Methyl effects on protein-ligand binding.

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：:Targeted imaging requires contrast agents that remain in the vasculature for extended periods of time. A new contrast agent is described in which gadolinium is encapsulated within an extremely stable carbon sphere, thus allowing for safe extended residence. Water solubility and small particle size is achieved with nov...

journal_title：Journal of medicinal chemistry

authors： MacFarland DK,Walker KL,Lenk RP,Wilson SR,Kumar K,Kepley CL,Garbow JR

更新日期：2008-07-10 00:00:00

abstract：:Drugs exert desired and undesired effects based on their binding interactions with protein target(s) and off-target(s), providing evidence for drug efficacy and toxicity. Pioglitazone and rosiglitazone possess a common functional core, glitazone, which is considered a privileged scaffold upon which to build a drug sel...

journal_title：Journal of medicinal chemistry

authors： Hoffmann BR,El-Mansy MF,Sem DS,Greene AS

更新日期：2012-10-11 00:00:00

abstract：:Oxadiazoles, like the benzoyl group in a series of imidazo[1,2-a]pyrimidines, have been found to be metabolically stable alternatives to ester groups in benzodiazepine-receptor ligands. This change has lead to a number of compounds which bind to the receptors and which exhibit potent agonist activity in a food-motivat...

journal_title：Journal of medicinal chemistry

authors： Tully WR,Gardner CR,Gillespie RJ,Westwood R

更新日期：1991-07-01 00:00:00

abstract：:Modification of the 2(S)-methylbutyryl moiety of mevinolin led to a series of side chain ester derivatives. A systematic exploration of the structure-activity relationships showed that the introduction of an additional aliphatic group on the carbon alpha to the carbonyl group increased potency. This observation led to...

journal_title：Journal of medicinal chemistry

authors： Hoffman WF,Alberts AW,Anderson PS,Chen JS,Smith RL,Willard AK

更新日期：1986-05-01 00:00:00

abstract：:A series of homo- and heterodimeric ligands containing kappa agonist and mu agonist/antagonist pharmacophores joined by a linker chain of varying lengths was synthesized and evaluated in vitro by their binding affinity at mu, delta, and kappa opioid receptors. The functional activities of these compounds were measured...

journal_title：Journal of medicinal chemistry

authors： Peng X,Knapp BI,Bidlack JM,Neumeyer JL

更新日期：2006-01-12 00:00:00

abstract：:A series of N2-[(acylamino)alkyl]-6,7-dimethoxy-2,4-quinazolinediamines was synthesized as potential alpha 1-adrenoceptor antagonists. When administered to spontaneously hypertensive rats at 10 mg/kg po, a number of propanediamine derivatives showed good antihypertensive activity, whereas the ethanediamine derivatives...

journal_title：Journal of medicinal chemistry

authors： Manoury PM,Binet JL,Dumas AP,Lefèvre-Borg F,Cavero I

更新日期：1986-01-01 00:00:00

abstract：:Several derivatives of 4,5-disubstituted imidazole, 2,4,5-trisubstituted pyrimidine, 2-substituted purine, thiazolo[3,2-alpha]purine, [1,3]thiazino[3,2-alpha]purine, thiazolo[2,3-i]purine, [1,3]thiazino-[2,3-i]purine, and 6-substituted pyrazolo[3,4-d]pyrimidine were synthesized and tested as inhibitors of the xanthine...

journal_title：Journal of medicinal chemistry

authors： Biagi G,Costantini A,Costantino L,Giorgi I,Livi O,Pecorari P,Rinaldi M,Scartoni V

更新日期：1996-06-21 00:00:00

abstract：:Five dipeptidomimetic-based model prodrugs containing ketomethylene amide bond replacements were synthesized from readily available alpha,beta-unsaturated gamma-ketoesters. The model drug (BnOH) was attached to the C-terminus or to one of the side chain positions of the dipeptidomimetic. The stability, the affinity fo...

journal_title：Journal of medicinal chemistry

authors： Våbenø J,Nielsen CU,Ingebrigtsen T,Lejon T,Steffansen B,Luthman K

更新日期：2004-09-09 00:00:00

abstract：:The active site of lanosterol 14alpha-demethylase (CYP51) was investigated via MCSS functional group mapping and LUDI calculations. Several non-azole lead molecules were obtained by coupling structure-based de novo design with chemical synthesis and biological evaluation. All of the lead molecules exhibited a strong i...

journal_title：Journal of medicinal chemistry

authors： Ji H,Zhang W,Zhang M,Kudo M,Aoyama Y,Yoshida Y,Sheng C,Song Y,Yang S,Zhou Y,Lü J,Zhu J

更新日期：2003-02-13 00:00:00

abstract：:A number of analogues of ibotenic acid [(RS)-3-hydroxy-5- isoxazoleglycine ] were synthesized; they were tested as excitants on neurons in the cat spinal cord, by using microelectrophoretic techniques, and as inhibitors of the binding of kainic acid (KA) in vitro, by using synaptic membranes prepared from rat brains. ...

journal_title：Journal of medicinal chemistry

authors： Krogsgaard-Larsen P,Nielsen EO,Curtis DR

更新日期：1984-05-01 00:00:00

abstract：:Several compounds having portions of the camptothecin ring system were prepared. These compounds were screened against L1210 lymphoid leukemia with negative results. Two of the analogs which contained the pyridine and hydroxylactone D and E rings were also screened for inhibition of DNA and RNA syntheses in HeLa cells...

journal_title：Journal of medicinal chemistry

authors： Horwitz SB,Bristol JA,Comins DL,Davenport RW,Kane MJ,Lyle RE,Maloney JR,Portlock DE

更新日期：1975-05-01 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：:Virulence gene expression in Staphylococcus aureus is tightly regulated by intricate networks of transcriptional regulators and two-component signal transduction systems. There is now an emerging body of evidence to suggest that the blockade of S. aureus virulence gene expression significantly attenuates infection in ...

journal_title：Journal of medicinal chemistry

authors： Gordon CP,Williams P,Chan WC

更新日期：2013-02-28 00:00:00

abstract：:The oxazolidinone antibacterials target the 50S subunit of prokaryotic ribosomes. To gain insight into their mechanism of action, the crystal structure of the canonical oxazolidinone, linezolid, has been determined bound to the Haloarcula marismortui 50S subunit. Linezolid binds the 50S A-site, near the catalytic cent...

journal_title：Journal of medicinal chemistry

authors： Ippolito JA,Kanyo ZF,Wang D,Franceschi FJ,Moore PB,Steitz TA,Duffy EM

更新日期：2008-06-26 00:00:00

abstract：:A series of trans-platinum(IV) complexes with functionalized aromatic carboxylate ligands, cis,cis,trans-Pt(NH3)2Cl2(CO2C6H4R)2 (R = H (3), p-vinyl (4), p-methoxy (5), p-iodo (6), p-cyano (7), or o-carboxyl (8)) was synthesized and characterized by spectroscopic methods. Crystal structures of 3, 4, 7, and 8 were obtai...

journal_title：Journal of medicinal chemistry

authors： Ang WH,Pilet S,Scopelliti R,Bussy F,Juillerat-Jeanneret L,Dyson PJ

更新日期：2005-12-15 00:00:00

abstract：:Etoxadrol (2a), one of the eight possible optical isomers of 2-ethyl-2-phenyl-4-(2-piperidyl)-1,3-dioxolane, was synthesized from (S,S)-1-(2-piperidyl)-1,2-ethanediol, which was obtained from cleavage of dexoxadrol (1a, (S,S)-2,2-diphenyl-4-(2-piperidyl)-1,3-dioxolane). The absolute configuration of etoxadrol hydrochl...

journal_title：Journal of medicinal chemistry

authors： Thurkauf A,Zenk PC,Balster RL,May EL,George C,Carroll FI,Mascarella SW,Rice KC,Jacobson AE,Mattson MV

更新日期：1988-12-01 00:00:00

abstract：:A series of alpha,alpha-diaryl-1-piperidinebutanols was evaluated for antiarrhythmic activity in the coronary ligated dog model. Structure-activity relationship studies indicated that the 2,6-dimethylpiperidine group yielded compounds with the best antiarrhythmic profiles in this series. The length of the methylene ch...

journal_title：Journal of medicinal chemistry

authors： Hoefle ML,Blouin LT,Fleming RW,Hastings S,Hinkley JM,Mertz TE,Steffe TJ,Stratton CS

更新日期：1991-01-01 00:00:00

abstract：:On the basis of a mu opioid receptor (MOR) homology model and the isosterism concept, three generations of 14-heteroaromatically substituted naltrexone derivatives were designed, synthesized, and evaluated as potential MOR-selective ligands. The first-generation ligands appeared to be MOR-selective, whereas the second...

journal_title：Journal of medicinal chemistry

authors： Yuan Y,Zaidi SA,Elbegdorj O,Aschenbach LC,Li G,Stevens DL,Scoggins KL,Dewey WL,Selley DE,Zhang Y

更新日期：2013-11-27 00:00:00

abstract：:Classical potential energy calculations are reported for a series of 11 structurally diverse substrates, products, and inhibitors of dihydrofolate reductase. In almost every case, the calculations reveal a range of potential biologically active conformations accessible to the molecule, and geometry optimization with m...

journal_title：Journal of medicinal chemistry

authors： Andrews PR,Sadek M,Spark MJ,Winkler DA

更新日期：1986-05-01 00:00:00

abstract：:Bifunctional quinolinonyl DKA derivatives were first described as nonselective inhibitors of 3'-processing (3'-P) and strand transfer (ST) functions of HIV-1 integrase (IN), while 7-aminosubstituted quinolinonyl derivatives were proven IN strand transfer inhibitors (INSTIs) that also displayed activity against ribonuc...

journal_title：Journal of medicinal chemistry

authors： Pescatori L,Métifiot M,Chung S,Masoaka T,Cuzzucoli Crucitti G,Messore A,Pupo G,Madia VN,Saccoliti F,Scipione L,Tortorella S,Di Leva FS,Cosconati S,Marinelli L,Novellino E,Le Grice SF,Pommier Y,Marchand C,Costi R,Di

更新日期：2015-06-11 00:00:00

abstract：:(N)-Methanocarba adenosine 5'-methyluronamides containing known A(3) AR (adenosine receptor)-enhancing modifications, i.e., 2-(arylethynyl)adenine and N(6)-methyl or N(6)-(3-substituted-benzyl), were nanomolar full agonists of human (h) A(3)AR and highly selective (K(i) ∼0.6 nM, N(6)-methyl 2-(halophenylethynyl) analo...

journal_title：Journal of medicinal chemistry

authors： Tosh DK,Deflorian F,Phan K,Gao ZG,Wan TC,Gizewski E,Auchampach JA,Jacobson KA

更新日期：2012-05-24 00:00:00

abstract：:G-protein-coupled receptor 52 (GPR52) is an orphan Gs-coupled G-protein-coupled receptor. GPR52 inhibits dopamine D2 receptor signaling and activates dopamine D1/N-methyl-d-aspartate receptors via intracellular cAMP accumulation, and therefore, GPR52 agonists may have potential as a novel class of antipsychotics. A se...

journal_title：Journal of medicinal chemistry

authors： Setoh M,Ishii N,Kono M,Miyanohana Y,Shiraishi E,Harasawa T,Ota H,Odani T,Kanzaki N,Aoyama K,Hamada T,Kori M

更新日期：2014-06-26 00:00:00

abstract：:Isoform-selective antagonists of the lysophosphatidic acid (LPA) G-protein coupled receptors (GPCRs) have important potential uses in cell biology and clinical applications. Novel phosphonothioate and fluoromethylene phosphonate analogues of carbacyclic phosphatidic acid (ccPA) were prepared by chemical synthesis. The...

journal_title：Journal of medicinal chemistry

authors： Xu Y,Jiang G,Tsukahara R,Fujiwara Y,Tigyi G,Prestwich GD

更新日期：2006-08-24 00:00:00

abstract：:CrtN has been identified as an attractive and druggable target for treating pigmented Staphylococcus aureus infections. More than 100 new compounds were synthesized, which target the overwhelming the defects of the CrtN inhibitor 1. Analogues 23a and 23b demonstrated a significant activity against pigmented S. aureus ...

journal_title：Journal of medicinal chemistry

authors： Li B,Ni S,Mao F,Chen F,Liu Y,Wei H,Chen W,Zhu J,Lan L,Li J

更新日期：2018-01-11 00:00:00

abstract：:The 2'-chloro derivatives of etoposide and 4 beta-(arylamino)-4'-O-demethylpodophyllotoxins have been synthesized and evaluated for their inhibitory activity against the human DNA topoisomerase II as well as for their activity in causing cellular protein-linked DNA breakage. The results showed that none of the compoun...

journal_title：Journal of medicinal chemistry

authors： Hu H,Wang ZQ,Liu SY,Cheng YC,Lee KH

更新日期：1992-03-06 00:00:00

abstract：:The alpha- and beta-D-lyxofuranosyl analogues of the naturally occurring nucleosides have been synthesized and their antiviral properties examined. The alpha anomers were prepared by glycosylation of purine and pyrimidine aglycons with tetra-O-acetyl-alpha-D-lyxofuranose, followed by removal of the blocking groups. Th...

journal_title：Journal of medicinal chemistry

authors： Gosselin G,Bergogne MC,De Rudder J,De Clercq E,Imbach JL

更新日期：1987-06-01 00:00:00

abstract：:Mycobacterium abscessus (Mab) is a rapidly growing species of multidrug-resistant nontuberculous mycobacteria that has emerged as a growing threat to individuals with cystic fibrosis and other pre-existing chronic lung diseases. Mab pulmonary infections are difficult, or sometimes impossible, to treat and result in ac...

journal_title：Journal of medicinal chemistry

authors： Whitehouse AJ,Thomas SE,Brown KP,Fanourakis A,Chan DS,Libardo MDJ,Mendes V,Boshoff HIM,Floto RA,Abell C,Blundell TL,Coyne AG

更新日期：2019-08-08 00:00:00

abstract：:A series of 3-(arylureido)-5-phenyl-1,4-benzodiazepines, nonpeptidal antagonists of the peptide hormone cholecystokinin (CCK), are described. Derived by reasoned modification of the CCK-A selective 3-carboxamido-1,4-benzodiazepine, MK-329, this paper chronicles the development of potent, orally effective compounds in ...

journal_title：Journal of medicinal chemistry

authors： Bock MG,DiPardo RM,Evans BE,Rittle KE,Whitter WL,Garsky VM,Gilbert KF,Leighton JL,Carson KL,Mellin EC

更新日期：1993-12-24 00:00:00

abstract：:5-(Ethylsulfonyl)-2-(naphthalen-2-yl)benzo[d]oxazole (ezutromid, 1) is a first-in-class utrophin modulator that has been evaluated in a phase 2 clinical study for the treatment of Duchenne muscular dystrophy (DMD). Ezutromid was found to undergo hepatic oxidation of its 2-naphthyl substituent to produce two regioisome...

journal_title：Journal of medicinal chemistry

authors： Chatzopoulou M,Claridge TDW,Davies KE,Davies SG,Elsey DJ,Emer E,Fletcher AM,Harriman S,Robinson N,Rowley JA,Russell AJ,Tinsley JM,Weaver R,Wilkinson IVL,Willis NJ,Wilson FX,Wynne GM

更新日期：2020-03-12 00:00:00