2-Aryloxymethyl-2,3,5,6-tetrahydro-1,4-oxazines, a new class of antidepressants.

abstract：:The parasitic trypanosomes Trypanosoma brucei and T. cruzi are responsible for significant human suffering in the form of human African trypanosomiasis (HAT) and Chagas disease. Drugs currently available to treat these neglected diseases leave much to be desired. Herein we report optimization of a novel class of N-(2-...

journal_title：Journal of medicinal chemistry

authors： Russell S,Rahmani R,Jones AJ,Newson HL,Neilde K,Cotillo I,Rahmani Khajouei M,Ferrins L,Qureishi S,Nguyen N,Martinez-Martinez MS,Weaver DF,Kaiser M,Riley J,Thomas J,De Rycker M,Read KD,Flematti GR,Ryan E,Tanghe S,R

更新日期：2016-11-10 00:00:00

abstract：:We report herein further insight into the biological activities displayed by a series of 2-hydroxyisoquinoline-1,3(2H,4H)-diones (HIDs). Substitution of the N-hydroxyimide two-metal binding pharmacophore at position 4 by carboxamido side chains was previously shown by us to be fruitful for this scaffold, since strong ...

journal_title：Journal of medicinal chemistry

authors： Suchaud V,Bailly F,Lion C,Calmels C,Andréola ML,Christ F,Debyser Z,Cotelle P

更新日期：2014-06-12 00:00:00

abstract：:A series of novel tetrahydropyridinecarboxamide TRPV1 antagonists were prepared and evaluated in an effort to optimize properties of previously described lead compounds from piperazinecarboxamide series. The compounds were evaluated for their ability to block capsaicin and acid-induced calcium influx in CHO cells expr...

journal_title：Journal of medicinal chemistry

authors： Tafesse L,Kanemasa T,Kurose N,Yu J,Asaki T,Wu G,Iwamoto Y,Yamaguchi Y,Ni C,Engel J,Tsuno N,Patel A,Zhou X,Shintani T,Brown K,Hasegawa T,Shet M,Iso Y,Kato A,Kyle DJ

更新日期：2014-08-14 00:00:00

abstract：:A series of transition-state analogues having heterocyclythio C-termini has been synthesized and evaluated for inhibition of human renin. Addition of mercaptoheterocycles to a chiral Boc-amino epoxide intermediate led, after several steps, to the target [(2R,3S)-3-(BocPheHis-amino)-4-cyclohexyl-2-hydroxy-1-butyl]thio ...

journal_title：Journal of medicinal chemistry

authors： Ashton WT,Cantone CL,Meurer LC,Tolman RL,Greenlee WJ,Patchett AA,Lynch RJ,Schorn TW,Strouse JF,Siegl PK

更新日期：1992-05-29 00:00:00

abstract：:The dengue virus (DENV) and West Nile Virus (WNV) NS2B-NS3 proteases are attractive targets for the development of dual-acting therapeutics against these arboviral pathogens. We present the synthesis and extensive biological evaluation of inhibitors that contain benzyl ethers of 4-hydroxyphenylglycine as non-natural p...

journal_title：Journal of medicinal chemistry

authors： Behnam MA,Graf D,Bartenschlager R,Zlotos DP,Klein CD

更新日期：2015-12-10 00:00:00

abstract：:The increase in the incidence of both hospital- and community-acquired antibiotic-resistant infections is a major concern to the healthcare community. There have been only two new classes of antibiotics approved by the FDA over the past 40 years, and clearly there is a growing need for additional antimicrobial agents....

journal_title：Journal of medicinal chemistry

authors： Vooturi SK,Cheung CM,Rybak MJ,Firestine SM

更新日期：2009-08-27 00:00:00

abstract：:A common pharmacophore for compounds structurally related to nitraquazone has been derived. Using this pharmacophore, new structures have been designed, synthesized, and evaluated for their inhibitory potencies against cyclic adenosine 5'-monophosphate (cAMP) specific phosphodiesterase (PDE 4). From these compounds, 4...

journal_title：Journal of medicinal chemistry

authors： Crespo MI,Pagès L,Vega A,Segarra V,López M,Doménech T,Miralpeix M,Beleta J,Ryder H,Palacios JM

更新日期：1998-10-08 00:00:00

abstract：:New antiproliferative compounds, dimethyl-5H-pyrido[3,2-a]phenoxazin-5-ones (1-6), tetrahydro-5H-benzopyrido[2,3-j]phenoxazin-5-ones (7-9), and 5H-benzopyrido[3,2-a]phenoxazin-5-ones (10-12) were synthesized and evaluated against representative human neoplastic cell lines. Dimethyl derivatives 1-6 were more active aga...

journal_title：Journal of medicinal chemistry

authors： Bolognese A,Correale G,Manfra M,Lavecchia A,Novellino E,Pepe S

更新日期：2006-08-24 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：:Agouti-related protein (AGRP) is a potent orexigenic peptide that antagonizes the melanocortin-3 and -4 receptors (MC3R and MC4R). While the C-terminal domain of AGRP, AGRP(87-132), is equipotent to the full-length peptide, further truncation decreases potency at the MC3R and MC4R. Herein, we report AGRP-derived pepti...

journal_title：Journal of medicinal chemistry

authors： Ericson MD,Wilczynski A,Sorensen NB,Xiang Z,Haskell-Luevano C

更新日期：2015-06-11 00:00:00

abstract：:N delta-Acyl derivatives of the potent folylpolyglutamate synthetase (FPGS) inhibitor N alpha-(4-amino-4-deoxypteroyl)-L-ornithine (APA-L-Orn) were synthesized from N alpha-(4-amino-4-deoxy-N10-formylpteroyl)-L-ornithine by reaction with an N-(acyloxy)succinimide or acyl anhydride, followed by deformylation with base....

journal_title：Journal of medicinal chemistry

authors： Rosowsky A,Bader H,Cucchi CA,Moran RG,Kohler W,Freisheim JH

更新日期：1988-07-01 00:00:00

abstract：:DoMCoSAR is a novel approach for statistically determining the docking mode that is consistent with a structure-activity relationship. The approach establishes the binding mode for the compounds in a chemical series with the assumption that all molecules exhibit the same binding mode. It involves three stages. In the ...

journal_title：Journal of medicinal chemistry

authors： Vieth M,Cummins DJ

更新日期：2000-08-10 00:00:00

abstract：:Four hybrid antibiotics combining structural features of chloramphenicol (1a), sparsomycin (2b), lincomycin (5c), and puromycin (6d)--lincophenicol (1c), chloramlincomycin (5a), sparsolincomycin (5b), and sparsopuromycin (6b)--were synthesized. They were investigated as inhibitors of several partial reactions of proca...

journal_title：Journal of medicinal chemistry

authors： Zemlicka J,Fernandez-Moyano MC,Ariatti M,Zurenko GE,Grady JE,Ballesta JP

更新日期：1993-04-30 00:00:00

abstract：:Overexpression of the HER2 receptor is observed in about 30% of breast and ovarian cancers and is often associated with an unfavorable prognosis. We have recently designed an anti-HER2 peptide (AHNP) based on the structure of the CDR-H3 loop of the anti-HER2 rhumAb 4D5 and showed that this peptide can mimic some funct...

journal_title：Journal of medicinal chemistry

authors： Berezov A,Zhang HT,Greene MI,Murali R

更新日期：2001-08-02 00:00:00

abstract：:The cardiotonic 1,3-dihydro-3,3-dimethyl-5-(1,4,5,6-tetrahydro-6-oxo-3- pyridazinyl)-2H-indol-2-one (1, LY195115) is a potent, competitive inhibitor (Ki = 80 nM) of sarcoplasmic reticulum derived phosphodiesterase (SR-PDE). Moreover, the compound is a potent positive inotrope both in vitro and in vivo. To assist furth...

journal_title：Journal of medicinal chemistry

authors： Robertson DW,Jones ND,Krushinski JH,Pollock GD,Swartzendruber JK,Hayes JS

更新日期：1987-04-01 00:00:00

abstract：:The design, synthesis and pharmacological evaluation of a novel class of Dmt-Tic dipeptide analogues are described. These resulting analogues bearing different C-terminal functionalities were found to bind to the human delta receptor with high affinity. One specific class of dipeptides bearing urea/thiourea functional...

journal_title：Journal of medicinal chemistry

authors： Pagé D,Naismith A,Schmidt R,Coupal M,Labarre M,Gosselin M,Bellemare D,Payza K,Brown W

更新日期：2001-07-19 00:00:00

abstract：:A series of novel cephalosporin compounds which have 3-[(aminopyrimidiniumyl)thio]methyl substituents was synthesized. They show high antimicrobial activity against various bacterial species including Pseudomonas aeruginosa. Structure-activity relationships with various thiopyrimidines, thiopyrimidiniums, bicyclic thi...

journal_title：Journal of medicinal chemistry

authors： Kim YZ,Lim JC,Yeo JH,Bang CS,Kim WS,Kim SS,Woo YM,Yang DH,Oh H,Nahm K

更新日期：1994-10-28 00:00:00

abstract：:A novel series of 2-[(2,3-dihydro-1H-indol-1-yl)methyl]melatonin analogues has been prepared to probe the steric and electronic properties of the binding pocket of the MT(2) receptor accommodating the "out-of-plane" substituent of MT(2)-selective antagonists. The acetamide (6b) bearing an usubstituted indoline moiety ...

journal_title：Journal of medicinal chemistry

authors： Zlotos DP,Attia MI,Julius J,Sethi S,Witt-Enderby PA

更新日期：2009-02-12 00:00:00

abstract：:A series of 2-aminotetralins, substituted with a methoxy or a hydroxy group on the 5- or 7-position, and with varying N-alkyl or N-arylalkyl substituents, were prepared and evaluated in binding assays for human dopamine (DA) D2, D3, and D4 receptors. Some members of this series were prepared in former studies, but wer...

journal_title：Journal of medicinal chemistry

authors： van Vliet LA,Tepper PG,Dijkstra D,Damsma G,Wikström H,Pugsley TA,Akunne HC,Heffner TG,Glase SA,Wise LD

更新日期：1996-10-11 00:00:00

abstract：:The in vivo antitumor activity and in vitro metabolic dealkylation have been measured for an homologous series of 3-alkyl-1-(4-carbamoylphenyl)-3-methyltriazenes and have been compared with their partition coefficients. This investigation has shown that the extent of oxidative metabolism in vitro and the antitumor act...

journal_title：Journal of medicinal chemistry

authors： Wilman DE,Cox PJ,Goddard PM,Hart LI,Merai K,Newell DR

更新日期：1984-07-01 00:00:00

abstract：:Compounds that simultaneously activate the three peroxisome proliferator-activated receptor (PPAR) subtypes alpha, gamma, and delta hold potential to address the adverse metabolic and cardiovascular conditions associated with diabetes and the metabolic syndrome. We recently identified the indanylacetic acid moiety as ...

journal_title：Journal of medicinal chemistry

authors： Rudolph J,Chen L,Majumdar D,Bullock WH,Burns M,Claus T,Dela Cruz FE,Daly M,Ehrgott FJ,Johnson JS,Livingston JN,Schoenleber RW,Shapiro J,Yang L,Tsutsumi M,Ma X

更新日期：2007-03-08 00:00:00

abstract：:1 (MTC-220), a conjugate of paclitaxel and a muramyl dipeptide analogue, has been synthesized as a novel agent of dual antitumor growth and metastasis activities. In vitro and in vivo tests show that 1 retains its ability to inhibit tumor growth. It is superior to paclitaxel in its ability to prevent tumor metastasis ...

journal_title：Journal of medicinal chemistry

authors： Ma Y,Zhao N,Liu G

更新日期：2011-04-28 00:00:00

abstract：:A series of commercial phenyl-, heteroaryl-, alkyl-, and alkenylboronic acids were evaluated for their FAAH and MGL inhibitory activities. The compounds were generally selective for FAAH, with IC50 in the nanomolar or low-micromolar range. Eight of these compounds inhibited MGL with IC50 in the micromolar range. The m...

journal_title：Journal of medicinal chemistry

authors： Minkkilä A,Saario SM,Käsnänen H,Leppänen J,Poso A,Nevalainen T

更新日期：2008-11-27 00:00:00

abstract：:In this paper we report the systematic search for new, potent, and selective DPP II inhibitors. A study of the structure-activity relationship was conducted starting from aminoacyl pyrrolidides as lead compounds. Rational exploration of the P(1) and P(2) building blocks led to the discovery of some very potent DPP II ...

journal_title：Journal of medicinal chemistry

authors： Senten K,Van der Veken P,De Meester I,Lambeir AM,Scharpé S,Haemers A,Augustyns K

更新日期：2003-11-06 00:00:00

abstract：:Inhibitor of apoptosis proteins (IAPs) are promising anticancer targets, given their roles in the evasion of apoptosis. Several peptidomimetic IAP antagonists, with inherent selectivity for cellular IAP (cIAP) over X-linked IAP (XIAP), have been tested in the clinic. A fragment screening approach followed by structure...

journal_title：Journal of medicinal chemistry

authors： Johnson CN,Ahn JS,Buck IM,Chiarparin E,Day JEH,Hopkins A,Howard S,Lewis EJ,Martins V,Millemaggi A,Munck JM,Page LW,Peakman T,Reader M,Rich SJ,Saxty G,Smyth T,Thompson NT,Ward GA,Williams PA,Wilsher NE,Chessari G

更新日期：2018-08-23 00:00:00

abstract：:Thrombin is a serine protease responsible for blood coagulation. Since thrombin inhibitors appear to be effective in the treatment and prevention of thrombotic and embolic disorders, considerable attention has been focused on the structure and interactions of this enzyme. In this work, to evaluate the relative free en...

journal_title：Journal of medicinal chemistry

authors： Guimarães CR,Bicca de Alencastro R

更新日期：2002-11-07 00:00:00

abstract：:An approach to the development of new anticandidal drugs is described that employs peptides as carriers of toxic agents into cells. 5-Flurorcytosine (5-FC) was chosen as a toxic agent with which to prepare 5-FC-peptide conjugates as models to test the carrier proposal. Model compounds were synthesized and then tested ...

journal_title：Journal of medicinal chemistry

authors： Steinfeld AS,Naider F,Becker JM

更新日期：1979-09-01 00:00:00

abstract：:Several 3-arylamino and 3-alkoxy-nor-beta-lapachone derivatives were synthesized in moderate to high yields and found to be highly potent against cancer cells SF295 (central nervous system), HCT8 (colon), MDA-MB435 (melanoma), and HL60 (leukemia), with IC(50) below 2 microM. The arylamino para-nitro and the 2,4-dimeth...

journal_title：Journal of medicinal chemistry

authors： da Silva EN Jr,de Deus CF,Cavalcanti BC,Pessoa C,Costa-Lotufo LV,Montenegro RC,de Moraes MO,Pinto Mdo C,de Simone CA,Ferreira VF,Goulart MO,Andrade CK,Pinto AV

更新日期：2010-01-14 00:00:00

abstract：:Angiotensin-converting enzyme 2 (ACE2), a recently identified human homologue of angiotensin-converting enzyme, is a zinc metallocarboxypeptidase which may play a unique role in cardiovascular and renal function. Here we report the discovery of potent and selective inhibitors of ACE2, which have been identified by eva...

journal_title：Journal of medicinal chemistry

authors： Mores A,Matziari M,Beau F,Cuniasse P,Yiotakis A,Dive V

更新日期：2008-04-10 00:00:00

abstract：:A family of analogues of des-AA(1,2,5)-[DTrp(8)/D2Nal(8)]-SRIF that contain a 4-(N-isopropyl)-aminomethylphenylalanine (IAmp) at position 9 was identified that has high affinity and selectivity for human somatostatin receptor subtype 1 (sst1). The binding affinities of des-AA(1,2,5)-[DTrp(8),IAmp(9)]-SRIF (c[H-Cys-Lys...

journal_title：Journal of medicinal chemistry

authors： Rivier JE,Hoeger C,Erchegyi J,Gulyas J,DeBoard R,Craig AG,Koerber SC,Wenger S,Waser B,Schaer JC,Reubi JC

更新日期：2001-06-21 00:00:00