Abstract：
:The synthesis and biological evaluation of the two known phenolic metabolites of paclitaxel are described. The C3'-phenolic metabolite 2 of paclitaxel was prepared from 7-(triethylsilyl)-baccatin III (8) and enantioenriched N-benzoyl-2-azetidinone 7. The C2-phenolic metabolite 3 was synthesized from paclitaxel (1a) via selective C2 debenzoylation and reacylation.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Park H,Hepperle M,Boge TC,Himes RH,Georg GIdoi
10.1021/jm960142xsubject
Has Abstractpub_date
1996-07-05 00:00:00pages
2705-9issue
14eissn
0022-2623issn
1520-4804pii
jm960142xjournal_volume
39pub_type
杂志文章abstract：:A new structurally distinct class of 14-membered-ring macrolides is characterized by a keto-function instead of the cladinose sugar, well-known for its fragility even in weakly acidic media. This new class called ketolides is endowed with remarkable antibacterial activity against macrolide-resistant strains. A complet...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm970852i
更新日期：1998-08-27 00:00:00
abstract：:Pyrimidine biosynthesis presents an attractive drug target in malaria parasites due to the absence of a pyrimidine salvage pathway. A set of compounds designed to inhibit the Plasmodium falciparum pyrimidine biosynthetic enzyme dihydroorotate dehydrogenase (PfDHODH) was synthesized. PfDHODH-specific inhibitors with lo...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm060687j
更新日期：2007-01-25 00:00:00
abstract：:Small molecule inhibitors of PARP-1 have been pursued by various organizations as potential therapeutic agents either capable of sensitizing cytotoxic treatments or acting as stand-alone agents to combat cancer. As one of the strategies to expand our portfolio of PARP-1 inhibitors, we pursued unsaturated heterocycles ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm900697r
更新日期：2009-11-12 00:00:00
abstract：:Hydroxyurea, hydroxyguanidine, and some thiosemicarbazones have been shown to have anticancer and antiviral activities. One of their possible sites of action is the enzyme ribonucleotide reductase (RR). Combination of the structural features of these compounds led to the design and synthesis of the Schiff bases of N-h...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00146a022
更新日期：1985-08-01 00:00:00
abstract：:Type II beta-turn mimics and polyproline II helix mimics based upon diastereoisomeric 5.6.5 spiro bicyclic scaffolds have provided two pairs of Pro-Leu-Gly-NH(2) (PLG) peptidomimetics with contrasting dopamine receptor modulating activities. Compounds 1a and 3a were found to be positive allosteric modulators of the do...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm801575w
更新日期：2009-04-09 00:00:00
abstract：:A series of N-naphthylethyl amide derivatives were synthesized and evaluated as melatonin receptor ligands. The affinity of each compound for the melatonin receptor was determined by binding studies using [2-125I]iodomelatonin on ovine pars tuberalis membrane homogenates. Structure-activity relationships led to the co...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00046a006
更新日期：1994-09-30 00:00:00
abstract：:A series of amide analogues of the 2,2'-dithiobis(1H-indole-3-alkaonic acid) class of tyrosine kinase inhibitors have been prepared, by reaction of 1H-indole-3-alkanamides (8) with S2Cl2, and separation of the desired disulfides from the initial mixtures of mono-, di-, and trisulfides formed. These amides were evaluat...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00031a009
更新日期：1994-03-04 00:00:00
abstract：:Recent trends in drug discovery include methods to identify dual and triple activating drugs. This approach is being successfully employed in malaria, cancer, asthma, insulin resistance, etc. Molecular field analysis has been employed in correlating pharmacological data and field parameters. In this paper we introduce...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm049383s
更新日期：2005-04-21 00:00:00
abstract：:Melanin concentrating hormone (MCH) is involved in regulation of food intake and energy homeostasis. Antagonists of the MCH receptor are expected to affect food intake and weight gain, making MCH-R1 an attractive target for obesity treatment. Herein, we report the discovery of a novel, orally active series of MCH-R1 a...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm049035q
更新日期：2005-04-07 00:00:00
abstract：:The recent discovery that the formaldehyde conjugates of doxorubicin and daunorubicin, Doxoform and Daunoform, are cytotoxic to resistant human breast cancer cells prompted the search for hydrolytically more stable anthracycline-formaldehyde conjugates. Doxoform and Daunoform consist of two molecules of the parent dru...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm970739s
更新日期：1998-04-09 00:00:00
abstract：:In an attempt to relate the hallucinogenic potencies in man of some biologically important amphetamines and phenethylamines, the 1-octanol-water partition coefficients for 11 amphetamines were determined. Using these values and published Hansch pi constants, the log P for 17 additional amines was estimated. It was fou...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00236a023
更新日期：1975-02-01 00:00:00
abstract：:Compstatin peptides are complement inhibitors that bind and inhibit cleavage of complement C3. Peptide binding is enhanced by hydrophobic interactions; however, poor solubility promotes aggregation in aqueous environments. We have designed new compstatin peptides derived from the W4A9 sequence (Ac-ICVWQDWGAHRCT-NH2, c...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm501345y
更新日期：2015-01-22 00:00:00
abstract：:Monoamine oxidase (MAO) exists in two forms distinguishable by substrate specificity. Inhibition of MAO A is believed to be responsible for the antidepressant activity of MAO inhibitors. A group of N-arylacetamides are highly specific inhibitors of MAO A, some with IC50 values in the 10-100 nM range. The requirements ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00039a021
更新日期：1994-06-24 00:00:00
abstract：:The natural dibenzylbutyrolactone type lignanolide (-)-arctigenin (2), an inhibitor of human immunodeficiency virus type-1 (HIV-1) replication in infected human cell systems, was found to suppress the integration of proviral DNA into the cellular DNA genome. In the present study 2 was tested with purified HIV-1 integr...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm950387u
更新日期：1996-01-05 00:00:00
abstract：:A one-pot synthesis of ageladine A and analogues is reported. The key Pictet-Spengler reaction between 2-aminohistamine and aryl aldehydes has been successfully utilized for the synthesis of the natural product and 14 analogues. These compounds were screened for their matrix metalloprotease (MMP) and kinase inhibition...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm200039m
更新日期：2011-04-14 00:00:00
abstract：:A series of imidazo[1,5-alpha]quinoxalin-4-ones and imidazo[1,5-alpha]quinoxaline ureas containing substituted phenyl groups at the 3-position was developed. Compounds within the imidazo[1,5-alpha]quinoxaline urea series had high affinity for the GABAA/benzodiazepine receptor complex with varying in vitro efficacy, al...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm960070+
更新日期：1996-09-13 00:00:00
abstract：:A series of N-aryl-N'-(2-chloroethyl)ureas (CEUs) and derivatives were synthesized and evaluated for antiproliferative activity against a wide panel of tumor cell lines. Systematic structure--activity relationship (SAR) studies indicated that: (i) a branched alkyl chain or a halogen at the 4-position of the phenyl rin...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm0010264
更新日期：2001-03-01 00:00:00
abstract：:MTH1 is a member of the nudix phosphohydrolase superfamily of enzymes, and it is involved in nucleotide pool homeostasis. The protein exerts its scavenging action by hydrolyzing oxidized nucleotides, thus avoiding their misincorporation into replicating DNA. Recent reports have validated its inhibition as a potential ...
journal_title：Journal of medicinal chemistry
pub_type： 评论,杂志文章
doi：10.1021/acs.jmedchem.6b00283
更新日期：2016-03-24 00:00:00
abstract：:Naturally occurring carbapenem antibiotics having a double bond in the side chain, when refluxed in chloroform containing quarternary alkylammonium halides, were converted into Z isomers in high yields. The mechanism of this new equilibration involves intramolecular proton transfer from the carboxylic acid to the carb...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00359a600
更新日期：1983-05-01 00:00:00
abstract：:The synthesis and biological evaluation of novel prodrugs for use in the antibody directed enzyme prodrug therapy (ADEPT) of cancer based on the cytotoxic antibiotic duocarmycin SA (1) are described. In this approach, we investigated the influence of the sugar moiety of the glycosidic prodrug on the QIC(50) values as ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm8009102
更新日期：2009-01-22 00:00:00
abstract：:Specific interactions between Src homology 2 (SH2) domain-containing proteins and the phosphotyrosine-containing counterparts play significant role in cellular protein tyrosine kinase (PTK) signaling pathways. The SH2 domain inhibitors could potentially serve as drug candidates in treating human diseases. Here we have...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm301610q
更新日期：2013-04-11 00:00:00
abstract：:In this study, we developed an assignment-free approach for rapid identification of ligand-binding sites in target proteins by using NMR. With a sophisticated cell-free stable isotope-labeling procedure that introduces (15)N- or (13)C-labels to specific atoms of target proteins, this approach requires only a single se...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm4014357
更新日期：2013-11-27 00:00:00
abstract：:Caspases are cysteine proteases that specifically cleave Asp-Xxx bonds. They are key agents in inflammation and apoptosis and are attractive targets for therapy against inflammation, neurodegeneration, ischemia, and cancer. Many caspase structures are known, but most involve either peptide or protein inhibitors, unatt...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm0305523
更新日期：2004-05-06 00:00:00
abstract：:Derivatives of 4-aryl-4-(dimethylamino)cyclohexan-1-ones substituted by m-hydroxy groups were obtained by using as a key reaction the displacement of cyanide from the alpha-aminonitrile of 1,4-cyclohexanedione ketal, with the THP ether of m-hydroxyphenylmagnesium bromide. A number of the products show narcotic antagon...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00135a019
更新日期：1981-03-01 00:00:00
abstract：:The discovery and synthesis of a new series of pyrimidines as potent sigma-1 receptor (σ1R) antagonists, associated with pharmacological antineuropathic pain activity, are the focus of this article. The new compounds were evaluated in vitro in σ-1 and σ-2 receptor binding assays. The nature of the pyrimidine scaffold ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm501207r
更新日期：2014-12-26 00:00:00
abstract：:5'-(Bromoacetamido)-2',5'-dideoxyuridine (3) and derivatives (8, 10, 12, and 14) substituted at the 5-position with bromo, iodo, fluoro, and ethyl groups have been synthesized as potential inhibitors of enzymes that metabolize pyrimidine nucleosides. Also prepared were 2',5'-dideoxyuridine derivatives (4-6) substitute...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00388a031
更新日期：1987-05-01 00:00:00
abstract：:Building on insights gained from the discovery of the antimalarial ozonide arterolane (OZ277), we now describe the structure-activity relationship (SAR) of the antimalarial ozonide artefenomel (OZ439). Primary and secondary amino ozonides had higher metabolic stabilities than tertiary amino ozonides, consistent with t...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.6b01586
更新日期：2017-04-13 00:00:00
abstract：:A family of analogues of des-AA(1,2,5)-[DTrp(8)/D2Nal(8)]-SRIF that contain a 4-(N-isopropyl)-aminomethylphenylalanine (IAmp) at position 9 was identified that has high affinity and selectivity for human somatostatin receptor subtype 1 (sst1). The binding affinities of des-AA(1,2,5)-[DTrp(8),IAmp(9)]-SRIF (c[H-Cys-Lys...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm010037+
更新日期：2001-06-21 00:00:00
abstract：:Antivirulence strategies are now attracting interest for the inherent mechanism of action advantages. In our previous work, diapophytoene desaturase (CrtN) was identified to be an attractive and drugable target for fighting pigmented S. aureus infections. In this research, we developed a series of effective benzocyclo...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.6b00122
更新日期：2016-05-26 00:00:00
abstract：:Non-nucleoside inhibitors of HIV reverse transcriptase (NNRTIs), albeit not the mainstays of HIV/AIDS treatment, have become increasingly important in highly active antiretroviral therapy (HAART) due to their unique mechanism of action. Several years ago our group identified the alkenyldiarylmethanes (ADAMs) as a pote...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm070382k
更新日期：2007-10-04 00:00:00
