Abstract：
:Dihydrocodeinone oxime (1) under Beckmann rearrangement conditions gave a product (2) that facilitated the preparation of (-)-11 alpha-substituted 1,2,3,4,5,6-hexahydro-6 alpha,7-(methyleneoxy)-2,6-methano-3-benzazocines, a hitherto little-examined series of morphine partial structures. Compounds 7a and 12 gave good levels of agonist antinociceptive activity. Masking of the 8-oxygen function, as in 6 and 8, dramatically reduced mouse hot-plate activity, as did its loss (9).
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Cittern PA,Kapoor VK,Parfitt RTdoi
10.1021/jm00160a022subject
Has Abstractpub_date
1986-10-01 00:00:00pages
1929-33issue
10eissn
0022-2623issn
1520-4804journal_volume
29pub_type
杂志文章abstract：:Electron deficient, bivalent sulfur atoms have two areas of positive electrostatic potential, a consequence of the low-lying σ* orbitals of the C-S bond that are available for interaction with electron donors including oxygen and nitrogen atoms and, possibly, π-systems. Intramolecular interactions are by far the most ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm501853m
更新日期：2015-06-11 00:00:00
abstract：:A series of natural epimers of alpha-homonojirimycin and its N-alkylated derivatives have been prepared to investigate the contribution of the different chiral centers and conformation of the specificity and potency of inhibition of glycosidases. These epimers and N-alkylated derivatives are alpha-homonojirimycin (1),...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm970836l
更新日期：1998-07-02 00:00:00
abstract：:Farnesoid X receptor (FXR) agonists are emerging as important potential therapeutics for the treatment of nonalcoholic steatohepatitis (NASH) patients, as they exert positive effects on multiple aspects of the disease. FXR agonists reduce lipid accumulation in the liver, hepatocellular inflammation, hepatic injury, an...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.9b01621
更新日期：2020-04-23 00:00:00
abstract：:Treatment with HIV-1 protease inhibitors, a component of highly active antiretroviral therapy (HAART), often results in viral resistance. Structural and biochemical characterization of a 6X protease mutant arising from in vitro selection with compound 1, a C 2-symmetric diol protease inhibitor, has been previously des...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm800149m
更新日期：2008-10-23 00:00:00
abstract：:3alpha-(diphenylmethoxy)tropane (benztropine) and its analogues are tropane ring-containing dopamine uptake inhibitors that display binding and behavioral profiles that are distinct from cocaine. We previously prepared a benztropine-based photoaffinity label [125I]-(N-[4-(4'-azido-3'-iodophenyl)butyl]-3alpha-[bis(4'-f...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm0101904
更新日期：2001-12-06 00:00:00
abstract：:3-Phenylpiperidines (PPEs) have been thoroughly investigated in view of their interesting dopaminergic activity, and the N-n-propyl substitution has been suggested as the most effective among several PPEs differently substituted on the phenyl ring. In previous studies, we found that the dimethyl substitution on the ph...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm9708700
更新日期：1998-12-03 00:00:00
abstract：:Conformationally restricted 2'-spironucleosides and their prodrugs were synthesized as potential anti-HCV agents. Although the replicon activity of the new agents containing pyrimidine bases was modest, the triphosphate of a 2'-oxetane cytidine analogue demonstrated potent intrinsic biochemical activity against the NS...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm401224y
更新日期：2014-03-13 00:00:00
abstract：:The use of deuteration in medicinal chemistry has exploded in the past years, and the FDA has recently approved the first deuterium-labeled drug. Precision deuteration goes beyond the pure and simple amelioration of the pharmacokinetic parameters of a drug and might provide an opportunity when facing problems in terms...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章,评审
doi：10.1021/acs.jmedchem.8b01808
更新日期：2019-06-13 00:00:00
abstract：:There is currently no ideal radiotracer for imaging of protein synthesis rate (PSR) by positron emission tomography (PET). Existing fluorine-18-labeled amino acid-based radiotracers predominantly visualize amino acid transporter processes, and in many cases they are not incorporated into nascent proteins at all. Other...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.6b00968
更新日期：2016-10-27 00:00:00
abstract：:The five dopamine receptor subtypes (D1-5) are activated by the endogenous catecholamine dopamine. Sustained research has sought to identify selective ligands for receptor subtypes. In particular, activation of the D1 receptor has attracted attention due to its promising role in neurological diseases. Initial attempts...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章,评审
doi：10.1021/acs.jmedchem.8b01767
更新日期：2019-01-10 00:00:00
abstract：:We have previously reported that rhodacyanine dyes, such as 1 and 2, exhibited a potent inhibitory effect on the growth of several tumor cells and that 4-oxothiazolidine (rhodanine) was an essential moiety for antitumor activity. On the basis of our foregoing work, two types of rhodacyanine dyes, which categorized int...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm970590k
更新日期：1998-01-01 00:00:00
abstract：:A 2A adenosine receptor antagonists usually have bi- or tricyclic N aromatic systems with varying substitution patterns to achieve desired receptor affinity and selectivity. Using a pharmacophore model designed by overlap of nonxanthine type of previously known A 2A antagonists, we synthesized a new class of compounds...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm701594y
更新日期：2008-08-14 00:00:00
abstract：:Human topoisomerase I (TopoI) is recognized as a valuable target for the development of effective antitumor agents. Structure-based virtual screening was applied to the discovery of structurally diverse TopoI inhibitors. From 23 compounds selected by virtual screening, a total of 14 compounds were found to be TopoI in...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm100387d
更新日期：2010-11-11 00:00:00
abstract：:The programmed cell death or apoptosis plays both physiological and pathological roles in biology. Anomalous activation of apoptosis has been associated with malignancies. The intrinsic mitochondrial pathway of apoptosis activation occurs through a multiprotein complex named the apoptosome. We have discovered molecule...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm701195j
更新日期：2008-02-14 00:00:00
abstract：:A study of the effect of aromatic substitution on 5-HT2, D2, and alpha 1 receptor affinity in a subseries of new and previously synthesized 1-piperazino-3-phenylindans indicated that high 5-HT2 selectivity could be obtained in 5-substituted derivatives. Accordingly, a series of 5-substituted derivatives was synthesize...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00071a007
更新日期：1993-09-17 00:00:00
abstract：:Sulbactam (1) is a beta-lactamase inhibitor with limited oral bioavailability. Lipophilic double-ester prodrug sulbactam pivoxil (2) significantly improves the oral absorption of sulbactam, as does the mutual prodrug double ester sultamicillin (3). We have found that double-ester prodrugs of sulbactam terminating in a...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00163a055
更新日期：1990-01-01 00:00:00
abstract：:The discovery of an exceptionally potent series of thrombin receptor (PAR-1) antagonists based on the natural product himbacine is described. Optimization of this series has led to the discovery of 4 (SCH 530348), a potent, oral antiplatelet agent that is currently undergoing Phase-III clinical trials for acute corona...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm800180e
更新日期：2008-06-12 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 series of C7-O- and C20-O-amidated 2,3-dehydrosilybin (DHS) derivatives ((+/-)-1a-f and (+/-)-2), as well as a set of alkenylated DHS analogues ((+/-)-4a-f), were designed and de novo synthesized. A diesteric derivative of DHS ((+/-)-3) and two C23 esterified DHS analogues ((+/-)-5a and (+/-)-5b) were also prepared ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm900735p
更新日期：2009-12-10 00:00:00
abstract：:Two routes for the synthesis of 6-substtituted 8-azaguanosine analogues are described. 2,5,6-Triamino-4(3H)-pyrimidinethione (1) was converted by methylation, nitrosation, and acetylation to -n-acetyl-7-(methylthio)-3H-1,2,3-triazolo[4,5-d]pyrimidin-5-amine (5). The reaction of 5 with 2,3,5-tri-O-acetyl-D-ribofuranosy...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00232a004
更新日期：1976-10-01 00:00:00
abstract：:Structure/activity studies on atrial natriuretic peptide ANP (1-28) have highlighted three portions of the native molecule as necessary for its biological responses. We have linked these three regions and excised the remaining segments to produce a family of small analogues (less than half the size of the parent) whic...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00083a003
更新日期：1992-03-06 00:00:00
abstract：:The chelating drugs BAL (2,3-dimercaptopropanol), EDTA (ethylenediaminetetraacetic acid), and penicillamine (2-amino-3-mercapto-3-methylbutanoic acid), which are used for metal poisoning, are toxic and there is a real need for alternatives, especially for severe cases. A novel approach for treatment of heavy-metal poi...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00142a028
更新日期：1981-10-01 00:00:00
abstract：:A series of novel tetrahydropyridinecarboxamide TRPV1 antagonists were prepared and evaluated in an effort to optimize properties of previously described lead compounds from piperazinecarboxamide series. The compounds were evaluated for their ability to block capsaicin and acid-induced calcium influx in CHO cells expr...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm500818a
更新日期：2014-08-14 00:00:00
abstract：:Protein tyrosine phosphatases (PTPases) are involved in the control of tyrosine phosphorylation levels in the cell and are believed to be crucial for the regulation of a multitude of cellular functions. A detailed understanding of the role played by PTPases in various signaling pathways has not yet been achieved, and ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm990329z
更新日期：2000-01-27 00:00:00
abstract：:The ionization and lipophilicity behavior of the antihistamine (H1-receptor antagonist) cetirizine was investigated, showing the drug to exist almost exclusively as a zwitterion in the pH region 3.5-7.5. In this pH range, its octanol/water lipophilicity is constant and low compared to cationic antihistamines (log D = ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm9704311
更新日期：1998-03-12 00:00:00
abstract：:A set of 30 substituted 5,5'-diphenyl-2-thioxoimidazolidin-4-one (thiohydantoins) derivatives was synthesized, and their affinity for the human CB(1) cannabinoid receptor has been evaluated. These compounds are derived from the previously described cannabinoid ligands 5,5'-diphenylimidazolidine-2,4-dione (hydantoins)....
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm049263k
更新日期：2005-04-07 00:00:00
abstract：:Starting with 2,6-dichlorophenyl isothiocyanate, 1-(2-aminoethyl)-2-cyano-3-(2,6-dichlorophenyl)guanidine (2) was prepared in three steps. In contrast to the corresponding thiourea 1, this compound was essentially inactive as an antihypertensive agent. ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00186a027
更新日期：1980-12-01 00:00:00
abstract：:2,5-Bis(4-guanylphenyl)-1,3-oxazole, 2,5-bis(4-guanylphenyl)-1,3,4-oxadiazole and -1,3,4-thiadiazole, and 3,6-bis(4-guanylphenyl)pyridazine and several of their "cyclic guanyl" analogues have been synthesized. 2,5-Bis(4-guanylphenyl)-1,3-oxazole and -1,3,4-thiadiazole showed good activity, whithout acute toxicity, aga...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00179a022
更新日期：1980-05-01 00:00:00
abstract：:A new paradigm for drug research has emerged, namely the deliberate search for molecules able to selectively affect the proliferation, differentiation, and migration of adult stem cells within the tissues in which they exist. Recently, there has been significant interest in medicinal chemistry toward the discovery and...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章,评审
doi：10.1021/jm500838d
更新日期：2015-04-09 00:00:00
abstract：:The endocannabinoid 2-arachidonoylglycerol (2-AG) plays a major role in many physiological processes, and its action is quickly terminated via enzymatic hydrolysis catalyzed by monoglyceride lipase (MGL). Regulating its endogenous level could offer therapeutic opportunities; however, few selective MGL inhibitors have ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm900461w
更新日期：2009-12-10 00:00:00
