Abstract：
:Several compounds having portions of the camptothecin ring system were prepared. These compounds were screened against L1210 lymphoid leukemia with negative results. Two of the analogs which contained the pyridine and hydroxylactone D and E rings were also screened for inhibition of DNA and RNA syntheses in HeLa cells. Each of these analogs had decreased activity as compared with comptothecin and there was no degradation of DNA in the HeLa cells. This suggest that the D and E rings are not a sufficient requirement for camptothecin-like activity.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Horwitz SB,Bristol JA,Comins DL,Davenport RW,Kane MJ,Lyle RE,Maloney JR,Portlock DEdoi
10.1021/jm00239a024keywords:
subject
Has Abstractpub_date
1975-05-01 00:00:00pages
535-7issue
5eissn
0022-2623issn
1520-4804journal_volume
18pub_type
杂志文章abstract：:There is urgent need for new therapeutic strategies to fight the global threat of antibiotic resistance. The focus of this Perspective is on chemical agents that target the most common mechanisms of antibiotic resistance such as enzymatic inactivation of antibiotics, changes in cell permeability, and induction/activat...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.7b00215
更新日期：2017-10-26 00:00:00
abstract：:A variety of N-(phenylsulfonyl)-N-phenylglycines 5, N-(phenylsulfonyl)-2-phenylglycines 6, and N-(phenylsulfonyl)anthranilic acids 7 were prepared as analogues of the N-(phenylsulfonyl)glycine 1 aldose reductase inhibitors. In the rat lens assay, several derivatives of 5 display greater inhibitory activity than the co...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00121a027
更新日期：1989-01-01 00:00:00
abstract：:Changes in expression and dysfunctional signaling of TrkA/B/C receptors and oncogenic Trk fusion proteins are found in neurological diseases and cancers. Here, we describe the development of a first 18F-labeled optimized lead suitable for in vivo imaging of Trk, [18F]TRACK, which is radiosynthesized with ease from a n...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.7b01607
更新日期：2018-02-22 00:00:00
abstract：:1-(3'-Diethylaminopropyl)-3-(substituted phenylmethylene)pyrrolidines were synthesized and evaluated for CQ-resistant reversal activity. In general the compounds of the series elicit better biological response than their phenylmethyl analogues. The most active compound 4b has been evaluated in vivo in detail, and the ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm000083u
更新日期：2000-09-07 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：:A series of 1-[1-(3,4-dimethoxy-1H-2-benzopyran-1-yl)alkyl]-4-arylpiperazines that shows hypotensive activity in the conscious rat has been investigated. Structure-activity relationships are described. A typical example that was investigated in greater detail is 1-[2-(3,4-dihydro-6,7-dimethoxy-1H-2-benzopyran-1-yl)eth...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00343a015
更新日期：1982-01-01 00:00:00
abstract：:There is compelling evidence that Bax channel activity stimulates cytochrome c release leading ultimately to cell death, which is a key event in ischemic injuries and neurodegenerative diseases. Here 3,6-dibromocarbazole piperazine derivatives of 2-propanol are described as the first small and potent modulators of the...
journal_title：Journal of medicinal chemistry
pub_type： 信件
doi：10.1021/jm034107j
更新日期：2003-10-09 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：:Singlet oxygen can severely damage biological tissue, which is exploited in photodynamic therapy (PDT). In PDT, the effective range is limited by the distribution of the photosensitizer (PS) and the illuminated area. However, no distinction is made between healthy and pathological tissue, which can cause undesired dam...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.9b01873
更新日期：2020-02-27 00:00:00
abstract：:By modification of key carboxylate, hydrophobic, and zinc-binding groups projected from a sterically restricted terphenyl scaffold, a series of simple and nonpeptide mimetics of the Cys-Val-Ile-Met tetrapeptide substrate of protein farnesyltransferase (FTase) have been designed and synthesized. A crystal structure of ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm0103099
更新日期：2002-01-03 00:00:00
abstract：:PRMT3 catalyzes the asymmetric dimethylation of arginine residues of various proteins. It is crucial for maturation of ribosomes and has been implicated in several diseases. We recently disclosed a highly potent, selective, and cell-active allosteric inhibitor of PRMT3, compound 4. Here, we report comprehensive struct...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.7b01674
更新日期：2018-02-08 00:00:00
abstract：:The benzothiadiazine dioxide (BTD) derivatives are potent nonnucleoside human cytomegalovirus (HCMV) inhibitors. As part of our comprehensive structure-activity relationship study of these compounds, we have now synthesized N,N- and N,O-dibenzyl derivatives with different para-substituents (alkyl, phenyl, electron-don...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm000033p
更新日期：2000-08-24 00:00:00
abstract：:Several optically active N-(indol-3-ylglyoxylyl)amino acid derivatives were synthesized and tested for [3H]flunitrazepam displacing activity in bovine brain membranes. IC50 values were measured and revealed that the D form of the amino acid moiety of the compounds was more potent than both the L form and racemic form,...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00132a004
更新日期：1989-12-01 00:00:00
abstract：:Proton magnetic spectra have been recorded for muscarine and two biologically active cyclopentane analogues. In order to observe homonuclear intramolecular nuclear Overhauser effects, the -N+(CH3)3 signal was irradiated and increases in integrated intensities for other key signals in the molecule were observed. The re...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00205a028
更新日期：1978-07-01 00:00:00
abstract：:Antitumor activity in mice was observed for the oxime of the previously reported ethyl [6-amino-4-[(1-methyl-2-phenyl-2-oxoethyl)amino]-5-nitropyridin -2-yl] carbamate (8) and several related compounds. These compounds are precursors of the active ethyl pyrido[3,4-b]pyrazin-7-ylcarbamates (e.g., 4), which are potent a...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00098a014
更新日期：1992-10-02 00:00:00
abstract：:The receptor CRM1 is responsible for the nuclear export of many tumor-suppressor proteins and viral ribonucleoproteins. This renders CRM1 an interesting target for therapeutic intervention in diverse cancer types and viral diseases. Structural studies of Saccharomyces cerevisiae CRM1 ( Sc ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.0c00143
更新日期：2020-07-23 00:00:00
abstract：:Eucalyptin A (1), together with two known compounds 2 and 3 exhibiting potent inhibition on HGF/c-Met axis, was discovered from the fruits of Eucalyptus globulus. 1 possessed an unprecedented carbon framework of phloroglucinol-coupled sesquiterpenoid, and its structure was elucidated by spectroscopic method and ECD ca...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm3007454
更新日期：2012-09-27 00:00:00
abstract：:Derivatives of benzofuran- and indole-2-sulfonamide were prepared for evaluation as topically active ocular hypotensive agents. These compounds were found to be excellent inhibitors of carbonic anhydrase and to lower intraocular pressure in a rabbit model of ocular hypertension. However, the development of these compo...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00164a045
更新日期：1990-02-01 00:00:00
abstract：:Neuroactive steroids that allosterically modulate GABAA receptors have potential uses as anticonvulsants, anxiolytics, and sedative-hypnotic agents. Recently, a series of pregnanes substituted with simple alkyl groups at the 3 beta-position were synthesized and found to be active in vitro. The present report describes...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm9605344
更新日期：1997-01-03 00:00:00
abstract：:Symmetrical and asymmetrical fluorinated phenyltriazolyl-thiodigalactoside derivatives have been synthesized and evaluated as inhibitors of galectin-1 and galectin-3. Systematic tuning of the phenyltriazolyl-thiodigalactosides' fluoro-interactions with galectin-3 led to the discovery of inhibitors with exceptional aff...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.7b01626
更新日期：2018-02-08 00:00:00
abstract：:Dihydropyrimidinones such as compound 12 exhibited high binding affinity and subtype selectivity for the cloned human alpha(1a) receptor. Systematic modifications of 12 led to identification of highly potent and subtype-selective compounds such as (+)-30 and (+)-103, with high binding affinity (K(i) = 0.2 nM) for alph...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm990200p
更新日期：1999-11-18 00:00:00
abstract：:n-Octyl, n-dodecyl, and n-hexadecyl alpha- and gamma-esters of methotrexate (MTX) were compared with the previously described alpha- and gamma-n-butyl esters and with MTX as inhibitors of dihydrofolate reductase (DHFR) and human leukemic lymphoblasts (CEM cells) in culture. The overall order of activity in both test s...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00371a009
更新日期：1984-05-01 00:00:00
abstract：:A novel, potent, and orally bioavailable inhibitor of hepatitis C RNA replication targeting NS4B, compound 4t (PTC725), has been identified through chemical optimization of the 6-(indol-2-yl)pyridine-3-sulfonamide 2 to improve DMPK and safety properties. The focus of the SAR investigations has been to identify the opt...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm401621g
更新日期：2014-03-13 00:00:00
abstract：:The proteasome plays a crucial role in degradation of normal proteins that happen to be constitutively or inducibly unstable, and in this capacity it plays a regulatory role. Additionally, it degrades abnormal/damaged/mutant/misfolded proteins, which serves a quality-control function. Inhibitors of the proteasome have...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.6b01379
更新日期：2017-02-23 00:00:00
abstract：:The EP(3) receptor on the platelet mediates prostaglandin E(2) potentiation of thrombogenic coagonists including collagen and adenosine diphosphate (ADP). A pharmacophore driven approach led to the identification of diverse peri-substituted heterocycles as potent and selective EP(3) receptor antagonists. A simultaneou...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm9005912
更新日期：2010-01-14 00:00:00
abstract：:The synthesis and in vitro structure-activity relationships (SAR) of a novel series of anilinoquinazolines as allosteric inhibitors of fructose-1,6-bisphosphatase (F16Bpase) are reported. The compounds have a different SAR as inhibitors of F16Bpase than anilinoquinazolines previously reported. Selective inhibition of ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm010496a
更新日期：2002-08-29 00:00:00
abstract：:The free fatty acid receptor 4 (FFA4 or GPR120) has appeared as an interesting potential target for the treatment of metabolic disorders. At present, most FFA4 ligands are carboxylic acids that are assumed to mimic the endogenous long-chain fatty acid agonists. Here, we report preliminary structure-activity relationsh...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.6b00685
更新日期：2016-10-13 00:00:00
abstract：:Attempts to directly drug the important oncogene KRAS have met with limited success despite numerous efforts across industry and academia. The KRASG12C mutant represents an "Achilles heel" and has recently yielded to covalent targeting with small molecules that bind the mutant cysteine and create an allosteric pocket ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.9b01720
更新日期：2020-05-14 00:00:00
abstract：:The coordination complex cyclo-tetrakis[bis(1-phenyl-3-methyl-4-benzoylpyrazolon-5-ato++ +)mu-o xotitanium(IV)] has been synthesized and characterized with IR and NMR spectroscopies and X-ray diffraction. The core of this species consists of an eight-membered Ti-mu-oxo ring with alternate short-long Ti-O bond lengths....
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm990539b
更新日期：2000-10-05 00:00:00
abstract：:Owing to the emergence of drug resistance and high morbidity and mortality, the need for novel anti-influenza A virus (IAV) drugs with divergent targets is highly sought after. Herein, we reveal the discovery of an anti-IAV agent as a dual inhibitor to block hemagglutinin-mediated adsorption and membrane fusion using ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.0c00312
更新日期：2020-07-09 00:00:00
