Abstract：
:Here we describe the design, synthesis, and pharmacological profile of 5-HT(1A) receptor ligands related to 1 (WAY-100635). The cyclohexyl moiety in 1 and its O-desmethylated analogue 3 were replaced by the bridgehead iodinated bridge-fused rings: adamantyl, cubyl, bicyclo[2.2.2]octyl, or bicyclo[2.2.1]heptyl. All analogues displayed a (sub)nanomolar affinity for the 5-HT(1A) receptor in vitro. Compounds 6b and 7b appeared to be selective for this receptor over other relevant receptors and could easily be iodinated with radioactive iodine-123. In humane hepatocytes, [(123)I]6b showed a low propensity for amide hydrolysis and a stable carbon-iodine bond. The biodistribution of [(123)I]6b and [(123)I]7b in rats revealed that the carbon-iodine bond was also stable in vivo. Unfortunately, the brain uptake and the specificity for both radioligands were significantly lower than those of the parent molecule 1. In conclusion, the designed tracers are not suitable for SPECT imaging.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Al Hussainy R,Verbeek J,van der Born D,Braker AH,Leysen JE,Knol RJ,Booij J,Herscheid JKdoi
10.1021/jm1009956subject
Has Abstractpub_date
2011-05-26 00:00:00pages
3480-91issue
10eissn
0022-2623issn
1520-4804journal_volume
54pub_type
杂志文章abstract：:N-(5,5-Diacetoxypent-1-yl)doxorubicin (1b) is an intensely cytotoxic doxorubicin analogue that retains full potency against tumor cells that express elevated levels of P-glycoprotein and are resistant to doxorubicin. 1b was designed to be hydrolyzed in the presence of carboxylate esterases to N-(5-oxypent-1-yl)doxorub...
journal_title：Journal of medicinal chemistry
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journal_title：Journal of medicinal chemistry
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pub_type： 杂志文章
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更新日期：1998-09-10 00:00:00
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journal_title：Journal of medicinal chemistry
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更新日期：2014-02-27 00:00:00
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journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00182a025
更新日期：1980-08-01 00:00:00
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journal_title：Journal of medicinal chemistry
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更新日期：2007-06-14 00:00:00
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更新日期：2011-11-10 00:00:00
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更新日期：2014-06-26 00:00:00
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更新日期：2001-08-16 00:00:00
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更新日期：2012-07-26 00:00:00
abstract：:A series of 2-aminotetralins, substituted with a methoxy or a hydroxy group on the 5- or 7-position, and with varying N-alkyl or N-arylalkyl substituents, were prepared and evaluated in binding assays for human dopamine (DA) D2, D3, and D4 receptors. Some members of this series were prepared in former studies, but wer...
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abstract：:Structure/activity studies on atrial natriuretic peptide ANP (1-28) have highlighted three portions of the native molecule as necessary for its biological responses. We have linked these three regions and excised the remaining segments to produce a family of small analogues (less than half the size of the parent) whic...
journal_title：Journal of medicinal chemistry
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doi：10.1021/jm00083a003
更新日期：1992-03-06 00:00:00
