Structure-activity relationships of a series of novel (piperazinylbutyl)thiazolidinone antipsychotic agents related to 3-[4-[4-(6-fluorobenzo[b]thien-3-yl)-1-piperazinyl]butyl]-2,5,5- trimethyl-4-thiazolidinone maleate.

abstract：:Fifteen 7-substituted 4-hydroxyquinoline-3-carboxylic acids have been designed to minimize covariance between the physicochemical substituent parameters: pi, MR, and sigmap. The molecules have been synthesized and evaluated for their ability to inhibit the respiration of Ehrlich ascites cells as a whole cell model and...

journal_title：Journal of medicinal chemistry

authors： Shah KJ,Coats EA

更新日期：1977-08-01 00:00:00

abstract：:A new group of potent inhibitors of glutamine synthetase was designed and synthesized. The X-ray structure of bacterial glutamine synthetase complexed with phosphinothricin was used for computer-aided structure-based design of the inhibitors, in which the methyl group of phosphinothricin was chosen as the modification...

journal_title：Journal of medicinal chemistry

authors： Berlicki Ł,Obojska A,Forlani G,Kafarski P

更新日期：2005-10-06 00:00:00

abstract：:9-acridinyl derivatives of 1,6-hexanediamine, 1,8-octanediamine, bis(3-aminopropyl)amine, N,N'-bis(3-amino-propyl)piperazine, and N-ethyl-1,6-hexanediamine in the form of their hydrochlorides were prepared in high yields and converted into potential hetero bis DNA intercalating diacridines. The corresponding potential...

journal_title：Journal of medicinal chemistry

authors： Hansen JB,Langvad E,Frandsen F,Buchardt O

更新日期：1983-10-01 00:00:00

abstract：:A series of peptidyl alpha-ketoacids and alpha-ketoesters was synthesized and studied as mu-calpain inhibitors. Docking studies revealed that the mu-calpain inhibitory activity of the compounds is influenced by hydrogen bonding interactions and the potential for ionic interaction with active site residues as well as p...

journal_title：Journal of medicinal chemistry

authors： Donkor IO,Assefa H,Liu J

更新日期：2008-07-24 00:00:00

abstract：:The formation of intramolecular hydrogen bonds has a very pronounced effect on molecular structure and properties. We study both aspects in detail with the aim of enabling a more rational use of this class of interactions in medicinal chemistry. On the basis of exhaustive searches in crystal structure databases, we de...

journal_title：Journal of medicinal chemistry

authors： Kuhn B,Mohr P,Stahl M

更新日期：2010-03-25 00:00:00

abstract：:Here we report on the design, synthesis, and biological characterization of novel κ opioid (KOP) receptor ligands of diphenethylamines. In opioid receptor binding and functional assays, the N-cyclobutylmethyl substituted derivative 4 (HS665) showed the highest affinity and selectivity for the KOP receptor and KOP agon...

journal_title：Journal of medicinal chemistry

authors： Spetea M,Berzetei-Gurske IP,Guerrieri E,Schmidhammer H

更新日期：2012-11-26 00:00:00

abstract：:Novel, lipophilic cycloSal triesters 4a-c and 5a-c were synthesized, respectively, from the ara- and ribo-configurated 2'-fluorinated-2', 3'-dideoxyadenosines 2 and 3. The cycloSal phosphotriesters were used as tools to study the effects of the two different sugar pucker conformations induced by two opposite configura...

journal_title：Journal of medicinal chemistry

authors： Meier C,Knispel T,Marquez VE,Siddiqui MA,De Clercq E,Balzarini J

更新日期：1999-05-06 00:00:00

abstract：:The synthesis of cis and trans isomers of N,N-N-trimethyl-2-phenoxycyclohexylammonium bromide, cis-N,N,-N-trimethyl-2(2',6'-xylyloxy)cyclohexylammonium bromide, and N,N-dimethyl-3-phenoxypiperidinium bromide is described. Their structures and conformations were determined by NMR and uv absorption spectroscopy, the min...

journal_title：Journal of medicinal chemistry

authors： Clark ER,Hughes IE,Smith CF

更新日期：1976-05-01 00:00:00

abstract：:c-Met has emerged as an attractive target for targeted cancer therapy because of its abnormal activation in many cancer cells. To identify high potent and selective c-Met inhibitors, we started with profiling the potency and in vitro metabolic stability of a reported hit 7. By rational design, a novel sulfonylpyrazolo...

journal_title：Journal of medicinal chemistry

authors： Ma Y,Sun G,Chen D,Peng X,Chen YL,Su Y,Ji Y,Liang J,Wang X,Chen L,Ding J,Xiong B,Ai J,Geng M,Shen J

更新日期：2015-03-12 00:00:00

abstract：:From the whole plant of Euphorbia peplus L., five new diterpenes based on a jatrophane skeleton (pepluanins A-E, 1-5) were isolated, together with two known analogues (6 and 7), which served to divulge in detail the structure-activity relationships within this class of P-glycoprotein inhibitors. The results revealed t...

journal_title：Journal of medicinal chemistry

authors： Corea G,Fattorusso E,Lanzotti V,Motti R,Simon PN,Dumontet C,Di Pietro A

更新日期：2004-02-12 00:00:00

abstract：:USP7 is a promising target for cancer therapy as its inhibition is expected to decrease function of oncogenes, increase tumor suppressor function, and enhance immune function. Using a structure-based drug design strategy, a new class of reversible USP7 inhibitors has been identified that is highly potent in biochemica...

journal_title：Journal of medicinal chemistry

authors： Leger PR,Hu DX,Biannic B,Bui M,Han X,Karbarz E,Maung J,Okano A,Osipov M,Shibuya GM,Young K,Higgs C,Abraham B,Bradford D,Cho C,Colas C,Jacobson S,Ohol YM,Pookot D,Rana P,Sanchez J,Shah N,Sun M,Wong S,Brocks

更新日期：2020-05-28 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：:3-Aminopyrrolidines bearing acyl substituents on either nitrogen and N-acylated 1,4-diazabicyclo[3.2.1]octanes are potent microfilaricides in the Litomosoides carinii gerbil test system but have no effect on adult worms. The high activity of the pyrrolidine derivatives establishes that diethylcarbamazine (DEC) like an...

journal_title：Journal of medicinal chemistry

authors： Sturm P,Cory M,Henry DW

更新日期：1977-10-01 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：:With the aim of increasing therapeutic indexes of novel cyclic depsinonapeptide pseudomycins, we synthesized and evaluated a series of mono-, di-, and trioxodioxolenylmethyl carbamate prodrugs (2 and 4) of pseudomycin B 1 and pseudomycin C' 3. It is rather encouraging to note that several members of the newly synthesi...

journal_title：Journal of medicinal chemistry

authors： Sun X,Rodriguez M,Zeckner D,Sachs B,Current W,Boyer R,Paschal J,McMillian C,Chen SH

更新日期：2001-08-02 00:00:00

abstract：:A method for preparing a variety of 7-alkyl-6,7- didehydromorphinans from the corresponding 6- morphinanones is described. The key intermediates in this sequence are the 7-formyl derivatives. The two epimeric B/C-trans-7-(1- hydroxypentyl ) morphinans ( 16a ,b) are stereochemically similar to the endo- ethanotetrahydr...

journal_title：Journal of medicinal chemistry

authors： Quick J,Herlihy P,Howes JF

更新日期：1984-05-01 00:00:00

abstract：:In silico ADMET (absorption, distribution, metabolism, excretion, and toxicity) models are important tools in combating late-stage attrition in the drug discovery process. This work shows how ADMET models can be combined to tailor predictions depending on one's needs. We demonstrate how the judicious use of data and c...

journal_title：Journal of medicinal chemistry

authors： O'Brien SE,de Groot MJ

更新日期：2005-02-24 00:00:00

abstract：:Potent and selective inhibitors of Dyrk1B kinase were developed to explore the hypothesis, based on siRNA studies, that Dyrk1B may be a resistance mechanism in cells undergoing a stress response. ...

journal_title：Journal of medicinal chemistry

authors： Kettle JG,Ballard P,Bardelle C,Cockerill M,Colclough N,Critchlow SE,Debreczeni J,Fairley G,Fillery S,Graham MA,Goodwin L,Guichard S,Hudson K,Ward RA,Whittaker D

更新日期：2015-03-26 00:00:00

abstract：:Sepsis, which is a systemic inflammatory response that follows a bacterial infection, has a high mortality rate and limited therapeutic options. Here we show that the antimicrobial peptide OH-CATH30, which naturally occurs in snake, selectively regulates the innate immune response to protect mice from lethal sepsis. T...

journal_title：Journal of medicinal chemistry

authors： Li SA,Xiang Y,Wang YJ,Liu J,Lee WH,Zhang Y

更新日期：2013-11-27 00:00:00

abstract：:Para-substituted analogues of the antimuscarinic agent caramiphen were synthesized and evaluated for their ability to bind to the M1 and M2 subtypes of the muscarinic receptor. The purpose of the set was to look for a possible relationship in binding affinity or receptor subtype selectivity with aromatic substituent p...

journal_title：Journal of medicinal chemistry

authors： Hudkins RL,DeHaven-Hudkins DL,Stubbins JF

更新日期：1991-10-01 00:00:00

abstract：:A series of thiazolothiazepines were prepared and tested against purified human immunodeficiency virus type-1 integrase (HIV-1 IN) and viral replication. Structure-activity studies reveal that the compounds possessing the pentatomic moiety SC(O)CNC(O) with two carbonyl groups are in general more potent against purifie...

journal_title：Journal of medicinal chemistry

authors： Neamati N,Turpin JA,Winslow HE,Christensen JL,Williamson K,Orr A,Rice WG,Pommier Y,Garofalo A,Brizzi A,Campiani G,Fiorini I,Nacci V

更新日期：1999-08-26 00:00:00

abstract：:The synthesis and in vitro and in vivo antibreast and antiprostate cancers activities of novel C-4 heteroaryl 13-cis-retinamides that modulate Mnk-eIF4E and AR signaling are discussed. Modifications of the C-4 heteroaryl substituents reveal that the 1H-imidazole is essential for high anticancer activity. The most pote...

journal_title：Journal of medicinal chemistry

authors： Mbatia HW,Ramalingam S,Ramamurthy VP,Martin MS,Kwegyir-Afful AK,Njar VC

更新日期：2015-02-26 00:00:00

abstract：:Three N-C8-bridged analogues 4-6 of the opiate etorphine (3) were synthesized and evaluated for opiate agonism and antagonism. In each case ring closure was effected by intramolecular N-alkylation with a suitably developed C8 side chain. Another key synthetic step was the selective monoprotection of diol 11, which all...

journal_title：Journal of medicinal chemistry

authors： Maurer PJ,Rapoport H

更新日期：1987-11-01 00:00:00

abstract：:The scaffold concept was applied to systematically determine, analyze, and compare core structures of kinase inhibitors. From publicly available inhibitors of the human kinome, scaffolds and cyclic skeletons were systematically extracted and organized taking activity data, structural relationships, and retrosynthetic ...

journal_title：Journal of medicinal chemistry

authors： Hu Y,Bajorath J

更新日期：2015-01-08 00:00:00

abstract：:Three analogs of luteinizing hormone-releasing hormone (LH-RH) of the structure less than Glu-His-Trp-Ser-Tyr-Gly-Gly-Leu-Arg-Pro-Gly-NH2, involving substitutions inpositions 1, 3, and 8 with nonprotein amino acids, have been synthesized by the solid-phase method. They are [pyro-L-alpha-(1-aminoadipic)]-LH-RH, [3-(2-n...

journal_title：Journal of medicinal chemistry

authors： Prasad KU,Roeske RW,Weitl FL,Vilchez-Martinez JA,Schally AV

更新日期：1976-04-01 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：:The synthesis and gastric antisecretory activities of the delta 4,5-cis, delta 4,5-trans, and 4,5-acetylenic analogues of 15-deoxy-16-hydroxy-16-methyl prostaglandin E1 methyl ester are described. The key step in the preparation of these compounds involved the stereospecific conjugate addition of a cuprate reagent to ...

journal_title：Journal of medicinal chemistry

authors： Collins PW,Dajani EZ,Pappo R,Gasiecki AF,Bianchi RG,Woods EM

更新日期：1983-06-01 00:00:00

abstract：:Some glycine, leucine and phenylalanine dipeptide derivatives of the transport inhibitory, tricycloaliphatic alpha-amino acid, adamantanine (1), have been synthesized using classical methods of peptide synthesis with the aim of improving the latter's bioavailability. Although test doses of glycyladamantanine and L-leu...

journal_title：Journal of medicinal chemistry

authors： Nagasawa HT,Elberling JA,Shirota FN

更新日期：1975-08-01 00:00:00

abstract：:Fragment-based lead discovery has over the years matured into an attractive alternative to high-throughput screening (HTS) for lead generation. Several techniques for screening libraries of typically 10(3)-10(4) fragments have been reported. In this work, the practical success rates that can be expected from the scree...

journal_title：Journal of medicinal chemistry

authors： Makara GM

更新日期：2007-07-12 00:00:00

abstract：:Protein phosphorylation is the most significant post-translational modification for regulating cellular activities, but site-specific modulation of phosphorylation is still challenging. Using three-dimensional NMR spectra, molecular dynamics simulations, and alanine mutations, we identified that the interaction networ...

journal_title：Journal of medicinal chemistry

authors： Wang Z,Song T,Guo Z,Cao K,Chen C,Feng Y,Wang H,Yin F,Zhou S,Dai J,Zhang Z

更新日期：2020-11-25 00:00:00