Peptide quantitative structure-activity relationships, a multivariate approach.

abstract：:The design, synthesis, and biological evaluation of a new class of inhibitors of thymidylate synthase (TS) is described. The molecular design was carried out by a repetitive crystallographic analysis of protein-ligand structures. At the onset of this project, we focused on the folate cofactor binding site of a high-re...

journal_title：Journal of medicinal chemistry

authors： Webber SE,Bleckman TM,Attard J,Deal JG,Kathardekar V,Welsh KM,Webber S,Janson CA,Matthews DA,Smith WW

更新日期：1993-03-19 00:00:00

abstract：:The dihydrochalcone derivatives of the bitter flavonoids naringin and neohesperedin are intensely sweet. Phyllodulcin is as sweet as the dihydrochalcones with similar taste properties although its structure apparently resembles that of bitter flavanone or flavone. Multifaceted approaches, including X-ray crystal struc...

journal_title：Journal of medicinal chemistry

authors： Shin W,Kim SJ,Shin JM,Kim SH

更新日期：1995-10-13 00:00:00

abstract：:MLL1 is a histone 3 lysine 4 (H3K4) methyltransferase and a promising new cancer therapeutic target. The catalytic activity of MLL1 is regulated by the formation of a core complex consisting of MLL1, WDR5, RbBP5, and Ash2L. The interaction between WDR5 and MLL1 plays an essential role in regulation of the H3K4 methylt...

journal_title：Journal of medicinal chemistry

authors： Karatas H,Townsend EC,Bernard D,Dou Y,Wang S

更新日期：2010-07-22 00:00:00

abstract：:Many nonquaternary ammonium muscarinic agonists have been developed over the last few years, but most of the existing compounds (e.g., arecoline, RS-86, AF-30) behave as weak partial agonists at cholinergic receptors in tissues of limited receptor reserve. The current paper describes the synthesis and biochemical asse...

journal_title：Journal of medicinal chemistry

authors： Saunders J,Showell GA,Snow RJ,Baker R,Harley EA,Freedman SB

更新日期：1988-02-01 00:00:00

abstract：:A C-4 hydroxylated metabolite (2, 3,3-dimethyl-3,4-dihydroisoquinolin-4-ol N-oxide) of the previously described cyclic nitrone free radical trap 1 (3,3-dimethyl-3,4-dihydroisoquinoline N-oxide, a cyclic analog of phenyl-tert-butylnitrone (PBN)) was isolated, identified, and synthesized. The metabolite (2), though a le...

journal_title：Journal of medicinal chemistry

authors： Thomas CE,Bernardelli P,Bowen SM,Chaney SF,Friedrich D,Janowick DA,Jones BK,Keeley FJ,Kehne JH,Ketteler B,Ohlweiler DF,Paquette LA,Robke DJ,Fevig TL

更新日期：1996-12-06 00:00:00

abstract：:TYK2 is an emerging drug target for various human autoimmune diseases. However, discovery of selective TYK2 inhibitor over other JAK family members (i.e., JAK1, 2, 3) by targeting the catalytically active site (Janus Homologue 1 (JH1) domain) is challenging. This Viewpoint discusses the discovery of a series of N-meth...

journal_title：Journal of medicinal chemistry

authors： Chang Y,Xu S,Ding K

更新日期：2019-10-24 00:00:00

abstract：:Starting from the lead isodaphnetin, a natural product inhibitor of DPP-4 discovered through a target fishing docking based approach, a series of novel 2-phenyl-3,4-dihydro-2H-benzo[f]chromen-3-amine derivatives as potent DPP-4 inhibitors are rationally designed utilizing highly efficient 3D molecular similarity based...

journal_title：Journal of medicinal chemistry

authors： Li S,Xu H,Cui S,Wu F,Zhang Y,Su M,Gong Y,Qiu S,Jiao Q,Qin C,Shan J,Zhang M,Wang J,Yin Q,Xu M,Liu X,Wang R,Zhu L,Li J,Xu Y,Jiang H,Zhao Z,Li J,Li H

更新日期：2016-07-28 00:00:00

abstract：:The benzothiadiazine dioxide (BTD) derivatives are potent nonnucleoside human cytomegalovirus (HCMV) inhibitors. As part of our comprehensive structure-activity relationship study of these compounds, we have now synthesized N,N- and N,O-dibenzyl derivatives with different para-substituents (alkyl, phenyl, electron-don...

journal_title：Journal of medicinal chemistry

authors： Martinez A,Gil C,Abasolo MI,Castro A,Bruno AM,Perez C,Prieto C,Otero J

更新日期：2000-08-24 00:00:00

abstract：:A library of 3-hydroxy-2,3-dihydropyridones was synthesized, and their activities as antiandrogens were tested in the human prostate cancer cell line LNCaP. Structure-activity relationship (SAR) studies resulted in the identification of a potent compound whose activity is comparable to that of MDV3100. Homology modeli...

journal_title：Journal of medicinal chemistry

authors： Pepe A,Pamment M,Kim YS,Lee S,Lee MJ,Beebe K,Filikov A,Neckers L,Trepel JB,Malhotra SV

更新日期：2013-11-14 00:00:00

abstract：:Taking advantage of a proposed hydrophobic region on 5-HT2 receptors previously identified by radioligand-binding studies utilizing various phenylisopropylamine derivatives, we prepared and evaluated several N1 - and/or C7-alkyl-substituted derivatives of alpha-methyltryptamine in order to improve its affinity and sel...

journal_title：Journal of medicinal chemistry

authors： Glennon RA,Chaurasia C,Titeler M

更新日期：1990-10-01 00:00:00

abstract：:Described in this paper is the synthesis and pharmacological activity of five metabolites of the angiotensin II antagonist tasosartan (1). Of particular interest is the effect of the additional acidic group of the enol metabolite (8) on activity. As suggested by the structural-activity relationship of other angiotensi...

journal_title：Journal of medicinal chemistry

authors： Ellingboe JW,Collini MD,Quagliato D,Chen J,Antane M,Schmid J,Hartupee D,White V,Park CH,Tanikella T,Bagli JF

更新日期：1998-10-22 00:00:00

abstract：:A structure-activity study was carried out to determine the importance of the N-terminal amino acids of hCGRP8-37 in binding and antagonistic activity to CGRP receptors. Therefore, fragments of hCGRP8-37 as well as analogs obtained by the replacement of residues 9-12 by L-alanine were synthesized by solid-phase peptid...

journal_title：Journal of medicinal chemistry

authors： Mimeault M,Quirion R,Dumont Y,St-Pierre S,Fournier A

更新日期：1992-06-12 00:00:00

abstract：:Partition properties, that is partition coefficients and enthalpies (delta Hp degree) and entropies (delta Sp degree) of partition, have been measured for 50 benzoic acids in the 1-octanol/water system, and their role in QSAR (quantitative structure-activity relationship) analysis examined. The novel hydrophobic param...

journal_title：Journal of medicinal chemistry

authors： Da YZ,Ito K,Fujiwara H

更新日期：1992-09-04 00:00:00

abstract：:It is now plausible to dock libraries of 10 million molecules against targets over several days or weeks. When the molecules screened are commercially available, they may be rapidly tested to find new leads. Although docking retains important liabilities (it cannot calculate affinities accurately nor even reliably ran...

journal_title：Journal of medicinal chemistry

authors： Irwin JJ,Shoichet BK

更新日期：2016-05-12 00:00:00

abstract：:Quantitative structure-activity relationships (QSAR) have been established for the inhibition of dihydrofolate reductase and thymidylate synthetase by 2,4-diaminoquinazoline-glutamic acid analogues. For dihydrofolate reductase from both human acute lymphocytic leukemia cells and murine L1210R cells, QSAR's obtained wi...

journal_title：Journal of medicinal chemistry

authors： Chen BK,Horváth C,Bertino JR

更新日期：1979-05-01 00:00:00

abstract：:Three rationally designed pyrrolobenzodiazepine (PBD) drug-linkers have been synthesized via intermediate 19 for use in antibody-drug conjugates (ADCs). They lack a cleavable trigger in the linker and consist of a maleimide for cysteine antibody conjugation, a hydrophilic spacer, and either an alkyne (6), triazole (7)...

journal_title：Journal of medicinal chemistry

authors： Gregson SJ,Masterson LA,Wei B,Pillow TH,Spencer SD,Kang GD,Yu SF,Raab H,Lau J,Li G,Lewis Phillips GD,Gunzner-Toste J,Safina BS,Ohri R,Darwish M,Kozak KR,Dela Cruz-Chuh J,Polson A,Flygare JA,Howard PW

更新日期：2017-12-14 00:00:00

abstract：:Conformational restriction of previously disclosed acyclic (diphenylethyl)diphenylacetamides led to the discovery of several potent inhibitors of acyl CoA:cholesterol acyltransferase (ACAT). cis-[2-(4-Hydroxyphenyl)-1-indanyl]diphenylacetamide (4a) was the most potent ACAT inhibitor identified (IC50 = 0.04 microM in a...

journal_title：Journal of medicinal chemistry

authors： Vaccaro W,Amore C,Berger J,Burrier R,Clader J,Davis H,Domalski M,Fevig T,Salisbury B,Sher R

更新日期：1996-04-12 00:00:00

abstract：:Vitamin D receptor (VDR) antagonists prevent the VDR activation function helix 12 from folding into its active conformation, thus affecting coactivator recruitment and antagonizing the transcriptional regulation induced by 1α,25-dihydroxyvitamin D3. Here, we report the crystal structure of the zebrafish VDR ligand-bin...

journal_title：Journal of medicinal chemistry

authors： Belorusova AY,Chalhoub S,Rovito D,Rochel N

更新日期：2020-09-10 00:00:00

abstract：:Indoleamine 2,3-dioxygenase (IDO-1) is emerging as an important new therapeutic target for the treatment of cancer, neurological disorders, and other diseases that are characterized by pathological tryptophan metabolism. However, only a few structural classes are known to be IDO-1 inhibitors. In this study, a natural ...

journal_title：Journal of medicinal chemistry

authors： Yang S,Li X,Hu F,Li Y,Yang Y,Yan J,Kuang C,Yang Q

更新日期：2013-11-14 00:00:00

abstract：:Various basic esters of nitrogen (2) and carbocyclic (3 and 4) analogs of cannabinoids were synthesized using dicyclohexylcarbodiimide in methylene chloride. The compounds in the three series werw studied in selected pharmacological tests in mice, rats, dogs, and cats. It was shown that making the basic ester from the...

journal_title：Journal of medicinal chemistry

authors： Razdan RK,Terris BZ,Pars HG,Plotnikoff NP,Dodge PW,Dren AT,Kyncl J,Somani P

更新日期：1976-04-01 00:00:00

abstract：:(+)-12-Fluoro-13,14-dihydroprostaglandin F2alpha methyl ester (2a) and (+)-15-epi-12-fluoro-13,14-dihydroprostaglandin F2alpha methyl ester (2b) were prepared from the readily available (-)-7-fluorospiro[bicyclo[2.2.1]hept-5-ene-2,2'-[1,3]dioxolane]-7-methanol (3). Fluoroprostaglandins 2a and 2b possess truly signific...

journal_title：Journal of medicinal chemistry

authors： Grieco PA,Takigawa T

更新日期：1981-07-01 00:00:00

abstract：:In our effort to discover DPP-4 inhibitors with added benefits over currently commercially available DPP-4 inhibitors, MK-3102 (omarigliptin), was identified as a potent and selective dipeptidyl peptidase 4 (DPP-4) inhibitor with an excellent pharmacokinetic profile amenable for once-weekly human dosing and selected a...

journal_title：Journal of medicinal chemistry

authors： Biftu T,Sinha-Roy R,Chen P,Qian X,Feng D,Kuethe JT,Scapin G,Gao YD,Yan Y,Krueger D,Bak A,Eiermann G,He J,Cox J,Hicks J,Lyons K,He H,Salituro G,Tong S,Patel S,Doss G,Petrov A,Wu J,Xu SS,Sewall C,Zhang X,

更新日期：2014-04-24 00:00:00

abstract：:Resistance to β-lactam antibiotics can be mediated by metallo-β-lactamase enzymes (MBLs). An MBL inhibitor could restore the effectiveness of β-lactams. We report on the evaluation of approved thiol-containing drugs as inhibitors of NDM-1, VIM-1, and IMP-7. Drugs were assessed by a novel assay using a purchasable fluo...

journal_title：Journal of medicinal chemistry

authors： Klingler FM,Wichelhaus TA,Frank D,Cuesta-Bernal J,El-Delik J,Müller HF,Sjuts H,Göttig S,Koenigs A,Pos KM,Pogoryelov D,Proschak E

更新日期：2015-04-23 00:00:00

abstract：:We recently reported the bioinspired synthesis of a highly potent nonpeptidic xanthone, 2c (AM-0016), with potent antibacterial activity against MRSA. Herein, we report a thorough structure-activity relationship (SAR) analysis of a series of nonpeptidic amphiphilic xanthone derivatives in an attempt to identify more p...

journal_title：Journal of medicinal chemistry

authors： Koh JJ,Zou H,Lin S,Lin H,Soh RT,Lim FH,Koh WL,Li J,Lakshminarayanan R,Verma C,Tan DT,Cao D,Beuerman RW,Liu S

更新日期：2016-01-14 00:00:00

abstract：:Di-tert-butyl (E)-4,4'-stilbenedicarboxylate and tert-butyl 4-vinylbenzoate were copolymerized with maleic anhydride and tert-butyl 4-maleimidobenzoate, individually and respectively. After conversion into polyanions, these four copolymers exhibited activity against four HIV-1 strains: IIIb, BaL, JR-CSF, and 92UG037. ...

journal_title：Journal of medicinal chemistry

authors： Savage AM,Li Y,Matolyak LE,Doncel GF,Turner SR,Gandour RD

更新日期：2014-08-14 00:00:00

abstract：:On the basis of our finding that the antitumor effect of 5-{4-[(1-methylcyclohexyl)methoxy]benzyl}thiazolidine-2,4-dione, a thiazolidinedione peroxisome proliferator-activated receptor (PPAR)γ agonist, was, in part, attributable to its ability to block glucose uptake independently of PPARγ, we used its PPARγ-inactive ...

journal_title：Journal of medicinal chemistry

authors： Wang D,Chu PC,Yang CN,Yan R,Chuang YC,Kulp SK,Chen CS

更新日期：2012-04-26 00:00:00

abstract：:Based on the X-ray cocrystal structure of the Tang-Ghosh heptapeptide inhibitor 1 (OM00-3), a series of macroheterocyclic analogues were designed and synthesized. Analogues containing dithia, dioxa, oxathia, and carbathia macrocycles were synthesized by methods relying on ring-closing olefin metathesis for the dioxa a...

journal_title：Journal of medicinal chemistry

authors： Hanessian S,Yang G,Rondeau JM,Neumann U,Betschart C,Tintelnot-Blomley M

更新日期：2006-07-27 00:00:00

abstract：:Cationic amphiphiles derived from aminoglycosides (AGs) have been shown to exhibit enhanced antimicrobial activity. Through the attachment of hydrophobic residues such as linear alkyl chains on the AG backbone, interesting antibacterial and antifungal agents with a novel mechanism of action have been developed. Herein...

journal_title：Journal of medicinal chemistry

authors： Fosso MY,Shrestha SK,Green KD,Garneau-Tsodikova S

更新日期：2015-12-10 00:00:00

abstract：:Gene therapy based on gene delivery is a promising strategy for the treatment of human disease. Here we present data on structure/biological activity of new biodegradable cholesterol-based cationic lipids with various heterocyclic cationic head groups and linker types. Enhanced accumulation of nucleic acids in the cel...

journal_title：Journal of medicinal chemistry

authors： Medvedeva DA,Maslov MA,Serikov RN,Morozova NG,Serebrenikova GA,Sheglov DV,Latyshev AV,Vlassov VV,Zenkova MA

更新日期：2009-11-12 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