Synthesis and SAR studies of 2-oxoquinoline derivatives as CB2 receptor inverse agonists.

abstract：:Extensions and refinements of the receptor mapping method as originally developed by Crippen are presented. In a set of newly developed algorithms measures are taken to reduce the number of required energy parameters to a statistically acceptable degree. The most important measure is the incorporation of lipophilicity...

journal_title：Journal of medicinal chemistry

authors： Linschoten MR,Bultsma T,IJzerman AP,Timmerman H

更新日期：1986-02-01 00:00:00

abstract：:The synthesis of the first 4-amino-3-carboxy-beta-carboline derivative (35) is described. This synthesis is based on ozonolysis of the 4-vinyl-beta-carboline-3-carboxamide 17 to give the 4-aldehyde 20 and potassium permanganate oxidation of the latter to the 4-carboxylic acid 34 followed by a DPPA-promoted Curtius rea...

journal_title：Journal of medicinal chemistry

authors： Dorey G,Dubois L,Prodo de Carvalho LP,Potier P,Dodd RH

更新日期：1995-01-06 00:00:00

abstract：:In a previous study, a cocrystal structure of PPARγ bound to 2-chloro-N-(3-chloro-4-((5-chlorobenzo[d]thiazol-2-yl)thio)phenyl)-4-(trifluoromethyl)benzenesulfonamide (1, T2384) revealed two orthosteric pocket binding modes attributed to a concentration-dependent biochemical activity profile. However, 1 also bound an a...

journal_title：Journal of medicinal chemistry

authors： Hughes TS,Shang J,Brust R,de Vera IMS,Fuhrmann J,Ruiz C,Cameron MD,Kamenecka TM,Kojetin DJ

更新日期：2016-11-23 00:00:00

abstract：:A series of novel linear aliphatic amine-linked triaryl derivatives as inhibitors of PD-1/PD-L1 were designed, synthesized, and evaluated in vitro and in vivo. In this chemical series, compound 58 showed the most potent inhibitory activity and binding affinity with hPD-L1, with an IC50 value of 12 nM and a KD value of...

journal_title：Journal of medicinal chemistry

authors： Guo J,Luo L,Wang Z,Hu N,Wang W,Xie F,Liang E,Yan X,Xiao J,Li S

更新日期：2020-11-25 00:00:00

abstract：:Several 4-benzyl analogues of 5-ethyl-6-methyl-4-(phenylthio)pyridin-2(1H)-ones were synthesized and evaluated for their anti-HIV-l activities. Key transformations include metalation at the 4-C-position of 5-ethyl-2-methoxy-6-methyl-3-pivaloylaminopyridine (5) and its coupling with benzyl bromide or benzaldehyde deriv...

journal_title：Journal of medicinal chemistry

authors： Dollé V,Nguyen CH,Legraverend M,Aubertin AM,Kirn A,Andreola ML,Ventura M,Tarrago-Litvak L,Bisagni E

更新日期：2000-10-19 00:00:00

abstract：:Building on the previously and successfully applied hypothesis that stereochemical complication in the proximity of the critical cationic head of a cholinergic agonist would result in subtype selective compounds, we synthesized a series of chiral derivatives of furmethide and 5-methylfurmethide, with the aim of obtain...

journal_title：Journal of medicinal chemistry

authors： Scapecchi S,Nesi M,Matucci R,Bellucci C,Buccioni M,Dei S,Guandalini L,Manetti D,Martini E,Marucci G,Romanelli MN,Teodori E,Cirilli R

更新日期：2008-07-10 00:00:00

abstract：:Somatostatin-14 (somatostatin) and its clinically available analogues octreotide, lanreotide, and vapreotide are potent inhibitors of growth hormone, insulin, and glucagon release. Recently, a novel backbone cyclic somatostatin analogue c(GABA-Phe-Trp-(D)Trp-Lys-Thr-Phe-GlyC3-NH(2)) (analogue 1, PTR 3173) that possess...

journal_title：Journal of medicinal chemistry

authors： Gazal S,Gelerman G,Ziv O,Karpov O,Litman P,Bracha M,Afargan M,Gilon C

更新日期：2002-04-11 00:00:00

abstract：:The synthesis, biological activity, and molecular modeling studies of C-ring-modified camptothecins are reported. A general synthetic protocol, based on "C-5 camptothecin (C-5-CPT) enolate chemistry", allows one to obtain various C5-substituted analogues. All new compounds, obtained as 1:1 epimeric mixtures, were test...

journal_title：Journal of medicinal chemistry

authors： Samorì C,Guerrini A,Varchi G,Fontana G,Bombardelli E,Tinelli S,Beretta GL,Basili S,Moro S,Zunino F,Battaglia A

更新日期：2009-02-26 00:00:00

abstract：:The synthesis and biological evaluation of a novel paclitaxel photoaffinity probe is described. The synthesis involved the preparation of an azide-containing C13 side chain through a Staudinger cycloaddition followed by a lipase-mediated kinetic resolution to obtain the azetidinone in 99% ee. Coupling of the enantiopu...

journal_title：Journal of medicinal chemistry

authors： Spletstoser JT,Flaherty PT,Himes RH,Georg GI

更新日期：2004-12-16 00:00:00

abstract：:Analogues of the previously reported potent cytotoxic spiro[(dihydropyrazine-2,5-dione)-6,3'-(2',3'-dihydrothieno[2,3-b]naphtho-4',9'-dione)] derivatives (3, 3') were prepared to explore new structural requirements at the diketopiperazine domain for the cytotoxic activity. The in vitro activity was evaluated against t...

journal_title：Journal of medicinal chemistry

authors： Gomez-Monterrey I,Campiglia P,Carotenuto A,Stiuso P,Bertamino A,Sala M,Aquino C,Grieco P,Morello S,Pinto A,Ianelli P,Novellino E

更新日期：2008-05-22 00:00:00

abstract：:Antagonism of mercaptopropionic acid (MPA) induced convulsions, reflecting a GABAergic mechanism, was observed in a series of 1-aryl-3-(aminoalkylidene)oxindoles. Optimal MPA antagonism was associated with 3-halo, 3-alkyl, and/or 4-alkoxy substituents in the pendant aryl ring and with (dimethylamino)methylene, 1-(dime...

journal_title：Journal of medicinal chemistry

authors： Sarges R,Howard HR,Koe BK,Weissman A

更新日期：1989-02-01 00:00:00

abstract：:A series of quinolone and naphthyridine antibacterial agents possessing as the C7-heterocycle bicyclic 2,5-diazabicyclo[n.2.m]alkanes, where n = 2, 3 and m = 1, 2, and a series including 4-aminopiperidine and 3-amino-8-azabicyclo[3.2.1]octanes have been prepared and evaluated in vitro and in vivo for antibacterial act...

journal_title：Journal of medicinal chemistry

authors： Kiely JS,Hutt MP,Culbertson TP,Bucsh RA,Worth DF,Lesheski LE,Gogliotti RD,Sesnie JC,Solomon M,Mich TF

更新日期：1991-02-01 00:00:00

abstract：:New transition-state analogues bearing C-termini derived from alpha-mercaptoalkanoic acids, esters, and amides were prepared and evaluated as inhibitors of human renin. Addition of alpha-mercaptoalkanoate esters to a chiral Boc-amino epoxide intermediate led ultimately to the target [(2R,3S)-3-(BocPheHis-amino)-4-cycl...

journal_title：Journal of medicinal chemistry

authors： Ashton WT,Cantone CL,Tolman RL,Greenlee WJ,Lynch RJ,Schorn TW,Strouse JF,Siegl PK

更新日期：1992-07-24 00:00:00

abstract：:A series of 26 derivatives of the novel muscarinic antagonist 3-(2-benzofuranyl)quinuclidin-2-ene (1) has been synthesized and evaluated for muscarinic and antimuscarinic properties. The affinity of the compounds was determined by competition experiments in homogenates of cerebral cortex, heart, parotid gland, and uri...

journal_title：Journal of medicinal chemistry

authors： Nordvall G,Sundquist S,Johansson G,Glas G,Nilvebrant L,Hacksell U

更新日期：1996-08-16 00:00:00

abstract：:A series of S-alkylated derivatives of 5-mercapto-2'-deoxyuridine have been prepared by alkylation of the preformed nucleoside. Two of these compounds, the S-propargyl and S-allyl derivatives, have shown significant antiviral activity against Herpes simplex type 1 in HeLa TK- cells but appear to be less effective in t...

journal_title：Journal of medicinal chemistry

authors： Dinan FJ,Bardos TJ

更新日期：1980-05-01 00:00:00

abstract：:N-Substituted cis-4a-(3-hydroxyphenyl)-8a-methyloctahydroisoquinolines (6a-g) were designed and synthesized as conformationally constrained analogues of the trans-3,4-dimethyl-4-(3-hydroxyphenyl)piperidine (4) class of opioid receptor pure antagonists. The methyloctahydroisoquinolines 6a-g can exist in conformations w...

journal_title：Journal of medicinal chemistry

authors： Carroll FI,Chaudhari S,Thomas JB,Mascarella SW,Gigstad KM,Deschamps J,Navarro HA

更新日期：2005-12-29 00:00:00

abstract：:Aldehyde dehydrogenase (ALDH) activity is commonly used as a marker to identify cancer stem-like cells. The three ALDH1A isoforms have all been individually implicated in cancer stem-like cells and in chemoresistance; however, which isoform is preferentially expressed varies between cell lines. We sought to explore th...

journal_title：Journal of medicinal chemistry

authors： Huddle BC,Grimley E,Buchman CD,Chtcherbinine M,Debnath B,Mehta P,Yang K,Morgan CA,Li S,Felton J,Sun D,Mehta G,Neamati N,Buckanovich RJ,Hurley TD,Larsen SD

更新日期：2018-10-11 00:00:00

abstract：:In the course of further chemical modification of the novel antidiabetic pioglitazone (AD-4833, U-72,107), a series of 5-[4-(2- or 4-azolylalkoxy)benzyl- or -benzylidene]-2,4-thiazolidinediones was prepared and evaluated for hypoglycemic and hypolipidemic activities in insulin-resistant, genetically obese, and diabeti...

journal_title：Journal of medicinal chemistry

authors： Sohda T,Mizuno K,Momose Y,Ikeda H,Fujita T,Meguro K

更新日期：1992-07-10 00:00:00

abstract：:The synthesis of new meridianin derivatives is described. The indolic ring system was substituted at the C-4 to C-7 positions either by a bromine atom or by nitro or amino groups. Additionally, an iodine atom or various aryl groups were introduced at the C-5 position of the 2-aminopyrimidine ring. These compounds as w...

journal_title：Journal of medicinal chemistry

authors： Giraud F,Alves G,Debiton E,Nauton L,Théry V,Durieu E,Ferandin Y,Lozach O,Meijer L,Anizon F,Pereira E,Moreau P

更新日期：2011-07-14 00:00:00

abstract：:The resurgence of tuberculosis (TB), the incidence of drug-resistant strains of Mycobacterium tuberculosis (MTB), and the coinfection between TB and HIV have led to serious infections, high mortality, and a global health threat, resulting in the urgent search for new classes of antimycobacterial agents. Herein, we rep...

journal_title：Journal of medicinal chemistry

authors： Guo S,Song Y,Huang Q,Yuan H,Wan B,Wang Y,He R,Beconi MG,Franzblau SG,Kozikowski AP

更新日期：2010-01-28 00:00:00

abstract：:Angiogenesis is a requirement for the sustained growth and proliferation of solid tumors, and the development of new compounds that induce a sustained inhibition of the proangiogenic signaling generated by tumor hypoxia still remains as an important unmet need. In this work, we describe a new antiangiogenic compound (...

journal_title：Journal of medicinal chemistry

authors： Marín-Ramos NI,Alonso D,Ortega-Gutiérrez S,Ortega-Nogales FJ,Balabasquer M,Vázquez-Villa H,Andradas C,Blasco-Benito S,Pérez-Gómez E,Canales Á,Jiménez-Barbero J,Marquina A,del Prado JM,Sánchez C,Martín-Fontecha M,López-Rodrí

更新日期：2015-05-14 00:00:00

abstract：:A metabolism-based approach toward the optimization of a series of N-arylsulfonamide-based γ-secretase inhibitors is reported. The lead cyclohexyl analogue 6 suffered from extensive oxidation on the cycloalkyl motif by cytochrome P450 3A4, translating into poor human liver microsomal stability. Knowledge of the metabo...

journal_title：Journal of medicinal chemistry

authors： Stepan AF,Karki K,McDonald WS,Dorff PH,Dutra JK,Dirico KJ,Won A,Subramanyam C,Efremov IV,O'Donnell CJ,Nolan CE,Becker SL,Pustilnik LR,Sneed B,Sun H,Lu Y,Robshaw AE,Riddell D,O'Sullivan TJ,Sibley E,Capetta S,Atch

更新日期：2011-11-24 00:00:00

abstract：:The constitution of chlorpromazine has been studied in the context of its phototoxicity. Electron transfer from the side chain to the aromatic nucleus of the drug contributes to its instability to light. Even without the side chain, however, chlorophenothiazines appear to be very photolabile, so that it is unlikely th...

journal_title：Journal of medicinal chemistry

authors： Bunce NJ,Kumar Y,Ravanal L

更新日期：1979-02-01 00:00:00

abstract：:Three phosphapeptides designed to mimic two distinct tetrahedral intermediates formed during either the synthesis or hydrolysis of glutathionylspermidine (Gsp) were synthesized and evaluated as inhibitors of the bifunctional enzyme Gsp synthetase/amidase. While the polyamine-containing phosphapeptides were determined ...

journal_title：Journal of medicinal chemistry

authors： Chen S,Lin CH,Kwon DS,Walsh CT,Coward JK

更新日期：1997-11-07 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：:The synthesis of a series of novel, potent angiotensin converting enzyme (ACE) inhibitors containing saturated bicyclic amino acids in place of proline is described. Octahydroindole-2-carboxylic acid, octahydroisoindole-1-carboxylic acid, and octahydro-3-oxoisoindole-1-carboxylic acid can replace proline in both sulfh...

journal_title：Journal of medicinal chemistry

authors： Blankley CJ,Kaltenbronn JS,DeJohn DE,Werner A,Bennett LR,Bobowski G,Krolls U,Johnson DR,Pearlman WM,Hoefle ML

更新日期：1987-06-01 00:00:00

abstract：:N(α)-Boc-l-Asp(OBn)-l-Lys(Z)-OtBu (reversin 121, 1), an inhibitor of the P-gp ABC transporter, was used to conceive compounds inhibiting the drug efflux occurring through the Hoechst 33342 and daunorubicin transport sites of P-gp, respectively H and R sites. Replacement of the aspartyl residue by trans-4-hydroxy-l-pro...

journal_title：Journal of medicinal chemistry

authors： Arnaud O,Koubeissi A,Ettouati L,Terreux R,Alamé G,Grenot C,Dumontet C,Di Pietro A,Paris J,Falson P

更新日期：2010-09-23 00:00:00

abstract：:Acyclic nucleosides 1-[[2-hydroxy-1-(hydroxymethyl)ethoxy] methyl]-5-benzyluracil (DHPBU) (1) and 1-[[2-hydroxy-1-(aminomethyl)ethoxy]methyl]-5-benzyluracil (AHPBU) (2) have been synthesized by direct coupling of bis(trimethylsilyl)-5-benzyluracil with the corresponding chloromethyl ether, followed by removal of the b...

journal_title：Journal of medicinal chemistry

authors： Lin TS,Liu MC

更新日期：1985-07-01 00:00:00

abstract：:Phenyl-substituted analogues of 2-[(phenylmethyl)sulfonyl]pyridine 1-oxide preemergent herbicides were examined in order to determine quantitative relationships between structure and activity against the following three weed species: switch grass (Panicum virgatum L.), barnyard grass (Echinochloa crusgalli L. Beauv.),...

journal_title：Journal of medicinal chemistry

authors： Doweyko AM,Bell AR,Minatelli JA,Relyea DI

更新日期：1983-04-01 00:00:00

abstract：:Screening of our internal chemical collection against the neuropeptide Y5 (NPY Y5) receptor allowed the identification of a benzoxazine derivative 5f as a hit that showed moderate affinity (IC(50) = 300 nM). With the aim of improving the in vitro potency, a series of 2-benzoxazinone derivatives have been synthesized a...

journal_title：Journal of medicinal chemistry

authors： Torrens A,Mas J,Port A,Castrillo JA,Sanfeliu O,Guitart X,Dordal A,Romero G,Fisas MA,Sánchez E,Hernández E,Pérez P,Pérez R,Buschmann H

更新日期：2005-03-24 00:00:00