Abstract：
:(+)-12-Fluoro-13,14-dihydroprostaglandin F2alpha methyl ester (2a) and (+)-15-epi-12-fluoro-13,14-dihydroprostaglandin F2alpha methyl ester (2b) were prepared from the readily available (-)-7-fluorospiro[bicyclo[2.2.1]hept-5-ene-2,2'-[1,3]dioxolane]-7-methanol (3). Fluoroprostaglandins 2a and 2b possess truly significant separations of antifertility activity from smooth-muscle stimulating properties. In addition, our studies showed that 2a and 2b were totally inert toward the placental 15-hydroxyprostaglandin dehydrogenase.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Grieco PA,Takigawa Tdoi
10.1021/jm00139a014subject
Has Abstractpub_date
1981-07-01 00:00:00pages
839-43issue
7eissn
0022-2623issn
1520-4804journal_volume
24pub_type
杂志文章abstract：:Acyclic nucleosides 1-[[2-hydroxy-1-(hydroxymethyl)ethoxy] methyl]-5-benzyluracil (DHPBU) (1) and 1-[[2-hydroxy-1-(aminomethyl)ethoxy]methyl]-5-benzyluracil (AHPBU) (2) have been synthesized by direct coupling of bis(trimethylsilyl)-5-benzyluracil with the corresponding chloromethyl ether, followed by removal of the b...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00145a023
更新日期：1985-07-01 00:00:00
abstract：:A series of 9-hydrazono-4H-pyrido[1,2-a]pyrimidin-4-ones was prepared. The compounds were evaluated in the rat passive cutaneous anaphylaxis test for antiallergic activity. Structure-activity relationship studies revealed that the presence of a monosubstituted hydrazone moiety in position 9 and an unsubstituted 2-posi...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00362a008
更新日期：1983-08-01 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：:The increase in the incidence of both hospital- and community-acquired antibiotic-resistant infections is a major concern to the healthcare community. There have been only two new classes of antibiotics approved by the FDA over the past 40 years, and clearly there is a growing need for additional antimicrobial agents....
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm900519b
更新日期：2009-08-27 00:00:00
abstract：:4-[4-(N-Substituted (thio)carbamoyl)-1-piperazinyl]-6,7-dimethoxyquinazoline derivatives such as KN1022 are potent inhibitors of the phosphorylation of platelet derived growth factor receptor (PDGFR). Structure activity relationships in the (thio)urea moiety, the phenyl ring itself, the linker between these two moieti...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm0201114
更新日期：2002-09-26 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：:The dopamine D3 receptor (D3R) is a target for developing medications to treat substance use disorders. D3R-selective compounds with high affinity and varying efficacies have been discovered, providing critical research tools for cell-based studies that have been translated to in vivo models of drug abuse. D3R antagon...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm501512b
更新日期：2015-07-23 00:00:00
abstract：:A gadolinium complex of 1,4,7,10-tetraazacyclododecane-1,4,7-trisacetic acid (DO3A) and benzothiazole-aniline (BTA) of the type [Gd(DO3A-BTA)(H2O)] has been prepared for use as a single molecule theranostic agent. The kinetic inertness and r1 relaxivity (= 3.84 mM(-1) s(-1)) of the complex compare well with those of s...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm401206t
更新日期：2013-10-24 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：:Neuroactive steroids that allosterically modulate GABAA receptors have potential uses as anticonvulsants, anxiolytics, and sedative-hypnotic agents. Recently, a series of pregnanes substituted with simple alkyl groups at the 3 beta-position were synthesized and found to be active in vitro. The present report describes...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm9605344
更新日期：1997-01-03 00:00:00
abstract：:We present and thoroughly characterize a large collection of 3,4-dihydropyrimidin-2(1H)-ones as A2BAR antagonists, an emerging strategy in cancer (immuno) therapy. Most compounds selectively bind A2BAR, with a number of potent and selective antagonists further confirmed by functional cyclic adenosine monophosphate exp...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.0c01431
更新日期：2021-01-14 00:00:00
abstract：:A new series of calcium channel agonists structurally related to Bay K8644, containing NO donor furoxans and the related furazans unable to release NO, is described. The racemic mixtures were studied for their action on L-type Ca(2+) channels expressed in cultured rat insulinoma RINm5F cells. All the products proved t...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm031109v
更新日期：2004-05-06 00:00:00
abstract：:Novel analogues of MKC442 (6-benzyl-1-(ethoxymethyl)-5-isopropylpyrimidine-2,4(1H,3H)-dione) were synthesized by reaction of 6-[(3,5-dimethylphenyl)fluoromethyl]-5-ethyluracil (5) with ethoxymethyl chloride and formaldehyde acetals. The Sonogashira reaction was carried out on the N1-(p-iodobenzyl)oxy]methyl derivative...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm500139a
更新日期：2014-06-26 00:00:00
abstract：:A series of α-ketooxazoles containing conformational constraints in the C2 acyl side chain of 2 (OL-135) were examined as inhibitors of fatty acid amide hydrolase (FAAH). Only one of the two possible enantiomers displayed potent FAAH inhibition (S vs R enantiomer), and their potency is comparable or improved relative ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm101597x
更新日期：2011-04-28 00:00:00
abstract：:Various lines of evidence, including molecular modeling studies, imply that the endoethylenic bridge of 3,8-diazabicyclo[3.2. 1]octanes (DBO, 1) plays an essential role in modulating affinity toward mu opioid receptors. This hypothesis, together with the remarkable analgesic properties observed for N(3) propionyl, N(8...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm991140q
更新日期：2000-06-01 00:00:00
abstract：:Novel bisbenzimidazole inhibitors of bacterial type IA topoisomerase are of interest for the development of new antibacterial agents that are impacted by target-mediated cross resistance with fluoroquinolones. The present study demonstrates the successful synthesis and evaluation of bisbenzimidazole analogues as Esche...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm5003028
更新日期：2014-06-26 00:00:00
abstract：:A new approach to generating information on ligand receptor interactions within the binding pocket of G protein-coupled receptors has been developed, called Biophysical Mapping (BPM). Starting from a stabilized receptor (StaR), minimally engineered for thermostability, additional single mutations are then added at pos...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm2003798
更新日期：2011-07-14 00:00:00
abstract：:A series of potent nonpeptide inhibitors of the HIV protease have been identified. Using the structure of compound 3 bound to the HIV protease, bis tertiary amide inhibitor 9 was designed and prepared. Compound 9 was found to be about 17 times more potent than 3, and the structure of the protein-ligand complex of 9 re...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm960092w
更新日期：1996-07-05 00:00:00
abstract：:Protein tyrosine phosphatase 1B (PTP1B) is a negative regulator of the insulin and leptin receptor pathways and thus an attractive therapeutic target for diabetes and obesity. Starting with a high micromolar lead compound, structure-based optimization of novel PTP1B inhibitors by extension of the molecule from the enz...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm0702478
更新日期：2007-09-20 00:00:00
abstract：:A series of cyclopropane-based conformationally restricted analogues of histamine, the "folded" cis-analogues, i.e., (1S,2R)-2-(aminomethyl)-1-(1H-imidazol-4-yl)cyclopropane (11), (1S,2S)-2-(2-aminoethyl)-1-(1H-imidazol-4-yl)cyclopropane (13), and their enantiomers ent-11 and ent-13, and the "extended" trans-analogues...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm020415q
更新日期：2003-05-08 00:00:00
abstract：:Penicillin-binding proteins represent well-established, validated, and still very promising targets for the design and development of new antibacterial agents. The transglycosylase domain of penicillin-binding proteins is especially important, as it catalyzes polymerization of glycan chains, using the peptidoglycan pr...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.5b01482
更新日期：2015-12-24 00:00:00
abstract：:There has been significant interest in developing a transient receptor potential A1 (TRPA1) antagonist for the treatment of pain due to a wealth of data implicating its role in pain pathways. Despite this, identification of a potent small molecule tool possessing pharmacokinetic properties allowing for robust in vivo ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.6b00039
更新日期：2016-03-24 00:00:00
abstract：:The previous paper reported on the synthesis and pharmacological evaluation of N-(6-amino-3-pyridyl)-N'-bicycloalkyl-N"-cyanoguanidine derivatives, from among which three compounds were selected as potent potassium-channel openers. In the present study, selected compounds were tested for antagonism of potassium-induce...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00039a011
更新日期：1994-06-24 00:00:00
abstract：:Dipeptidyl peptidase IV (DPP-IV) inhibition has the potential to become a valuable therapy for type 2 diabetes. The synthesis and structure-activity relationship of a new DPP-IV inhibitor class, N-substituted-glycyl-2-cyanopyrrolidines, are described as well as the path that led from clinical development compound 1-[2...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm030091l
更新日期：2003-06-19 00:00:00
abstract：:Dimeric DNA cross-linking compounds have emerged as important new antitumor agents. We report the synthesis and biochemical evaluation of a select set of dimeric mitomycins in which the two mitomycin units are tethered at either the mitomycin C(7) amino or the aziridine N(1a) positions. Significantly, mitomycin C (1) ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm010090y
更新日期：2001-10-11 00:00:00
abstract：:Multifunctional ligands with agonist bioactivities at μ/δ opioid receptors (MOR/DOR) and antagonist bioactivity at the neurokinin-1 receptor (NK1R) have been designed and synthesized. These peptide-based ligands are anticipated to produce better biological profiles (e.g., higher analgesic effect with significantly les...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.5b01170
更新日期：2015-11-12 00:00:00
abstract：:A series of tricyclic analogues of 9-oxo-9H-xanthene-4-acetic acid have been prepared and evaluated for their ability to cause hemorrhagic necrosis in subcutaneously implanted colon 38 tumors in mice, in an effort to extend the structure-activity relationships for this series. As was found previously with analogues of...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00106a003
更新日期：1991-02-01 00:00:00
abstract：:The medicinal chemistry community has directed considerable efforts toward the discovery of selective inhibitors of interleukin-2 inducible T-cell kinase (ITK), given its role in T-cell signaling downstream of the T-cell receptor (TCR) and the implications of this target for inflammatory disorders such as asthma. We h...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm501998m
更新日期：2015-05-14 00:00:00
abstract：:A novel class of 21-aminosteroids has been developed. Compounds within this series are potent inhibitors of iron-dependent lipid peroxidation in rat brain homogenates with IC50's as low as 3 microM. Furthermore, selected members enhance early neurological recovery and survival in a mouse head injury model. Significant...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00166a010
更新日期：1990-04-01 00:00:00
abstract：:The synthesis of 15 methyl or unsubstituted 1,2,3-triazoles, 1,2,4-triazoles, and tetrazoles additionally substituted with a 1-azabicyclo[2.2.2]octan-3-yl group is described. The potency and efficacy of these compounds as muscarinic ligands were determined in radioligand binding assays using [3H]oxotremorine and [3H]q...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00085a016
更新日期：1992-04-03 00:00:00
