Discovery of 6-(Fluoro-(18)F)-3-(1H-pyrrolo[2,3-c]pyridin-1-yl)isoquinolin-5-amine ([(18)F]-MK-6240): A Positron Emission Tomography (PET) Imaging Agent for Quantification of Neurofibrillary Tangles (NFTs).

abstract：:1H-Indolo[3',2':4,5]pyrido[3,2-b]-2-penten-5-olide (6) and 1H,5H-indolo[3',2'-c]-6,7-dihydro-2-pyridone (7), rigid analogues of methyl 4-ethyl-beta-carboline-3-carboxylate (8) and N-methyl-4-ethyl-beta-carboline-3-carboxamide (9), respectively, were synthesized and their in vitro binding affinities to the central type...

journal_title：Journal of medicinal chemistry

authors： Dorey G,Poissonnet G,Potier MC,Prado de Carvalho L,Venault P,Chapouthier G,Rossier J,Potier P,Dodd RH

更新日期：1989-08-01 00:00:00

abstract：:The insertion of single 1,4-disubstituted 1,2,3-triazoles as metabolically stable bioisosteres of trans-amide bonds (triazole scan) was recently applied to the 177Lu-labeled tumor-targeting analog of minigastrin, [Nle15]MG11. The reported novel mono-triazolo-peptidomimetics of [Nle15]MG11 showed either improved resist...

journal_title：Journal of medicinal chemistry

authors： Grob NM,Schmid S,Schibli R,Behe M,Mindt TL

更新日期：2020-05-14 00:00:00

abstract：:A focused library approach identifying novel leads to develop a potent ORL1 antagonist is described. Beginning from a compound identified by random screening, an exploratory library that exhibited a diverse display of pharmacophores was designed. After evaluating ORL1 antagonistic activity, a highly focused library wa...

journal_title：Journal of medicinal chemistry

authors： Goto Y,Arai-Otsuki S,Tachibana Y,Ichikawa D,Ozaki S,Takahashi H,Iwasawa Y,Okamoto O,Okuda S,Ohta H,Sagara T

更新日期：2006-02-09 00:00:00

abstract：:Fragment-based NMR screening, X-ray crystallography, structure-based design, and focused chemical library design were used to identify novel inhibitors for BACE-1. A rapid optimization of an initial NMR hit was achieved by a combination of NMR and a functional assay, resulting in the identification of an isothiourea h...

journal_title：Journal of medicinal chemistry

authors： Wang YS,Strickland C,Voigt JH,Kennedy ME,Beyer BM,Senior MM,Smith EM,Nechuta TL,Madison VS,Czarniecki M,McKittrick BA,Stamford AW,Parker EM,Hunter JC,Greenlee WJ,Wyss DF

更新日期：2010-02-11 00:00:00

abstract：:Novel N-substituted derivatives of acyclovir (1a) were synthesized and evaluated for their antiviral, antimetabolic, and antitumor cell properties in vitro. Monomethylation of 1a at positions 1, 7, and N-2 gave compounds 2-4, respectively. When positions 1 and N-2 were linked together by an isopropeno group, the tricy...

journal_title：Journal of medicinal chemistry

authors： Boryski J,Golankiewicz B,De Clercq E

更新日期：1988-07-01 00:00:00

abstract：:The synthesis and in vitro structure-activity relationships (SAR) of a novel series of anilinoquinazolines as allosteric inhibitors of fructose-1,6-bisphosphatase (F16Bpase) are reported. The compounds have a different SAR as inhibitors of F16Bpase than anilinoquinazolines previously reported. Selective inhibition of ...

journal_title：Journal of medicinal chemistry

authors： Wright SW,Carlo AA,Carty MD,Danley DE,Hageman DL,Karam GA,Levy CB,Mansour MN,Mathiowetz AM,McClure LD,Nestor NB,McPherson RK,Pandit J,Pustilnik LR,Schulte GK,Soeller WC,Treadway JL,Wang IK,Bauer PH

更新日期：2002-08-29 00:00:00

abstract：:A series of 3-imino-2-indolones are the first published, high-affinity antagonists of the galanin GAL3 receptor. One example, 1,3-dihydro-1-phenyl-3-[[3-(trifluoromethyl)phenyl]imino]-2H-indol-2-one (9), was shown to have high affinity for the human GAL3 receptor (Ki=17 nM) and to be highly selective for GAL3 over a b...

journal_title：Journal of medicinal chemistry

authors： Konkel MJ,Lagu B,Boteju LW,Jimenez H,Noble S,Walker MW,Chandrasena G,Blackburn TP,Nikam SS,Wright JL,Kornberg BE,Gregory T,Pugsley TA,Akunne H,Zoski K,Wise LD

更新日期：2006-06-29 00:00:00

abstract：:2,6,8-Trichloro-7-methylpurine (3) was converted to 2-chloro-8,9-dihydro-7-methyl-8-thioxopurin-6(1H)-one (5) by utilizing the difference in reactivity of the 2-, 6-, and 8-positions in the trichloropurine ring system to nucleophilic displacement. Compound 5 was subsequently glycosylated with 1-O-acetyl-2,3,5-tri-O-be...

journal_title：Journal of medicinal chemistry

authors： Henry EM,Kini GD,Larson SB,Robins RK,Alaghamandan HA,Smee DF

更新日期：1990-08-01 00:00:00

abstract：:Female sexual arousal disorder (FSAD) is a highly prevalent sexual disorder affecting up to 40% of women. We describe herein our efforts to identify a selective neutral endopeptidase (NEP) inhibitor as a potential treatment for FSAD. The rationale for this approach, together with a description of the medicinal chemist...

journal_title：Journal of medicinal chemistry

authors： Pryde DC,Maw GN,Planken S,Platts MY,Sanderson V,Corless M,Stobie A,Barber CG,Russell R,Foster L,Barker L,Wayman C,Van Der Graaf P,Stacey P,Morren D,Kohl C,Beaumont K,Coggon S,Tute M

更新日期：2006-07-13 00:00:00

abstract：:In this Perspective, recent advances and challenges in the development of GPR119 agonists as new oral antidiabetic drugs will be discussed. Such agonists are expected to exhibit a low risk to induce hypoglycemia as well as to have a beneficial impact on body weight. Many pharmaceutical companies have been active in th...

journal_title：Journal of medicinal chemistry

authors： Ritter K,Buning C,Halland N,Pöverlein C,Schwink L

更新日期：2016-04-28 00:00:00

abstract：:Developing methods to incorporate protein flexibility into structure-based drug design is an important challenge. Our approach uses multiple protein structures (MPS) to create a receptor-based pharmacophore model of the desired target. We have previously demonstrated the success of the method by applying it to human i...

journal_title：Journal of medicinal chemistry

authors： Meagher KL,Lerner MG,Carlson HA

更新日期：2006-06-15 00:00:00

abstract：:Cyclopropylcarboxylic acids and esters and cyclopropylmethanols incorporating bromophenol moieties were investigated as inhibitors of the carbonic anhydrase enzyme (CA; EC 4.2.1.1). The cis- and trans-esters 5 and 6 were obtained from the reaction of 4-allyl-1,2-dimethoxybenzene (4) with ethyl diazoacetate, which afte...

journal_title：Journal of medicinal chemistry

authors： Boztaş M,Çetinkaya Y,Topal M,Gülçin İ,Menzek A,Şahin E,Tanc M,Supuran CT

更新日期：2015-01-22 00:00:00

abstract：:Benzimidazoles carrying the 2-hydroxy-3-(isopropylamino)propoxy side chain at either the C-4 or C-5 ring positions were synthesized and investigated for beta-adrenergic blocking activity. Both compounds demonstrated beta2 selectivity when evaluated in guinea pig atrial and tracheal preparations. The C-4 isomer was 17 ...

journal_title：Journal of medicinal chemistry

authors： Crooks CR,Wright J,Callery PS,Moreton JE

更新日期：1979-02-01 00:00:00

abstract：:A close analogue of the antileukemic agent 5,8-dideaza-N10 propargylfolic acid (2) was synthesized by replacing the propargyl moiety of 2 with a cyanomethyl group. This compound, N10-(cyanomethyl)-5,8-dideazafolic acid (3), was evaluated for its antifolate and antitumor activities in several biological test systems. A...

journal_title：Journal of medicinal chemistry

authors： Nair MG,Salter DC,Kisliuk RL,Gaumont Y,North G,Sirotnak FM

更新日期：1983-04-01 00:00:00

abstract：:The discovery of potent and pan-genotypic HCV NS5A inhibitors faces many challenges including the significant diversity among genotypes, substantial potency shift conferred on some key resistance-associated variants, inconsistent SARs between different genotypes and mutants, and the lacking of models of inhibitor/prot...

journal_title：Journal of medicinal chemistry

authors： Yu W,Tong L,Hu B,Zhong B,Hao J,Ji T,Zan S,Coburn CA,Selyutin O,Chen L,Rokosz L,Agrawal S,Liu R,Curry S,McMonagle P,Ingravallo P,Asante-Appiah E,Chen S,Kozlowski JA

更新日期：2016-11-23 00:00:00

abstract：:Fluorescence spectrometry data by Tyulmenkov and Klinge (Arch. Biochem. Biophys. 2000, 381, 135-142) suggest the presence of a second binding site in both subtypes ER alpha and ER beta of the estrogen receptor (ER). A cavity previously described as a solvent channel was located in close proximity to the steroid bindin...

journal_title：Journal of medicinal chemistry

authors： van Hoorn WP

更新日期：2002-01-31 00:00:00

abstract：:A series of 4(6)- and 5-phenyl-substituted 2-amino- and 2-[(alkoxycarbonyl)amino]-1,4,5,6-tetrahydropyrimidines were prepared and evaluated for central nervous system (CNS) effects in animal models. Several 5-phenyl-substituted compounds possessed potent antidepressant activity and all compounds in this series were de...

journal_title：Journal of medicinal chemistry

authors： Weinhardt K,Wallach MB,Marx M

更新日期：1985-06-01 00:00:00

abstract：:Series of N-alkylated derivatives of 2-amino-4,6-dihydroxyindan 3 and 6-amino-1,3-dihydroxybenzocycloheptene 2 were prepared for pharmacological testing as congeners of 2-amino-5,7-dihydroxytetralin, which elicits dopaminergic effects in a variety of assays. All of the subject compounds demonstrated a lower order of d...

journal_title：Journal of medicinal chemistry

authors： Cannon JG,Pease JP,Hamer RL,Ilhan M,Bhatnagar RK,Long JP

更新日期：1984-02-01 00:00:00

abstract：:The proteasome plays a crucial role in degradation of normal proteins that happen to be constitutively or inducibly unstable, and in this capacity it plays a regulatory role. Additionally, it degrades abnormal/damaged/mutant/misfolded proteins, which serves a quality-control function. Inhibitors of the proteasome have...

journal_title：Journal of medicinal chemistry

authors： Perez C,Li J,Parlati F,Rouffet M,Ma Y,Mackinnon AL,Chou TF,Deshaies RJ,Cohen SM

更新日期：2017-02-23 00:00:00

abstract：:The limited efficacy and considerable side effects of currently available therapies for the treatment of hepatitis C virus (HCV) infection have prompted significant efforts toward the development of safe and effective new therapeutics. The pentapeptide alpha-ketoamides of type 1 were weak HCV inhibitors with a binding...

journal_title：Journal of medicinal chemistry

authors： Chen KX,Njoroge FG,Pichardo J,Prongay A,Butkiewicz N,Yao N,Madison V,Girijavallabhan V

更新日期：2005-10-06 00:00:00

abstract：:GPR52 is an orphan G protein-coupled receptor (GPCR) that has been recently implicated as a potential drug target of Huntington's disease (HD), an incurable monogenic neurodegenerative disorder. In this research, we found that striatal knockdown of GPR52 reduces mHTT levels in adult HdhQ140 mice, validating GPR52 as a...

journal_title：Journal of medicinal chemistry

authors： Wang C,Zhang YF,Guo S,Zhao Q,Zeng Y,Xie Z,Xie X,Lu B,Hu Y

更新日期：2021-01-28 00:00:00

abstract：:Since the discovery of indoleamine 2,3-dioxygenase 1 (IDO1) as an attractive target for anticancer therapy in 2003, the search for inhibitors has been intensely pursued both in academia and in pharmaceutical companies. Many novel IDO1 inhibitor scaffolds have been described, and a few potent compounds have entered cli...

journal_title：Journal of medicinal chemistry

authors： Röhrig UF,Majjigapu SR,Vogel P,Zoete V,Michielin O

更新日期：2015-12-24 00:00:00

abstract：:Syntheses of several tripeptide analogues of leupeptin containing C-terminal argininal, lysinal, or ornithinal units are presented. The synthetic analogues were tested as inhibitors of trypsin, plasmin, and kallikrein. (Benzyloxycarbonyl)-L-leucyl-L-leucyl-L-argininal (2a) was significantly less effective as an inhibi...

journal_title：Journal of medicinal chemistry

authors： McConnell RM,Barnes GE,Hoyng CF,Gunn JM

更新日期：1990-01-01 00:00:00

abstract：:The endocannabinoid 2-arachidonoylglycerol (2-AG) plays a major role in many physiological processes, and its action is quickly terminated via enzymatic hydrolysis catalyzed by monoglyceride lipase (MGL). Regulating its endogenous level could offer therapeutic opportunities; however, few selective MGL inhibitors have ...

journal_title：Journal of medicinal chemistry

authors： Matuszak N,Muccioli GG,Labar G,Lambert DM

更新日期：2009-12-10 00:00:00

abstract：:The synthesis of five amino phosphorus derivatives, 1a-e, is described. The derivatives were incorporated into a series (18) of analogues of the 5-14 portion of angiotensinogen, in most cases at the scissile Leu-Val bond. The resultant compounds were tested in vitro for their ability to inhibit human plasma renin. Rep...

journal_title：Journal of medicinal chemistry

authors： Allen MC,Fuhrer W,Tuck B,Wade R,Wood JM

更新日期：1989-07-01 00:00:00

abstract：:The calothrixins are quinone-based natural products isolated from Calothrix cyanobacteria which show potent antiproliferative properties against several cancer cell lines. Preliminary mechanistic studies suggest that the biological mode of action of the calothrixins may be linked to their ability to undergo redox cycl...

journal_title：Journal of medicinal chemistry

authors： Bernardo PH,Chai CL,Heath GA,Mahon PJ,Smith GD,Waring P,Wilkes BA

更新日期：2004-09-23 00:00:00

abstract：:Three novel, N-acyl-pro-pyrrolidine-type, inhibitors of prolyl oligopeptidase (POP) with nanomolar activities were synthesized and their binding analyzed to the host enzyme in the light of X-ray diffraction and molecular modeling studies. We were interested in the alteration in the binding affinity at the S3 site as a...

journal_title：Journal of medicinal chemistry

authors： Kánai K,Arányi P,Böcskei Z,Ferenczy G,Harmat V,Simon K,Bátori S,Náray-Szabo G,Hermecz I

更新日期：2008-12-11 00:00:00

abstract：:The synthesis and testing of potential multisubstrate inhibitors of tyrosine-specific protein kinases are described. One of the substrates, ATP, was mimicked by the known kinase inhibitor 5'-[4-(fluorosulfonyl)benzoyl]adenosine, which was covalently linked via the sulfonyl moiety to tyrosine mimics. The resulting mult...

journal_title：Journal of medicinal chemistry

authors： Kruse CH,Holden KG,Pritchard ML,Feild JA,Rieman DJ,Greig RG,Poste G

更新日期：1988-09-01 00:00:00

abstract：:The pro-inflammatory mediator macrophage migration inhibitory factor (MIF) is produced by immune and endocrine cells and inhibits the antiinflammatory activities of glucocorticoids. MIF also catalyzes the tautomerization of the non-naturally occurring D-isomer of dopachrome, phenylpyruvate, and certain catecholamines,...

journal_title：Journal of medicinal chemistry

authors： Dios A,Mitchell RA,Aljabari B,Lubetsky J,O'Connor K,Liao H,Senter PD,Manogue KR,Lolis E,Metz C,Bucala R,Callaway DJ,Al-Abed Y

更新日期：2002-06-06 00:00:00

abstract：:We have previously reported that compounds dimethyl-substituted on the phenyl ring of N-n-propyl-3-phenylpiperidines (PPEs) have a high (nM) affinity and selectivity toward the D(4) dopamine receptor (D(4) DAR) with m,p-dimethyl PPE (1) having the highest affinity and selectivity. In the present paper we have investig...

journal_title：Journal of medicinal chemistry

authors： Macchia M,Cervetto L,Demontis GC,Longoni B,Minutolo F,Orlandini E,Ortore G,Papi C,Sbrana A,Macchia B

更新日期：2003-01-02 00:00:00