine and amidine functions at P1 was investigated. While the amidrazone and the amine series displayed limited oral absorption, the amidine series demonstrated generally good oral absorption and strong antithrombotic activity; the single-digit picomolar Ki achieved from this series is among the best yet reported. The present work highlights the benzamidine compound 11f (LB30812) that exhibits excellent overall profiles of potency, oral absorption and antithrombotic efficacy.
- Lee, Koo,Jung, Won-Hyuk,Park, Cheol Won,Park, Hee Dong,Lee, Sun Hwa,Kwon, O Hwan
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p. 1017 - 1022
(2007/10/03)
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- Selective factor Xa inhibitors
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Novel compounds, their salts and compositions related thereto having activity against mammalian factor Xa are disclosed. The compounds are useful in vitro or in vivo for preventing or treating coagulation disorders.
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- Large scale preparation of protected 4-aminomethylbenzamidine. Application to the synthesis of the thrombin inhibitor, melagatran
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To allow the preparation of melagatran on a multigram scale, we have investigated several approaches for the synthesis of the key intermediate 4- aminomethylbenzamidine. The only industrially suitable pathway relies on the preparation of an N-hydroxyimino
- Lila, Christine,Gloanec, Philippe,Cadet, Laurence,Herve, Yolande,Fournier, Jean,Leborgne, Fabrice,Verbeuren, Tony J.,De Nanteuil, Guillaume
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p. 4419 - 4429
(2007/10/03)
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