Antitubercular 2,8-bis(alkylaminomethyl)phenazines.

abstract：:The glutamine antagonist 6-diazo-5-oxo-l-norleucine (DON, 1) has shown robust anticancer efficacy in preclinical and clinical studies, but its development was halted due to marked systemic toxicities. Herein we demonstrate that DON inhibits glutamine metabolism and provides antitumor efficacy in a murine model of glio...

journal_title：Journal of medicinal chemistry

authors： Rais R,Jančařík A,Tenora L,Nedelcovych M,Alt J,Englert J,Rojas C,Le A,Elgogary A,Tan J,Monincová L,Pate K,Adams R,Ferraris D,Powell J,Majer P,Slusher BS

更新日期：2016-09-22 00:00:00

abstract：:2-(3',4',5'-Trimethoxybenzoyl)-3-amino-5-aryl/heteroaryl thiophene derivatives were synthesized and evaluated for antiproliferative activity, inhibition of tubulin polymerization, and cell cycle effects. SARs were elucidated with various substitutions on the aryl moiety 5-position of the thienyl ring. Substituents at ...

journal_title：Journal of medicinal chemistry

authors： Romagnoli R,Baraldi PG,Remusat V,Carrion MD,Cara CL,Preti D,Fruttarolo F,Pavani MG,Tabrizi MA,Tolomeo M,Grimaudo S,Balzarini J,Jordan MA,Hamel E

更新日期：2006-10-19 00:00:00

abstract：:Previous work has shown that incorporation of either 1-aminocyclohexanecarboxylic acid (Ac6c) or alpha-methyl-p-phosphonophenylalanine ((alpha-Me)Ppp) in the phosphotyrosyl (pTyr) C-proximal position (pY + 1 residue) of Grb2 SH2 domain binding peptides confers high affinity. The tetralin-based (S)-2-amino-6-phosphonot...

journal_title：Journal of medicinal chemistry

authors： Oishi S,Karki RG,Kang SU,Wang X,Worthy KM,Bindu LK,Nicklaus MC,Fisher RJ,Burke TR Jr

更新日期：2005-02-10 00:00:00

abstract：:Ring-constrained adenosine analogues have been designed to act as dual agonists at tissue-protective A(1) and A(3) adenosine receptors (ARs). 9-Ribosides transformed into the ring-constrained (N)-methanocarba-2-chloro-5'-uronamides consistently lost affinity at A(1)/A(2A)ARs and gained at A(3)AR. Among 9-riboside deri...

journal_title：Journal of medicinal chemistry

authors： Jacobson KA,Gao ZG,Tchilibon S,Duong HT,Joshi BV,Sonin D,Liang BT

更新日期：2005-12-29 00:00:00

abstract：:Tocainide and related optically active chiral alpha-aminoanilides were synthesized and tested in vivo via the hot plate test to evaluate their central analgesic action. The aims of the study were to verify if a) the increase in lipophilicity, obtained by the introduction of an alkyl group on the steric center (3f-i), ...

journal_title：Journal of medicinal chemistry

authors： Corbo F,Franchini C,Lentini G,Muraglia M,Ghelardini C,Matucci R,Galeotti N,Vivoli E,Tortorella V

更新日期：2007-04-19 00:00:00

abstract：:A practical combination of comparative modeling and NMR spectroscopy was used to generate a three-dimensional structure of the response regulator protein, Spo0F. The backbone structure obtained compares to the Spo0F Y13S mutant X-ray structure with an rmsd of 2.0 A. We provide results which suggest that structures obt...

journal_title：Journal of medicinal chemistry

authors： Podlogar BL,Leo GC,McDonnell PA,Loughney DA,Caldwell GW,Barrett JF

更新日期：1997-10-10 00:00:00

abstract：:Nicotinic acetylcholine receptors (nAChRs) have been investigated for developing drugs that can potentially treat various central nervous system disorders. Considerable evidence supports the hypothesis that modulation of the cholinergic system through activation and/or desensitization/inactivation of nAChR holds promi...

journal_title：Journal of medicinal chemistry

authors： Yu LF,Zhang HK,Caldarone BJ,Eaton JB,Lukas RJ,Kozikowski AP

更新日期：2014-10-23 00:00:00

abstract：:The N-arginyl derivative of methionine-enkephalin (fragment 60-65 of beta-lipotropin) has been shown to be equiactive with the parent pentapeptide, despite the fact that the tyrosine amino group in this compound has been neutralized by the formation of an amide linkage. A series of N-(amino acid) derivatives of (-)-5,...

journal_title：Journal of medicinal chemistry

authors： Bélanger PC,Scheigetz J,Young RN,Charleson SE,Hudgin RL,Engelhardt EL

更新日期：1981-11-01 00:00:00

abstract：:Human African trypanosomiasis (HAT) is a neglected tropical disease caused by the protozoan parasite Trypanosoma brucei . Because drugs in use against HAT are toxic and require intravenous dosing, new drugs are needed. Initiating lead discovery campaigns by using chemical scaffolds from drugs approved for other indica...

journal_title：Journal of medicinal chemistry

authors： Patel G,Karver CE,Behera R,Guyett PJ,Sullenberger C,Edwards P,Roncal NE,Mensa-Wilmot K,Pollastri MP

更新日期：2013-05-23 00:00:00

abstract：:A series of 2,2-diarylethylamine derivatives has been examined for potential antidepressant activity in the tetrabenazine (TBZ) test. Diethanolamine 4 (McN-4187) was one of the more potent compounds despite its polar alcohol functionalities [ED50 values of 15 mg/kg (exploratory activity) and 1.5 mg/kg (ptosis)]. Struc...

journal_title：Journal of medicinal chemistry

authors： Maryanoff BE,Nortey SO,Gardocki JF

更新日期：1984-08-01 00:00:00

abstract：:The imidazoquinoline (R)-5,6-Dihydro-N,N-dimethyl-4H-imidazo[4,5,1-ij]quinolin-5-amine [(R)-3] is a potent dopamine agonist when tested in animals but surprisingly shows very low affinity in in vitro binding assays. When incubated with mouse or monkey liver S9 microsomes, (R)-3 is metabolized by N-demethylation and ox...

journal_title：Journal of medicinal chemistry

authors： Heier RF,Dolak LA,Duncan JN,Hyslop DK,Lipton MF,Martin IJ,Mauragis MA,Piercey MF,Nichols NF,Schreur PJ,Smith MW,Moon MW

更新日期：1997-02-28 00:00:00

abstract：:Compound 1 (SKI-606, bosutinib), a 7-alkoxy-4-[(2,4-dichloro-5-methoxyphenyl)amino]-3-quinolinecarbonitrile, is a potent inhibitor of Src kinase activity. We previously reported that analogs of 1 with thiophene groups at C-7 retained the Src activity of the parent compound. The corresponding C-7 furan analogs were pre...

journal_title：Journal of medicinal chemistry

authors： Boschelli DH,Wu B,Ye F,Wang Y,Golas JM,Lucas J,Boschelli F

更新日期：2006-12-28 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 JmjC oxygenases catalyze the N-demethylation of N(ε)-methyl lysine residues in histones and are current therapeutic targets. A set of human 2-oxoglutarate analogues were screened using a unified assay platform for JmjC demethylases and related oxygenases. Results led to the finding that daminozide (N-(dimethylamin...

journal_title：Journal of medicinal chemistry

authors： Rose NR,Woon EC,Tumber A,Walport LJ,Chowdhury R,Li XS,King ON,Lejeune C,Ng SS,Krojer T,Chan MC,Rydzik AM,Hopkinson RJ,Che KH,Daniel M,Strain-Damerell C,Gileadi C,Kochan G,Leung IK,Dunford J,Yeoh KK,Ratcliffe PJ

更新日期：2012-07-26 00:00:00

abstract：:Catechol O-methyltransferase (COMT) is the enzyme responsible for the O-methylation of endogenous neurotransmitters and of xenobiotic substances and hormones incorporating catecholic structures. COMT is a druggable biological target for the treatment of various central and peripheral nervous system disorders, includin...

journal_title：Journal of medicinal chemistry

authors： Kiss LE,Soares-da-Silva P

更新日期：2014-11-13 00:00:00

abstract：:The effect of substitution of the pyrrolo- and indolo-N atoms in tetrahydronaltrindole (TNTI), tetrahydrooxymorphindole (TOMI), and 17-cyclopropylmethyl-3,14-dihydroxy-4,5-epoxy-4'-phenyl-6,7:2',3'-pyrrolomorphinan (4) is reported. In opioid functional assays 4 were potent deltaopioid receptor (DOR) antagonists while ...

journal_title：Journal of medicinal chemistry

authors： Srivastava SK,Shefali S,Miller CN,Aceto MD,Traynor JR,Lewis JW,Husbands SM

更新日期：2004-12-16 00:00:00

abstract：:Fatty acid amide hydrolase (FAAH) degrades neuromodulating fatty acid amides including anandamide (endogenous cannabinoid agonist) and oleamide (sleep-inducing lipid) at their sites of action and is intimately involved in their regulation. Herein we report the discovery of a potent, selective, and efficacious class of...

journal_title：Journal of medicinal chemistry

authors： Boger DL,Miyauchi H,Du W,Hardouin C,Fecik RA,Cheng H,Hwang I,Hedrick MP,Leung D,Acevedo O,Guimarães CR,Jorgensen WL,Cravatt BF

更新日期：2005-03-24 00:00:00

abstract：:A series of 5-nitrofuran-2- and 3-carboxamides bearing alkylating side-chains has been synthesized and tested for their ability to radiosensitize selectively hypoxic Chinese hamster cells (V79) to the lethal effects of ionizing radiation and also for their ability to act directly and selectively as cytotoxic drugs on ...

journal_title：Journal of medicinal chemistry

authors： Naylor MA,Stephens MA,Cole S,Threadgill MD,Stratford IJ,O'Neill P,Fielden EM,Adams GE

更新日期：1990-09-01 00:00:00

abstract：:In a previous study, a cocrystal structure of PPARγ bound to 2-chloro-N-(3-chloro-4-((5-chlorobenzo[d]thiazol-2-yl)thio)phenyl)-4-(trifluoromethyl)benzenesulfonamide (1, T2384) revealed two orthosteric pocket binding modes attributed to a concentration-dependent biochemical activity profile. However, 1 also bound an a...

journal_title：Journal of medicinal chemistry

authors： Hughes TS,Shang J,Brust R,de Vera IMS,Fuhrmann J,Ruiz C,Cameron MD,Kamenecka TM,Kojetin DJ

更新日期：2016-11-23 00:00:00

abstract：:Human coagulation factor XIa (FXIa), a serine protease activated by site-specific cleavage of factor XI by thrombin, FXIIa, or autoactivation, is a critical enzyme in the amplification phase of the coagulation cascade. To investigate the potential of FXIa inhibitors as safe anticoagulants, a series of potent, selectiv...

journal_title：Journal of medicinal chemistry

authors： Lin J,Deng H,Jin L,Pandey P,Quinn J,Cantin S,Rynkiewicz MJ,Gorga JC,Bibbins F,Celatka CA,Nagafuji P,Bannister TD,Meyers HV,Babine RE,Hayward NJ,Weaver D,Benjamin H,Stassen F,Abdel-Meguid SS,Strickler JE

更新日期：2006-12-28 00:00:00

abstract：:A series of 4-substituted fluoronucleosides have been synthesized in order to address the toxicity issue of the parent compound 7, and after in vitro evaluation, the cyclopropylamino analog 1f was selected for in vivo study. In mice, this compound exhibited a significantly improved toxicity profile. Administered orall...

journal_title：Journal of medicinal chemistry

authors： Yang Q,Kang J,Zheng L,Wang XJ,Wan N,Wu J,Qiao Y,Niu P,Wang SQ,Peng Y,Wang Q,Yu W,Chang J

更新日期：2015-05-14 00:00:00

abstract：:In only four chemical steps from naturally occurring artemisinin (1), trioxane dimers 6 and 7 were prepared on a multigram scale in overall 32-44% yields. In mice, both isonicotinate N-oxide dimer 6 and isobutyric acid dimer 7 were considerably more antimalarially efficacious than clinically used sodium artesunate (2)...

journal_title：Journal of medicinal chemistry

authors： Posner GH,McRiner AJ,Paik IH,Sur S,Borstnik K,Xie S,Shapiro TA,Alagbala A,Foster B

更新日期：2004-02-26 00:00:00

abstract：:New ruthenium(II) and iron(II) organometallic compounds of general formula [(η(5)-C5H5)M(PP)Lc][PF6], bearing carbohydrate derivative ligands (Lc), were prepared and fully characterized and the crystal structures of five of those compounds were determined by X-ray diffraction studies. Cell viability of colon cancer HC...

journal_title：Journal of medicinal chemistry

authors： Florindo PR,Pereira DM,Borralho PM,Rodrigues CM,Piedade MF,Fernandes AC

更新日期：2015-05-28 00:00:00

abstract：:A series of novel, disulfide-constrained human beta-melanocyte stimulating hormone (beta-MSH)-derived peptides were optimized for in vitro melanocortin-4 receptor (MC-4R) binding affinity, agonist efficacy, and selectivity. The most promising of these, analogue 18, was further studied in vivo using chronic rat food in...

journal_title：Journal of medicinal chemistry

authors： Mayer JP,Hsiung HM,Flora DB,Edwards P,Smith DP,Zhang XY,Gadski RA,Heiman ML,Hertel JL,Emmerson PJ,Husain S,O'brien TP,Kahl SD,Smiley DL,Zhang L,Dimarchi RD,Yan LZ

更新日期：2005-05-05 00:00:00

abstract：:Spirocyclic scaffolds are incorporated in various approved drugs and drug candidates. The increasing interest in less planar bioactive compounds has given rise to the development of synthetic methodologies for the preparation of spirocyclic scaffolds. In this Perspective, we summarize the diverse synthetic routes to o...

journal_title：Journal of medicinal chemistry

authors： Hiesinger K,Dar'in D,Proschak E,Krasavin M

更新日期：2021-01-14 00:00:00

abstract：:5-Alkyl- and 5-arylalkyl-3-methylenedihydrofuran-2-ones 13a-e, 3-alkylidenedihydrofuran-2-ones 18a-c, and 3-methylenepyrrolidin-2-ones 16a-e were synthesized utilizing ethyl 2-diethoxyphosphoryl-4-nitroalkanoates 9a-e as common intermediates. All obtained compounds were tested against L-1210, HL-60, and NALM-6 leukemi...

journal_title：Journal of medicinal chemistry

authors： Janecki T,Błaszczyk E,Studzian K,Janecka A,Krajewska U,Rózalski M

更新日期：2005-05-19 00:00:00

abstract：:We previously reported that [[N-[3beta-hydroxyllup-20(29)-en-28-oyl]-7-aminoheptyl]carbamoyl]methane (A43D, 4) was a potent HIV-1 entry inhibitor. However, 4 was inactive against HIV-2 virus, suggesting the structural requirements for targeting these two retroviruses are different. In this study, a series of new betul...

journal_title：Journal of medicinal chemistry

authors： Dang Z,Lai W,Qian K,Ho P,Lee KH,Chen CH,Huang L

更新日期：2009-12-10 00:00:00

abstract：:Largazole 4a and analogues with modifications at the C7 position, as well as 2,4'-bithiazole 5a, have been synthesized using an acyclic cross-metathesis of the corresponding depsipeptide structures assembled by N-C6(O) or C15(O)-N lactam formation. Similar to the parent system 4a, the series of largazole depsipeptides...

journal_title：Journal of medicinal chemistry

authors： Souto JA,Vaz E,Lepore I,Pöppler AC,Franci G,Alvarez R,Altucci L,de Lera AR

更新日期：2010-06-24 00:00:00

abstract：:A series of eight C5-substituted analogues of (+-)-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine (1) have been prepared by the directed lithiation-alkylation (and acylation) of its (+-)-N-tert-butylformamidinyl derivative 2 followed by formamidine solvolysis. An additional 10 analogues were prepared by elaborati...

journal_title：Journal of medicinal chemistry

authors： Monn JA,Thurkauf A,Mattson MV,Jacobson AE,Rice KC

更新日期：1990-03-01 00:00:00

abstract：:We previously reported the discovery of 4-[(Z)-(4-bromophenyl)(ethoxyimino)methyl]-1'-[(2,4-dimethyl-3-pyridinyl)carbonyl]-4'-methyl-1,4'-bipiperidine N-oxide 1 (SCH 351125) as an orally bioavailable human CCR5 antagonist for the treatment of HIV-1 infection. Herein, we describe in detail the discovery of 1 from our i...

journal_title：Journal of medicinal chemistry

authors： Palani A,Shapiro S,Josien H,Bara T,Clader JW,Greenlee WJ,Cox K,Strizki JM,Baroudy BM

更新日期：2002-07-04 00:00:00