Abstract：
:Several pairs of cannabinoid isomers were synthesized and tested for psychotropic activity in rhesus monkeys. Two regularities were observed: (a) In the absence of the other substituents, the equatorial stereochemistry of the substituent at C-1 determines activity. (b) Two groups of THC-type cannabinoids which differ only in that the chemical groupings in one of them at C-1, C-2 are situated at C-1, C-6 in the other (but retain their stereochemistry) have almost equivalent psychotropic activity.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Mechoulam R,Lander N,Varkony TH,Kimmel I,Becker O,Ben-Zvi Z,Edery H,Porath Gdoi
10.1021/jm00184a002subject
Has Abstractpub_date
1980-10-01 00:00:00pages
1068-72issue
10eissn
0022-2623issn
1520-4804journal_volume
23pub_type
杂志文章abstract：:Much has been discussed about the proper physicochemical properties (e.g., molecular weight, hydrophobicity, etc.) that should be considered when utilizing fragment leads in drug design. However, little has been reported as to what emphasis, if any, should be placed on the potency of the resulting fragment leads. In t...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm060511h
更新日期：2006-11-30 00:00:00
abstract：:In humans, bitter taste is mediated by 25 TAS2Rs. Many compounds, including certain active pharmaceutical ingredients, excipients, and nutraceuticals, impart their bitter taste (or in part) through TAS2R8 activation. However, effective TAS2R8 blockers that can either suppress or reduce the bitterness of these compound...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.0c00388
更新日期：2020-05-14 00:00:00
abstract：:4-(2-Methoxyphenyl)-2-[4(5)-methyl-5(4)-imidazolylmethyl]thiazole (5) is a highly potent member of a structurally novel series of selective serotonin-3 receptor antagonists. The synthesis of tritiated 5 and its binding profile in neuroblastoma-glioma 108-15 cells are described. Furthermore, in vivo studies in rat with...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00173a017
更新日期：1990-11-01 00:00:00
abstract：:Taking advantage of a proposed hydrophobic region on 5-HT2 receptors previously identified by radioligand-binding studies utilizing various phenylisopropylamine derivatives, we prepared and evaluated several N1 - and/or C7-alkyl-substituted derivatives of alpha-methyltryptamine in order to improve its affinity and sel...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00172a016
更新日期：1990-10-01 00:00:00
abstract：:9,11-Secoestradiol (9) and 11-hydroxy-9,11-secoestradiol (12) have been synthesized starting from 17-acetoxyestradiol 3-methyl ether (1) and found to possess significant antifertility activity in rats. 3-Methoxy-9,11-seco-9-oxo-17beta-acetoxyestra-1,3,5(10)-trien-11-oic acid (2), prepared by CrO3 oxidation of 1, on h...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00241a026
更新日期：1975-07-01 00:00:00
abstract：:Nitrosourea derivatives 9--13 which utilize phensuximide (1) as the carrier were synthesized as potential central nervous system antitumor agents. The N-(2-chloroethyl)-N-nitrosourea 13 was active in the mouse ependymoblastoma brain-tumor system, as well as the intraperitoneal L1210 leukemia system. ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00177a024
更新日期：1980-03-01 00:00:00
abstract：:The construction of bioactive peptides using β-amino acid-containing sequence patterns is a very promising strategy to obtain analogues that exhibit properties of high interest for medicinal chemistry applications. β-Amino acids have been shown to modulate the conformation, dynamics, and proteolytic susceptibility of ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm5010896
更新日期：2014-12-11 00:00:00
abstract：:Described in this paper is the synthesis and pharmacological activity of five metabolites of the angiotensin II antagonist tasosartan (1). Of particular interest is the effect of the additional acidic group of the enol metabolite (8) on activity. As suggested by the structural-activity relationship of other angiotensi...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm970690q
更新日期：1998-10-22 00:00:00
abstract：:[4-Threonine, 7-glycine]oxytocin and [1-(L-2-hydroxy-3-mercaptopropanoic acid), 4-threonine, 7-glycine]oxytocin (hydroxy[Thr4, Gly7]oxytocin) were synthesized by a combination of solid-phase and classical methods of peptide synthesis. A protected octapeptide was synthesized by the solid-phase method and following ammo...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00211a025
更新日期：1977-01-01 00:00:00
abstract：:Gossypol and 17 derivatives were tested as inhibitors of aldose reductase from human placenta. Gossypol and a number of the derivatives were potent inhibitors. The order of inhibitory activity was interpreted in relation to the Kador-Sharpless pharmacophor model for the aldose reductase inhibitor site. The structural ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00115a021
更新日期：1991-11-01 00:00:00
abstract：:The antibacterial properties of glycopeptide antibiotics are based on their interaction with the d-Ala-d-Ala containing pentapeptide of bacterial peptidoglycan. The hydrophobic amides of vancomycin (1), teicoplanin (2), teicoplanin aglycon (3), and eremomycin (4) were compared with similar amides of minimally or low a...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm020320o
更新日期：2003-03-27 00:00:00
abstract：:Vps34 (the human class III phosphoinositide 3-kinase) is a lipid kinase involved in vesicle trafficking and autophagy and therefore constitutes an interesting target for cancer treatment. Because of the lack of specific Vps34 kinase inhibitors, we aimed to identify such compounds to further validate the role of this l...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm5013352
更新日期：2015-01-08 00:00:00
abstract：:Analogues of angiotensin II and III (ANG II and ANG III) in which the tyrosine and/or phenylalanine residues were substituted have been synthesized by the solid-phase method and purified by (carboxymethyl)cellulose chromatography and reversed-phase HPLC. The antagonist and agonist potencies of these peptides were dete...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00383a015
更新日期：1985-06-01 00:00:00
abstract：:Ghrelin, a gut-derived orexigenic hormone, is an endogenous ligand of the growth hormone secretagogue receptor (GHS-R). Centrally administered ghrelin has been shown to cause hunger and increase food intake in rodents. Inhibition of ghrelin actions with ghrelin antibody, peptidyl GHS-R antagonists, and antisense oligo...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm0510934
更新日期：2006-04-20 00:00:00
abstract：:The crystal and molecular structure of metyrapone, a powerful inhibitor of certain cytochromes P-450, is described. Cytochrome P-450 enzymes are involved in metabolic processes, including those activating insecticides, drugs, and carcinogens. Metyrapone inhibits both the adrenal cytochrome P-450 catalyzing 11-beta-hyd...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00363a008
更新日期：1983-09-01 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：:A series of novel β-carboline-based N-heterocyclic carbenes was prepared via Mannich reaction between methyl 1-(dimethoxymethyl)-9H-pyrido[3,4-b]indole-3-carboxylate, formaldehyde, and primary amines. All compounds were evaluated for their antiproliferative activity using human breast cancer and lung cancer cell lines...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.5b00016
更新日期：2015-04-23 00:00:00
abstract：:Using easily accessible keto-trioxanes 7a-g as the starting materials, a series of new variously functionalized 1,2,4-trioxanes 10-36 have been prepared and evaluated for antimalarial activity against multi-drug-resistant Plasmodium yoelii nigeriensis in mice in the dose range of 24 mg/kg x 4 days to 96 mg/kg x 4 days...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm051130r
更新日期：2006-05-04 00:00:00
abstract：:Lead-like drugs, or drugs below molecular weight 300, are an important and sometimes overlooked component of the current pharmacopeia and contemporary medicinal chemistry practice. To examine the recent state-of-the-art in lead-like drug discovery, we surveyed recent drug approvals from 2011 to 2017 and top 200 prescr...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章,评审
doi：10.1021/acs.jmedchem.8b00407
更新日期：2018-12-13 00:00:00
abstract：:Bioorthogonal chemistry has become one of the main driving forces in current chemical biology, inspiring the search for novel biocompatible chemospecific reactions for the past decade. Alongside the well-established labeling strategies that originated the bioorthogonal paradigm, we have recently proposed the use of he...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm500531z
更新日期：2014-06-26 00:00:00
abstract：:Tankyrases are poly(ADP-ribose) polymerases that have many cellular functions. They play pharmaceutically important roles, at least in telomere homeostasis and Wnt signaling, by covalently ADP-ribosylating target proteins and consequently regulating their functions. These features make tankyrases potential targets for...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm201510p
更新日期：2012-02-09 00:00:00
abstract：:In pursuit of truncated glucagon analogues that can interact with the glucagon receptor with substantial binding affinity, 23 truncated glucagon analogues have been designed and synthesized. These truncated analogues consist of several fragments of glucagon with 11 or 12 amino acid residues (1-4), conformationally con...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm000453e
更新日期：2001-04-26 00:00:00
abstract：:The lack of molecules endowed with selective and potent agonistic activity toward the hA2B adenosine receptors has limited the studies on this pharmacological target and consequently the evaluation of its therapeutic potential. We report the design and the synthesis of the first potent (EC50 in the nanomolar range) an...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm061170a
更新日期：2007-01-25 00:00:00
abstract：:We disclose optimization efforts based on the novel non-nucleoside adenosine deaminase (ADA) inhibitor, 4 (K(i) = 680 nM). Structure-based drug design utilizing the crystal structure of the 4/ADA complex led to discovery of 5 (K(i) = 11 nM, BA = 30% in rats). Furthermore, from metabolic considerations, we discovered t...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm0499559
更新日期：2004-05-20 00:00:00
abstract：:Isoform-selective antagonists of the lysophosphatidic acid (LPA) G-protein coupled receptors (GPCRs) have important potential uses in cell biology and clinical applications. Novel phosphonothioate and fluoromethylene phosphonate analogues of carbacyclic phosphatidic acid (ccPA) were prepared by chemical synthesis. The...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm060351+
更新日期：2006-08-24 00:00:00
abstract：:Chain-extended analogues of methotrexate were synthesized by condensation of 4-amino-4-deoxy-N10-methylpteroic acid with esters of L-alpha-aminoadipic, L-alpha-aminopimelic, and L-alpha-aminosuberic acids, followed by ester hydrolysis with acid or base. Coupling was accomplished in up to 85% yield by the use of the pe...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00366a012
更新日期：1983-12-01 00:00:00
abstract：:A series of [(3-aryl-1,2-benzisoxazol-6-yl)oxy]acetic acids was synthesized and tested for diuretic activity in saline-loaded mice and in conscious, water-loaded dogs. The structural requirements for good diuretic activity in both mice and dogs were found to be very specific. In summary, the compounds with the best di...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00343a008
更新日期：1982-01-01 00:00:00
abstract：:The pathology of chronic dermal ulcers is characterized by excessive proteolytic activity which degrades extracellular matrix (required for cell migration) and growth factors and their receptors. The overexpression of MMP-3 (stromelysin-1) and MMP-13 (collagenase-3) is associated with nonhealing wounds, whereas active...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm0308038
更新日期：2003-07-31 00:00:00
abstract：:The constitution of chlorpromazine has been studied in the context of its phototoxicity. Electron transfer from the side chain to the aromatic nucleus of the drug contributes to its instability to light. Even without the side chain, however, chlorophenothiazines appear to be very photolabile, so that it is unlikely th...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00188a016
更新日期：1979-02-01 00:00:00
abstract：:The synthesis of chiral 1,5-benzothiazepines 2a-c, 14a-c, 15c, and 16a prepared from cysteine is described. In vitro inhibition of angiotensin converting enzyme (ACE) is reported for each compound. Compound 2c was the most potent in vitro having an IC50 of 2.95 nM. The ester of 2c, i.e. 14c, was found to inhibit the A...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00148a024
更新日期：1985-10-01 00:00:00
