Spiro[(dihydropyrazin-2,5-dione)-6,3'-(2',3'-dihydrothieno[2,3-b]naphtho-4',9'-dione)]-based cytotoxic agents: structure-activity relationship studies on the substituent at N4-position of the diketopiperazine domain.

abstract：:A series of cis- and trans-dihydroxycotahydrobenzo[f]quinoline congeners of dopamine has been prepared, in which the N substitutent is H, ethyl, or n-propyl. The trans isomers include the dopamine moiety held rigidly in an antiperiplanar diposition which is believed to be necessary for certian central and peripheral d...

journal_title：Journal of medicinal chemistry

authors： Cannon JG,Suarez-Gutierrez C,Lee T,Long JP,Costall B,Fortune DH,Naylor RJ

更新日期：1979-04-01 00:00:00

abstract：:The preparation and testing of the two racemic diastereoisomers and the four optically active enantiomers of the title compound in in vitro and in vivo models for determining potential antipsychotic activity are described. Both racemic diastereoisomers and two of the four chiral enantiomers are potent and long-acting ...

journal_title：Journal of medicinal chemistry

authors： Welch WM,Ewing FE,Harbert CA,Weissman A,Koe BK

更新日期：1980-08-01 00:00:00

abstract：:We designed a series of benzoic acid derivatives containing the biphenyl ether or biphenyl template on the RHS and a phenylethanolaminotetraline (PEAT) skeleton, which was prepared by highly stereoselective synthesis, to generate two structurally different lead compounds ( 10c, 10m) with a good balance of potency, sel...

journal_title：Journal of medicinal chemistry

authors： Imanishi M,Nakajima Y,Tomishima Y,Hamashima H,Washizuka K,Sakurai M,Matsui S,Imamura E,Ueshima K,Yamamoto T,Yamamoto N,Ishikawa H,Nakano K,Unami N,Hamada K,Matsumura Y,Takamura F,Hattori K

更新日期：2008-08-14 00:00:00

abstract：:Identification of a selective inhibitor for a particular protein kinase without inhibition of other kinases is critical for use as a biological tool or drug. However, this is very difficult because there are hundreds of homologous kinases and their kinase domains including the ATP binding pocket have a common folding ...

journal_title：Journal of medicinal chemistry

authors： Honma T,Yoshizumi T,Hashimoto N,Hayashi K,Kawanishi N,Fukasawa K,Takaki T,Ikeura C,Ikuta M,Suzuki-Takahashi I,Hayama T,Nishimura S,Morishima H

更新日期：2001-12-20 00:00:00

abstract：:Novel N,N-disubstituted indol-3-ylglyoxylamides (1-56), bearing different combinations of substituents R 1-R 5, were synthesized and evaluated as ligands of the translocator protein (TSPO), the 18 kDa protein representing the minimal functional unit of the "peripheral-type benzodiazepine receptor" (PBR). Most of the n...

journal_title：Journal of medicinal chemistry

authors： Da Settimo F,Simorini F,Taliani S,La Motta C,Marini AM,Salerno S,Bellandi M,Novellino E,Greco G,Cosimelli B,Da Pozzo E,Costa B,Simola N,Morelli M,Martini C

更新日期：2008-09-25 00:00:00

abstract：:An efficient and general method has been developed for fluorine-18 labeling of beta-blockers that possess the propanolamine moiety. A new synthetically versatile intermediate, 3-(1-(benzyloxy)propan-2-yl)-2-oxooxazolidin-5-yl)methyl 4-methylbenzenesulfonate (13), was prepared and can be conjugated to any phenoxy core....

journal_title：Journal of medicinal chemistry

authors： Stephenson KA,Wilson AA,Meyer JH,Houle S,Vasdev N

更新日期：2008-08-28 00:00:00

abstract：:A series of neutral, lipophilic 99mTc mixed-ligand complexes of the general formula 99mTcOL1L2, where L1H2 is an N-substituted bis-(2-mercaptoethyl)amine, [X-CH2CH2N(CH2CH2SH)2], [SNS], and L2H is a monodentate thiol (RSH), [S], has been synthesized and evaluated in rodents for potential use in brain blood flow imagin...

journal_title：Journal of medicinal chemistry

authors： Pirmettis IC,Papadopoulos MS,Chiotellis E

更新日期：1997-08-01 00:00:00

abstract：:To probe the space at the floor of the orthosteric ligand binding site in the dopamine D(1) receptor, four methylated analogues of dihydrexidine (DHX) were synthesized with substitutions at the 7 and 8 positions. The 8α-axial, 8β-equatorial, and 7α-equatorial were synthesized by photochemical cyclization of appropriat...

journal_title：Journal of medicinal chemistry

authors： Cueva JP,Gallardo-Godoy A,Juncosa JI,Vidi PA,Lill MA,Watts VJ,Nichols DE

更新日期：2011-08-11 00:00:00

abstract：:The amide functional group plays a key role in the composition of biomolecules, including many clinically approved drugs. Bioisosterism is widely employed in the rational modification of lead compounds, being used to increase potency, enhance selectivity, improve pharmacokinetic properties, eliminate toxicity, and acq...

journal_title：Journal of medicinal chemistry

authors： Kumari S,Carmona AV,Tiwari AK,Trippier PC

更新日期：2020-11-12 00:00:00

abstract：:8-Methoxy-1-oxo-2,3-dihydro-1H-cyclopenta]a]naphthalene (4) was converted to the oxalyl derivative (7) by treatment with diethyl oxalate in the presence of sodium ethoxide. Compound 7 in the form of the sodium salt was alkylated with ethyl bromoacetate in DMF to 2-(carbethoxymethyl)-8-methoxy-1-oxo-2,3-dihydro-1H-cycl...

journal_title：Journal of medicinal chemistry

authors： Kundu NG

更新日期：1980-05-01 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：:Angiogenesis is vital for solid tumor growth, and its prevention is a proven strategy for the treatment of disease states such as cancer. The vascular endothelial growth factor (VEGF) pathway provides several opportunities by which small molecules can act as inhibitors of endothelial proliferation and migration. Criti...

journal_title：Journal of medicinal chemistry

authors： La DS,Belzile J,Bready JV,Coxon A,DeMelfi T,Doerr N,Estrada J,Flynn JC,Flynn SR,Graceffa RF,Harriman SP,Larrow JF,Long AM,Martin MW,Morrison MJ,Patel VF,Roveto PM,Wang L,Weiss MM,Whittington DA,Teffera Y,Zhao Z

更新日期：2008-03-27 00:00:00

abstract：:We have previously shown that the oral administration of the small molecule hPTHR1 agonist PCO371 and its lead compound, 1 (CH5447240) results in PTH-like calcemic and hypophostemic activity in thyroparathyroidectomized rats. However, 1 was converted to a reactive metabolite in a human liver microsome assay. In this a...

journal_title：Journal of medicinal chemistry

authors： Nishimura Y,Esaki T,Isshiki Y,Furuta Y,Mizutani A,Kotake T,Emura T,Watanabe Y,Ohta M,Nakagawa T,Ogawa K,Arai S,Noda H,Kitamura H,Shimizu M,Tamura T,Sato H

更新日期：2020-05-28 00:00:00

abstract：:A primary goal of lead optimization is to identify compounds with improved absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties. A number of reports have linked computed molecular properties to desirable in vivo ADMET outcomes, but a significant limitation of these analyses is the failure t...

journal_title：Journal of medicinal chemistry

authors： Sutherland JJ,Raymond JW,Stevens JL,Baker TK,Watson DE

更新日期：2012-07-26 00:00:00

abstract：:A series of bisalkamine esters, bis-basic ethers, and bis-basic ketones of carbazole, N-ethylcarbazole, dibenzofuran, and dibenzothiophene was synthesized and evaluated for antiviral activity. The series also included two bis-basic alkanes of N-ethylcarbazole and one bis-basic carboxamide of dibenzofuran. Structure-ac...

journal_title：Journal of medicinal chemistry

authors： Albrecht WL,Fleming RW,Horgan SW,Mayer GD

更新日期：1977-03-01 00:00:00

abstract：:Novel monocyclic cyanoenones examined to date display unique features regarding chemical reactivity as Michael acceptors and biological potency. Remarkably, in some biological assays, the simple structure is more potent than pentacyclic triterpenoids (e.g., CDDO and bardoxolone methyl) and tricycles (e.g., TBE-31). Am...

journal_title：Journal of medicinal chemistry

authors： Zheng S,Santosh Laxmi YR,David E,Dinkova-Kostova AT,Shiavoni KH,Ren Y,Zheng Y,Trevino I,Bumeister R,Ojima I,Wigley WC,Bliska JB,Mierke DF,Honda T

更新日期：2012-05-24 00:00:00

abstract：:Closely related analogs of the 5-HT1A receptor agonist cis-(3aR)-(-)-2,3,3a,4,5,9b-hexahydro-3-propyl-1H-benz[e]indole-9- carboxamide (1, U93385) were synthesized and pharmacologically evaluated. 9-Carboxamide analogs with varied nitrogen substitution (R2) were synthesized, and their serotonergic activity was evaluate...

journal_title：Journal of medicinal chemistry

authors： Haadsma-Svensson SR,Svensson K,Duncan N,Smith MW,Lin CH

更新日期：1995-02-17 00:00:00

abstract：:Glycogen synthase kinase -3 (GSK-3) is a key enzyme involved in numerous physiological events and in major diseases, such as Alzheimer's disease, diabetes, and cardiac hypertrophy. Indirubins are bis-indoles that can be generated from various natural sources or chemically synthesized. While rather potent and selective...

journal_title：Journal of medicinal chemistry

authors： Vougogiannopoulou K,Ferandin Y,Bettayeb K,Myrianthopoulos V,Lozach O,Fan Y,Johnson CH,Magiatis P,Skaltsounis AL,Mikros E,Meijer L

更新日期：2008-10-23 00:00:00

abstract：:A set of 4-quinolone-3-carboxylic acids bearing different substituents on the condensed benzene ring was designed and synthesized as potential HIV-1 integrase inhibitors structurally related to elvitegravir. Some of the new compounds proved to be able to inhibit the strand transfer step of the virus integration proces...

journal_title：Journal of medicinal chemistry

authors： Pasquini S,Mugnaini C,Tintori C,Botta M,Trejos A,Arvela RK,Larhed M,Witvrouw M,Michiels M,Christ F,Debyser Z,Corelli F

更新日期：2008-08-28 00:00:00

abstract：:Starting from the structure of the novel nonpeptidic angiotensin II antagonist DuP 753, a series of more rigid analogues was prepared by replacing the biphenyl part of DuP 753 with a naphthalene ring. Five different regioisomers (compounds 6a-e) were synthesized, and receptor binding in rat smooth muscle cell preparat...

journal_title：Journal of medicinal chemistry

authors： Bühlmayer P,Criscione L,Fuhrer W,Furet P,de Gasparo M,Stutz S,Whitebread S

更新日期：1991-10-01 00:00:00

abstract：:Benzopyran selective estrogen receptor beta agonist-1 (SERBA-1) shows potent, selective binding and agonist function in estrogen receptor beta (ERbeta) in vitro assays. X-ray crystal structures of SERBA-1 in ERalpha and beta help explain observed beta-selectivity of this ligand. SERBA-1 in vivo demonstrates involution...

journal_title：Journal of medicinal chemistry

authors： Norman BH,Dodge JA,Richardson TI,Borromeo PS,Lugar CW,Jones SA,Chen K,Wang Y,Durst GL,Barr RJ,Montrose-Rafizadeh C,Osborne HE,Amos RM,Guo S,Boodhoo A,Krishnan V

更新日期：2006-10-19 00:00:00

abstract：:Natural lipid nanocarriers, exosomes, carry cell-signaling materials such as DNA and RNA for intercellular communications. Exosomes derived from cancer cells contribute to the progression and metastasis of cancer cells by transferring oncogenic signaling molecules to neighboring and remote premetastatic sites. Therefo...

journal_title：Journal of medicinal chemistry

authors： Tamura R,Balabanova A,Frakes SA,Bargmann A,Grimm J,Koch TH,Yin H

更新日期：2019-02-28 00:00:00

abstract：:Structure-activity relationship studies of substituted arylsulfoanilides as antiproliferatives, which are mediated by the partial depletion of intracellular Ca(2+) stores, resulted in the identification of compounds with micromolar activity against lung cancer cells in a growth inhibition assay. Incorporating the subs...

journal_title：Journal of medicinal chemistry

authors： Natarajan A,Guo Y,Harbinski F,Fan YH,Chen H,Luus L,Diercks J,Aktas H,Chorev M,Halperin JA

更新日期：2004-10-07 00:00:00

abstract：:8-β-d-Glucopyranosylgenistein (1), the major component of Genista tenera, was synthesized and showed an extensive therapeutical impact in the treatment of STZ-induced diabetic rats, producing normalization of fasting hyperglycemia and amelioration of excessive postprandial glucose excursions and and increasing β-cell ...

journal_title：Journal of medicinal chemistry

authors： Jesus AR,Dias C,Matos AM,de Almeida RF,Viana AS,Marcelo F,Ribeiro RT,Macedo MP,Airoldi C,Nicotra F,Martins A,Cabrita EJ,Jiménez-Barbero J,Rauter AP

更新日期：2014-11-26 00:00:00

abstract：:A potent and selective Factor IXa (FIXa) inhibitor was subjected to a series of liver microsomal incubations, which generated a number of metabolites. Using automated ligand identification system-affinity selection (ALIS-AS) methodology, metabolites in the incubation mixture were prioritized by their binding affinitie...

journal_title：Journal of medicinal chemistry

authors： Zhang T,Liu Y,Yang X,Martin GE,Yao H,Shang J,Bugianesi RM,Ellsworth KP,Sonatore LM,Nizner P,Sherer EC,Hill SE,Knemeyer IW,Geissler WM,Dandliker PJ,Helmy R,Wood HB

更新日期：2016-03-10 00:00:00

abstract：:Novel analogues of the class III antiarrhythmic agent 1-[2-hydroxy-2-[4-[(methylsulfonyl)amino]phenyl]ethyl]-3-methyl-1H- imidazolium chloride, 1 (CK-1649), were prepared and investigated for their class III electrophysiological activity on isolated canine cardiac Purkinje fibers and ventricular muscle tissue. Structu...

journal_title：Journal of medicinal chemistry

authors： Lis R,Davey DD,Morgan TK Jr,Lumma WC Jr,Wohl RA,Jain VK,Wan CN,Argentieri TM,Sullivan ME,Cantor EH

更新日期：1987-12-01 00:00:00

abstract：:Cancer cells generally generate higher amounts of reactive oxygen species than normal cells. On the basis of this difference, prodrugs have been developed (e.g., hydroxyferrocifen), which remain inactive in normal cells, but become activated in cancer cells. In this work we describe novel aminoferrocene-based prodrugs...

journal_title：Journal of medicinal chemistry

authors： Hagen H,Marzenell P,Jentzsch E,Wenz F,Veldwijk MR,Mokhir A

更新日期：2012-01-26 00:00:00

abstract：:An extension of the Mannich reaction, in which aminomethylation of the five position of uracil, is reported. Thus, primary and secondary alkylamines and primary aromatic amines containing ring-activating groups led to the title compounds 3-10. Compound 11 in which the aromatic ring contains the ring-deactivating nitro...

journal_title：Journal of medicinal chemistry

authors： Delia TJ,Scovill JP,Munslow WD,Burckhalter JH

更新日期：1976-02-01 00:00:00

abstract：:New and greatly improved preparations of the 12alpha,1'beta- (5) and 12beta,1'beta- (6) glucuronides of dihydroartemisinin (DHA, 2) are reported using anomeric hydroxy and imidate glucuronate intermediates. Comparison of the synthetic and natural materials shows that the human metabolite of DHA is the 12alpha-epimer 5...

journal_title：Journal of medicinal chemistry

authors： O'Neill PM,Scheinmann F,Stachulski AV,Maggs JL,Park BK

更新日期：2001-04-26 00:00:00

abstract：:Structure for the adduct of carbonic anhydrase II with 1-N-(4-sulfamoylphenyl-ethyl)-2,4,6-trimethylpyridinium perchlorate, a membrane-impermeant antitumor sulfonamide, is reported. The phenylethyl moiety fills the active site, making van der Waals interactions with side chains of Gln192, Val121, Phe131, Leu198, Thr20...

journal_title：Journal of medicinal chemistry

authors： Menchise V,De Simone G,Alterio V,Di Fiore A,Pedone C,Scozzafava A,Supuran CT

更新日期：2005-09-08 00:00:00