Abstract：
:The synthesis of a series of 1-phenoxy-3-[[(substituted-amido)alkyl]amino]-2-propanols is described. Many of the compounds are more potent than propanolol as beta blockers, while having cardioselectivity comparable to that of practolol, when given intravenously to anesthetized cats. The structure-activity relationships shown by this series of compounds provide further evidence that the addition of substituents to the alkylamino moeity of a beta blocker can confer cardioselectivity and that amidic substituents are remarkably effective.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Lare MS,Smith LHdoi
10.1021/jm00353a004subject
Has Abstractpub_date
1982-11-01 00:00:00pages
1286-92issue
11eissn
0022-2623issn
1520-4804journal_volume
25pub_type
杂志文章abstract：:Matrix metalloprotease 12 plays a significant role in airway inflammation and remodeling. Increased expression and production of MMP-12 have been found in the lung of human COPD patients. MMP408 (14), a potent and selective MMP-12 inhibitor, was derived from a potent matrix metalloprotease 2 and 13 inhibitor via lead ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm900093d
更新日期：2009-04-09 00:00:00
abstract：:The design, synthesis, and activity of a novel series of 2,5-substituted tryptamine derivatives at vascular 5HT1B-like receptors is described. Several important auxiliary binding sites of the 5HT1B-like receptor have been proposed following various modifications to the 2-substituent and especially to the methylene- or...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm9605849
更新日期：1997-07-18 00:00:00
abstract：:5-Oxo-ETE is the most powerful eosinophil chemoattractant among lipid mediators. Eosinophil infiltration into the lungs of asthmatics may be responsible for the late phase of inflammatory asthma. We have designed and synthesized a 5-oxo-ETE receptor antagonist, the purpose of which is to prevent eosinophil migration t...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm400480j
更新日期：2013-05-09 00:00:00
abstract：:Dihydrofuro[3,4-c]pyridinones are the first class of small molecules reported to inhibit the cytolytic effects of the lymphocyte toxin perforin. A lead structure was identified from a high throughput screen, and a series of analogues were designed and prepared to explore structure-activity relationships around the cor...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm801063n
更新日期：2008-12-11 00:00:00
abstract：:This study aims to identify inhibitors that bind at the interface of HIV-1 integrase (IN) and human LEDGF/p75, which represents a novel target for anti-HIV therapy. To date, only a few such inhibitors have been reported. Here structure-based virtual screening was performed to search for the inhibitors from an in-house...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm301226a
更新日期：2012-11-26 00:00:00
abstract：:The endocannabinoid system consists of two cannabinoid receptors (CB1 and CB2), endogenous ligands (endocannabinoids), and the enzymes involved in the metabolism of the endocannabinoids, including fatty acid amide hydrolase (FAAH) and monoglyceride lipase (MGL). In the present study, virtual screening of MGL inhibitor...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm060394q
更新日期：2006-07-27 00:00:00
abstract：:Necrosis is the main mode of cell death, which leads to multiple clinical conditions affecting hundreds of millions of people worldwide. Its molecular mechanisms are poorly understood, hampering therapeutics development. Here, we identify key proteolytic activities essential for necrosis using various biochemical appr...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.0c01683
更新日期：2021-01-31 00:00:00
abstract：:A novel series of nonsteroidal heterocycles was discovered which display cell-type selective, high-affinity (nanomolar) binding to the progesterone receptors from TE85 osteosarcoma cells but > 1 microM binding affinity to the progesterone receptors from T47D and ZR75 human breast carcinoma cells. Structure-activity re...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00025a004
更新日期：1995-12-08 00:00:00
abstract：:The poor solubility of the thymidylate synthase (TS) inhibiting antifolate 10-propargyl-5,8-dideazafolic acid has posed problems for its clinical use and is probably responsible for its renal toxicity. The insolubility is caused by the 2-amino-3,4-dihydro-4-oxopyrimidine moiety of the drug which stabilizes the solid s...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00124a018
更新日期：1989-04-01 00:00:00
abstract：:A novel series of 16-substituted-4-azasteroids has been identified as potential tissue-selective androgen receptor modulators. These ligands display potent hAR binding and agonist activity, low virilizing potential, and good pharmacokinetic profiles in dogs. On the basis of its in vitro profile, 21 was evaluated in th...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm900880r
更新日期：2009-08-13 00:00:00
abstract：:Hepatocyte growth factor (HGF) is an important regulator of normal development and homeostasis, and dysregulated signaling through the HGF receptor, Met, contributes to tumorigenesis, tumor progression, and metastasis in numerous human malignancies. The development of selective small-molecule inhibitors of oncogenic t...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm800791f
更新日期：2009-02-26 00:00:00
abstract：:Transient receptor potential canonical 3/6/7 (TRPC3/6/7) are highly homologous receptor-operated nonselective cation channels. Despite their physiological significance, very few selective and potent agonists are available for functional examination of these channels. Using a cell-based high throughput screening approa...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.7b00304
更新日期：2017-06-08 00:00:00
abstract：:Activation of the IRE-1/XBP-1 pathway has been linked to many human diseases. We report a novel fluorescent tricyclic chromenone inhibitor, D-F07, in which we incorporated a 9-methoxy group onto the chromenone core to enhance its potency and masked the aldehyde to achieve long-term efficacy. Protection of the aldehyde...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.9b00269
更新日期：2019-06-13 00:00:00
abstract：:A number of analogues of thapsigargin have been synthesized by alkylating or acylating O-11 and O-12 in the lactol obtained by reducing thapsigargicin. Introduction of alpha-disposed substituents decreased the Ca(2+)-ATPase inhibitory potency of the analogue, whereas the enzyme was more tolerant toward beta-disposed s...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00002a009
更新日期：1995-01-20 00:00:00
abstract：:As part of an effort to identify novel opioid receptor interactive agents, we recently prepared a series of 8-(substituted)amino analogues of cyclazocine. We found the chiral 8-phenylamino (NHC(6)H(5)) cyclazocine derivative to have subnanomolar affinity for kappa opioid receptors and a 2-fold lower affinity for mu, o...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm000119i
更新日期：2000-09-21 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：:We have synthesized a series of N-phenyl-N'-aralkyl and N-phenyl-N'-(1-phenylcycloalkyl)ureas as inhibitors of acyl-CoA:cholesterol acyltransferase (ACAT). This intracellular enzyme is thought to be responsible for the esterification of dietary cholesterol; hence inhibition of this enzyme could reduce diet-induced hyp...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00074a011
更新日期：1993-10-29 00:00:00
abstract：:The intense intrinsic fluorescence emissions from several clinically relevant camptothecin drugs have been exploited in order to study the structural basis of drug binding to human serum albumin. Both HPLC and time-resolved fluorescence spectroscopic methodologies were employed to characterize the associations of camp...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00027a005
更新日期：1994-01-07 00:00:00
abstract：:Quantitative structure-activity relationships (QSAR) of a series of 6-anilinouracil derivatives were developed for their inhibitory activity against the wild-type DNA polymerase III (pol III) and a mutant enzyme, pol III/azp-12, derived from Bacillus subtilis. Interaction between inhibitors and both enzymes appears to...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00368a013
更新日期：1984-02-01 00:00:00
abstract：:We report the solid-phase synthesis and antagonistic potencies of 25 analogues (1-25) of [1-(beta-mercapto-beta,beta-pentamethylenepropionic acid),2-O-ethyl-D-tyrosine,4-valine]arginine-vasopressin (d(CH2)5D-Tyr(Et)2-VAVP) (A) and of the related Ile4 (D) and [D-Phe2,Ile4] (E) analogues, potent antagonists of the antid...
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：:Verrucarin A (2) was epoxidized to give the beta-9,10-epoxide 7 (major product) and alpha-9,10-epoxide 9 (minor product). The beta-epoxide 7 and its acetate 8 exhibit high in vivo antileukemic activity against P-388 mouse leukemia, whereas 2 and 9 are inactive. Epoxidation of verrucarin B (3) and roridin A (1) to thei...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00183a018
更新日期：1980-09-01 00:00:00
abstract：:A series of 1-imidazolyl(alkyl)-substituted quinoline, isoquinoline, naphthalene, benzo[b]furan, and benzo[b]thiophene derivatives was synthesized as dual inhibitors of thromboxane A(2) synthase (P450 TxA(2)) and aromatase (P450 arom). Dual inhibition of these enzymes could be a novel strategy for the treatment of mam...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm991180u
更新日期：2000-05-04 00:00:00
abstract：:The F9/Yde/Fml pilus, tipped with the FmlH adhesin, has been shown to provide uropathogenic Escherichia coli (UPEC) a fitness advantage in urinary tract infections (UTIs). Here, we used X-ray structure guided design to optimize our previously described ortho-biphenyl Gal and GalNAc FmlH antagonists such as compound 1 ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.8b01561
更新日期：2019-01-24 00:00:00
abstract：:Protein tyrosine phosphatases (PTPs) constitute a diverse family of enzymes that, together with protein tyrosine kinases, control the level of intracellular tyrosine phosphorylation, thus regulating many cellular functions. PTP1B negatively regulates insulin signaling, in part, by dephosphorylating key tyrosine residu...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm011100y
更新日期：2002-04-25 00:00:00
abstract：:Cyclin-dependent kinases (cdk) have recently raised considerable interest in view of their essential role in the regulation of the cell division cycle. The structure-activity relationships of cdk inhibition showed that the 1, 3; and 7 positions of the purine ring must remain free, probably for a direct interaction, in...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm960666x
更新日期：1997-02-14 00:00:00
abstract：:With the aim of increasing therapeutic indexes of novel cyclic depsinonapeptide pseudomycins, we synthesized and evaluated a series of mono-, di-, and trioxodioxolenylmethyl carbamate prodrugs (2 and 4) of pseudomycin B 1 and pseudomycin C' 3. It is rather encouraging to note that several members of the newly synthesi...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm000425w
更新日期：2001-08-02 00:00:00
abstract：:A series of cis- and trans-dihydroxycotahydrobenzo[f]quinoline congeners of dopamine has been prepared, in which the N substitutent is H, ethyl, or n-propyl. The trans isomers include the dopamine moiety held rigidly in an antiperiplanar diposition which is believed to be necessary for certian central and peripheral d...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00190a002
更新日期：1979-04-01 00:00:00
abstract：:HIV-1 maturation can be impaired by altering protease (PR) activity, the structure of the Gag-Pol substrate, or the molecular interactions of viral structural proteins. Here we report the synthesis and characterization of new cationic N,N-dimethyl[70]fulleropyrrolidinium iodide derivatives that inhibit more than 99% o...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.6b00994
更新日期：2016-12-22 00:00:00
abstract：:A series of 3-(1,2-disubstituted-1H-benzimidazol-5-yl)-N-hydroxyacrylamides (1) were designed and synthesized as HDAC inhibitors. Extensive SARs have been established for in vitro potency (HDAC1 enzyme and COLO 205 cellular IC(50)), liver microsomal stability (t(1/2)), cytochrome P450 inhibitory (3A4 IC(50)), and clog...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm2003552
更新日期：2011-07-14 00:00:00
abstract：:A novel lysine-based trifunctional chelate 3 was designed, synthesized, and characterized and bears both a chelating moiety (CHX-A' ') for sequestering radiometals (86Y or 111In) and the near-infrared dye Cy5.5 for dual modality PET (or SPECT) and fluorescence imaging, respectively. Successful conjugation of 3 to the ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm070657w
更新日期：2007-09-20 00:00:00
