Evaluation of Homobivalent Carbolines as Designed Multiple Ligands for the Treatment of Neurodegenerative Disorders.

abstract：:New 5'-O-carbonate prodrugs of zidovudine (AZT) have been synthesized in order to enhance its uptake by HIV-1 infected cells, to improve its anti-HIV potency, and to optimize the intramolecular cyclic rearrangement process related to the 5'-O-(4-hydroxybutyl) carbonate moiety. Evidence of this prodrug rearrangement wa...

journal_title：Journal of medicinal chemistry

authors： Vlieghe P,Clerc T,Pannecouque C,Witvrouw M,De Clercq E,Salles JP,Kraus JL

更新日期：2001-08-30 00:00:00

abstract：:Constitutive activation of signal transducer and activator of transcription 3 (STAT3) has been validated as an attractive therapeutic target for cancer therapy. To stop both STAT3 activation and dimerization, a viable strategy is to design inhibitors blocking its SH2 domain phosphotyrosine binding site that is respons...

journal_title：Journal of medicinal chemistry

authors： Yu W,Xiao H,Lin J,Li C

更新日期：2013-06-13 00:00:00

abstract：:A group of compounds, structurally related to metoprolol, in which the aromatic nucleus is formally moved stepwise away from the ethanolamine side chain, has been studied as adrenergic agonists and antagonists. All the compounds were active on the adrenergic receptors and showed similar affinity for the receptor regar...

journal_title：Journal of medicinal chemistry

authors： Lövgren K,Hedberg A,Nilsson JL

更新日期：1981-04-01 00:00:00

abstract：:A novel class of artemisinin analogs, N-alkyl-11-aza-9-desmethylartemisinins 17-29, were synthesized via ozonolysis and acid-catalyzed cyclization of precursor amides 5-16. These amides were prepared through condensation of an activated ester of the known intermediate acid 2 with the corresponding primary amine. The a...

journal_title：Journal of medicinal chemistry

authors： Avery MA,Bonk JD,Chong WK,Mehrotra S,Miller R,Milhous W,Goins DK,Venkatesan S,Wyandt C,Khan I

更新日期：1995-12-22 00:00:00

abstract：:Recently described biphenyl analogues of the antituberculosis drug PA-824 displayed improved potencies against M. tuberculosis but were poorly soluble. Heterobiaryl analogues of these, in which the first phenyl ring was replaced with various 5-membered ring heterocycles, were prepared with the aim of identifying poten...

journal_title：Journal of medicinal chemistry

authors： Sutherland HS,Blaser A,Kmentova I,Franzblau SG,Wan B,Wang Y,Ma Z,Palmer BD,Denny WA,Thompson AM

更新日期：2010-01-28 00:00:00

abstract：:The need for a readily available Gd(III) bifunctional chelate for protein conjugation has led to the development of LDTPA (N,N-bis[2-[N',N'-bis(carboxymethyl)amino]- ethyl]-4-amino-L-phenyl-alanine). The benzylamine group is readily converted to the isothiocyanato group (SCN-LDTPA) by treatment of the lithium salt of ...

journal_title：Journal of medicinal chemistry

authors： Deal KA,Motekaitis RJ,Martell AE,Welch MJ

更新日期：1996-08-02 00:00:00

abstract：:A single pot dipolar cycloaddition reaction/Cope elimination sequence was developed to access novel 1,4,6,7-tetrahydro-5H-[1,2,3]triazolo[4,5-c]pyridine P2X7 antagonists that contain a synthetically challenging chiral center. The structure-activity relationships of the new compounds are described. Two of these compoun...

journal_title：Journal of medicinal chemistry

authors： Chrovian CC,Soyode-Johnson A,Peterson AA,Gelin CF,Deng X,Dvorak CA,Carruthers NI,Lord B,Fraser I,Aluisio L,Coe KJ,Scott B,Koudriakova T,Schoetens F,Sepassi K,Gallacher DJ,Bhattacharya A,Letavic MA

更新日期：2018-01-11 00:00:00

abstract：:A new series of quinazolinone derivatives was synthesized and evaluated as nonimidazole H 3 receptor inverse agonists. 2-Methyl-3-(4-[[3-(1-pyrrolidinyl)propyl]oxy]phenyl)-5-(trifluoromethyl)-4(3 H)-quinazolinone ( 1) was identified as a promising derivative for further evaluation following optimization of key paramet...

journal_title：Journal of medicinal chemistry

authors： Nagase T,Mizutani T,Ishikawa S,Sekino E,Sasaki T,Fujimura T,Ito S,Mitobe Y,Miyamoto Y,Yoshimoto R,Tanaka T,Ishihara A,Takenaga N,Tokita S,Fukami T,Sato N

更新日期：2008-08-14 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：:6,6,8-Triethyldesmosdumotin B (2) was discovered as a MDR-selective flavonoid with significant in vitro anticancer activity against a multidrug resistant (MDR) cell line (KB-VIN) but without activity against the parent cells (KB). Additional 2 analogues were synthesized and evaluated to determine the effect of B-ring ...

journal_title：Journal of medicinal chemistry

authors： Nakagawa-Goto K,Chang PC,Lai CY,Hung HY,Chen TH,Wu PC,Zhu H,Sedykh A,Bastow KF,Lee KH

更新日期：2010-09-23 00:00:00

abstract：:5,6-cis-Penem derivatives have been synthesized and evaluated as anti-MRSA antibiotics. The cis-penems 5 and 6 showed potent activities against not only MRSA but also a wide variety of bacteria including beta-lactamase-producing microorganisms. These compounds were designed to have high affinity to the penicillin-bind...

journal_title：Journal of medicinal chemistry

authors： Ishiguro M,Tanaka R,Namikawa K,Nasu T,Inoue H,Nakatsuka T,Oyama Y,Imajo S

更新日期：1997-07-04 00:00:00

abstract：:Constraining the conformation of flexible peptides is a proven strategy to increase potency, selectivity, and metabolic stability. The focus has mostly been on constraining the backbone dihedral angles; however, the correct orientation of the amino acid side chains (χ-space) that constitute the peptide pharmacophore i...

journal_title：Journal of medicinal chemistry

authors： Van der Poorten O,Knuhtsen A,Sejer Pedersen D,Ballet S,Tourwé D

更新日期：2016-12-22 00:00:00

abstract：:Bufotenine (5-hydroxy-N,N-dimethyltryptamine) has been reported to be behaviorally inactive or only very weakly active in man and animals; this may be a consequence of its low partition coefficient and resultant inability to penetrate the blood--brain barrier. The acetyl, propionyl, butyryl, isobutyryl, and pivalyl es...

journal_title：Journal of medicinal chemistry

authors： Glennon RA,Gessner PK,Godse DD,Kline BJ

更新日期：1979-11-01 00:00:00

abstract：:We have previously described the design and development of CI-988, a peptoid analogue of CCK-4 with excellent binding affinity and selectivity for the CCK-B receptor. Due to its anxiolytic profile in animal models of anxiety, this compound was developed as a clinical candidate. However, during its development, it was ...

journal_title：Journal of medicinal chemistry

authors： Trivedi BK,Padia JK,Holmes A,Rose S,Wright DS,Hinton JP,Pritchard MC,Eden JM,Kneen C,Webdale L,Suman-Chauhan N,Boden P,Singh L,Field MJ,Hill D

更新日期：1998-01-01 00:00:00

abstract：:Erythromycin A is normally formulated for children as its 2'-ethyl succinate, a taste-free prodrug. Unfortunately, the prodrug hydrolyzes at a measurable rate in the medicine bottle, leading to the vile-tasting erythromycin. We have prepared derivatives of erythromycin B as putative paediatric prodrugs, taking advanta...

journal_title：Journal of medicinal chemistry

authors： Bhadra PK,Morris GA,Barber J

更新日期：2005-06-02 00:00:00

abstract：:A novel, potent, and orally bioavailable inhibitor of hepatitis C RNA replication targeting NS4B, compound 4t (PTC725), has been identified through chemical optimization of the 6-(indol-2-yl)pyridine-3-sulfonamide 2 to improve DMPK and safety properties. The focus of the SAR investigations has been to identify the opt...

journal_title：Journal of medicinal chemistry

authors： Zhang N,Zhang X,Zhu J,Turpoff A,Chen G,Morrill C,Huang S,Lennox W,Kakarla R,Liu R,Li C,Ren H,Almstead N,Venkatraman S,Njoroge FG,Gu Z,Clausen V,Graci J,Jung SP,Zheng Y,Colacino JM,Lahser F,Sheedy J,Mollin A

更新日期：2014-03-13 00:00:00

abstract：:Endothelin-converting enzyme-2 (ECE-2), a member of M13 family of zinc metallopeptidases, has previously been shown to process a number of neuropeptides including those derived from prodynorphin, proenkephalin, proSAAS, and amyloid precursor protein. ECE-2, unlike ECE-1, exhibits restricted neuroendocrine distribution...

journal_title：Journal of medicinal chemistry

authors： Gagnidze K,Sachchidanand,Rozenfeld R,Mezei M,Zhou MM,Devi LA

更新日期：2008-06-26 00:00:00

abstract：:The synthesis of several 8-carboxy-6-sulfamyldibenz[b,f][1,4]oxazepines and -thiazepines is described. The results of diuretic screening lend support to the thesis that activity is strongly dependent on the conformational mobility of 4-substituents in the 3-amino-5-sulfamylbenzoic acids. ...

journal_title：Journal of medicinal chemistry

authors： Allen RC,Reitano PA,Urbach H

更新日期：1978-08-01 00:00:00

abstract：:As part of our studies to develop novel retinoids with increased affinity and selectivity for the retinoid X receptor (RXR) subfamily, we have designed and synthesized a series of (E,E,E)-7-(1,2,3, 4-tetrahydroquinolin-6-yl)-7-alkyl-6-fluoro-3-methylhepta-2, 4, 6-trienoic acid derivatives. These tetrahydroquinolines, ...

journal_title：Journal of medicinal chemistry

authors： Hibi S,Kikuchi K,Yoshimura H,Nagai M,Tai K,Hida T

更新日期：1998-08-13 00:00:00

abstract：:To probe the space at the floor of the orthosteric ligand binding site in the dopamine D(1) receptor, four methylated analogues of dihydrexidine (DHX) were synthesized with substitutions at the 7 and 8 positions. The 8α-axial, 8β-equatorial, and 7α-equatorial were synthesized by photochemical cyclization of appropriat...

journal_title：Journal of medicinal chemistry

authors： Cueva JP,Gallardo-Godoy A,Juncosa JI,Vidi PA,Lill MA,Watts VJ,Nichols DE

更新日期：2011-08-11 00:00:00

abstract：:Cysteine proteases play an important role in cell migration and tumor metastasis. Therefore, their inhibitors are of colossal interest, having potential to be developed as effective antimetastatic drugs for tumor chemotherapy. Traditionally, secondary metabolites from streptomyces show a wide range of diversity with r...

journal_title：Journal of medicinal chemistry

authors： Singh JP,Tamang S,Rajamohanan PR,Jima NC,Chakraborty G,Kundu GC,Gaikwad SM,Khan MI

更新日期：2010-07-22 00:00:00

abstract：:The structure-based design, chemical synthesis, and biological evaluation of peptide-derived human rhinovirus (HRV) 3C protease (3CP) inhibitors are described. These compounds incorporate various Michael acceptor moieties and are shown to irreversibly bind to HRV serotype 14 3CP with inhibition activities (kobs/[I]) r...

journal_title：Journal of medicinal chemistry

authors： Dragovich PS,Webber SE,Babine RE,Fuhrman SA,Patick AK,Matthews DA,Lee CA,Reich SH,Prins TJ,Marakovits JT,Littlefield ES,Zhou R,Tikhe J,Ford CE,Wallace MB,Meador JW 3rd,Ferre RA,Brown EL,Binford SL,Harr JE,DeLisle

更新日期：1998-07-16 00:00:00

abstract：:11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) has been widely considered by the pharmaceutical industry as a target to treat metabolic syndrome in type II diabetics. We hypothesized that central nervous system (CNS) penetration might be required to see efficacy. Starting from a previously reported pyrimidine comp...

journal_title：Journal of medicinal chemistry

authors： Goldberg FW,Dossetter AG,Scott JS,Robb GR,Boyd S,Groombridge SD,Kemmitt PD,Sjögren T,Gutierrez PM,deSchoolmeester J,Swales JG,Turnbull AV,Wild MJ

更新日期：2014-02-13 00:00:00

abstract：:Seven transmembrane receptors (7TMRs), also known as G-protein-coupled receptors (GPCRs), have proven to be valuable targets for the development of therapeutics. The expansion of our understanding of 7TMR downstream signaling pathways beyond G-proteins has broadened our appreciation of the versatility of these cell su...

journal_title：Journal of medicinal chemistry

authors： Correll CC,McKittrick BA

更新日期：2014-08-28 00:00:00

abstract：:Thirty-five analogues of Phe-Leu-Glu-Glu-Leu, the pentapeptide sequence 5-9 of bovine prothrombin precursor, were synthesized and assayed as potential substrates or inhibitors of rat liver vitamin K dependent carboxylase. Carboxylation of substrate was determined by measuring the incorporation of carbon-24 labeled bic...

journal_title：Journal of medicinal chemistry

authors： Rich DH,Lehrman SR,Kawai M,Goodman HL,Suttie JW

更新日期：1981-06-01 00:00:00

abstract：:A series of analogues of the (S)-2-Amino-3-(3-hydroxy-5-methyl-isoxazol-4-yl)propionic acid (AMPA) receptor agonist BnTetAMPA (5b) were synthesized and characterized pharmacologically in radioligand binding assays at native and cloned AMPA receptors and functionally by two-electrode voltage clamp electrophysiology at ...

journal_title：Journal of medicinal chemistry

authors： Wang SY,Larsen Y,Navarrete CV,Jensen AA,Nielsen B,Al-Musaed A,Frydenvang K,Kastrup JS,Pickering DS,Clausen RP

更新日期：2016-03-10 00:00:00

abstract：:Pseudomonas aeruginosa is a causative agent of chronic infections in immunocompromised patients. Disruption of quorum sensing circuits is an attractive strategy for treating diseases associated with P. aeruginosa infection. In this study, we designed and synthesized a series of gingerol analogs targeting LasR, a maste...

journal_title：Journal of medicinal chemistry

authors： Choi H,Ham SY,Cha E,Shin Y,Kim HS,Bang JK,Son SH,Park HD,Byun Y

更新日期：2017-12-14 00:00:00

abstract：:Synthetic routes were developed to access a variety of novel 1-aryl-2H,4H-tetrahydro-1,2,4-triazin-3-one analogs which were evaluated as 5-lipoxygenase (5-LO) inhibitors. The parent structure, 1-phenylperhydro-1,2,4-triazin-3-one (4), was found to be a selective inhibitor of 5-LO in broken cell, intact cell, and human...

journal_title：Journal of medicinal chemistry

authors： Bhatia PA,Brooks CD,Basha A,Ratajczyk JD,Gunn BP,Bouska JB,Lanni C,Young PR,Bell RL,Carter GW

更新日期：1996-09-27 00:00:00

abstract：:Substrate-selective inhibition or modulation of the activity of γ-secretase, which is responsible for the generation of amyloid-β peptides, might be an effective strategy for prevention and treatment of Alzheimer's disease. We have shown that helical β-peptide foldamers are potent and specific inhibitors of γ-secretas...

journal_title：Journal of medicinal chemistry

authors： Imamura Y,Umezawa N,Osawa S,Shimada N,Higo T,Yokoshima S,Fukuyama T,Iwatsubo T,Kato N,Tomita T,Higuchi T

更新日期：2013-02-28 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