Abstract：
:Tertiary sulfonamidomethyl esters of benzylpenicillin (4) were synthesised and evaluated as a new class of potential prodrugs for beta-lactam antibiotics. Their hydrolysis in aqueous buffers was studied by HPLC and reveal a U-shaped pH rate profile with a pH-independent process extending from ca. pH 2 to ca. pH 10. This pathway is characterised by kinetic data that are consistent with a unimolecular mechanism involving rate-limiting iminium ion formation and penicillinoate expulsion. Benzylpenicillin and the corresponding sulfonamide are the ultimate products detected and isolated, indicating that beta-lactam ring opening is much slower than ester hydrolysis. As expected from the high reactivity, benzylpenicillin esters (4) displayed similar in vitro antibacterial activity to benzylpenicillin itself. Compared to the benzylpenicillin derivatives, sulfonamidomethyl esters of benzoic, clofibric and valproic acids display a much higher stability, giving rise to a Brønsted beta1g value of -0.96 and suggesting that tertiary sulfonamidomethyl esters may be useful prodrugs for carboxylic acid drugs with pKa > 4.
journal_name
Bioorg Med Chemjournal_title
Bioorganic & medicinal chemistryauthors
Iley J,Barroso H,Moreira R,Lopes F,Calheiros Tdoi
10.1016/s0968-0896(00)00099-7subject
Has Abstractpub_date
2000-07-01 00:00:00pages
1629-36issue
7eissn
0968-0896issn
1464-3391pii
S0968-0896(00)00099-7journal_volume
8pub_type
杂志文章abstract：:A new class of 4-aminoquinoline derivatives based on the natural product isatin scaffold were designed and synthesized for biological evaluation against three strains of the malaria parasite Plasmodium falciparum. These derivatives showed anti-plasmodial IC(50) values in the ranges of 1.3-0.079 and 2.0-0.050muM agains...
journal_title：Bioorganic & medicinal chemistry
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更新日期：2005-05-02 00:00:00
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journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2009.05.017
更新日期：2009-07-01 00:00:00
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pub_type： 杂志文章
doi：10.1016/j.bmc.2013.11.005
更新日期：2014-01-01 00:00:00
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journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2013.06.043
更新日期：2013-09-01 00:00:00
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doi：10.1016/j.bmc.2011.04.001
更新日期：2011-05-15 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：2009-04-15 00:00:00
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journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2007.09.034
更新日期：2008-01-01 00:00:00
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pub_type： 杂志文章
doi：10.1016/j.bmc.2011.10.022
更新日期：2012-01-01 00:00:00
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journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2007.10.058
更新日期：2008-02-01 00:00:00
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journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/s0968-0896(99)00062-0
更新日期：1999-07-01 00:00:00
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pub_type： 杂志文章
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更新日期：2015-11-01 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：2014-08-01 00:00:00
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journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2005.08.029
更新日期：2006-01-15 00:00:00
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journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2006.10.022
更新日期：2007-01-15 00:00:00
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journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/s0968-0896(97)00163-6
更新日期：1997-12-01 00:00:00
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journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2007.05.052
更新日期：2007-08-15 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：2009-02-01 00:00:00
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journal_title：Bioorganic & medicinal chemistry
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更新日期：2005-02-01 00:00:00
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journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/0968-0896(96)00086-7
更新日期：1996-08-01 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：2010-04-01 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：2014-12-15 00:00:00
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journal_title：Bioorganic & medicinal chemistry
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更新日期：2010-08-01 00:00:00
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journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/s0968-0896(00)82053-2
更新日期：1994-10-01 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：2010-05-15 00:00:00
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pub_type： 杂志文章
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更新日期：2009-08-15 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：2010-06-01 00:00:00
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journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2007.02.009
更新日期：2007-04-15 00:00:00
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journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/j.bmc.2010.12.033
更新日期：2011-01-15 00:00:00
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journal_title：Bioorganic & medicinal chemistry
pub_type： 杂志文章
doi：10.1016/0968-0896(94)00139-t
更新日期：1995-01-01 00:00:00
