Abstract：
:Certain structural similarities between prostaglandins with close-packed side chains and the perhydrocyclopentanophenanthrene nucleus of steroids prompted the synthesis and biological evaluation of 6beta, 17 beta-dihydroxy-5alpha-androstane-2alpha-carboxylic acid (30), its 6-deoxy derivative 28, and the corresponding 6-deoxy-2beta derivative 29 in an attempt to evaluate carbocyclic acids as potential prostaglandin analogs. Preliminary in vitro studies on isolated guinea pig ileum have shown weakly specific, prostaglandin-stimulated smooth muscle antagonism for 28 when compared with antagonism of bradykinin- and acetylcholine-induced contractions. Complete dose-response curves for 28 on prostaglandin-stimulated guinea pig ileum have shown a reduction in the maxium response and a decrease in the slope of the curve, indicating a noncompetitive type of inhibition for this type of derivative.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Venton DL,Counsell RE,Sanner JH,Sierra Kdoi
10.1021/jm00235a002keywords:
subject
Has Abstractpub_date
1975-01-01 00:00:00pages
9-16issue
1eissn
0022-2623issn
1520-4804journal_volume
18pub_type
杂志文章abstract：:We report the synthesis and antiviral activity of a new family of non-nucleoside antivirals, derived from the 4-keto-1,2-oxathiole-2,2-dioxide (beta-keto-gamma-sultone) heterocyclic system. Several 4- and 5-substituted-5H-1,2-oxathiole-2,2-dioxide derivatives were found to have a selective inhibitory activity against ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm8014662
更新日期：2009-03-26 00:00:00
abstract：:A series of pseudodipeptide amides are described that inhibit Ras protein farnesyltransferase (PFTase). These inhibitors are truncated versions of the C-terminal tetrapeptide (CAAX motif) of Ras that serves as the signal sequence for PFTase-catalyzed protein farnesylation. In contrast to CAAX peptidomimetics previousl...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00020a010
更新日期：1995-09-29 00:00:00
abstract：:The active metabolite (2) of the novel immunosuppressive agent leflunomide (1) has been shown to inhibit the enzyme dihydroorotate dehydrogenase (DHODH). This enzyme catalyzes the fourth step in de novo pyrimidine biosynthesis. A series of analogues of the active metabolite 2 have been synthesized. Their in vivo biolo...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm9604437
更新日期：1996-11-08 00:00:00
abstract：:High-resolution, three-dimensional structures of vancomycin and aglyco-vancomycin in DMSO were determined by nuclear magnetic resonance, metric matrix distance geometry, and molecular dynamics calculations. Conformational flexibility fast on the NMR time scale was examined by ensemble-based calculations which apply th...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm9705972
更新日期：1998-06-04 00:00:00
abstract：:The synthesis and in vitro and in vivo antibreast and antiprostate cancers activities of novel C-4 heteroaryl 13-cis-retinamides that modulate Mnk-eIF4E and AR signaling are discussed. Modifications of the C-4 heteroaryl substituents reveal that the 1H-imidazole is essential for high anticancer activity. The most pote...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm501792c
更新日期：2015-02-26 00:00:00
abstract：:Pyrimidine biosynthesis presents an attractive drug target in malaria parasites due to the absence of a pyrimidine salvage pathway. A set of compounds designed to inhibit the Plasmodium falciparum pyrimidine biosynthetic enzyme dihydroorotate dehydrogenase (PfDHODH) was synthesized. PfDHODH-specific inhibitors with lo...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm060687j
更新日期：2007-01-25 00:00:00
abstract：:Compound 7 was identified as a potent (IC50 = 14 nM), selective, and orally bioavailable (F = 70% in mouse) inhibitor of protein kinase B/Akt. While promising efficacy was observed in vivo, this compound showed effects on depolarization of Purkinje fibers in an in vitro assay and CV hypotension in vivo. Guided by an X...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm0701019
更新日期：2007-06-28 00:00:00
abstract：:Cyclopentenones containing a 4-(methylsulfonyl)phenyl group in the 3-position and a phenyl ring in the 2-position are selective inhibitors of cyclooxygenase-2 (COX-2). The selectivity for COX-2 over COX-1 is dramatically improved by substituting the 2-phenyl group with halogens in the meta position or by replacing the...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm980642l
更新日期：1999-04-08 00:00:00
abstract：:The vinyl ethers of choline and of its alpha- and beta-methyl homologues were prepared to determine their cholinergic effects and to determine whether a separation of the dual physiologic activity (nicotinic and muscarinic) reported for the vinyl ether of choline could be achieved by this modification. A literature me...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00229a015
更新日期：1976-07-01 00:00:00
abstract：:We previously reported a potent small molecule Mer tyrosine kinase inhibitor UNC1062. However, its poor PK properties prevented further assessment in vivo. We report here the sequential modification of UNC1062 to address DMPK properties and yield a new potent and highly orally bioavailable Mer inhibitor, 11, capable o...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm500749d
更新日期：2014-08-28 00:00:00
abstract：:Multidrug resistance (MDR) is a major cause of failure in cancer chemotherapy. P-glycoprotein (P-gp), a promiscuous drug efflux pump, has been extensively studied for its association with MDR due to overexpression in cancer cells. Several P-gp inhibitors or modulators have been investigated in clinical trials in hope ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章,评审
doi：10.1021/acs.jmedchem.7b01457
更新日期：2018-06-28 00:00:00
abstract：:Thalidomide, 2-(2,6-dioxo-3-piperidinyl)-1H-isoindole-1,3(2H)-dione, has been shown to inhibit angiogenesis, the formation of new blood vessels from existing vasculature. As a result, there is renewed interest in this drug as a potential therapy for solid tumors. Thalidomide forms a number of metabolites and has been ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm0304820
更新日期：2004-04-22 00:00:00
abstract：:We have previously shown [Cys-Trp-Arg-Nva-Arg-Tyr-NH(2)](2), 1, to be a moderately selective neuropeptide Y (NPY) Y(4) receptor agonist. Toward improving the selectivity and potency for Y(4) receptors, we studied the effects of dimerizing H-Trp-Arg-Nva-Arg-Tyr-NH(2) using various diamino-dicarboxylic acids containing ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm050907d
更新日期：2006-04-20 00:00:00
abstract：:A novel series of 2- and 3-substituted 1,8-dihydroxy-9(10H)-anthracenones were synthesized and tested for their inhibitory activity against 5-lipoxygenase (5-LO) in bovine polymorphonuclear leukocytes and the growth of human keratinocytes. Structure-activity relationships are discussed with respect to the following re...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00037a017
更新日期：1994-05-27 00:00:00
abstract：:Nicotinic acetylcholine receptors (nAChRs) have been investigated for developing drugs that can potentially treat various central nervous system disorders. Considerable evidence supports the hypothesis that modulation of the cholinergic system through activation and/or desensitization/inactivation of nAChR holds promi...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章,评审
doi：10.1021/jm401937a
更新日期：2014-10-23 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：:A series of 1-(p-nitrophenyl)-2-aminoethanol derivatives and their morpholine analogues have been synthesized and pharmacologically investigated in order to confirm some pharmacological observations made with the N-isopropyl-substituted compounds. In agreement with the previously obtained results, the weak alpha-adren...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00192a023
更新日期：1979-06-01 00:00:00
abstract：:ERAP1 is an endoplasmic reticulum-resident zinc aminopeptidase that plays an important role in the immune system by trimming peptides for loading onto major histocompatibility complex proteins. Here, we report discovery of the first inhibitors selective for ERAP1 over its paralogues ERAP2 and IRAP. Compound 1 (N-(N-(2...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.9b00293
更新日期：2020-01-09 00:00:00
abstract：:Libraries of novel trisubstituted benzimidazoles were created through rational drug design. A good number of these benzimidazoles exhibited promising MIC values in the range of 0.5-6 μg/mL (2-15 μM) for their antibacterial activity against Mtb H37Rv strain. Moreover, five of the lead compounds also exhibited excellent...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm1012006
更新日期：2011-01-13 00:00:00
abstract：:An alpha-sialoside linked to acrylamide by a short connector (5-acetamido-2-O-(N-acryloyl-8-amino-5-oxaoctyl)-2,6-anhydro-3,5-d ideoxy-D-galacto-alpha-nonulopyranosonoic acid, 1) was prepared. Compound 1 formed high molecular weight copolymers with acrylamide, derivatives of acrylamide, and/or vinylpyrrolidone upon ph...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00046a027
更新日期：1994-09-30 00:00:00
abstract：:Fragment-based drug design exploits initial screening of low molecular weight compounds and their concomitant affinity improvement. The multitude of possible chemical modifications highlights the necessity to obtain structural information about the binding mode of a fragment. Herein we describe a novel NMR methodology...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.7b00845
更新日期：2017-11-09 00:00:00
abstract：:As part of a program aimed at the discovery of antinociceptive therapy for inflammatory conditions, a screening hit was found to inhibit microsomal prostaglandin E synthase-1 (mPGES-1) with an IC50 of 17.4 μM. Structural information was used to improve enzyme potency by over 1000-fold. Addition of an appropriate subst...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.5b01249
更新日期：2016-01-14 00:00:00
abstract：:Tankyrases (TNKS/TNKS2) belong to the poly(ADP-ribose) polymerase family. Inhibition of their enzymatic activities attenuates the Wnt/β-catenin signaling, which plays an important role in cancer pathogenesis. We previously reported the discovery of RK-287107, a spiroindoline-based, highly selective, potent tankyrase i...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.0c00045
更新日期：2020-04-23 00:00:00
abstract：:A series of 6-beta-thiosaccharide analogues of morphine-6-glucuronide (M6G) and codeine-6-glucuronide (C6G) were synthesized and evaluated with the objective of preparing an analogue of M6G with improved biological activity. The affinity of the thiosaccharide analogues of M6G and C6G was examined by competitive bindin...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm049554t
更新日期：2004-11-04 00:00:00
abstract：:Kadsurenone, a specific receptor antagonist of platelet-activating factor (PAF), and its analogues were prepared from derivatives of cinnamyl alcohol and (allyloxy)phenol. Racemic kadsurenone, resolvable by a Chiralpak column at low temperatures, has an IC50 value of 2 X 10(-7) M, which is about 50% of the activity of...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00384a023
更新日期：1987-01-01 00:00:00
abstract：:Four 11-(1-piperazinyl)-5H-pyrrolo[2,1-c][1,4]benzodiazepines were prepared and evaluated as central nervous system agents. All were active psychotropic agents as determined by animal screening tests. The most interesting compound, 11-(1-piperazinyl)-5H-pyrrolo[2,1-c][1,4]benzodiazepine, showed dual activity as an ant...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00178a020
更新日期：1980-04-01 00:00:00
abstract：:The problem of structure-activity relationships in sulfonamide type compounds is tackled on the ground that both bacteriostatic activities and structural indices must be referred to the specific individual forms assumed by sulfa drugs in the active solutions. The frequency value of the symmetric stretching mode of the...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00244a002
更新日期：1975-10-01 00:00:00
abstract：:A series of tetrazole amide derivatives of (+/-)-2-dodecyl-alpha-phenyl-N-(2,4,6-trimethoxyphenyl)-2H-tetrazole-5- acetamide (1) was prepared and evaluated for their ability to inhibit acyl-CoA: cholesterol O-acyltransferase (ACAT) in vitro and to lower plasma total cholesterol in vivo. For this series of compounds, o...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm960170f
更新日期：1996-06-07 00:00:00
abstract：:Neurofibrillary tangles (NFTs) made up of aggregated tau protein have been identified as the pathologic hallmark of several neurodegenerative diseases including Alzheimer's disease. In vivo detection of NFTs using PET imaging represents a unique opportunity to develop a pharmacodynamic tool to accelerate the discovery...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.6b00166
更新日期：2016-05-26 00:00:00
abstract：:The four stereoisomers of the muscarinic agonist 7 have been synthesized from enantiomerically pure exo-azanorbornane esters (13a,b). The esters were obtained in optically active form by separation of the carboxamide diastereomers 12a,b, formed from the borane complex of exo-azanorbornane-3-carboxylate 10 and a chiral...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00083a016
更新日期：1992-03-06 00:00:00
