4x6o: Difference between revisions

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== Publication Abstract from PubMed ==

~~Antithrombotic agents that are inhibitors of factor XIa~~ (~~FXIa~~) ~~have~~ the ~~potential~~ to ~~demonstrate robust efficacy with a low bleeding risk profile. Herein, we describe a series~~ of ~~tetrahydroquinoline~~ (~~THQ~~) ~~derivatives as FXIa~~ inhibitors. ~~Compound 1 was identified as a potent~~ and ~~selective tool compound for proof of concept studies. It exhibited excellent antithrombotic efficacy in rabbit thrombosis models~~ and ~~did not prolong bleeding times. This demonstrates proof of concept for the FXIa mechanism in animal models with a reversible, small molecule inhibitor~~.

The structure-activity relationships (SAR) of six-membered ring replacements for the imidazole ring scaffold is described. This work led to the discovery of the potent and selective pyridine (S)-23 and pyridinone (+/-)-24 factor XIa inhibitors. SAR and X-ray crystal structure data highlight the key differences between imidazole and six-membered ring analogs.

~~Tetrahydroquinoline Derivatives as Potent~~ and ~~Selective Factor~~ XIa ~~Inhibitors~~.,~~Quan ML~~, ~~Wong PC~~, ~~Wang C~~, ~~Woerner F~~, ~~Smallheer~~ JM~~, Barbera FA~~, Bozarth JM, ~~Brown RL, Harpel MR, Luettgen JM, Morin PE, Peterson T, Ramamurthy V, Rendina AR~~, Rossi KA~~, Watson CA~~, Wei A, ~~Zhang G~~, Seiffert D, Wexler RR J Med Chem. 2014 ~~Jan 17~~. PMID:~~24405333~~<ref>PMID:~~24405333~~</ref>

Pyridine and pyridinone-based factor XIa inhibitors.,Corte JR, Fang T, Hangeland JJ, Friends TJ, Rendina AR, Luettgen JM, Bozarth JM, Barbera FA, Rossi KA, Wei A, Ramamurthy V, Morin PE, Seiffert DA, Wexler RR, Quan ML Bioorg Med Chem Lett. 2014 Dec 31. pii: S0960-894X(14)01358-4. doi:, 10.1016/j.bmcl.2014.12.050. PMID:25592713<ref>PMID:25592713</ref>

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>

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 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
-Antithrombotic agents that are inhibitors of factor XIa (FXIa) have the potential to demonstrate robust efficacy with a low bleeding risk profile. Herein, we describe a series of tetrahydroquinoline (THQ) derivatives as FXIa inhibitors. Compound 1 was identified as a potent and selective tool compound for proof of concept studies. It exhibited excellent antithrombotic efficacy in rabbit thrombosis models and did not prolong bleeding times. This demonstrates proof of concept for the FXIa mechanism in animal models with a reversible, small molecule inhibitor.
+The structure-activity relationships (SAR) of six-membered ring replacements for the imidazole ring scaffold is described. This work led to the discovery of the potent and selective pyridine (S)-23 and pyridinone (+/-)-24 factor XIa inhibitors. SAR and X-ray crystal structure data highlight the key differences between imidazole and six-membered ring analogs.
-Tetrahydroquinoline Derivatives as Potent and Selective Factor XIa Inhibitors.,Quan ML, Wong PC, Wang C, Woerner F, Smallheer JM, Barbera FA, Bozarth JM, Brown RL, Harpel MR, Luettgen JM, Morin PE, Peterson T, Ramamurthy V, Rendina AR, Rossi KA, Watson CA, Wei A, Zhang G, Seiffert D, Wexler RR J Med Chem. 2014 Jan 17. PMID:24405333<ref>PMID:24405333</ref>
+Pyridine and pyridinone-based factor XIa inhibitors.,Corte JR, Fang T, Hangeland JJ, Friends TJ, Rendina AR, Luettgen JM, Bozarth JM, Barbera FA, Rossi KA, Wei A, Ramamurthy V, Morin PE, Seiffert DA, Wexler RR, Quan ML Bioorg Med Chem Lett. 2014 Dec 31. pii: S0960-894X(14)01358-4. doi:, 10.1016/j.bmcl.2014.12.050. PMID:25592713<ref>PMID:25592713</ref>
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>