Abstract：
:The arachidonic acid metabolizing enzymes cyclooxygenase-2 (COX-2) and lipoxygenases (LOXs) have been found to be implicated in a variety of cancers, including prostate cancer. To develop new therapeutic treatments, it therefore seemed interesting to design dual COX-2/5-LOX inhibitors. We report here the synthesis and in vitro pharmacological properties of diarylpyrazole derivatives that have in their structure key pharmacophoric elements to obtain optimal interaction with subsites of active pockets in both enzyme systems. Using a molecular modeling approach, a set of SAR data is proposed, highlighting the importance of the sulfonyl group of one of the aryl moieties in terms of proliferation inhibition and/or apoptosis induction.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Pommery N,Taverne T,Telliez A,Goossens L,Charlier C,Pommery J,Goossens JF,Houssin R,Durant F,Hénichart JPdoi
10.1021/jm0407761keywords:
subject
Has Abstractpub_date
2004-12-02 00:00:00pages
6195-206issue
25eissn
0022-2623issn
1520-4804journal_volume
47pub_type
杂志文章abstract：:Thalidomide, 2-(2,6-dioxo-3-piperidinyl)-1H-isoindole-1,3(2H)-dione, has been shown to inhibit angiogenesis, the formation of new blood vessels from existing vasculature. As a result, there is renewed interest in this drug as a potential therapy for solid tumors. Thalidomide forms a number of metabolites and has been ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm0304820
更新日期：2004-04-22 00:00:00
abstract：:A number of derivatives of 4-amino-6-hydroxy-2-mercaptopyrimidine ( 5) were synthesized and biologically evaluated as A 3 adenosine receptor (A 3 AR) antagonists. The new compounds were designed as open chain analogues of a triazolopyrimidinone derivative displaying submicromolar affinity for the A 3 AR, which had bee...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm701159t
更新日期：2008-03-27 00:00:00
abstract：:Glucose flux through glucokinase (GK) controls insulin release from the pancreas in response to high glucose concentrations. Glucose flux through GK also contributes to reducing hepatic glucose output. Because many individuals with type 2 diabetes appear to have an inadequacy or defect in one or both of these processe...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm401116k
更新日期：2013-10-10 00:00:00
abstract：:Analogues of nicotinic acid adenine dinucleotide phosphate (NAADP) with substitution at either the 4- or the 5-position position of the nicotinic acid moiety have been synthesized from NADP enzymatically using Aplysia californica ADP-ribosyl cyclase or mammalian NAD glycohydrolase. Substitution at the 4-position of th...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm1007209
更新日期：2010-11-11 00:00:00
abstract：:N-Acyl amino acids directly bind mitochondria and function as endogenous uncouplers of UCP1-independent respiration. We found that administration of N-acyl amino acids to mice improves glucose homeostasis and increases energy expenditure, indicating that this pathway might be useful for treating obesity and associated...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.8b00029
更新日期：2018-04-12 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：:[4-Phenylalanine]oxytocin was prepared from Z-Cys(Bzl)-Tyr(Bzl)-Ile-Phe-Asn-Cys(Bzl)-Pro-Leu-Gly-NG2 (4) by deprotection with Na in NH3 followed by cyclization of the resulting disulfhydryl compound with ICH2CH2I. The protected peptide 4 was prepared from Boc-Asn-Cys(Bzl)-Pro-Leu-Gly-NH2 by the stepwise solution metho...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00244a014
更新日期：1975-10-01 00:00:00
abstract：:The sequence and configuration of amino acids in the cytostatic cyclic tetrapeptide WF-3161 are established as cyclo(L-Leu-L-Pip-L-Aoe-D-Phe) where Pip = pipecolic acid and Aoe = 2-amino-8-oxo-9,10-epoxydecanoic acid. In chloroform, WF-3161 adopts a conformation with a possible gamma-turn between Leu NH and Aoe C = O ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00161a046
更新日期：1986-11-01 00:00:00
abstract：:The potency of second generation antisense oligonucleotides (ASOs) in animals was increased 3- to 5 -fold (ED(50) approximately 2-5 mg/kg) without producing hepatotoxicity, by reducing ASO length (20-mer to 14-mer) and by employing novel nucleoside modifications that combine structural elements of 2'-O-methoxyethyl re...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm801294h
更新日期：2009-01-08 00:00:00
abstract：:1-(2-Phenoxyethyl)-1H-imidazole was found to be an inhibitor of thromboxane (TxA2) synthetase, but it also inhibited the adrenal cytochrome P-450 enzyme steroid 11 beta-hydroxylase. The preparation of a series of analogues is described, and activity against TxA2 synthetase, PGI2 synthetase, cyclooxygenase, and steroid...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00148a009
更新日期：1985-10-01 00:00:00
abstract：:Privileged structures are ligand substructures that are widely used to generate high-affinity ligands for more than one type of receptor. To explain this, we surmised that there must be some common feature in the target proteins. For a set of class A GPCRs, we found a good correlation between conservation patterns of ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm0309452
更新日期：2004-02-12 00:00:00
abstract：:The synthesis of chiral 1,5-benzothiazepines 2a-c, 14a-c, 15c, and 16a prepared from cysteine is described. In vitro inhibition of angiotensin converting enzyme (ACE) is reported for each compound. Compound 2c was the most potent in vitro having an IC50 of 2.95 nM. The ester of 2c, i.e. 14c, was found to inhibit the A...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00148a024
更新日期：1985-10-01 00:00:00
abstract：:Two products without phosphoryl groups, 1-O-octadecyl-2-O-acetyl-3-O-[gamma-(dimethylamino)propyl]glycerol and its quaternary salt, were synthesized from 1-O-octadecyl-2-O-benzylglycerol. In comparison with PAF-acether, they lost aggregating and bronchoconstrictive activities and did not show any antagonistic effects....
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00146a019
更新日期：1985-08-01 00:00:00
abstract：:Glycosylation of ethyl 3(5)-(bromomethyl)pyrazole-5(3)-carboxylate (3) and 3(5)-(bromomethyl)pyrazole-5(3)-carboxamide (4) with poly-O-acetylated sugars via an acid-catalyzed fusion method afforded the corresponding ethyl 3-(bromomethyl)pyrazole-5-carboxylate and 3-(bromomethyl)pyrazole-5-carboxamide substituted nucle...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00193a011
更新日期：1979-07-01 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：:All three amino-substituted 3-beta-D-ribofuranosyl-1,2,4-triazolo[4,3-b]pyridazines (5, 19, and 20) structurally related to formycin A were prepared and tested for their antitumor and antiviral activity in cell culture. Dehydrative coupling of 4-amino-5-chloro-3-hydrazinopyridazine (7) with 3,4,6-tri-O-benzoyl-2,5-anh...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00127a024
更新日期：1989-07-01 00:00:00
abstract：:The synthesis of water-soluble, unsymmetrical, trisulfonated zinc phthalocyanines (ZnPcS3) as single products of the ring expansion of boron tri(4-sulfo)subphthalocyanine (SubPc) is reported. The novel, water-soluble trisulfo-SubPcB(OH) was prepared via hydrolysis of the tris(4-chlorosulfonyl)SubPcB(Br) which in turn ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm9702488
更新日期：1997-11-21 00:00:00
abstract：:Esophageal adenocarcinoma (EAC) is a molecularly heterogeneous disease that is rising rapidly in incidence and has poor prognosis. We developed a heterobivalent peptide to target detection of early Barrett's neoplasia by combining monomer heptapeptides specific for either EGFR or ErbB2 in a heterodimer configuration. ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.8b00405
更新日期：2018-06-28 00:00:00
abstract：:The paullones represent a novel class of small molecule cyclin-dependent kinase (CDK) inhibitors. To investigate structure-activity relationships and to develop paullones with antitumor activity, derivatives of the lead structure kenpaullone (9-bromo-7,12-dihydroindolo[3,2-d][1]benzazepin-6(5H)-one, 4a) were synthesiz...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm9900570
更新日期：1999-07-29 00:00:00
abstract：:Potential E- and P-selectin inhibitors were synthesized to explore a hydrophobic area on the E-selectin surface and the PSGL-1 protein binding site on the P-selectin surface that was recently defined by crystallography. Three series of mannose-based compounds (libraries A, B, and C) were synthesized using solution pha...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm010390f
更新日期：2002-04-11 00:00:00
abstract：:A series of tetramisole derivatives was synthesized and tested for inhibitory activity against alkaline phosphatase which was partially purified from a murine ascitic neoplasm resistant to 6-thiopurines (Sarcoma 180/TG). These agents included derivatives substituted with halogens, CH3, or NO2 groups at either the meta...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00214a021
更新日期：1977-04-01 00:00:00
abstract：:Tyrosine kinases often play pivotal roles in the pathogenesis of cancer and are good candidates for therapeutic intervention and targeted molecular imaging. The precursor synthesis, radiosynthesis, and biological characterization of a fluorine-18 analog of dasatinib, a multitargeted kinase inhibitor, are reported. Com...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm070342g
更新日期：2007-11-15 00:00:00
abstract：:2-Phenylpyrroles were synthesized as conformationally restricted analogues of the substituted benzamide sultopride and the butyrophenones haloperidol and fluanisone. Dopamine antagonistic activity is maintained if the 2-phenylpyrrole side chain is linked to the pharmacophoric N-ethylpyrrolidine moiety of sultopride or...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00394a028
更新日期：1987-11-01 00:00:00
abstract：:Group VIA calcium-independent phospholipase A(2) (GVIA iPLA(2)) has recently emerged as a novel pharmaceutical target. We have now explored the structure-activity relationship between fluoroketones and GVIA iPLA(2) inhibition. The presence of a naphthyl group proved to be of paramount importance. 1,1,1-Trifluoro-6-(na...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm901872v
更新日期：2010-05-13 00:00:00
abstract：:2,6,8-Trichloro-7-methylpurine (3) was converted to 2-chloro-8,9-dihydro-7-methyl-8-thioxopurin-6(1H)-one (5) by utilizing the difference in reactivity of the 2-, 6-, and 8-positions in the trichloropurine ring system to nucleophilic displacement. Compound 5 was subsequently glycosylated with 1-O-acetyl-2,3,5-tri-O-be...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00170a013
更新日期：1990-08-01 00:00:00
abstract：:Small-molecule fluorescence imaging in the second near-infrared (NIR-II, 1000-1700 nm) window has gained increasing interest in clinical application. Till now, very few studies have been exploited in the small-molecule fluorophores with both excitation and emission in the NIR-II window. Inspired by the indocyanine gre...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.8b01682
更新日期：2019-02-28 00:00:00
abstract：:2,5-Bis(4-guanylphenyl)-1,3-oxazole, 2,5-bis(4-guanylphenyl)-1,3,4-oxadiazole and -1,3,4-thiadiazole, and 3,6-bis(4-guanylphenyl)pyridazine and several of their "cyclic guanyl" analogues have been synthesized. 2,5-Bis(4-guanylphenyl)-1,3-oxazole and -1,3,4-thiadiazole showed good activity, whithout acute toxicity, aga...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00179a022
更新日期：1980-05-01 00:00:00
abstract：:The enantiomers of the aminothiazole analogues of the known dopaminergic agonists apomorphine (1) and 2-aminohydroxytetralin (2) have been prepared. The absolute configurations of the enantiomers of 2,6-diaminotetrahydrobenzothiazole have been established by X-ray crystallographic analysis. Dopamine (DA) autoreceptor ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00386a009
更新日期：1987-03-01 00:00:00
abstract：:A variety of 2,3-disubstituted 5,7-dimethyl-1,8-naphthyridines was synthesized and tested in saline-loaded rats for their diuretic properties. The 2-amino-3-carbomethoxy and four 2-amino-3-N-alkylcarbamoyl compounds exhibited significant activity as measured by volume output; however, they were generally less potent t...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00216a021
更新日期：1977-06-01 00:00:00
abstract：:A new computational method for the in situ generation of small molecules within the binding site of a protein is described. The method has been evaluated using two well-studied systems, dihydrofolate reductase and thymidylate synthase. The method has also been used to guide improvements to inhibitors of HIV-1 protease...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00003a010
更新日期：1995-02-03 00:00:00
