Abstract：
:N-(5,5-Diacetoxypent-1-yl)doxorubicin (DAPDOX) (3), a new, water-soluble analogue of doxorubicin, has been synthesized by coupling doxorubicin with 5-oxopentane-1,1-diacetate in the presence of NaBH3CN. This analogue was designed to be converted to the corresponding aldehyde, N-(5-oxopent-1-yl)doxorubicin, in the presence of carboxylate hydrolases, enzymes that are ubiquitous in tissue. DAPDOX had a half-life of several days in 0.05 M phosphate or 0.05 M acetate buffer solution at pH 4.0. However, in 0.05 M phosphate buffer at pH 7.4 in the presence of 20 unit equiv of porcine liver carboxylate esterase, the half-life of DAPDOX was less than 1 min. N-(5-acetoxypent-1-yl)doxorubicin (4), which should give rise to N-(5-hydroxypent-1-yl)doxorubicin on esterase-mediated hydrolysis, and N-(pent-1-yl)doxorubicin (5), were also prepared for comparative biological studies. DAPDOX was 150 times more potent than doxorubicin at inhibiting the growth of Chinese hamster ovary (CHO) cells in culture. The compound retained the same degree of potency against a CHO subline 100-fold resistant to doxorubicin (CHO/DOX) that expressed elevated levels of P-glycoprotein. Compounds 4 and 5, on the other hand, were no more effective than doxorubicin at inhibiting the growth of CHO cells and were 4-7-fold less potent against the CHO/DOX subline. DAPDOX is representative of a new structural class of doxorubicin analogues with unique chemical and biological properties.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Cherif A,Farquhar Ddoi
10.1021/jm00095a017keywords:
subject
Has Abstractpub_date
1992-08-21 00:00:00pages
3208-14issue
17eissn
0022-2623issn
1520-4804journal_volume
35pub_type
杂志文章abstract：:Novel tumor-targeting theranostic conjugates 1 and 2, bearing either a fluorine-labeled prosthetic as a potential (18)F-PET radiotracer (1) or a fluorescence probe (2) for internalization studies in vitro, were designed and synthesized. We confirmed efficient internalization of 2 in biotin-receptor positive (BR+) canc...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
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更新日期：2015-03-12 00:00:00
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更新日期：2016-09-22 00:00:00
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pub_type： 杂志文章
doi：10.1021/jm00244a002
更新日期：1975-10-01 00:00:00
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journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00205a024
更新日期：1978-07-01 00:00:00
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journal_title：Journal of medicinal chemistry
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doi：10.1021/jm980084a
更新日期：1998-07-16 00:00:00
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pub_type： 杂志文章
doi：10.1021/jm200334c
更新日期：2011-08-11 00:00:00
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journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00111a025
更新日期：1991-07-01 00:00:00
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doi：10.1021/jm00375a003
更新日期：1984-09-01 00:00:00
abstract：:Inspired by the previously reported superior gene transfer efficacies of amine headgroup-containing cationic lipids to their hydroxy counterparts, in the present structure-activity investigation we have compared the relative in vitro gene transfer efficacies of eight newly synthesized structural analogues of our previ...
journal_title：Journal of medicinal chemistry
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doi：10.1021/jm050128x
更新日期：2005-06-02 00:00:00
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pub_type： 杂志文章
doi：10.1021/jm101018r
更新日期：2011-02-10 00:00:00
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更新日期：2002-03-14 00:00:00
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pub_type： 杂志文章
doi：10.1021/jm00371a013
更新日期：1984-05-01 00:00:00
abstract：:In our ongoing program aimed at the design, synthesis, and biological evaluation of novel gem-difluoromethylenated glycosidase inhibitors, gem-4,4-difluoromethylenated iminosugars (5-9) were synthesized. The biological evaluation of these synthetic iminosugars showed that the gem-difluoromethylenyl group generally red...
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doi：10.1021/jm060066q
更新日期：2006-05-18 00:00:00
abstract：:The early and later eluting [(99m)TcO]depreotide products on RP-HPLC were confirmed to be the anti and syn diastereomers, respectively, based on proton NMR and circular dichroism spectroscopy. NMR provided evidence of a folded, conformationally constrained structure for the syn diastereomer. The syn diastereomer is pr...
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pub_type： 杂志文章
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更新日期：2007-09-06 00:00:00
abstract：:5-Bromotryptophan (5-BrTrp) is the most potent amino acid derivative reported in the literature to inhibit the gelation of hemoglobin S (from sickle cell anemia patients). Trp-Trp is also more potent than Trp as an antigelation agent. Therefore, we have prepared a series of dipeptides containing 5-BrTrp and evaluated ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00174a008
更新日期：1990-12-01 00:00:00
abstract：:A new family of chelating agents based on 4-(substituted-carbamoyl)-3-hydroxy-2-pyridinones is reported. These have optional terminal substituents on the nitrogens, and the hydroxypyridonate (HOPO) rings are attached to molecular backbones through amide linkages. A very important feature of the methyl-substituted liga...
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更新日期：1995-07-07 00:00:00
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更新日期：2008-04-10 00:00:00
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更新日期：2012-06-14 00:00:00
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更新日期：2018-04-12 00:00:00
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journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
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abstract：:Nitroimidazoles undergo a bioreduction in viable hypoxic tissue, resulting in trapping within these tissues, as demonstrated by misonidazole. A radioiodinated analogue of misonidazole (IVM, (E)-5-(2-Nitroimidazolyl)-4-hydroxy-1-iodopent-1-ene, 3) has been synthesized by halodestannylation, for evaluation as an imaging...
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pub_type： 杂志文章
doi：10.1021/jm00111a036
更新日期：1991-07-01 00:00:00
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journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm9605851
更新日期：1996-12-20 00:00:00
abstract：:Several new phospholipid-ara-C conjugates have been prepared and tested as prodrugs of the parent ara-C. The new derivative include ara-CMP-L-dipalmitin, ara-CDP-L-distearin, ara-CDP-L dimyristin, ara-CDP-L-diolein, and the radioactively labeled derivative ara-CDP-L-di[1-14C]palmitin. In addition, the unusually stable...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00353a010
更新日期：1982-11-01 00:00:00
abstract：:Carbamate derivatives of bile acids were synthesized with the aim of systematically exploring the potential for farnesoid X receptor (FXR) modulation endowed with occupancy of the receptor's back door, localized between loops H1-H2 and H4-H5. Since it was previously shown that bile acids bind to FXR by projecting the ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm060294k
更新日期：2006-07-13 00:00:00
