Bivalent diketopiperazine-based tropomysin receptor kinase C (TrkC) antagonists.

abstract：:Seven 3-alkyl-4-aryl-1,5-dihydro-2H-pyrrol-2-ones were prepared as potential inhibitors of cardiac cAMP phosphodiesterase (PDE). The design of these compounds made use of rolipram, a known inhibitor of the brain cAMP PDE isozyme, as a lead structure and was guided by a model which describes the features required for p...

journal_title：Journal of medicinal chemistry

authors： Lampe JW,Chou YL,Hanna RG,Di Meo SV,Erhardt PW,Hagedorn AA 3rd,Ingebretsen WR,Cantor E

更新日期：1993-04-16 00:00:00

abstract：:A new series of N-aryl-N'-3,4-dihydro-2,2-dimethyl-2H-1-benzopyran-4-yl)ureas bearing an alkoxycarbonylamino group at the 6-position were synthesized and examined as putative anticancer agents targeting sirtuins in glioma cells. On the basis of computational docking combined to in vitro sirtuin 1/2 inhibition assays, ...

journal_title：Journal of medicinal chemistry

authors： Schnekenburger M,Goffin E,Lee JY,Jang JY,Mazumder A,Ji S,Rogister B,Bouider N,Lefranc F,Miklos W,Mathieu V,de Tullio P,Kim KW,Dicato M,Berger W,Han BW,Kiss R,Pirotte B,Diederich M

更新日期：2017-06-08 00:00:00

abstract：:The tremendous therapeutic potential of voltage-gated sodium channels (Na(v)s) has been the subject of many studies in the past and is of intense interest today. Na(v)1.7 channels in particular have received much attention recently because of strong genetic validation of their involvement in nociception. Here we summa...

journal_title：Journal of medicinal chemistry

authors： de Lera Ruiz M,Kraus RL

更新日期：2015-09-24 00:00:00

abstract：:The antiseizure activity of benzodiazepines (BDZs) 1-5 in mice and rats as animal models is described. These BDZs have selective efficacy for alpha2beta3gamma2 and alpha3beta3gamma2 GABA(A)-receptors. Significant anticonvulsant activity with little or no motor impairment and therapeutic indexes (TI) of 2.8-44 (mice, i...

journal_title：Journal of medicinal chemistry

authors： Rivas FM,Stables JP,Murphree L,Edwankar RV,Edwankar CR,Huang S,Jain HD,Zhou H,Majumder S,Sankar S,Roth BL,Ramerstorfer J,Furtmüller R,Sieghart W,Cook JM

更新日期：2009-04-09 00:00:00

abstract：:Acid ceramidase (AC) is an intracellular cysteine amidase that catalyzes the hydrolysis of the lipid messenger ceramide. By regulating ceramide levels in cells, AC may contribute to the regulation of cancer cell proliferation and senescence and to the response to cancer therapy. We recently identified the antitumoral ...

journal_title：Journal of medicinal chemistry

authors： Pizzirani D,Pagliuca C,Realini N,Branduardi D,Bottegoni G,Mor M,Bertozzi F,Scarpelli R,Piomelli D,Bandiera T

更新日期：2013-05-09 00:00:00

abstract：:Forty-eight cationically substituted pentamidine congeners possessing benzofuran rings were synthesized by a copper mediated heteroannulation of substituted o-iodophenols with phenyl acetylenes. Activities of compounds 1-48 against Trypanosoma brucei rhodesiense, Plasmodium falciparum, and Leishmania donovani and cyto...

journal_title：Journal of medicinal chemistry

authors： Bakunov SA,Bakunova SM,Bridges AS,Wenzler T,Barszcz T,Werbovetz KA,Brun R,Tidwell RR

更新日期：2009-09-24 00:00:00

abstract：:Mechanism-based inhibitors of human cytomegalovirus (HCMV) protease have been designed based on the pyrrolidine-5,5-trans-lactam ring system. New routes to the beta-methyl-, desmethyl-, and alpha-methyl-pyrrolidine-5,5-trans-lactam templates have been developed from 2,4-diaminobutyric acid. ESI/MS studies have shown t...

journal_title：Journal of medicinal chemistry

authors： Borthwick AD,Angier SJ,Crame AJ,Exall AM,Haley TM,Hart GJ,Mason AM,Pennell AM,Weingarten GG

更新日期：2000-11-16 00:00:00

abstract：:In an effort to identify selective ligands for the estrogen receptor subtype ERbeta, a series of aryl benzthiophenes was synthesized. In a radioligand binding assay and reporter gene assays in HeLa and SH-SY5Y cells, compounds were characterized as ERbeta-selective agonists. By targeting ERbeta in the brain, these com...

journal_title：Journal of medicinal chemistry

authors： Schopfer U,Schoeffter P,Bischoff SF,Nozulak J,Feuerbach D,Floersheim P

更新日期：2002-03-28 00:00:00

abstract：:Two isomeric 6-endo- and 6-exo-(3',4'-dihydroxyphenyl) derivatives (1 and 2) of 2-azabicyclo[2.2.2]octane were synthesized as semirigid analogues of dopamine (DA) to help evaluate the preferred conformation of dopamine at the uptake site of the presynaptic nerve terminal and at the DA receptor. Against the uptake of 0...

journal_title：Journal of medicinal chemistry

authors： Law SJ,Morgan JM,Masten LW,Borne RF,Arana GW,Kula NS,Baldessarini RJ

更新日期：1982-03-01 00:00:00

abstract：:The binding affinities at rat A1, A2a, and A3 adenosine receptors of a wide range of derivatives of adenosine have been determined. Sites of modification include the purine moiety (1-, 3-, and 7-deaza; halo, alkyne, and amino substitutions at the 2- and 8-positions; and N6-CH2-ring, -hydrazino, and -hydroxylamino) and...

journal_title：Journal of medicinal chemistry

authors： Siddiqi SM,Jacobson KA,Esker JL,Olah ME,Ji XD,Melman N,Tiwari KN,Secrist JA 3rd,Schneller SW,Cristalli G

更新日期：1995-03-31 00:00:00

abstract：:Ligands for retinoid X receptors (RXRs), "rexinoids", are attracting interest as candidates for therapy of type 2 diabetes and Alzheimer's and Parkinson's diseases. However, current screening methods for rexinoids are slow and require special apparatus or facilities. Here, we created 7-hydroxy-2-oxo-6-(3,5,5,8,8-penta...

journal_title：Journal of medicinal chemistry

authors： Yamada S,Kawasaki M,Fujihara M,Watanabe M,Takamura Y,Takioku M,Nishioka H,Takeuchi Y,Makishima M,Motoyama T,Ito S,Tokiwa H,Nakano S,Kakuta H

更新日期：2019-10-10 00:00:00

abstract：:The synthesis and antiviral activity of a number of 3'-C-difluoromethyl and 3'-deoxy-3'-C-fluoromethyl nucleosides are reported. The 3'-C-difluoromethyl nucleosides 26a and 26b were obtained by treatment of the corresponding 2',5'-di-O-protected-3'-C-formyl nucleosides 25a and 25b with (diethylamino)sulfur trifluoride...

journal_title：Journal of medicinal chemistry

authors： Bamford MJ,Coe PL,Walker RT

更新日期：1990-09-01 00:00:00

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：:Membrane-bound aminopeptidase P (AP-P) participates in the degradation of bradykinin in several vascular beds. We have developed an inhibitor of AP-P called apstatin (1) (N-[(2S, 3R)-3-amino-2-hydroxy-4-phenyl-butanoyl]-L-prolyl-L-prolyl-L-al aninam ide); IC50,human = 2.9 microM. In the rat, apstatin can potentiate th...

journal_title：Journal of medicinal chemistry

authors： Maggiora LL,Orawski AT,Simmons WH

更新日期：1999-07-01 00:00:00

abstract：:Recently, the tryptophan-containing noncationizable opioid peptides emerged with atypical structure and unexpected in vivo activity. Herein, we describe analogs of the naturally occurring mixed κ/μ-ligand c[Phe-d-Pro-Phe-Trp] 1 (CJ-15,208). Receptor affinity, selectivity, and agonism/antagonism varied upon enlarging m...

journal_title：Journal of medicinal chemistry

authors： De Marco R,Bedini A,Spampinato S,Cavina L,Pirazzoli E,Gentilucci L

更新日期：2016-10-13 00:00:00

abstract：:9,10-Didehydro-6-methyl-8beta-arylergolines 2, in which the carboxyl group of lysergic acid and isolysergic acid is replaced by various aryl groups, were prepared in two steps by alkylation of aromatic substrates with the tetracyclic allylic alcohol 3, followed by aromatization with MnO2. The new ergolines 2 have mode...

journal_title：Journal of medicinal chemistry

authors： Bach NJ,Kornfeld EC,Dorman DE

更新日期：1977-08-01 00:00:00

abstract：:We present a novel protein-ligand docking method that accurately accounts for both ligand and receptor flexibility by iteratively combining rigid receptor docking (Glide) with protein structure prediction (Prime) techniques. While traditional rigid-receptor docking methods are useful when the receptor structure does n...

journal_title：Journal of medicinal chemistry

authors： Sherman W,Day T,Jacobson MP,Friesner RA,Farid R

更新日期：2006-01-26 00:00:00

abstract：:A new class of potential antitumor agents inspired by the enediyne antitumor antibiotics has been synthesized: the 1,2-dialkynylimidazoles. The aza-Bergman rearrangement of these 1,2-dialkynylimidazoles has been investigated theoretically at the B3LYP/6-31G(d,p) level and experimentally by measuring the kinetics of re...

journal_title：Journal of medicinal chemistry

authors： Laroche C,Li J,Kerwin SM

更新日期：2011-07-28 00:00:00

abstract：:In colorectal cancer, adenomatous polyposis coli (APC) interacts with Rho guanine-nucleotide-exchange factor 4 (Asef), thereby stimulating aberrant colorectal-cancer-cell migration. Consequently, the APC-Asef interaction represents a promising therapeutic target for mitigating colorectal-cancer migration. In this stud...

journal_title：Journal of medicinal chemistry

authors： Yang X,Zhong J,Zhang Q,Qian J,Song K,Ruan C,Xu J,Ding K,Zhang J

更新日期：2018-09-13 00:00:00

abstract：:Benzimidazole-N-oxide modifications of potent lipophilic dihydrofolate reductase (DHFR) inhibitors (e.g., methylbenzoprim 1 and dichlorobenzoprim 2) have been prepared by base-promoted cyclization of the nitrophenylbenzylamino groups to explore the possibility that abrogation of DHFR-inhibitory activity might reveal c...

journal_title：Journal of medicinal chemistry

authors： Richardson ML,Croughton KA,Matthews CS,Stevens MF

更新日期：2004-07-29 00:00:00

abstract：:Truncated N(6)-substituted-(N)-methanocarba-adenosine derivatives with 2-hexynyl substitution were synthesized to examine parallels with corresponding 4'-thioadenosines. Hydrophobic N(6) and/or C2 substituents were tolerated in A3AR binding, but only an unsubstituted 6-amino group with a C2-hexynyl group promoted high...

journal_title：Journal of medicinal chemistry

authors： Nayak A,Chandra G,Hwang I,Kim K,Hou X,Kim HO,Sahu PK,Roy KK,Yoo J,Lee Y,Cui M,Choi S,Moss SM,Phan K,Gao ZG,Ha H,Jacobson KA,Jeong LS

更新日期：2014-02-27 00:00:00

abstract：:Several known alpha-amino acid analogues and a new compound, N-chloroacetylphosphoramidate, a carbamyl phosphate analogue, were screened as antitumor agents. All gave 50% growth inhibition of cultures of human epidemeroid carcinoma of the nasopharynx at dosage levels of 2-8 mug/ml while showing no activity against L12...

journal_title：Journal of medicinal chemistry

authors： Glover GI,Nelson SO,Kaeder GR

更新日期：1977-03-01 00:00:00

abstract：:2-, 6-, And 8-alkylated (methyl, ethyl, and vinyl) adenosine analogues were synthesized by a palladium-catalyzed cross-coupling of a tetraalkyltin with the halogenated purine nucleosides. The synthesis of the 8-substituted analogues was accomplished using a transient protection procedure. The 6-alkylated-9-beta-D-ribo...

journal_title：Journal of medicinal chemistry

authors： Van Aerschot AA,Mamos P,Weyns NJ,Ikeda S,De Clercq E,Herdewijn PA

更新日期：1993-10-01 00:00:00

abstract：:Targeting of DNA secondary structures, such as G-quadruplexes, is now considered an appealing opportunity for drug intervention in anticancer therapy. So far, efforts made in the discovery of chemotypes able to target G-quadruplexes mainly succeeded in the identification of a number of polyaromatic compounds featuring...

journal_title：Journal of medicinal chemistry

authors： Cosconati S,Rizzo A,Trotta R,Pagano B,Iachettini S,De Tito S,Lauri I,Fotticchia I,Giustiniano M,Marinelli L,Giancola C,Novellino E,Biroccio A,Randazzo A

更新日期：2012-11-26 00:00:00

abstract：:Pseudomonas aeruginosa is a causative agent of chronic infections in immunocompromised patients. Disruption of quorum sensing circuits is an attractive strategy for treating diseases associated with P. aeruginosa infection. In this study, we designed and synthesized a series of gingerol analogs targeting LasR, a maste...

journal_title：Journal of medicinal chemistry

authors： Choi H,Ham SY,Cha E,Shin Y,Kim HS,Bang JK,Son SH,Park HD,Byun Y

更新日期：2017-12-14 00:00:00

abstract：:Multiple recent studies have focused on unraveling the content of the medicinal chemist's toolbox. Here, we present an investigation of chemical reactions and molecules retrieved from U.S. patents over the past 40 years (1976-2015). We used a sophisticated text-mining pipeline to extract 1.15 million unique whole reac...

journal_title：Journal of medicinal chemistry

authors： Schneider N,Lowe DM,Sayle RA,Tarselli MA,Landrum GA

更新日期：2016-05-12 00:00:00

abstract：:A series of 4-anilinoquinoline-linked aniline mustards of widely varying mustard reactivity were prepared and evaluated for their antitumor activity. The compounds were designed as minor grove binding agents, where the aniline mustard ring is itself part of the DNA-binding ligand. While there was a general trend for c...

journal_title：Journal of medicinal chemistry

authors： Gravatt GL,Baguley BC,Wilson WR,Denny WA

更新日期：1991-05-01 00:00:00

abstract：:A series of 2-(tetrahydroisoquinolin-2-ylmethyl)- and 2-(isoindolin-2-ylmethyl)imidazolines were prepared and tested for alpha 1- and alpha 2-adrenoceptor affinity with radioligand binding. Several compounds, 5-fluoro-(5h), 5-chloro-(5j), 5,8-dimethoxy- (5r), and 5,8-dimethoxy- (5r),1-methyl- (5s) 2-(tetrahydroisoquin...

journal_title：Journal of medicinal chemistry

authors： Clark RD,Berger J,Garg P,Weinhardt KK,Spedding M,Kilpatrick AT,Brown CM,MacKinnon AC

更新日期：1990-02-01 00:00:00

abstract：:Nicotinamide N-methyltransferase (NNMT) is a metabolic enzyme that methylates nicotinamide (NAM) using cofactor S-adenosylmethionine (SAM). NNMT overexpression has been linked to diabetes, obesity, and various cancers. In this work, structure-based rational design led to the development of potent and selective alkynyl...

journal_title：Journal of medicinal chemistry

authors： Policarpo RL,Decultot L,May E,Kuzmič P,Carlson S,Huang D,Chu V,Wright BA,Dhakshinamoorthy S,Kannt A,Rani S,Dittakavi S,Panarese JD,Gaudet R,Shair MD

更新日期：2019-11-14 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