Abstract：
:2-Aminopyridine-3,5-dicarbonitrile compounds were previously identified as mimetics of dominant-negative prion protein mutants and inhibit prion replication in cultured cells. Here, we report findings from a comprehensive structure-activity relationship study of the 6-aminopyridine-3,5-dicarbonitrile scaffold. We identify compounds with significantly improved bioactivity (approximately 40-fold) against replication of the infectious prion isoform (PrPSc) and suitable pharmacokinetic profiles to warrant evaluation in animal models of prion disease.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
May BC,Zorn JA,Witkop J,Sherrill J,Wallace AC,Legname G,Prusiner SB,Cohen FEdoi
10.1021/jm061045zsubject
Has Abstractpub_date
2007-01-11 00:00:00pages
65-73issue
1eissn
0022-2623issn
1520-4804journal_volume
50pub_type
杂志文章abstract：:Plasmodium falciparum lactate dehydrogenase (pfLDH) is a key enzyme for energy generation of malarial parasites and is a potential antimalarial chemotherapeutic target. It is known that the oxamate moiety, a pyruvate analog, alone shows higher inhibition against pfLDH than human LDHs, suggesting that it can be used fo...
journal_title：Journal of medicinal chemistry
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abstract：:The iodinated analogue of 1-[2-(4-aminophenyl)ethyl]-4-[3-(trifluoromethyl)phenyl]piperazine (PAPP), IPAPP (4), and the corresponding azido compound azido-IPAPP (5) were synthesized. The corresponding no-carrier-added 125I (T1/2 = 60 days, 35-60 keV) labeled compounds were also prepared. High specific binding was obse...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00123a006
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abstract：:Homologous recombination repair (HRR), a crucial approach in DNA damage repair, is an attractive target in cancer therapy and drug design. The Bloom syndrome protein (BLM) is a 3'-5' DNA helicase that performs an important role in HRR regulation. However, limited studies about BLM inhibitors and their biological effec...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.9b00083
更新日期：2019-03-28 00:00:00
abstract：:Selectively substituted hydantoins 1 (15 examples), 4-hydroxy-2-imidazolidinones 2 (13 examples), 2-imidazolones 3 (10 examples), 2-imidazolidinones 4 (four examples), vicinal diamines 5 (two examples), and simple amino acid derivatives 6 (four examples) have been prepared and evaluated in the maximal electroshock sei...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm50001a012
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abstract：:Thirteen newly synthesized or resynthesized diamine-platinum(II) complexes were characterized, and their cytotoxic activities (IC50) were tested on parental and resistant ovarian cancer cell lines. They represent models of conjugates between biologically active vectors and cytotoxic Pt(II) moieties within the "drug ta...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm049508t
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abstract：:A combination of molecular modeling and structure-activity relationship studies has been used to fine-tune CB2 selectivity in the chromenopyrazole ring, a versatile CB1/CB2 cannabinoid scaffold. Thus, a series of 36 new derivatives covering a wide range of structural diversity has been synthesized, and docking studies...
journal_title：Journal of medicinal chemistry
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pub_type： 杂志文章
doi：10.1021/jm990462r
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doi：10.1021/jm00227a005
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journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
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更新日期：2007-12-27 00:00:00
abstract：:Recent studies have indicated several therapeutic applications for delta opioid agonists and antagonists. To exploit the therapeutic potential of delta opioids developing a structural basis for the activity of ligands at the delta opioid receptor is essential. The conformationally sampled pharmacophore (CSP) method (B...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm0612463
更新日期：2007-04-19 00:00:00
abstract：:The adenosine antagonist 9-chloro-2-(2-furanyl)[1,2,4]triazolo[1,5-c]quinazolin-5-amine (CGS15943) binds to human A3 receptors with high affinity (Ki = 14 nM), while it lacks affinity at rat A3 receptors. Acylated derivatives of the 5-amino group and other modifications were prepared in an effort to provide A3 subtype...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm960482i
更新日期：1996-10-11 00:00:00
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journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm5007947
更新日期：2014-07-24 00:00:00
abstract：:Bioorthogonal chemistry has become one of the main driving forces in current chemical biology, inspiring the search for novel biocompatible chemospecific reactions for the past decade. Alongside the well-established labeling strategies that originated the bioorthogonal paradigm, we have recently proposed the use of he...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm500531z
更新日期：2014-06-26 00:00:00
abstract：:A group of compounds, structurally related to metoprolol, in which the aromatic nucleus is formally moved stepwise away from the ethanolamine side chain, has been studied as adrenergic agonists and antagonists. All the compounds were active on the adrenergic receptors and showed similar affinity for the receptor regar...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00136a014
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abstract：:A series of N-(cyclopropylmethyl)-14 beta-substituted-normorphine analogues was synthesized and tested for opioid agonist and antagonist activity in the guinea pig ileum and mouse vas deferens preparations. The 14 beta-bromo compound proved to be a pure antagonist equal in potency to naloxone in the guinea pig ileum a...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00134a018
更新日期：1981-02-01 00:00:00
abstract：:The pyridine C-nucleosides 5-beta-D-ribofuranosylnicotinamide and its N-methylpyridinium derivative (1 and 2), which are isosteric and isoelectronic, respectively, to nicotinamide nucleoside were synthesized. Condensation of 3-bromo-5-lithiopyridine with 2,4:3,5-di-O-benzylidene-D-aldehydoribose (7) afforded an allo/a...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00388a030
更新日期：1987-05-01 00:00:00
abstract：:The potent inhibitory activity of novel 2-benzyltetralone and 2-benzylidenetetralone derivatives vs liver microsomal retinoic acid metabolizing enzymes and a MCF-7 CYP26A1 cell assay is described. In the liver microsomal assay, the 2-biphenylmethyl-6-hydroxytetralone derivatives 16a and 16b were found to be potent inh...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm0501681
更新日期：2005-11-17 00:00:00
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journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00147a027
更新日期：1985-09-01 00:00:00
abstract：:It is common practice to calculate large numbers of molecular descriptors, apply variable selection procedures to reduce the numbers, and then construct multiple linear regression (MLR) models with biological activity. The significance of these models is judged using the usual statistical tests. Unfortunately, these t...
journal_title：Journal of medicinal chemistry
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更新日期：2005-02-10 00:00:00
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journal_title：Journal of medicinal chemistry
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更新日期：2005-04-07 00:00:00
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journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm030951y
更新日期：2004-02-12 00:00:00
abstract：:Family 18 chitinases play an essential role in a range of pathogens and pests. Several inhibitors are known, including the potent inhibitors argadin and allosamidin, and the structures of these in complex with chitinases have been elucidated. Recent structural analysis has revealed that CI-4 [cyclo-(L-Arg-D-Pro)] inhi...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm049940a
更新日期：2004-11-04 00:00:00
abstract：:Substance P (Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Met-NH2) and the C-terminal partial sequences down to the tripeptide were synthesized by a solid-phase method. These peptides were assayed for vasodilator, spasmogenic, and venoconstrictor properties using three preparations, viz. the hind limb blood flow of the dog...
journal_title：Journal of medicinal chemistry
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abstract：:Peroxisome proliferator-activated receptor gamma (PPARgamma) is well-known as the receptor of thiazolidinedione antidiabetic drugs. In this paper, we present a successful example of employing structure-based virtual screening, a method that combines shape-based database search with a docking study and analogue search,...
journal_title：Journal of medicinal chemistry
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更新日期：2006-05-04 00:00:00
abstract：:Bis (1-aziridinyl)(hexahydro-1H-azepin-1-yl)phosphine sulfide, an active anticancer agent with low hematopoietic toxicity in animals and man, was recommended several years ago for breast cancer adjuvant chemotherapy as an alternate drug to thiotepa. This hope had led to the syntheses of aziridinylallylaminophosphine o...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00228a014
更新日期：1976-06-01 00:00:00
abstract：:We have synthesized a library of thiosemicarbazones and screened them against three parasitic cysteine proteases, cruzain, falcipain-2, and rhodesain, and against the respective parasite sources of these three proteases, Trypanosoma cruzi, Plasmodium falciparum, and Trypanosoma brucei. The screens identified compounds...
journal_title：Journal of medicinal chemistry
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更新日期：2004-06-03 00:00:00
abstract：:Mutant epidermal growth factor receptor (EGFR) is a major driver of non-small-cell lung cancer (NSCLC). Marketed first generation inhibitors, such as erlotinib, effect a transient beneficial response in EGFR mutant NSCLC patients before resistance mechanisms render these inhibitors ineffective. Secondary oncogenic EGF...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.6b01894
更新日期：2017-04-13 00:00:00
abstract：:Since the discovery of the serotonin 4 receptor (5-HT(4)R), a large number of receptor ligands have been studied. The safety concerns and the lack of market success of these ligands have mainly been attributed to their lack of selectivity. In this study we describe the discovery of N-[(4-piperidinyl)methyl]-1H-indazol...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm300573d
更新日期：2012-11-26 00:00:00
abstract：:A new series of pyrazolotriazolopyrimidines bearing different substitutions on the phenylcarbamoyl moieties at the N5 position, being highly potent and selective human A(3) adenosine receptor antagonists, is described. The compounds represent an extension and an improvement of our previous work on this class of compou...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm0109614
更新日期：2002-02-14 00:00:00
