Abstract：
:Racemic ethyl 5-amino-1,2-dihydro-2-methyl-3-phenylpyrido[3,4-b]pyrazine-7- carbamate (1a) has shown antitumor activity in a variety of in vivo experiments. The preparation of the R and S isomers gave compounds with significant differences in potency in several biological tests.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Temple C Jr,Rener GAdoi
10.1021/jm00129a012subject
Has Abstractpub_date
1989-09-01 00:00:00pages
2089-92issue
9eissn
0022-2623issn
1520-4804journal_volume
32pub_type
杂志文章abstract：:Doxazolidine (doxaz) is a new anthracycline anticancer agent. While structurally similar to doxorubicin (dox), doxaz acts via a distinct mechanism to selectively enhance anticancer activity over cardiotoxicity, the most significant clinical impediment to successful anthracycline treatment. Here, we describe the synthe...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm300714p
更新日期：2012-07-26 00:00:00
abstract：:Previously, we reported the thiourea antagonists 2a and 2b as potent and high affinity TRPV1 antagonists. For further optimization of the lead compounds, a series of their amide and alpha-substituted amide surrogates were investigated and novel chiral N-(2-benzyl-3-pivaloyloxypropyl) 2-[4-(methylsulfonylamino)phenyl]p...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm701049p
更新日期：2008-01-10 00:00:00
abstract：:Probucol (1) and probucol analogues with the substitutions at the disulfide-linked carbon (2, 3) and an additional substitution at a tert-butyl of each phenolic ring (4) were tested for their ability to lower total serum cholesterol and prevent aortic atherosclerosis in modified Watanabe heritable hyperlipidemic (WHHL...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00105a046
更新日期：1991-01-01 00:00:00
abstract：:From a series of small fragments that was designed to probe the histamine H(4) receptor (H(4)R), we previously described quinoxaline-containing fragments that were grown into high affinity H(4)R ligands in a process that was guided by pharmacophore modeling. With a scaffold hopping exercise and using the same in silic...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm800876b
更新日期：2008-12-25 00:00:00
abstract：:Development of Grb2 Src homology 2 (SH2) domain binding inhibitors has important implications for treatment of a variety of diseases, including several cancers. In cellular studies, inhibitors of Grb2 SH2 domain binding have to date been large, highly charged peptides which relied on special transport devices for cell...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm980388x
更新日期：1999-01-14 00:00:00
abstract：:The synthesis, biological activity, and molecular modeling studies of C-ring-modified camptothecins are reported. A general synthetic protocol, based on "C-5 camptothecin (C-5-CPT) enolate chemistry", allows one to obtain various C5-substituted analogues. All new compounds, obtained as 1:1 epimeric mixtures, were test...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm801153y
更新日期：2009-02-26 00:00:00
abstract：:Two 12-amino-6,7,8,11-tetrahydro-7,11-methanocycloocta[b]quinoline derivatives [9-Me(Et)] (syn-huprines) have been obtained by condensation of known 7-alkylbicyclo[3.3.1]non-6-en-3-ones with 2-(trifluoromethyl)aniline, followed by basic cyclization of the resulting imine, and chromatographic separation of the regioiso...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm010949b
更新日期：2001-12-20 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：:A recently discovered and structurally distinct class of antiepileptic drugs is the (arylalkyl)imidazoles. Two independently discovered representatives of this class, denzimol (alpha-[4-(2-phenylethyl)phenyl]-1H-imidazole-1-ethanol) and nafimidone (2-(1H-imidazol-1-yl)-1-(2-naphthalenyl)ethanone), are undergoing clini...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00159a004
更新日期：1986-09-01 00:00:00
abstract：:The preparation of 6-chloro-5-(cyclopentylmethyl)indan-1-carboxylic acid is described. This acid has good anti-inflammatory and analgesic activities without producing irritation in the gastrointestinal tract up to the highest tested dose. ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00369a033
更新日期：1984-03-01 00:00:00
abstract：:N5-Acetyl-N5-hydroxy-L-ornithyl-N5-acetyl-N5-hydroxy-L-ornithyl-N5-acety l- N5-hydroxy-L-ornithine, the functionally instrumental component of the albomycins and ferrichromes, has been incorporated as a "carrier" substructure into both carbacephalosporin and oxamazin type beta-lactam antibiotics. The previously synthe...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00107a014
更新日期：1991-03-01 00:00:00
abstract：:Reaction of 3'-acetylthymidine with phosphorus oxychloride in trimethyl phosphate yielded the phosphorodichloridate 5, which was subsequently reacted with aziridine, or 2,2-dimethylaziridine to give compounds 6 and 7, respectively. The 2,2-dimethylaziridine derivative 7 was considerably more active than 6 against leuk...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00139a024
更新日期：1981-07-01 00:00:00
abstract：:Pyrrolobenzoxazepinone (PBO) derivatives represent a new class of human immunodeficiency virus type 1 (HIV-1) non-nucleoside reverse transcriptase (RT) inhibitors (NNRTs) whose prototype is (+/-)-6-ethyl-6-phenylpyrrolo[2,1-d][1,5]benzoxazepin-7(6H)- one (6). Docking studies based on the three-dimensional structure of...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm990150o
更新日期：1999-10-21 00:00:00
abstract：:Treatment of a methanolic solution of 4-hydroxy-1-beta-D-ribofuranosyl-2-pyridinone (3-deazauridine, 1) with diazomethane gave 2-methoxy-1-beta-D-ribofuranosyl-4-pyridinone (2) and 4-methoxy-1-beta-D-ribofuranosyl-2-pyridinone (3a) in an approximate ratio of 1:2. Analogous treatment of 1 with diazomethane in the prese...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00245a005
更新日期：1975-11-01 00:00:00
abstract：:High throughput screening followed by a lead generation campaign uncovered a novel series of urea containing morpholinopyrimidine compounds which act as potent and selective dual inhibitors of mTORC1 and mTORC2. We describe the continued compound optimization campaign for this series, in particular focused on identify...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm501778s
更新日期：2015-03-12 00:00:00
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：:Aiming to image NTS1 overexpressing tumors, the diarylpyrazole glycoconjugate 8, derived from the potent NTS1 antagonist SR142948A, was synthesized taking advantage of the palladium-catalyzed aminocarbonylation reaction. The glycoconjugate 8 displayed excellent affinity and selectivity toward NTS1. Radiosynthesis proc...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm401491e
更新日期：2013-11-27 00:00:00
abstract：:9,10-Didehydro-6-methyl-8beta-arylergolines 2, in which the carboxyl group of lysergic acid and isolysergic acid is replaced by various aryl groups, were prepared in two steps by alkylation of aromatic substrates with the tetracyclic allylic alcohol 3, followed by aromatization with MnO2. The new ergolines 2 have mode...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00218a025
更新日期：1977-08-01 00:00:00
abstract：:Membrane-associated serine protease matriptase has been implicated in human diseases and might be a drug target. In the present study, a novel class of matriptase inhibitors targeting zymogen activation is developed by a combination of the screening of compound library using a cell-based matriptase activation assay an...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm200920s
更新日期：2011-11-10 00:00:00
abstract：:The 5'-phosphate (1) of the antiviral nucleoside 5-cyano-2'-deoxyuridine was synthesized and evaluated for inhibition of thymidylate synthetase purified from methotrexate-resistant Lactobacillus casei. Compound 1 was a potent competitive inhibitor with a K1 of 0.55 microns. Irreversible enzyme inhibition by this compo...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00195a028
更新日期：1979-09-01 00:00:00
abstract：:A unique strategy for the enhancement of secondary binding of an inhibitor to an enzyme has been demonstrated in the design of new human immunodeficiency virus (HIV) protease inhibitors. When the planar benzene ring of a 4-hydroxycoumarin lead compound (1a, Ki = 0.800 microM) was replaced with medium-sized (i.e., 7-9)...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00011a008
更新日期：1995-05-26 00:00:00
abstract：:A theoretically rigorous and computationally tractable methodology for the prediction of the free energies of binding of protein-ligand complexes is presented. The method formulated involves developing molecular dynamics trajectories of the enzyme, the inhibitor, and the complex, followed by a free energy component an...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm010175z
更新日期：2001-12-06 00:00:00
abstract：:A 256-compound library was evaluated in an anti-HIV screen to identify structural "mimics" of the fused tetracyclic indole compound 1 (IDC16) that conserve its anti-HIV activity without associated cytotoxicity. Four diheteroarylamide-type compounds, containing a common 5-nitroisobenzothiazole motif, were identified as...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.5b01357
更新日期：2016-03-10 00:00:00
abstract：:Partition properties, that is partition coefficients and enthalpies (delta Hp degree) and entropies (delta Sp degree) of partition, have been measured for 50 benzoic acids in the 1-octanol/water system, and their role in QSAR (quantitative structure-activity relationship) analysis examined. The novel hydrophobic param...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00096a014
更新日期：1992-09-04 00:00:00
abstract：:We synthesized 5-substituted pyrrolo[2,3-d]pyrimidine antifolates (compounds 5-10) with one-to-six bridge carbons and a benozyl ring in the side chain as antitumor agents. Compound 8 with a 4-carbon bridge was the most active analogue and potently inhibited proliferation of folate receptor (FR) α-expressing Chinese ha...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm401328u
更新日期：2013-12-27 00:00:00
abstract：:The phenolic "A-ring" of natural and synthetic estrogen receptor (ER) ligands was effectively replaced by a planar six-member ring formed through an intramolecular hydrogen bond within a salicylaldoxime. Thus, oxime 1, a structural analogue of a triarylethylene estrogen, showed a significant binding affinity for the E...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm010948j
更新日期：2001-11-22 00:00:00
abstract：:Substrate-selective inhibition or modulation of the activity of γ-secretase, which is responsible for the generation of amyloid-β peptides, might be an effective strategy for prevention and treatment of Alzheimer's disease. We have shown that helical β-peptide foldamers are potent and specific inhibitors of γ-secretas...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm301306c
更新日期：2013-02-28 00:00:00
abstract：:Fatty acid synthase (FAS) is necessary for growth and survival of tumor cells and is a promising drug target for oncology. Here, we report on the syntheses and activity of novel inhibitors of the thioesterase domain of FAS. Using the structure of orlistat as a starting point, which contains a beta-lactone as the centr...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm800321h
更新日期：2008-09-11 00:00:00
abstract：:Prevalence of drug-resistant bacteria has emerged to be one of the greatest threats in the 21st century. Herein, we report the development of a series of small molecular antibacterial agents that are based on the acylated reduced amide scaffold. These molecules display good potency against a panel of multidrug-resista...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.6b00640
更新日期：2016-09-08 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
