Design and syntheses of 1,6-naphthalene derivatives as selective HCMV protease inhibitors.

abstract：:MMP-12 plays a significant role in airway inflammation and remodeling. Increased expression and production of MMP-12 have been observed in the lungs of asthmatic patients. Compound 27 was identified as a potent and selective MMP-12 inhibitor possessing good physicochemical properties. In pharmacological studies, the c...

journal_title：Journal of medicinal chemistry

authors： Li W,Li J,Wu Y,Rancati F,Vallese S,Raveglia L,Wu J,Hotchandani R,Fuller N,Cunningham K,Morgan P,Fish S,Krykbaev R,Xu X,Tam S,Goldman SJ,Abraham W,Williams C,Sypek J,Mansour TS

更新日期：2009-09-10 00:00:00

abstract：:(E)-Vinylphosphonate ((E)-VP), a metabolically stable phosphate mimic at the 5'-end of the antisense strand, enhances the in vivo potency of siRNA. Here we describe a straightforward synthetic approach to incorporate a nucleotide carrying a vinylphosphonate (VP) moiety at the 5'-end of oligonucleotides under standard ...

journal_title：Journal of medicinal chemistry

authors： Parmar RG,Brown CR,Matsuda S,Willoughby JLS,Theile CS,Charissé K,Foster DJ,Zlatev I,Jadhav V,Maier MA,Egli M,Manoharan M,Rajeev KG

更新日期：2018-02-08 00:00:00

abstract：:A series of 2,3-dihydrobenzofuran-5-acetic acids and related compounds was prepared as potential antiinflammatory agents. As measured by the carrageenan-induced edema method for the preliminary screening test, introduction of a methyl group alpha to the acetic acid function enhanced the antiinflammatory activity, and ...

journal_title：Journal of medicinal chemistry

authors： Hirose N,Kuriyama S,Kato Y,Toyoshima S

更新日期：1976-02-01 00:00:00

abstract：:Inhibitor of secreted frizzled related protein-1 (sFRP-1) would be a novel potential osteogenic agent, since loss of sFRP-1 affects osteoblast proliferation, differentiation, and activity, resulting in improved bone mineral density, quality, and strength. We have identified small molecule diarylsulfone sulfonamide der...

journal_title：Journal of medicinal chemistry

authors： Gopalsamy A,Shi M,Stauffer B,Bahat R,Billiard J,Ponce-de-Leon H,Seestaller-Wehr L,Fukayama S,Mangine A,Moran R,Krishnamurthy G,Bodine P

更新日期：2008-12-25 00:00:00

abstract：:The 2,3-bis[[(N-methylcarbamoyl)oxy]methyl]-3-pyrroline 1-oxide 5 was synthesized and tested in the murine P388 lymphocytic leukemia model. The compound showed significant reproducible activity and was more potent than indicine N-oxide. 1-Methyl-2-phenyl-3,4-bis[[(N-2- propylcarbamoyl)oxy]methyl]-3-pyrroline N-oxide (...

journal_title：Journal of medicinal chemistry

authors： Anderson WK,Milowsky AS

更新日期：1987-11-01 00:00:00

abstract：:Quantitative structure-activity relationships (QSAR) have been established for the inhibition of dihydrofolate reductase and thymidylate synthetase by 2,4-diaminoquinazoline-glutamic acid analogues. For dihydrofolate reductase from both human acute lymphocytic leukemia cells and murine L1210R cells, QSAR's obtained wi...

journal_title：Journal of medicinal chemistry

authors： Chen BK,Horváth C,Bertino JR

更新日期：1979-05-01 00:00:00

abstract：:The currently accepted mechanism of trioxane antimalarial action involves generation of free radicals within or near susceptible sites probably arising from the production of distonic radical anions. An alternative mechanistic proposal involving the ionic scission of the peroxide group and consequent generation of a c...

journal_title：Journal of medicinal chemistry

authors： Drew MG,Metcalfe J,Dascombe MJ,Ismail FM

更新日期：2006-10-05 00:00:00

abstract：:Several 1,3-disubstituted and 1-substituted derivatives of 5-propionoxy-5-(1-phenylethyl)barbituric acid were synthesized and evaluated for analgesic activity. Three of these compounds, 1,3-bis(methoxymethyl)-5-propionoxy-5-(1-phenylethyl)barbituric acid (2), 1,3-dimethyl-5-propionoxy-5-(1-phenylethyl)barbituric acid...

journal_title：Journal of medicinal chemistry

authors： Vida JA,Samour CM,O'Dea MH,Reinhard JF

更新日期：1975-07-01 00:00:00

abstract：:Class IIb bacteriocins are ribosomally synthesized antimicrobial peptides comprising two different peptides synergistically acting in equal amounts for optimal potency. In this study, we demonstrate for the first time potent (nanomolar) antimicrobial activity of a representative class IIb bacteriocin, plantaricin S (P...

journal_title：Journal of medicinal chemistry

authors： Soliman W,Wang L,Bhattacharjee S,Kaur K

更新日期：2011-04-14 00:00:00

abstract：:We have previously reported a series of μ-opioid receptor (MOR) agonist/δ-opioid receptor (DOR) antagonist ligands to serve as potential nonaddictive opioid analgesics. These ligands have been shown to be active in vivo, do not manifest withdrawal syndromes or reward behavior in conditioned-place preference assays in ...

journal_title：Journal of medicinal chemistry

authors： Henry SP,Fernandez TJ,Anand JP,Griggs NW,Traynor JR,Mosberg HI

更新日期：2019-04-25 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

authors： Sosič I,Anderluh M,Sova M,Gobec M,Mlinarič Raščan I,Derouaux A,Amoroso A,Terrak M,Breukink E,Gobec S

更新日期：2015-12-24 00:00:00

abstract：:Adenosine induces glioma cell proliferation by means of an antiapoptotic effect, which is blocked by cotreatment with selective A(3) AR antagonists. In this study, a novel series of N(2)-substituted pyrazolo[3,4-d]pyrimidines 2a-u was developed as highly potent and selective A(3) AR antagonists. The most performing co...

journal_title：Journal of medicinal chemistry

authors： Taliani S,La Motta C,Mugnaini L,Simorini F,Salerno S,Marini AM,Da Settimo F,Cosconati S,Cosimelli B,Greco G,Limongelli V,Marinelli L,Novellino E,Ciampi O,Daniele S,Trincavelli ML,Martini C

更新日期：2010-05-27 00:00:00

abstract：:Acute lung injury (ALI) and idiopathic pulmonary fibrosis (IPF) are both serious public health problems with high incidence and mortality rate in adults, and with few drugs available for the efficient treatment in clinic. In this study, we identified that two known histone deacetylase (HDAC) inhibitors, suberanilohydr...

journal_title：Journal of medicinal chemistry

authors： Lu W,Yao X,Ouyang P,Dong N,Wu D,Jiang X,Wu Z,Zhang C,Xu Z,Tang Y,Zou S,Liu M,Li J,Zeng M,Lin P,Cheng F,Huang J

更新日期：2017-03-09 00:00:00

abstract：:A novel series of fully synthetic 8-azatetracyclines was prepared and evaluated for antibacterial activity. Compounds were identified that overcome both efflux (tet(K)) and ribosomal protection (tet(M)) tetracycline resistance mechanisms and are active against Gram-positive and Gram-negative organisms. Two compounds w...

journal_title：Journal of medicinal chemistry

authors： Clark RB,He M,Fyfe C,Lofland D,O'Brien WJ,Plamondon L,Sutcliffe JA,Xiao XY

更新日期：2011-03-10 00:00:00

abstract：:New analogs of cyclic amino acid-conjugated bile acids were synthesized, and their physicochemical and biological properties were compared with those of natural analogs. Ursodeoxycholic acid was amidated with D-proline, L-proline, 4-hydroxy-L-proline, and 4-methoxy-L-proline. Hyocholic and hyodeoxycholic acids were am...

journal_title：Journal of medicinal chemistry

authors： Roda A,Cerrè C,Manetta AC,Cainelli G,Umani-Ronchi A,Panunzio M

更新日期：1996-05-24 00:00:00

abstract：:Twenty-three acrylonitriles, substituted at position 2 with either triazoles or benzimidazoles and at position 3 with various substituted furan, thiophene, or phenyl rings, were prepared by Knoevenagel condensation and tested for in vitro cytotoxic potency on 11 human cancer cell lines. X-ray crystal analysis of two r...

journal_title：Journal of medicinal chemistry

authors： Saczewski F,Reszka P,Gdaniec M,Grünert R,Bednarski PJ

更新日期：2004-06-17 00:00:00

abstract：:(Trimethylsilyl)acetylene was coupled with 1-(2,3,5-tri-O-acetyl-beta-D- arabinofuranosyl)-5-iodouracil to give 1- (2,3,5-tri-O-acetyl-beta-D-arabinofuranosyl)-5-[2-(trimethylsilyl)eth yny l] uracil. Lindlar hydrogenation of 4 gave 1-(2,3,4-tri-O-acetyl-beta-D-arabinofuranosyl)-5(Z)-[2- (trimethylsilyl)vinyl]uracil. T...

journal_title：Journal of medicinal chemistry

authors： Robins MJ,Manfredini S,Wood SG,Wanklin RJ,Rennie BA,Sacks SL

更新日期：1991-07-01 00:00:00

abstract：:Eleven new 12-amino-6,7,10,11-tetrahydro-7, 11-methanocycloocta[b]quinoline derivatives [tacrine (THA)-huperzine A hybrids, rac-21-31] have been synthesized as racemic mixtures and tested as acetylcholinesterase (AChE) inhibitors. For derivatives unsubstituted at the benzene ring, the highest activity was obtained for...

journal_title：Journal of medicinal chemistry

authors： Camps P,El Achab R,Görbig DM,Morral J,Muñoz-Torrero D,Badia A,Eladi Baños J,Vivas NM,Barril X,Orozco M,Luque FJ

更新日期：1999-08-26 00:00:00

abstract：:To study the influence of substitution of CN for C identical to CH in the anti-herpes virus nucleoside 5-(propynyloxy)-2'-deoxyuridine (1), 5-[(cyanomethylene)oxy]-2'-deoxyuridine (2) was prepared. When the potassium salt of 5-hydroxy-2'-deoxyuridine was reacted with iodoacetonitrile in dry DMF, the bisalkylated produ...

journal_title：Journal of medicinal chemistry

authors： Huang GF,Okada M,De Clercq E,Torrence PF

更新日期：1981-04-01 00:00:00

abstract：:The DEDDh family of exonucleases plays essential roles in DNA and RNA metabolism in all kingdoms of life. Several viral and human DEDDh exonucleases can serve as antiviral drug targets due to their critical roles in virus replication. Here using RNase T and CRN-4 as the model systems, we identify potential inhibitors ...

journal_title：Journal of medicinal chemistry

authors： Huang KW,Hsu KC,Chu LY,Yang JM,Yuan HS,Hsiao YY

更新日期：2016-09-08 00:00:00

abstract：:The photoswitchable N-terminal diazo and triazene-dipeptide aldehydes 8a-d, 10a,b, and 17a,b present predominantly as the (E)-isomer, which purportedly binds deep in the S3 pocket of calpain. All compounds are potent inhibitors of m-calpain, with 8b being the most active (IC50 of 35 nM). The diazo-containing inhibitor...

journal_title：Journal of medicinal chemistry

authors： Abell AD,Jones MA,Neffe AT,Aitken SG,Cain TP,Payne RJ,McNabb SB,Coxon JM,Stuart BG,Pearson D,Lee HY,Morton JD

更新日期：2007-06-14 00:00:00

abstract：:A series of benzyl-substituted phthalonitriles, substituted at the 3-, 4-, and 4,5-positions, underwent varied condensations with phthalonitrile to give a series of protected (monohydroxy- and polyhydroxyphthalocyaninato)zinc(II) derivatives which were readily cleaved to give several hydroxyphthalocyanines (ZnPc) (pht...

journal_title：Journal of medicinal chemistry

authors： Hu M,Brasseur N,Yildiz SZ,van Lier JE,Leznoff CC

更新日期：1998-05-21 00:00:00

abstract：:Proteasomes of pathogenic microbes have become attractive targets for anti-infectives. Coevolving with its human host, Mycobacterium tuberculosis (Mtb) has developed mechanisms to resist host-imposed nitrosative and oxidative stresses. Genetic deletion or pharmacological inhibition of the Mtb proteasome (Mtb20S) rende...

journal_title：Journal of medicinal chemistry

authors： Zhan W,Hsu HC,Morgan T,Ouellette T,Burns-Huang K,Hara R,Wright AG,Imaeda T,Okamoto R,Sato K,Michino M,Ramjee M,Aso K,Meinke PT,Foley M,Nathan CF,Li H,Lin G

更新日期：2019-10-24 00:00:00

abstract：:Chemical probes of microRNA (miRNA) function are potential tools for understanding miRNA biology that also provide new approaches for discovering therapeutics for miRNA-associated diseases. MicroRNA-21 (miR-21) is an oncogenic miRNA that is overexpressed in most cancers and has been strongly associated with driving ch...

journal_title：Journal of medicinal chemistry

authors： Naro Y,Ankenbruck N,Thomas M,Tivon Y,Connelly CM,Gardner L,Deiters A

更新日期：2018-07-26 00:00:00

abstract：:Hydroxylated, methoxylated, and/or chlorinated 7-methyl-5,6,7,8,9,14-hexahydrodibenz[d,g]azecines were generally synthesized out of substituted 2-phenylethylamines and isochromanones by Bischler-Napieralski cyclization of the resulting benzamides to dibenzoquinolizines and the quaternization and cleavage of the centra...

journal_title：Journal of medicinal chemistry

authors： Mohr P,Decker M,Enzensperger C,Lehmann J

更新日期：2006-03-23 00:00:00

abstract：:Recent evidence suggests that intraneuronal metabolism of ethanol by catalase/H2O2 and an ethanol-inducible form of cytochrome P450 together generate acetaldehyde and oxygen radicals including the hydroxyl radical (HO.). Within the cytoplasm of serotonergic neurons, these metabolic processes would thus provide acetald...

journal_title：Journal of medicinal chemistry

authors： Han QP,Dryhurst G

更新日期：1996-03-29 00:00:00

abstract：:Analogues of the previously reported potent cytotoxic spiro[(dihydropyrazine-2,5-dione)-6,3'-(2',3'-dihydrothieno[2,3-b]naphtho-4',9'-dione)] derivatives (3, 3') were prepared to explore new structural requirements at the diketopiperazine domain for the cytotoxic activity. The in vitro activity was evaluated against t...

journal_title：Journal of medicinal chemistry

authors： Gomez-Monterrey I,Campiglia P,Carotenuto A,Stiuso P,Bertamino A,Sala M,Aquino C,Grieco P,Morello S,Pinto A,Ianelli P,Novellino E

更新日期：2008-05-22 00:00:00

abstract：:A computational chemistry study has been performed on a series of tetrahydropyrimidine-2-ones (THPs) as HIV-1 protease (HIV-1 PR) inhibitors. The present investigation focuses on the correlation of inhibitor-enzyme complexation energies (E(compl)), inhibitor solvation energies E(solv)[I], and both polar and nonpolar b...

journal_title：Journal of medicinal chemistry

authors： Nair AC,Jayatilleke P,Wang X,Miertus S,Welsh WJ

更新日期：2002-02-14 00:00:00

abstract：:Increased usage of daptomycin to treat infections caused by Gram-positive bacterial pathogens has resulted in emergence of resistant mutants. In a search for more effective daptomycin analogues through medicinal chemistry studies, we found that methylation at the nonproteinogenic amino acid kynurenine in daptomycin co...

journal_title：Journal of medicinal chemistry

authors： Chow HY,Po KHL,Gao P,Blasco P,Wang X,Li C,Ye L,Jin K,Chen K,Chan EWC,You X,Yi Tsun Kao R,Chen S,Li X

更新日期：2020-03-26 00:00:00

abstract：:RhoA is a member of Rho GTPases, a subgroup of the Ras superfamily of small GTP-binding proteins. RhoA, as an important regulator of diverse cellular signaling pathways, plays significant roles in cytoskeletal organization, transcription, and cell-cycle progression. The RhoA/ROCK inhibitors have emerged as a new promi...

journal_title：Journal of medicinal chemistry

authors： Deng J,Feng E,Ma S,Zhang Y,Liu X,Li H,Huang H,Zhu J,Zhu W,Shen X,Miao L,Liu H,Jiang H,Li J

更新日期：2011-07-14 00:00:00