Abstract：
:A series of nitrocoumarin and nitrochromene derivatives have been prepared and shown to inhibit the phosphatidylinositol-specific phospholipase C(PLC)(IC50 < 10 micrograms/mL) isolated from human melanoma. The inhibition of PLC by nitrocoumarin 4a was time-dependent and irreversible. The inhibition of PLC was shown to interfere with inositide metabolism in whole cells (IC50 = 4 micrograms/mL) in a manner consistent with their proposed mode of activity. Finally, the compounds were shown to be growth inhibitory to cultured melanoma cells (ID50 = 2 micrograms/mL), suggesting that PLC may be an attractive new target for chemotherapeutic intervention.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Perrella FW,Chen SF,Behrens DL,Kaltenbach RF 3rd,Seitz SPdoi
10.1021/jm00040a016subject
Has Abstractpub_date
1994-07-08 00:00:00pages
2232-7issue
14eissn
0022-2623issn
1520-4804journal_volume
37pub_type
杂志文章abstract：:Collective experience in structure-based lead progression has found electrostatic interactions to be more difficult to optimize than shape-based ones. A major reason for this is that the net electrostatic contribution observed includes a significant nonintuitive desolvation component in addition to the more intuitive ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm051105l
更新日期：2006-04-20 00:00:00
abstract：:A new approach to rapidly score protein-ligand interactions is tested on several protein-ligand systems. Results using this approach - the OWFEG free energy grid - are quite promising and are generally in better agreement with experiment (in some cases much better) than those obtained employing scoring techniques curr...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm000375v
更新日期：2001-02-15 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...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm060887v
更新日期：2007-09-06 00:00:00
abstract：:Aminoglycosides (AGs) constitute a major family of potent and broad-spectrum antibiotics disturbing protein synthesis through binding to the A site of 16S rRNA. Decades of widespread clinical use of AGs strongly reduced their clinical efficacy through the selection of resistant bacteria. Recently, conjugation of lipop...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.6b00818
更新日期：2016-10-27 00:00:00
abstract：:Rhenium-cyclized CCMSH analogues are novel melanoma-targeting metallopeptides with high tumor uptake, long tumor retention, and low background in normal tissues, which make these metallopeptides an ideal structural motif for designing novel melanoma-targeting agents. ReCCMSH has been derivatized with a 1,4,7,10-tetraa...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm010408m
更新日期：2002-07-04 00:00:00
abstract：:A series of novel cephalosporin compounds which have 3-[(aminopyrimidiniumyl)thio]methyl substituents was synthesized. They show high antimicrobial activity against various bacterial species including Pseudomonas aeruginosa. Structure-activity relationships with various thiopyrimidines, thiopyrimidiniums, bicyclic thi...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00048a018
更新日期：1994-10-28 00:00:00
abstract：:On the basis of the structures of several potent inhibitor molecules for gamma-aminobutryric acid aminotransferase (GABA-AT) that were previously reported, six modified fluorine-containing conformationally restricted analogues were designed, synthesized, and tested as GABA-AT inhibitors. The syntheses of all six molec...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm0608715
更新日期：2006-12-14 00:00:00
abstract：:Early studies in these laboratories of peptidomimetic structures containing a basic P1 moiety led to the highly potent and selective thrombin inhibitors 2 (Ki = 5.0 nM) and 3 (Ki = 0.1 nM). However, neither attains significant blood levels upon oral administration to rats and dogs. With the aim of improving pharmacoki...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm9705014
更新日期：1998-01-29 00:00:00
abstract：:Avermectins A2a, B1a, and B2a (1, 2, and 3) were acetylated to give 4"- and 23-acetates 4 and 5 and 4",23-diacetate 6 from 1, the 4"-and 5-acetates 7 and 8 and 4",5-diacetate 9 from 2, and triacetate 10 from 3. Structure proof by 300-MHz 1H NMR and mass spectral fragmentation is discussed for 10. Forcing acetylation c...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00348a010
更新日期：1982-06-01 00:00:00
abstract：:Nitrosourea derivatives 9--13 which utilize phensuximide (1) as the carrier were synthesized as potential central nervous system antitumor agents. The N-(2-chloroethyl)-N-nitrosourea 13 was active in the mouse ependymoblastoma brain-tumor system, as well as the intraperitoneal L1210 leukemia system. ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00177a024
更新日期：1980-03-01 00:00:00
abstract：:(E)-3-[[[[6-(2-Carboxyethenyl)-5-[[8-(4- methoxyphenyl)octyl]oxy]-2-pyridinyl]methyl]thio]methyl]benzoic acid (11, SB 201993) is a novel, potent LTB4 receptor antagonist. Compound 11 arose from a structure-activity study of a series of trisubstituted pyridines that demonstrated LTB4 receptor antagonist activity. The p...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00046a017
更新日期：1994-09-30 00:00:00
abstract：:Targeting of DNA secondary structures, such as G-quadruplexes, is now considered an appealing opportunity for drug intervention in anticancer therapy. So far, efforts made in the discovery of chemotypes able to target G-quadruplexes mainly succeeded in the identification of a number of polyaromatic compounds featuring...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm301019w
更新日期：2012-11-26 00:00:00
abstract：:Members of a series of basic amide and ester derivatives of 2-substituted pyrido[2,1-b]quinazoline-8-carboxylic acids were prepared and evaluated for their ability to prevent slow-reacting substance of anaphylaxis (SRS-A) induced contractions of guinea pig ilea. The results indicate that the presence of a branched-cha...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00365a016
更新日期：1983-11-01 00:00:00
abstract：:We describe here the syntheses and the biological properties of new alkylaminooxysterols. Compounds were synthesized through the trans-diaxial aminolysis of 5,6-alpha-epoxysterols with various natural amines including histamine, putrescine, spermidine, or spermine. The regioselective synthesis of these 16 new 5alpha-h...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm901063e
更新日期：2009-12-10 00:00:00
abstract：:Cell division cycle 25 (Cdc25) proteins are highly conserved dual specificity phosphatases that regulate cyclin-dependent kinases and represent attractive drug targets for anticancer therapies. To discover more potent and diverse inhibitors of Cdc25 biological activity, virtual screening was performed by docking 2.1 m...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm201624h
更新日期：2012-05-10 00:00:00
abstract：:To design and synthesize new potent and selective antagonists of the human A(3) adenosine receptor, pharmacophoric hypotheses were generated with the software Catalyst for a comprehensive set of compounds retrieved from previous literature. Three of these pharmacophores were used to drive the optimization of a molecul...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm051112+
更新日期：2006-07-13 00:00:00
abstract：:(E)-5-(2-Bromovinyl)-2'-deoxy-5'-O-(3-methyl-2-oxo-5-formyl-1,3,2- oxazaphosphacyclopentan-2-yl)uridine has been synthesized and, under physiological conditions and without the necessity for enzyme activity, has been shown to yield the 5'-nucleotide in vitro. Unfortunately this compound is not sufficiently stable in s...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00171a009
更新日期：1990-09-01 00:00:00
abstract：:Ligands from the naltrexamine series have consistently demonstrated agonist activity at kappa opioid receptors (KOR), with varying activity at the mu opioid receptor (MOR). Various 6 beta-cinnamoylamino derivatives were made with the aim of generating ligands with a KOR agonist/MOR partial agonist profile, as ligands ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm8015552
更新日期：2009-03-26 00:00:00
abstract：:The intense intrinsic fluorescence emissions from several clinically relevant camptothecin drugs have been exploited in order to study the structural basis of drug binding to human serum albumin. Both HPLC and time-resolved fluorescence spectroscopic methodologies were employed to characterize the associations of camp...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00027a005
更新日期：1994-01-07 00:00:00
abstract：:Mechanism-based inhibitors of human cytomegalovirus (HCMV) protease have been designed based on the pyrrolidine-5,5-trans-lactam ring system. New routes to the beta-methyl-, desmethyl-, and alpha-methyl-pyrrolidine-5,5-trans-lactam templates have been developed from 2,4-diaminobutyric acid. ESI/MS studies have shown t...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm000078q
更新日期：2000-11-16 00:00:00
abstract：:A series of 1,2,4-oxadiazoles has been prepared as ester bioisosteres and tested against 15 human rhinovirus serotypes, and the MIC80, the concentration which inhibits 80% or 12 of the serotypes tested, was determined. Homologation of the alkyl group attached to the oxadiazole ring resulted in a reduction in activity ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00041a022
更新日期：1994-07-22 00:00:00
abstract：:A series of 62 diarylamidine derivatives was evaluated for their antiproteolytic activity. In all but two of the compounds one or both of the amidino-substituted aryl moieties was either an indole or an indole-like ring. The latter included indene, benzimidazole, benzofuran, benzol[beta]thiophene, and several other re...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00205a005
更新日期：1978-07-01 00:00:00
abstract：:Alpha-galactoglycosphingolipids (alpha-GalGSLs) are unique immunostimulatory glycosphingolipids from marine sponges. Analysis of the glycosphingolipid composition of the marine sponge Axinella damicornis revealed the presence of a new alpha-GalGSL, damicoside (3a), which is the first alpha-GalGSL with a glycosylated g...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm050506y
更新日期：2005-11-17 00:00:00
abstract：:The clinical antileukemic drug amsacrine and analogues are thought to exert their biological activity by binding tightly but reversibly to DNA, with the acridine chromophore intercalated and the anilino group making additional binding contact in the minor groove of the double helix. In this binding model the steric en...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00365a014
更新日期：1983-11-01 00:00:00
abstract：:P2X receptor activation protects in heart failure models. MRS2339 3, a 2-chloro-AMP derivative containing a (N)-methanocarba (bicyclo[3.1.0]hexane) system, activates this cardioprotective channel. Michaelis-Arbuzov and Wittig reactions provided phosphonate analogues of 3, expected to be stable in vivo due to the C-P b...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm9018542
更新日期：2010-03-25 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：:We have previously identified phenylguanidine and phenyl-2-aminoimidazoline compounds as high affinity ligands with conflicting functional activity at the α2-adrenoceptor, a G-protein-coupled receptor with relevance in several neuropsychiatric conditions. In this paper we describe the design, synthesis, and pharmacolo...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm501635e
更新日期：2015-01-22 00:00:00
abstract：:We previously reported that [[N-[3beta-hydroxyllup-20(29)-en-28-oyl]-7-aminoheptyl]carbamoyl]methane (A43D, 4) was a potent HIV-1 entry inhibitor. However, 4 was inactive against HIV-2 virus, suggesting the structural requirements for targeting these two retroviruses are different. In this study, a series of new betul...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm9004253
更新日期：2009-12-10 00:00:00
abstract：:Structure-activity relationship studies of substituted arylsulfoanilides as antiproliferatives, which are mediated by the partial depletion of intracellular Ca(2+) stores, resulted in the identification of compounds with micromolar activity against lung cancer cells in a growth inhibition assay. Incorporating the subs...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm0496234
更新日期：2004-10-07 00:00:00
abstract：:The simulated binding profiles of acetylcholine, ACh, and the inhibitor (+/-)-2,3-dihydro-5,6- dimethoxy-2-[[1-(phenylmethyl)-4-piperidinyl]methyl]-1H-inden-1-on e hydrochloride (E2020), 1, and some of its analogs to acetylcholinesterase, AChE, were determined using full force field energetics and allowing complete co...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm950596e
更新日期：1996-10-25 00:00:00
