Abstract：
:In this paper we report the systematic search for new, potent, and selective DPP II inhibitors. A study of the structure-activity relationship was conducted starting from aminoacyl pyrrolidides as lead compounds. Rational exploration of the P(1) and P(2) building blocks led to the discovery of some very potent DPP II inhibitors which can be characterized by their high selectivity for DPP II with regard to DPP IV. Dab-Pip and Dab-Pip-2-CN were selected as the most promising inhibitors (IC(50) nM range) and will enable us to study the physiological role of DPP II and to differentiate between DPP II and DPP IV in biological systems.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Senten K,Van der Veken P,De Meester I,Lambeir AM,Scharpé S,Haemers A,Augustyns Kdoi
10.1021/jm0308803keywords:
subject
Has Abstractpub_date
2003-11-06 00:00:00pages
5005-14issue
23eissn
0022-2623issn
1520-4804journal_volume
46pub_type
杂志文章abstract：:Fragment-based lead discovery has over the years matured into an attractive alternative to high-throughput screening (HTS) for lead generation. Several techniques for screening libraries of typically 10(3)-10(4) fragments have been reported. In this work, the practical success rates that can be expected from the scree...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm0700316
更新日期：2007-07-12 00:00:00
abstract：:The quinazoline class was exploited to search for a new translocator protein (TSPO) fluorescent probe endowed with improved affinity and residence time (RT). Computational studies on an "in-house" collection of quinazoline derivatives, featuring highly steric demanding groups at the amide nitrogen, suggested that, des...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.7b01031
更新日期：2017-09-28 00:00:00
abstract：:An approach to the development of new anticandidal drugs is described that employs peptides as carriers of toxic agents into cells. 5-Flurorcytosine (5-FC) was chosen as a toxic agent with which to prepare 5-FC-peptide conjugates as models to test the carrier proposal. Model compounds were synthesized and then tested ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00195a019
更新日期：1979-09-01 00:00:00
abstract：:Basic side chains determine the pharmacology of selective estrogen receptor modulators such as tamoxifen or raloxifene. In this study we tried to turn the hormonal profile of (4R,5S)/(4S,5R)-4,5-bis(4-hydroxyphenyl)-2-imidazolines from agonistic to antagonistic by introduction of a dimethylaminoethane, a piperidin-1-y...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm040855c
更新日期：2005-01-27 00:00:00
abstract：:The pathology of chronic dermal ulcers is characterized by excessive proteolytic activity which degrades extracellular matrix (required for cell migration) and growth factors and their receptors. The overexpression of MMP-3 (stromelysin-1) and MMP-13 (collagenase-3) is associated with nonhealing wounds, whereas active...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm0308038
更新日期：2003-07-31 00:00:00
abstract：:LTX 109 is a synthetic antimicrobial peptidomimetic (SAMP) currently in clinical phase II trials for topical treatment of infections of multiresistant bacterial strains. All possible eight stereoisomers of the peptidomimetic have been synthesized and tested for antimicrobial effect, hemolysis, and hydrophobicity, reve...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm200450h
更新日期：2011-08-25 00:00:00
abstract：:The synthesis and sigma 1 and sigma 2 binding properties of several (+)- and (-)-2-benzyl- and 2-dimethylallyl-2'-substituted-5,9 alpha-dimethyl-6,7-benzomorphans (3 and 4) are presented. In agreement with previously reported binding data for 2-substituted 5,9 alpha-dimethyl-2'-hydroxy-6,7-benzomorphans (N-substituted...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00015a022
更新日期：1995-07-21 00:00:00
abstract：:In colorectal cancer, adenomatous polyposis coli (APC) interacts with Rho guanine-nucleotide-exchange factor 4 (Asef), thereby stimulating aberrant colorectal-cancer-cell migration. Consequently, the APC-Asef interaction represents a promising therapeutic target for mitigating colorectal-cancer migration. In this stud...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.8b01112
更新日期：2018-09-13 00:00:00
abstract：:A series of analogues of streptonigrin, in which the quinoline of ring B is replaced by isoquinoline and the substituted pyridine of ring C is replaced by phenyl, nitrophenyl, aminophenyl, or benzyl functions, have been prepared. Thus, 1-substituted isoquinoline-5,8-diones with 7-amino or 6-(alkylamino) groups were pr...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00110a018
更新日期：1991-06-01 00:00:00
abstract：:Several derivatives of erythro-beta-hydroxy-DL-aspartic acid (1) were prepared as a potential inhibitors of L-asparagine synthetase (ASase) from rat Novikoff hepatoma. Benzylation of 1 gave the dibenzyl ester 2 which upon coupling with carbobenzoxyglycine afforded the blocked dipeptide 3. Deblocking of 3 gave glycl-er...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00238a006
更新日期：1975-04-01 00:00:00
abstract：:In pursuit of truncated glucagon analogues that can interact with the glucagon receptor with substantial binding affinity, 23 truncated glucagon analogues have been designed and synthesized. These truncated analogues consist of several fragments of glucagon with 11 or 12 amino acid residues (1-4), conformationally con...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm000453e
更新日期：2001-04-26 00:00:00
abstract：:The endocannabinoid 2-arachidonoylglycerol (2-AG) plays a major role in many physiological processes, and its action is quickly terminated via enzymatic hydrolysis catalyzed by monoglyceride lipase (MGL). Regulating its endogenous level could offer therapeutic opportunities; however, few selective MGL inhibitors have ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm900461w
更新日期：2009-12-10 00:00:00
abstract：:A series of indolequinones bearing various functional groups has been synthesized, and the effects of substituents on the metabolism of the quinones by recombinant human NAD(P)H:quinone oxidoreductase (NQO1) were studied. Indolequinones were selected for study on the basis of the X-ray crystal structure of the human e...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm010884c
更新日期：2001-09-27 00:00:00
abstract：:125I-labeled (E)-18-iodo-17-octadecenoic acid (13) has been prepared and evaluated in rats to determine the myocardial uptake and retention and degree of in vivo deiodination of this model iodovinyl-substituted fatty acid, which contains no structural perturbation to inhibit metabolism. This new agent was prepared by ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00367a021
更新日期：1984-01-01 00:00:00
abstract：:A library of approximately 2000 small molecules biased toward inhibition of histone deacetylases was assayed for antimalarial activity in a high-throughput P. falciparum viability assay. Active compounds were cross-analyzed for induction of histone hyperacetylation in a human myeloma cell line to identify HDAC inhibit...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm801654y
更新日期：2009-04-23 00:00:00
abstract：:Extension of the structure-activity relationship studies that led to the discovery of the nonsedating potent muscle relaxant, antiinflammatory, and analgesic agent (E)-2-(4,6-difluoro-1-indanylidene)acetamide, 1, has given rise to (E)-2-(4-chloro-6-fluoro-1-indanylidene)-N-methylacetamide, 2. Compound 2 is a potent an...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm020068k
更新日期：2003-01-30 00:00:00
abstract：:The results of a high-throughput screening assay using the DENV-2 replicon showed that the 2,4-diaminoquinazoline derivative 4a has a high dengue virus inhibitory activity (EC(50) = 0.15 μM). A series of 2,4-diaminoquinazoline derivatives based on 4a as a lead compound were synthesized and subjected to structure-antid...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm2015952
更新日期：2012-04-12 00:00:00
abstract：:Peptide modification with fatty acids is an effective method to improve peptide performance. We previously investigated the fatty acid modification of R-lycosin-I, a cytotoxic peptide derived from lycosin-I from the venom of the spider Lycosa singoriensis. In this study, we further investigated the position effects of...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.9b01126
更新日期：2019-12-26 00:00:00
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...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00040a016
更新日期：1994-07-08 00:00:00
abstract：:We have rationally designed a sLe(x) mimetic based on molecular modeling, synthesized type II and type II' beta-turn dipeptides (3a,b), and evaluated their biological profiles both in vitro and in vivo. Against E-selectin-sLe(x) binding, the type II beta-turn dipeptide L-Ser-D-Glu 3a (IC50, 13 microM) and the type II'...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm970262k
更新日期：1997-10-24 00:00:00
abstract：:A series of 2,2-dimethyl-3,3-diphenyl-propanamides as novel glucocorticoid receptor modulators is reported. SAR exploration led to the identification of 4-hydroxyphenyl propanamide derivatives displaying good agonist activity in GR-mediated transrepression assays and reduced agonist activity in GR-mediated transactiva...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm100957a
更新日期：2010-12-09 00:00:00
abstract：:Dicarba analogues of the cyclic opioid peptides H-Tyr-c[d-Cys-Gly-Phe-d(or l)-Cys]NH2 were synthesized on solid phase by substituting allylglycines for the cysteines and cyclization by ring-closing metathesis between the side chains of the allylglycine residues. Mixtures of cis and trans isomers of the resulting olefi...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm061294n
更新日期：2007-03-22 00:00:00
abstract：:Cancer cells have high-affinity polyamine uptake systems with a low stringency for structural features. Putrescine, spermidine, and spermine have, therefore, been considered as potential vectors for the selective accumulation in tumors of therapeutically or diagnostically useful structures and elements. We envisaged N...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm010897q
更新日期：2001-10-25 00:00:00
abstract：:Hydroxylated, methoxylated, and/or chlorinated 7-methyl-5,6,7,8,9,14-hexahydrodibenz[d,g]azecines were generally synthesized out of substituted 2-phenylethylamines and isochromanones by Bischler-Napieralski cyclization of the resulting benzamides to dibenzoquinolizines and the quaternization and cleavage of the centra...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm051237e
更新日期：2006-03-23 00:00:00
abstract：:Bufotenine (5-hydroxy-N,N-dimethyltryptamine) has been reported to be behaviorally inactive or only very weakly active in man and animals; this may be a consequence of its low partition coefficient and resultant inability to penetrate the blood--brain barrier. The acetyl, propionyl, butyryl, isobutyryl, and pivalyl es...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00197a025
更新日期：1979-11-01 00:00:00
abstract：:Cdc7 serine/threonine kinase is a key regulator of DNA synthesis in eukaryotic organisms. Cdc7 inhibition through siRNA or prototype small molecules causes p53 independent apoptosis in tumor cells while reversibly arresting cell cycle progression in primary fibroblasts. This implies that Cdc7 kinase could be considere...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm100504d
更新日期：2010-10-28 00:00:00
abstract：:The weak antiallergic activity of 6-methyl-4-oxo-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidine-3-carbox yli c acid (1) in the rat reaginic passive cutaneous anaphylaxis test was enhanced by the introduction of an (arylamino)methylene moiety into position 9 of the pyridopyrimidine ring. Compound 34, (+)-6(S)-methyl-9-[...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00376a003
更新日期：1984-10-01 00:00:00
abstract：:Irreversible EGFR inhibitors can circumvent acquired resistance to first-generation reversible, ATP-competitive inhibitors in the treatment of non-small-cell lung cancer. They contain both a driver group, which assures target recognition, and a warhead, generally an acrylamide or propargylamide fragment that binds cov...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm901558p
更新日期：2010-03-11 00:00:00
abstract：:The synthesis and biological evaluation of a series of 2-substituted 5-phenyl-1,4-benzodiazepines, structurally related to tifluadom (5), the only benzodiazepine that acts simultaneously as a kappa-opioid agonist and a cholecystokinin-A (CCK-A) antagonist, are reported. The radioligand binding models used in these stu...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm950423p
更新日期：1996-02-16 00:00:00
abstract：:In an effort to identify selective ligands for the estrogen receptor subtype ERbeta, a series of aryl benzthiophenes was synthesized. In a radioligand binding assay and reporter gene assays in HeLa and SH-SY5Y cells, compounds were characterized as ERbeta-selective agonists. By targeting ERbeta in the brain, these com...
journal_title：Journal of medicinal chemistry
pub_type： 信件
doi：10.1021/jm015577l
更新日期：2002-03-28 00:00:00
