Novel quinolizidinyl derivatives as antiarrhythmic agents: 2. Further investigation.

abstract：:A series of 6-substituted purinyl alkoxycarbonyl amino acids were synthesized and evaluated for their ability to stimulate cytotoxic T lymphocytes (CTLs) and the mixed lymphocyte reaction (MLR). A few of these compounds, in particular [[5-[6-(N,N-dimethylamino)purin-9-yl]pentoxy]-carbonyl]D-arginine (BCH-1393, 4a), di...

journal_title：Journal of medicinal chemistry

authors： Zacharie B,Gagnon L,Attardo G,Connolly TP,St-Denis Y,Penney CL

更新日期：1997-08-29 00:00:00

abstract：:A range of cis- and trans-3-substituted 1-aminocyclobutane-1-carboxylic acids has been synthesized and evaluated for antagonism at excitatory amino acid receptor sites and for anticonvulsant activity. Potent and selective antagonist activity at N-methyl-D-aspartate (NMDA) receptor sites in neonatal rat motoneurones wa...

journal_title：Journal of medicinal chemistry

authors： Gaoni Y,Chapman AG,Parvez N,Pook PC,Jane DE,Watkins JC

更新日期：1994-12-09 00:00:00

abstract：:A study of the hydrolysis of 30 substituted-phenyl hippurates by the enzyme ficin has been made. From the results the following quantitative structure--activity relationship (QSAR) has been derived: log 1/Km = 0.79 pi'3 + 0.58 sigma + 0.28 MR4,5 + 3.70. In this expression Km is the Michaelis constant, pi'3 refers to t...

journal_title：Journal of medicinal chemistry

authors： Carotti A,Casini G,Hansch C

更新日期：1984-11-01 00:00:00

abstract：:The sponge-derived polyketide macrolides fijianolides A (1) and B (2), isolaulimalide and laulimalide, have taxol-like microtubule-stabilizing activity, and the latter exhibits potent cytotoxicity. Insight on the biogeographical and phenotypic variations of Cacospongia mycofijiensis is presented that will enable a fut...

journal_title：Journal of medicinal chemistry

authors： Johnson TA,Tenney K,Cichewicz RH,Morinaka BI,White KN,Amagata T,Subramanian B,Media J,Mooberry SL,Valeriote FA,Crews P

更新日期：2007-08-09 00:00:00

abstract：:Emerging studies have shown that mitochondrial DNA (mtDNA) is a potential target for cancer therapy. Herein, six cyclometalated Ir(III) complexes Ir1-Ir6 containing a series of extended planar diimine ligands have been designed and assessed for their efficacy as anticancer agents. Ir1-Ir6 show much higher cytotoxicity...

journal_title：Journal of medicinal chemistry

authors： Cao JJ,Zheng Y,Wu XW,Tan CP,Chen MH,Wu N,Ji LN,Mao ZW

更新日期：2019-04-11 00:00:00

abstract：:A novel series of oxime ligands has been synthesized that displays potent, specific activation of the retinoid X receptors (RXRs). The oximes of 3-substituted (tetramethyltetrahydronaphthyl)carbonylbenzoic acids are readily available by condensation with hydroxyl- or methoxylamine; alkylation of the hydroxyl oxime pro...

journal_title：Journal of medicinal chemistry

authors： Canan Koch SS,Dardashti LJ,Cesario RM,Croston GE,Boehm MF,Heyman RA,Nadzan AM

更新日期：1999-02-25 00:00:00

abstract：:The synthesis of four l-2'-deoxy-threose nucleoside phosphonates with the natural nucleobases adenine, thymine, cytosine, and guanosine has been performed. Especially the adenine containing analogue (PMDTA) was endowed with potent antiviral activity displaying an EC50 of 4.69 μM against HIV-1 and an EC50 value of 0.5 ...

journal_title：Journal of medicinal chemistry

authors： Liu C,Dumbre SG,Pannecouque C,Huang C,Ptak RG,Murray MG,De Jonghe S,Herdewijn P

更新日期：2016-10-27 00:00:00

abstract：:A series of new, structurally simple trichostatin A (TSA)-like straight chain hydroxamates were prepared and evaluated for their ability to inhibit partially purified human histone deacetylase 1 (HDAC-1). Some of these compounds such as 8m, 8n, 12, and 15b exhibited potent HDAC inhibitory activity with low nanomolar I...

journal_title：Journal of medicinal chemistry

authors： Woo SH,Frechette S,Abou Khalil E,Bouchain G,Vaisburg A,Bernstein N,Moradei O,Leit S,Allan M,Fournel M,Trachy-Bourget MC,Li Z,Besterman JM,Delorme D

更新日期：2002-06-20 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：:7-Substituted 3-aryl-1,6-naphthyridine-2,7-diamines and related 2-ureas are inhibitors of fibroblast growth factor receptor-1 (FGFR-1) and vascular endothelial growth factor receptor-2 (VEGFR-2). 3-(3,5-Dimethoxyphenyl) and 3-phenyl analogues were prepared from 7-acetamido-2-tert-butylureas by alkylation with benzyl o...

journal_title：Journal of medicinal chemistry

authors： Thompson AM,Delaney AM,Hamby JM,Schroeder MC,Spoon TA,Crean SM,Showalter HD,Denny WA

更新日期：2005-07-14 00:00:00

abstract：:N,N-Dialkylated leucine enkephalin analogues containing melphalan (Mel) in place of Phe4 were synthesized as potentially irreversible antagonists of the delta opioid receptor. These compounds, along with the corresponding Phe4 peptides, were tested for both agonist and antagonist activity in the GPI and MVD smooth mus...

journal_title：Journal of medicinal chemistry

authors： Lovett JA,Portoghese PS

更新日期：1987-09-01 00:00:00

abstract：:The effect of aromatic nitro compounds on the oxidative metabolism of representative type I (hexobarbital and aminopyrene) and type II (aniline and zoxazolamine) substrates by cytochrome P-450 dependent liver enzymes was studied. Nitro compounds (nitrobenzene, p-nitrobenzoate, 2-nitrofluorene, and 2-nitronaphthalene) ...

journal_title：Journal of medicinal chemistry

authors： Sternson LA,Gammans RE

更新日期：1976-01-01 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：:The binding constants of 15 phenothiazine derivatives to bovine serum albumin were obtained by a circular dichroic probe technique; The lipophilicity of the drugs, measured by a reversed-phase thin-layer technique using oleyl alcohol and methanol-water mixtures as the solvents, is expressed as RMw. The binding constan...

journal_title：Journal of medicinal chemistry

authors： Hulshoff A,Perrin JH

更新日期：1977-03-01 00:00:00

abstract：:The proprotein convertases (PCs) play an important role in protein precursor activation through processing at paired basic residues. However, significant substrate cleavage redundancy has been reported between PCs. The question remains whether specific PC inhibitors can be designed. This study describes the identifica...

journal_title：Journal of medicinal chemistry

authors： Levesque C,Fugère M,Kwiatkowska A,Couture F,Desjardins R,Routhier S,Moussette P,Prahl A,Lammek B,Appel JR,Houghten RA,D'Anjou F,Dory YL,Neugebauer W,Day R

更新日期：2012-12-13 00:00:00

abstract：:A series of renin inhibitors have been prepared and evaluated for their susceptibility to cleavage by the serine protease chymotrypsin. The compounds were designed by consideration of the structural requirements in the active-site region of renin and chymotrypsin. By systematic alteration of the P3 phenylalanine resid...

journal_title：Journal of medicinal chemistry

authors： Plattner JJ,Marcotte PA,Kleinert HD,Stein HH,Greer J,Bolis G,Fung AK,Bopp BA,Luly JR,Sham HL

更新日期：1988-12-01 00:00:00

abstract：:Eleven new 12-amino-6,7,10,11-tetrahydro-7, 11-methanocycloocta[b]quinoline derivatives [tacrine (THA)-huperzine A hybrids, rac-21-31] have been synthesized as racemic mixtures and tested as acetylcholinesterase (AChE) inhibitors. For derivatives unsubstituted at the benzene ring, the highest activity was obtained for...

journal_title：Journal of medicinal chemistry

authors： Camps P,El Achab R,Görbig DM,Morral J,Muñoz-Torrero D,Badia A,Eladi Baños J,Vivas NM,Barril X,Orozco M,Luque FJ

更新日期：1999-08-26 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：: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：: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：:2-Aminopyridine-3,5-dicarbonitrile compounds were previously identified as mimetics of dominant-negative prion protein mutants and inhibit prion replication in cultured cells. Here, we report findings from a comprehensive structure-activity relationship study of the 6-aminopyridine-3,5-dicarbonitrile scaffold. We iden...

journal_title：Journal of medicinal chemistry

authors： May BC,Zorn JA,Witkop J,Sherrill J,Wallace AC,Legname G,Prusiner SB,Cohen FE

更新日期：2007-01-11 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

abstract：:A topological substructural approach to molecular design (TOSS-MODE) has been introduced for the selection and design of anticancer compounds. A quantitative model that discriminates anticancer compounds from the inactive ones in a training series was obtained. This model permits the correct classification of 91.43% o...

journal_title：Journal of medicinal chemistry

authors： Estrada E,Uriarte E,Montero A,Teijeira M,Santana L,De Clercq E

更新日期：2000-05-18 00:00:00

abstract：:A variety of sesquiterpene lactones (SLs) possess considerable anti-inflammatory activity. Several studies have shown that they exert this effect in part by inhibiting the activation of the transcription factor NF-kappaB. In the present study we elaborated on the investigation of a data set of 103 structurally diverse...

journal_title：Journal of medicinal chemistry

authors： Wagner S,Hofmann A,Siedle B,Terfloth L,Merfort I,Gasteiger J

更新日期：2006-04-06 00:00:00

abstract：:A series of pyridine-2-carboxaldehyde N-oxide and pyridine-2-carboxaldehyde (thio)phosphoric hydrazones and two cupric chelates was synthesized. The hydrazones, chelates, and combinations of hydrazones and cupric chloride were tested against mice bearing P388 lymphocytic leukemia, Sarcoma 180, or Ehrlich carcinoma asc...

journal_title：Journal of medicinal chemistry

authors： Cates LA,Good DJ,Jones GS,Lemke TL

更新日期：1978-11-01 00:00:00

abstract：:Antimicrobial peptides (AMPs) are amphipathic molecules displaying broad-spectrum bactericidal activity, providing opportunities to develop a new generation of antibiotics. However, their use is limited either by poor metabolic stability or by high hemolytic activity. We herein addressed the potential of thiazole-base...

journal_title：Journal of medicinal chemistry

authors： Bonnel C,Legrand B,Simon M,Clavié M,Masnou A,Jumas-Bilak E,Kang YK,Licznar-Fajardo P,Maillard LT,Masurier N

更新日期：2020-09-10 00:00:00

abstract：:N-Acyl amino acids directly bind mitochondria and function as endogenous uncouplers of UCP1-independent respiration. We found that administration of N-acyl amino acids to mice improves glucose homeostasis and increases energy expenditure, indicating that this pathway might be useful for treating obesity and associated...

journal_title：Journal of medicinal chemistry

authors： Lin H,Long JZ,Roche AM,Svensson KJ,Dou FY,Chang MR,Strutzenberg T,Ruiz C,Cameron MD,Novick SJ,Berdan CA,Louie SM,Nomura DK,Spiegelman BM,Griffin PR,Kamenecka TM

更新日期：2018-04-12 00:00:00

abstract：:On the basis of structural data gathered during our ongoing HIV-1 protease inhibitors program, from which our clinical candidate TMC114 9 was selected, we have discovered new series of fused heteroaromatic sulfonamides. The further extension into the P2' region was aimed at identifying new classes of compounds with an...

journal_title：Journal of medicinal chemistry

authors： Surleraux DL,de Kock HA,Verschueren WG,Pille GM,Maes LJ,Peeters A,Vendeville S,De Meyer S,Azijn H,Pauwels R,de Bethune MP,King NM,Prabu-Jeyabalan M,Schiffer CA,Wigerinck PB

更新日期：2005-03-24 00:00:00

abstract：:Both HIV-EP1 (also called PRDII-BF1 or MBP-1), a zinc finger protein, and NF-kappa B, a Rel family protein, bind to kappa B site present in the enhancer of multiple cellular and viral genes involved in immune function and inflammatory response including HIV-1 LTR and human interferon beta gene. When cells are exposed ...

journal_title：Journal of medicinal chemistry

authors： Otsuka M,Fujita M,Aoki T,Ishii S,Sugiura Y,Yamamoto T,Inoue J

更新日期：1995-08-18 00:00:00

abstract：:There has been significant interest in developing a transient receptor potential A1 (TRPA1) antagonist for the treatment of pain due to a wealth of data implicating its role in pain pathways. Despite this, identification of a potent small molecule tool possessing pharmacokinetic properties allowing for robust in vivo ...

journal_title：Journal of medicinal chemistry

authors： Schenkel LB,Olivieri PR,Boezio AA,Deak HL,Emkey R,Graceffa RF,Gunaydin H,Guzman-Perez A,Lee JH,Teffera Y,Wang W,Youngblood BD,Yu VL,Zhang M,Gavva NR,Lehto SG,Geuns-Meyer S

更新日期：2016-03-24 00:00:00