Abstract：
:Four hybrid antibiotics combining structural features of chloramphenicol (1a), sparsomycin (2b), lincomycin (5c), and puromycin (6d)--lincophenicol (1c), chloramlincomycin (5a), sparsolincomycin (5b), and sparsopuromycin (6b)--were synthesized. They were investigated as inhibitors of several partial reactions of procaryotic and eucaryotic protein synthesis as well as potential antimicrobial agents. Lincophenicol (1c) was active as inhibitor of Escherichia coli ribosomal peptidyltransferase-catalyzed puromycin reaction. Both lincophenicol (1c) and sparsophenicol (1b) inhibited the binding of the iodophenol analogue of sparsomycin to E. coli ribosomes. The results are discussed in terms of a retro-inverso hypothesis advanced earlier for interpretation of biological activity of chloramphenicol (1a) and sparsophenicol (1b). Chloramlincomycin (5a) suppressed the growth of Streptococcus pyogenes with MIC 6.25 micrograms/mL.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Zemlicka J,Fernandez-Moyano MC,Ariatti M,Zurenko GE,Grady JE,Ballesta JPdoi
10.1021/jm00061a015subject
Has Abstractpub_date
1993-04-30 00:00:00pages
1239-44issue
9eissn
0022-2623issn
1520-4804journal_volume
36pub_type
杂志文章abstract：:Activators of nuclear factor-erythroid 2-related factor 2 (NRF2) could lead to promising therapeutics for prevention and treatment of oxidative stress and inflammatory disorders. Ubiquitination and subsequent degradation of the transcription factor NRF2 is mediated by Kelch-like ECH-associated protein-1 (KEAP1). Inhib...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.8b01133
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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,...
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pub_type： 杂志文章
doi：10.1021/jm00132a004
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pub_type： 杂志文章
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更新日期：2009-12-10 00:00:00
abstract：:Cyclin dependent kinases are a key family of kinases involved in cell cycle regulation and are an attractive target for cancer chemotherapy. The roles of four residues of the cyclin-dependent kinase active site in inhibitor selectivity were investigated by producing cyclin-dependent kinase 2 mutants bearing equivalent...
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pub_type： 杂志文章
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更新日期：2006-09-07 00:00:00
abstract：:As part of our studies on the design of agonists of the luteinizing hormone-releasing hormone (LH-RH), we have synthesized the [des-Gly-NH2(10)]-LH-RH N-methylhydrazide (1), the corresponding thiosemicarbazide (2), and the N-formyl- (3) N-acetyl- (4) and N-(trifluoroacetyl)hydrazide (5). Analogue 1 may be regarded as ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00134a021
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abstract：:Conjugation of pleuromutilin is an attractive strategy for the development of novel antibiotics and the fight against multiresistant bacteria as the class is associated with low rates of resistance and cross-resistance development. Herein, the preparation of 35 novel (+)-pleuromutilin conjugates is reported. Their des...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.0c01328
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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：:A series of 3-thioindolamidines (and 3-indolamidines) related to mixidine (1) was studied for cardiac-slowing properties, following the discovery of activity for prototype thioindole 2. Structure-activity relationships were explored, leading to many potent antitachycardiac agents (6-9, 12, 13, 15-17, 20, 23, 24, 30, 3...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00356a021
更新日期：1983-02-01 00:00:00
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pub_type： 杂志文章
doi：10.1021/jm0492709
更新日期：2005-02-10 00:00:00
abstract：:The lymphocyte-specific kinase (Lck) is a cytoplasmic tyrosine kinase of the Src family expressed in T cells and NK cells. Genetic evidence in both mice and humans demonstrates that Lck kinase activity is critical for signaling mediated by the T cell receptor (TCR), which leads to normal T cell development and activat...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm060435i
更新日期：2006-08-10 00:00:00
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journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00099a018
更新日期：1992-10-16 00:00:00
abstract：:In an attempt to rationalize the inability of phenolic benzocycloheptenylamines to activate dopamine (DA) D2 receptors, we have studied the conformational preferences and topography of 6,7,8,9-tetrahydro-1-hydroxy-N,N-dipropyl-5H-benzocyclohepten-6-++ +ylamine (1). Preferred conformations of 1 have been defined by use...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00124a007
更新日期：1989-04-01 00:00:00
abstract：:The standard of care for HIV-1 infection, highly active antiretroviral therapy (HAART), combines two or more drugs from at least two classes. Even with the success of HAART, new drugs with novel mechanisms are needed to combat viral resistance, improve adherence, and mitigate toxicities. Active site inhibitors of HIV-...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.9b01681
更新日期：2020-03-12 00:00:00
abstract：:A series of (fluorobenzyl)triazolo[4,5-c]pyridines was synthesized and tested for activity against maximal electroshock-induced seizures in rodents. The most promising compound, 14 (BW 534U87), which is a carbon-nitrogen isoster of a purine anticonvulsant, has a profile in rodents that suggests 14 will be free of emes...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00020a030
更新日期：1995-09-29 00:00:00
abstract：:Benzofuran, indan and tetrahydronaphthalene analogs of 3,4-(methylenedioxy)amphetamine (MDA) were prepared in order to examine the role of the dioxole ring oxygen atoms of MDA in interacting with the serotonin and catecholamine uptake carriers. The series of compounds was evaluated for discriminative stimulus effects ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00075a027
更新日期：1993-11-12 00:00:00
abstract：:We designed three novel positron emission tomography ligands, N-(4-(6-(isopropylamino)pyrimidin-4-yl)-1,3-thiazol-2-yl)-4-[(11)C]methoxy-N-methylbenzamide ([(11)C]6), 4-[(18)F]fluoroethoxy-N-[4-[6-(isopropylamino)pyrimidin-4-yl]-1,3-thiazol-2-yl]-N-methylbenzamide ([(18)F]7), and 4-[(18)F]fluoropropoxy-N-[4-[6-(isopro...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm201590g
更新日期：2012-03-08 00:00:00
abstract：:The present study evaluates the utility of the dihydropyridine in equilibrium pyridinium salt redox system for the specific delivery and sustained release of a model 2',3'-dideoxynucleoside to the brain of mice as the initial effort in a search for agents that may prove effective in reversing the complicating neurolog...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00123a020
更新日期：1989-03-01 00:00:00
abstract：:H(3) receptor antagonists based on a 2-aminoethylbenzofuran skeleton have been discovered, which are potent in vitro at human and rat H(3) receptors, with K(i) values of 0.1-5.8 nM. Analogues were discovered with potent (0.01-1 mg/kg) cognition and attention enhancing properties in animal models. One compound in parti...
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pub_type： 杂志文章
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更新日期：2005-01-13 00:00:00
abstract：:In the present paper we describe the synthesis of some dermorphin and deltorphin analogues beta-O- and alpha-C-glycosylated on the C-terminal amino acid residue and report their opioid receptor affinity and selectivity as well as their analgesic potency after subcutaneous injection in mice. ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm9810699
更新日期：1999-02-11 00:00:00
abstract：:A new and extensive set of 4-(6-iodo-H-imidazo[1,2-a]pyridin-2-yl)-N-dimethylbenzeneamine (IMPY) derivatives was synthesized and assayed for affinity toward human Abeta plaques. 6-Ethylthio- (12h), 6-cyano- (12e), 6-nitro- (12f), and 6-p-methoxybenzylthio- (15d) analogues were discovered to have high affinity (KI < 10...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm0702231
更新日期：2007-09-20 00:00:00
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journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00390a022
更新日期：1987-07-01 00:00:00
abstract：:Discoidin domain receptor 1 (DDR1) is an emerging potential molecular target for new anticancer drug discovery. We have discovered a series of 3-(2-(pyrazolo[1,5-a]pyrimidin-6-yl) ethynyl)benzamides that are selective and orally bioavailable DDR1 inhibitors. The two most promising compounds (7rh and 7rj) inhibited the...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
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更新日期：2013-04-25 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
pub_type： 杂志文章
doi：10.1021/jm030549j
更新日期：2004-06-03 00:00:00
abstract：:Although there are many estrogen receptor antagonists with improved tissue selectivity profiles compared with tamoxifen, optimal tissue selectivity has not yet been demonstrated. As such there is still a need for additional diversity and new chemical scaffolds to allow for exploration of improved tissue selectivity. H...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm020536q
更新日期：2003-04-10 00:00:00
abstract：:A series of new 9-phenanthrene amino alcohols has been prepared in which each compound bears from one to five halogen or halogen-containing moieties. A number of these compounds are extremely active against Plasmodium berghei in the mouse. Some structural requirements for optimal efficacy are considered. ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00244a012
更新日期：1975-10-01 00:00:00
abstract：:Novel heteroatom-incorporated antofine and cryptopleurine analogues were designed, synthesized, and tested against a panel of five cancer cell lines. Two new S-13-oxo analogues (11 and 16) exhibited potent cell growth inhibition in vitro (GI(50): 9 nM and 20 nM). Interestingly, both compounds displayed improved select...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
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更新日期：2011-07-28 00:00:00
abstract：:CC-chemokine receptor 5 (CCR5) is an attractive target for preventing the entry of human immunodeficiency virus 1 (HIV-1) into human host cells. Maraviroc is the only CCR5 antagonist, and it was marketed in 2007. To overcome the shortcomings of maraviroc, structure-based drug design was performed to minimize CYP450 in...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.8b01077
更新日期：2018-11-08 00:00:00
abstract：:Self-organizing maps were trained to separate high- and low-active propafenone-type inhibitors of P-glycoprotein. The trained maps were subsequently used to identify highly active compounds in a virtual screen of the SPECS compound library. ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm060604z
更新日期：2007-04-05 00:00:00
abstract：:A new family of chelating agents based on 4-(substituted-carbamoyl)-3-hydroxy-2-pyridinones is reported. These have optional terminal substituents on the nitrogens, and the hydroxypyridonate (HOPO) rings are attached to molecular backbones through amide linkages. A very important feature of the methyl-substituted liga...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00014a013
更新日期：1995-07-07 00:00:00
abstract：:Computational ADME (absorption, distribution, metabolism, and excretion) models may be used early in the drug discovery process in order to flag drug candidates with potentially problematic ADME profiles. We report the development, validation, and application of quantitative structure-property relationship (QSPR) mode...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm020491t
更新日期：2003-07-03 00:00:00
