Abstract：
:A series of thiophene-containing non-amidine factor Xa inhibitors is described. Simple methyl-substituted thiophene analogs were relatively weak inhibitors. However, introduction of hydrophilic substituents at C-4 or C-5 of the thiophene afforded inhibitors with low nanomolar potency. Optimization of the thiophene substituent at C-4 afforded subnanomolar inhibitors with improved in vitro anticoagulant activity. Incorporating basic amine substituents on the thiophene increased hydrophilicity and improved anticoagulant activity. The pharmacokinetic profile of one inhibitor was evaluated in dogs, and the X-ray crystal structure of this compound bound to factor Xa provides insight into the observed SAR for binding to factor Xa.
journal_name
Bioorg Med Chemjournal_title
Bioorganic & medicinal chemistryauthors
Kochanny MJ,Adler M,Ewing J,Griedel BD,Ho E,Karanjawala R,Lee W,Lentz D,Liang AM,Morrissey MM,Phillips GB,Post J,Sacchi KL,Sakata ST,Subramanyam B,Vergona R,Walters J,White KA,Whitlow M,Ye B,Zhao Z,Shaw KJdoi
10.1016/j.bmc.2006.12.019subject
Has Abstractpub_date
2007-03-01 00:00:00pages
2127-46issue
5eissn
0968-0896issn
1464-3391pii
S0968-0896(06)01009-1journal_volume
15pub_type
杂志文章abstract：:Endogenous opioid peptides consist of a conserved amino acid residue of Phe(3) and Phe(4), although their binding modes for opioid receptors have not been elucidated in detail. Endomorphin-2, which is highly selective and specific for the mu opioid receptor, possesses two Phe residues at the consecutive positions 3 an...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
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abstract：:The malarial parasite Plasmodium falciparum encodes for an alpha-carbonic anhydrase (CA) enzyme possessing catalytic properties distinct of that of the human host, which was only recently purified. A series of aromatic sulfonamides, most of which were Schiff's bases derived from sulfanilamide/homosulfanilamide/4-amino...
journal_title：Bioorganic & medicinal chemistry
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doi：10.1016/j.bmc.2004.10.015
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journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
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journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2013.05.004
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journal_title：Bioorganic & medicinal chemistry
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journal_title：Bioorganic & medicinal chemistry
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journal_title：Bioorganic & medicinal chemistry
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journal_title：Bioorganic & medicinal chemistry
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journal_title：Bioorganic & medicinal chemistry
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journal_title：Bioorganic & medicinal chemistry
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journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
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更新日期：2016-11-01 00:00:00
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journal_title：Bioorganic & medicinal chemistry
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journal_title：Bioorganic & medicinal chemistry
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更新日期：2008-01-01 00:00:00
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journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
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更新日期：2016-08-15 00:00:00
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journal_title：Bioorganic & medicinal chemistry
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journal_title：Bioorganic & medicinal chemistry
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journal_title：Bioorganic & medicinal chemistry
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journal_title：Bioorganic & medicinal chemistry
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更新日期：2019-01-01 00:00:00
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journal_title：Bioorganic & medicinal chemistry
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journal_title：Bioorganic & medicinal chemistry
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journal_title：Bioorganic & medicinal chemistry
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journal_title：Bioorganic & medicinal chemistry
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journal_title：Bioorganic & medicinal chemistry
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journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
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journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
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更新日期：2007-06-01 00:00:00
abstract：:Pyrazolopyrimidines are the fused heterocyclic ring systems which structurally resemble purines which prompted biological investigations to assess their potential therapeutic significance. They are known to play a crucial role in numerous disease conditions. The advent of their first bioactivity as adenosine antagonis...
journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章,评审
doi：10.1016/j.bmc.2013.07.027
更新日期：2013-09-15 00:00:00
