2p16: Difference between revisions

From Proteopedia
Jump to navigationJump to search
← Older editNewer edit →
OCA (talk | contribs)
Bots, Bureaucrats, journal, Administrators
3,330,058 edits
No edit summary
OCA (talk | contribs)
Bots, Bureaucrats, journal, Administrators
3,330,058 edits
No edit summary
Line 1: Line 1:
[[Image:2p16.gif|left|200px]]
{{Seed}}
[[Image:2p16.png|left|200px]]


<!--
<!--
Line 9: Line 10:
{{STRUCTURE_2p16|  PDB=2p16  |  SCENE=  }}  
{{STRUCTURE_2p16|  PDB=2p16  |  SCENE=  }}  


'''Factor Xa in Complex with the Inhibitor APIXABAN (BMS-562247) AKA 1-(4-METHOXYPHENYL)-7-OXO-6-(4-(2-OXO-1-PIPERIDINYL)PHENYL)-4,5,6,7-TETRAHYDRO-1H-PYRAZOLO[3, 4-C]PYRIDINE-3-CARBOXAMIDE'''
===Factor Xa in Complex with the Inhibitor APIXABAN (BMS-562247) AKA 1-(4-METHOXYPHENYL)-7-OXO-6-(4-(2-OXO-1-PIPERIDINYL)PHENYL)-4,5,6,7-TETRAHYDRO-1H-PYRAZOLO[3, 4-C]PYRIDINE-3-CARBOXAMIDE===




==Overview==
<!--
Efforts to identify a suitable follow-on compound to razaxaban (compound 4) focused on modification of the carboxamido linker to eliminate potential in vivo hydrolysis to a primary aniline. Cyclization of the carboxamido linker to the novel bicyclic tetrahydropyrazolopyridinone scaffold retained the potent fXa binding activity. Exceptional potency of the series prompted an investigation of the neutral P1 moieties that resulted in the identification of the p-methoxyphenyl P1, which retained factor Xa binding affinity and good oral bioavailability. Further optimization of the C-3 pyrazole position and replacement of the terminal P4 ring with a neutral heterocycle culminated in the discovery of 1-(4-methoxyphenyl)-7-oxo-6-(4-(2-oxopiperidin-1-yl)phenyl)-4,5,6,7-tetrah ydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide (apixaban, compound 40). Compound 40 exhibits a high degree of fXa potency, selectivity, and efficacy and has an improved pharmacokinetic profile relative to 4.
The line below this paragraph, {{ABSTRACT_PUBMED_17914785}}, adds the Publication Abstract to the page
(as it appears on PubMed at http://www.pubmed.gov), where 17914785 is the PubMed ID number.
-->
{{ABSTRACT_PUBMED_17914785}}


==About this Structure==
==About this Structure==
Line 31: Line 35:
[[Category: Protein inhibitor complex]]
[[Category: Protein inhibitor complex]]
[[Category: Serine protease]]
[[Category: Serine protease]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May  4 12:07:12 2008''
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 05:04:26 2008''
Retrieved from "https://proteopedia.org/2p16"