Antimycotic azoles. 7. Synthesis and antifungal properties of a series of novel triazol-3-ones.

abstract：:Because several well-studied strains of rats manifest spontaneous hypertension, we set out to design a renin inhibitor suitable for use in this species. On the basis of the sequence of the renin substrate, a series of substrate analogue inhibitory peptides were synthesized by systematically modifying the P5, P3, P2, P...

journal_title：Journal of medicinal chemistry

authors： Hui KY,Holtzman EJ,Quinones MA,Hollenberg NK,Haber E

更新日期：1988-09-01 00:00:00

abstract：:Three phosphapeptides designed to mimic two distinct tetrahedral intermediates formed during either the synthesis or hydrolysis of glutathionylspermidine (Gsp) were synthesized and evaluated as inhibitors of the bifunctional enzyme Gsp synthetase/amidase. While the polyamine-containing phosphapeptides were determined ...

journal_title：Journal of medicinal chemistry

authors： Chen S,Lin CH,Kwon DS,Walsh CT,Coward JK

更新日期：1997-11-07 00:00:00

abstract：:We have previously determined that Ac-D-Trp-Leu-Asp-Ile-Ile-Trp (peptide I), an endothelin antagonist, binds specifically (Ki = 1.9 microM) to the rat pituitary gonadotropin-releasing hormone (GnRH) receptor. Moreover, peptide I exhibits a GnRH agonistic activity, mediated directly by the GnRH receptor. We now report ...

journal_title：Journal of medicinal chemistry

authors： Yahalom D,Rahimipour S,Koch Y,Ben-Aroya N,Fridkin M

更新日期：2000-07-27 00:00:00

abstract：:Interesting analgesic activity approaching that of meperidine and codeine was observed in standard animal models for 8-chloro-3,4-dihydro-5-methoxy-2-pyrrolidinomethylnaphthalene (compound 7). This compound was orally effective and its analgesic activity was not reversed by the opiate antagonist, naloxone. A limited n...

journal_title：Journal of medicinal chemistry

authors： Welch WM,Plattner JJ,Stratten WP,Harbert CA

更新日期：1978-03-01 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

authors： Zhu GD,Gandhi VB,Gong J,Thomas S,Woods KW,Song X,Li T,Diebold RB,Luo Y,Liu X,Guan R,Klinghofer V,Johnson EF,Bouska J,Olson A,Marsh KC,Stoll VS,Mamo M,Polakowski J,Campbell TJ,Martin RL,Gintant GA,Penning TD,

更新日期：2007-06-28 00:00:00

abstract：:The steroidal sulfonylpyrazole 1 bound to the rat ventral prostate androgen receptor in vitro; it inhibited testosterone propionate induced increases in ventral prostate weight in vivo in the castrated, immature male rat with an ED50 of 15 mg/kg po. Compound 1 lacked androgenic activity in vivo in contrast to the pare...

journal_title：Journal of medicinal chemistry

authors： Christiansen RG,Bell MR,D'Ambra TE,Mallamo JP,Herrmann JL,Ackerman JH,Opalka CJ,Kullnig RK,Winneker RC,Snyder BW

更新日期：1990-08-01 00:00:00

abstract：:(N)-Methanocarba nucleosides containing bicyclo[3.1.0]hexane replacement of the ribose ring previously demonstrated selectivity as A(3) adenosine receptor (AR) agonists (5'-uronamides) or antagonists (5'-truncated). Here, these two series were modified in parallel at the adenine C2 position. N(6)-3-Chlorobenzyl-5'-N-m...

journal_title：Journal of medicinal chemistry

authors： Tosh DK,Chinn M,Ivanov AA,Klutz AM,Gao ZG,Jacobson KA

更新日期：2009-12-10 00:00:00

abstract：:On the basis of results previously obtained from structural and theoretical studies on beta-adrenergic drugs, a series of aliphatic oxime ether derivatives (AOEDs) was synthesized. As expected, pharmacological in vitro tests showed that compounds examined exhibit a marked and competitive antagonism at beta-adrenocepto...

journal_title：Journal of medicinal chemistry

authors： Macchia B,Balsamo A,Lapucci A,Martinelli A,Macchia F,Breschi MC,Fantoni B,Martinotti E

更新日期：1985-02-01 00:00:00

abstract：:Novel antibiotics are urgently needed to combat the rise of infections due to drug-resistant microorganisms. Numerous natural nucleosides and their synthetically modified analogues have been reported to have moderate to good antibiotic activity against different bacterial and fungal strains. Nucleoside-based compounds...

journal_title：Journal of medicinal chemistry

authors： Serpi M,Ferrari V,Pertusati F

更新日期：2016-12-08 00:00:00

abstract：:We have previously described a cyclic tetrapeptide, 1, that displays μ opioid receptor (MOPr) agonist and δ opioid receptor (DOPr) antagonist activity, a profile associated with a reduced incidence of opioid tolerance and dependence. Like many peptides, 1 has poor bioavailability. We describe here an analogue of 1 wit...

journal_title：Journal of medicinal chemistry

authors： Mosberg HI,Yeomans L,Anand JP,Porter V,Sobczyk-Kojiro K,Traynor JR,Jutkiewicz EM

更新日期：2014-04-10 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

authors： Singh C,Malik H,Puri SK

更新日期：2006-05-04 00:00:00

abstract：:A series of 3-(alkoxymethyl)-alpha-(N-substituted aminomethyl)-4-hydroxybenzyl alcohols was synthesized as potential bronchodilators. The ability to prevent effects against histamine-induced bronchoconstriction in guinea pigs was studied to determine their bronchodilating activity. Introduction of a methoxymethyl grou...

journal_title：Journal of medicinal chemistry

authors： Sohda S,Fujimoto M,Tamegai T,Hirose N

更新日期：1979-03-01 00:00:00

abstract：:Melanin concentrating hormone (MCH) is involved in regulation of food intake and energy homeostasis. Antagonists of the MCH receptor are expected to affect food intake and weight gain, making MCH-R1 an attractive target for obesity treatment. Herein, we report the discovery of a novel, orally active series of MCH-R1 a...

journal_title：Journal of medicinal chemistry

authors： McBriar MD,Guzik H,Xu R,Paruchova J,Li S,Palani A,Clader JW,Greenlee WJ,Hawes BE,Kowalski TJ,O'Neill K,Spar B,Weig B

更新日期：2005-04-07 00:00:00

abstract：:The active site of lanosterol 14alpha-demethylase (CYP51) was investigated via MCSS functional group mapping and LUDI calculations. Several non-azole lead molecules were obtained by coupling structure-based de novo design with chemical synthesis and biological evaluation. All of the lead molecules exhibited a strong i...

journal_title：Journal of medicinal chemistry

authors： Ji H,Zhang W,Zhang M,Kudo M,Aoyama Y,Yoshida Y,Sheng C,Song Y,Yang S,Zhou Y,Lü J,Zhu J

更新日期：2003-02-13 00:00:00

abstract：:The 18 kDa translocator protein (TSPO) is a mitochondrial protein whose basal density is altered in several diseases, with the result that the evaluation of its expression levels by means of molecular imaging techniques represents a promising diagnostic approach. Experimental procedures using a labeled ligand often ca...

journal_title：Journal of medicinal chemistry

authors： Taliani S,Da Pozzo E,Bellandi M,Bendinelli S,Pugliesi I,Simorini F,La Motta C,Salerno S,Marini AM,Da Settimo F,Cosimelli B,Greco G,Novellino E,Martini C

更新日期：2010-05-27 00:00:00

abstract：:Novel 3,5-bis(benzylidene)-1-[3-(2-hydroxyethylthio)propanoyl]piperidin-4-ones (3a-e) display potent cytotoxicity and a preferential lethality toward various neoplasms compared to some normal cells. The corresponding sulfonic acid analogues 5a-e and an isostere 4 demonstrated substantially lower activity. The leads 3d...

journal_title：Journal of medicinal chemistry

authors： Das U,Pati HN,Sakagami H,Hashimoto K,Kawase M,Balzarini J,De Clercq E,Dimmock JR

更新日期：2011-05-12 00:00:00

abstract：:This work reports on the synthesis, characterization, and in vitro cytotoxic activity of some new platinum(II), palladium(II), and gold(III) derivatives of methylsarcosinedithiocarbamate and its S-methyl ester, to study their behavior as potential antitumor agents. The biological activity of these compounds, as determ...

journal_title：Journal of medicinal chemistry

authors： Giovagnini L,Ronconi L,Aldinucci D,Lorenzon D,Sitran S,Fregona D

更新日期：2005-03-10 00:00:00

abstract：:We have determined an X-ray crystal structure for the N-methyl iodide derivative of the nonsteroidal contraceptive centchroman. The pendant aromatic substituents on C-3 and C-4 of the chroman system are nearly perpendicular to the plane of the chroman system, an orientation expected in such a chroman, but perturbed to...

journal_title：Journal of medicinal chemistry

authors： Ray S,Tandon A,Dwivedy I,Wilson SR,O'Neil JP,Katzenellenbogen JA

更新日期：1994-03-04 00:00:00

abstract：:A series of C-terminal peptide segments of gastrin, i.e., (tert-butyloxycarbonyl)-L-tryptophyl-L-methionyl-L-aspartic acid amide, (tert-butyloxycarbonyl)-glycyl-L-tryptophyl-L-methionyl-L-aspartic acid amide, (tert-butyloxy-carbonyl)-L-tyrosyl-glycyl-L-tryptophyl-L-methionyl-L-asp artic acid amide, and (benzyloxycarbo...

journal_title：Journal of medicinal chemistry

authors： Martinez J,Magous R,Lignon MF,Laur J,Castro B,Bali JP

更新日期：1984-12-01 00:00:00

abstract：:A series of indolequinones bearing various functional groups has been synthesized, and the effects of substituents on the metabolism of the quinones by recombinant human NAD(P)H:quinone oxidoreductase (NQO1) were studied. Indolequinones were selected for study on the basis of the X-ray crystal structure of the human e...

journal_title：Journal of medicinal chemistry

authors： Swann E,Barraja P,Oberlander AM,Gardipee WT,Hudnott AR,Beall HD,Moody CJ

更新日期：2001-09-27 00:00:00

abstract：:A series of new HIV-1 protease inhibitors with the hydroxyethylamine core and different phenyloxazolidinone P2 ligands were designed and synthesized. Variation of phenyl substitutions at the P2 and P2' moieties significantly affected the binding affinity and antiviral potency of the inhibitors. In general, compounds w...

journal_title：Journal of medicinal chemistry

authors： Ali A,Reddy GS,Nalam MN,Anjum SG,Cao H,Schiffer CA,Rana TM

更新日期：2010-11-11 00:00:00

abstract：:alpha-Fluoromethyl amino acids are enzyme-activated irreversible inhibitors of amino acid decarboxylases. Aromatic L-amino acid decarboxylase (AADC) is the enzyme responsible for the final step in the biosynthesis of both dopamine and serotonin via decarboxylation of L-dopa and 5-hydroxy-L-tryptophan, respectively. Ou...

journal_title：Journal of medicinal chemistry

authors： Zembower DE,Gilbert JA,Ames MM

更新日期：1993-02-05 00:00:00

abstract：:Novel N-substituted derivatives of acyclovir (1a) were synthesized and evaluated for their antiviral, antimetabolic, and antitumor cell properties in vitro. Monomethylation of 1a at positions 1, 7, and N-2 gave compounds 2-4, respectively. When positions 1 and N-2 were linked together by an isopropeno group, the tricy...

journal_title：Journal of medicinal chemistry

authors： Boryski J,Golankiewicz B,De Clercq E

更新日期：1988-07-01 00:00:00

abstract：:Pharmacophore, two-dimensional (2D), and three-dimensional (3D) quantitative structure-activity relationship (QSAR) modeling techniques were used to develop and test models capable of rationalizing and predicting human UDP-glucuronosyltransferase 1A4 (UGT1A4) substrate selectivity and binding affinity (as K(m,app)). T...

journal_title：Journal of medicinal chemistry

authors： Smith PA,Sorich MJ,McKinnon RA,Miners JO

更新日期：2003-04-24 00:00:00

abstract：:We recently introduced sulfated pentagalloylglucopyranoside (SPGG) as an allosteric inhibitor of factor XIa (FXIa) (Al-Horani et al., J. Med Chem. 2013, 56, 867-878). To better understand the SPGG-FXIa interaction, we utilized eight SPGG variants and a range of biochemical techniques. The results reveal that SPGG's su...

journal_title：Journal of medicinal chemistry

authors： Al-Horani RA,Desai UR

更新日期：2014-06-12 00:00:00

abstract：:4-(Dimethylamino)- and 4-(methylamino)-3'-arylspiro[cyclohexane-1,1'(3'H)-isobenzofuran] derivatives were prepared as analogues of previously reported 3-arylspiro[isobenzofuran-1(3H),4'-piperidines]. Metalation of benzanilide with n-butyllithium, addition of 4-(dimethylamino)cyclohexanone, and acidification afforded a...

journal_title：Journal of medicinal chemistry

authors： Martin LL,Worm M,Agnew MN,Kruse H,Wilker JC,Geyer HM 3rd

更新日期：1981-05-01 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

authors： Rosowsky A,Forsch R,Uren J,Wick M,Kumar AA,Freisheim JH

更新日期：1983-12-01 00:00:00

abstract：:As the number of cases and cancer-related deaths are projected to rise in upcoming years, it is urgent to find ways to prevent or treat cancer. As such, food-derived products have gained attention as potential chemopreventive agents due to their availability, safety, and low cost. Isothiocyanates, the breakdown produc...

journal_title：Journal of medicinal chemistry

authors： Frieben EE,Amin S,Sharma AK

更新日期：2019-06-13 00:00:00

abstract：:The relative simplicity and high specificity of peptide therapeutics has fueled recent interest. However, peptide and protein drugs generally require injection and suffer from low metabolic stability. We report here the design, synthesis, and characterization of fluorinated analogues of the gut hormone peptide, GLP-1....

journal_title：Journal of medicinal chemistry

authors： Meng H,Krishnaji ST,Beinborn M,Kumar K

更新日期：2008-11-27 00:00:00

abstract：:The JAK-STAT3 pathway regulates genes that are important in cell proliferation and thus is a promising target for cancer therapy. A high-throughput screening (HTS) campaign using an Apo-ONE Homogenous Caspase 3/7 assay in U266 cells identified 4-oxo-1-phenyl-1,4-dihydroquinoline-3-carboxylic acid ethyl ester 4 as a po...

journal_title：Journal of medicinal chemistry

authors： Xu J,Cole DC,Chang CP,Ayyad R,Asselin M,Hao W,Gibbons J,Jelinsky SA,Saraf KA,Park K

更新日期：2008-07-24 00:00:00