Regression analysis of the relationship between physical properties and the in vitro inhibition of monoamine oxidase by propynylamines.

abstract：:Selective inhibition of the isoforms of nitric oxide synthase (NOS) in pathologically elevated synthesis of nitric oxide has great therapeutic potential. We previously reported nitroarginine-containing dipeptide amides and some peptidomimetic analogues as potent and selective inhibitors of neuronal NOS (nNOS). Here we...

journal_title：Journal of medicinal chemistry

authors： Gómez-Vidal JA,Martásek P,Roman LJ,Silverman RB

更新日期：2004-01-29 00:00:00

abstract：:A series of 4-anilinoquinoline-linked aniline mustards of widely varying mustard reactivity were prepared and evaluated for their antitumor activity. The compounds were designed as minor grove binding agents, where the aniline mustard ring is itself part of the DNA-binding ligand. While there was a general trend for c...

journal_title：Journal of medicinal chemistry

authors： Gravatt GL,Baguley BC,Wilson WR,Denny WA

更新日期：1991-05-01 00:00:00

abstract：:Attempts to develop new (aryloxy)acetic acids with a better profile of diuretic and uricosuric activities as well as with fewer side effects have produced a series of compounds in which the ring system has been varied. Diuretic screening of these analogues in rats indicated that the great difference in the activity be...

journal_title：Journal of medicinal chemistry

authors： Koga H,Sato H,Dan T,Aoki B

更新日期：1991-09-01 00:00:00

abstract：:Twelve 1,4-naphthoquinones have been tested against the ascitic form of sarcoma 180 in Swiss mice. Statistical analysis shows that the most important molecular parameter determining their effectiveness in prolonging the life of mice bearing this tumor is their redox potentials. Although the toxicities of the compounds...

journal_title：Journal of medicinal chemistry

authors： Hodnett EM,Wongwiechintana C,Dunn WJ 3rd,Marrs P

更新日期：1983-04-01 00:00:00

abstract：:Coactivator-associated arginine methyltransferase 1 (CARM1) represents a valuable target for hormone-dependent tumors such as prostate and breast cancers. Here we report the enzyme and cellular characterization of the 1-benzyl-3,5-bis(3-bromo-4-hydroxybenzylidene)piperidin-4-one (7g) and its analogues 8a-l. Among them...

journal_title：Journal of medicinal chemistry

authors： Cheng D,Valente S,Castellano S,Sbardella G,Di Santo R,Costi R,Bedford MT,Mai A

更新日期：2011-07-14 00:00:00

abstract：:Inhibition of intestinal carboxylesterases may allow modification of the pharmacokinetics/pharmacodynamic profile of existing drugs by altering half-life or toxicity. Since previously identified diarylethane-1,2-dione inhibitors are decidedly hydrophobic, a modified dione scaffold was designed and elaborated into a >3...

journal_title：Journal of medicinal chemistry

authors： Young BM,Hyatt JL,Bouck DC,Chen T,Hanumesh P,Price J,Boyd VA,Potter PM,Webb TR

更新日期：2010-12-23 00:00:00

abstract：:Largazole 4a and analogues with modifications at the C7 position, as well as 2,4'-bithiazole 5a, have been synthesized using an acyclic cross-metathesis of the corresponding depsipeptide structures assembled by N-C6(O) or C15(O)-N lactam formation. Similar to the parent system 4a, the series of largazole depsipeptides...

journal_title：Journal of medicinal chemistry

authors： Souto JA,Vaz E,Lepore I,Pöppler AC,Franci G,Alvarez R,Altucci L,de Lera AR

更新日期：2010-06-24 00:00:00

abstract：:A series of 6,9-disubstituted purines were tested for their ability to bind to the benzodiazepine receptor in rat brain tissue. One of the most active compounds was 9-(3-aminobenzyl)-6-(dimethylamino)-9H-purine (44) with an IC50 = 0.9 microM, which was only 4.5-fold higher than the IC50 for chlordiazepoxide. Substitut...

journal_title：Journal of medicinal chemistry

authors： Kelley JL,McLean EW,Ferris RM,Howard JL

更新日期：1989-05-01 00:00:00

abstract：:Intervention in integrin-mediated cell adhesion and integrin signaling pathways is an ongoing area of research in medicinal chemistry and drug development. One key element in integrin-ligand interaction is the coordination of the bivalent cation at the metal ion-dependent adhesion site (MIDAS) by a carboxylic acid fun...

journal_title：Journal of medicinal chemistry

authors： Bollinger M,Manzenrieder F,Kolb R,Bochen A,Neubauer S,Marinelli L,Limongelli V,Novellino E,Moessmer G,Pell R,Lindner W,Fanous J,Hoffman A,Kessler H

更新日期：2012-01-26 00:00:00

abstract：:N-(R)- and N-(S)-lactylsphingosine and their corresponding dihydrosphingosine derivatives were synthesized. The antileukemic activities of these compounds were measured by MTT (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide) assay in human leukemia HL-60 cells. N-(R)- and N-(S)-Lactylsphingosine disp...

journal_title：Journal of medicinal chemistry

authors： Azuma H,Takao R,Shikata K,Niiro H,Tachibana T,Ogino K

更新日期：2003-07-31 00:00:00

abstract：:Four 11-(1-piperazinyl)-5H-pyrrolo[2,1-c][1,4]benzodiazepines were prepared and evaluated as central nervous system agents. All were active psychotropic agents as determined by animal screening tests. The most interesting compound, 11-(1-piperazinyl)-5H-pyrrolo[2,1-c][1,4]benzodiazepine, showed dual activity as an ant...

journal_title：Journal of medicinal chemistry

authors： Wright WB Jr,Greenblatt EN,Day IP,Quinones NQ,Hardy RA Jr

更新日期：1980-04-01 00:00:00

abstract：:A series of novel chiral 7-(1-, 3-, 4-, and 6-methyl-[(1R,4R)-2,5- diazabicyclo[2.2.1]heptan-2-yl]-substituted naphthyridines has been prepared with the aim of obtaining good in vitro and in vivo antibacterial agents with a decrease of the pseudoallergic type reaction when compared to that observed with 7[(1R,4R)-2,5-...

journal_title：Journal of medicinal chemistry

authors： Remuzon P,Bouzard D,Guiol C,Jacquet JP

更新日期：1992-07-24 00:00:00

abstract：:Novel heteroatom-incorporated antofine and cryptopleurine analogues were designed, synthesized, and tested against a panel of five cancer cell lines. Two new S-13-oxo analogues (11 and 16) exhibited potent cell growth inhibition in vitro (GI(50): 9 nM and 20 nM). Interestingly, both compounds displayed improved select...

journal_title：Journal of medicinal chemistry

authors： Yang X,Shi Q,Yang SC,Chen CY,Yu SL,Bastow KF,Morris-Natschke SL,Wu PC,Lai CY,Wu TS,Pan SL,Teng CM,Lin JC,Yang PC,Lee KH

更新日期：2011-07-28 00:00:00

abstract：:In the present work, we have designed and synthesized a series of arachidonic acid derivatives of general structure I which have been characterized as highly potent and selective inhibitors of anandamide transporter (IC(50) = 24-0.8 microM, K(i) > 1000-5000 nM for CB(1) and CB(2) cannabinoid receptors and vanilloid VR...

journal_title：Journal of medicinal chemistry

authors： López-Rodríguez ML,Viso A,Ortega-Gutiérrez S,Lastres-Becker I,González S,Fernández-Ruiz J,Ramos JA

更新日期：2001-12-20 00:00:00

abstract：:Glycogen synthase kinase 3beta (GSK-3beta) inhibition is expected to be a promising therapeutic approach for treating Alzheimer's disease. Previously we reported a series of 1,3,4-oxadiazole derivatives as potent and highly selective GSK-3beta inhibitors, however, the representative compounds 1a,b showed poor pharmaco...

journal_title：Journal of medicinal chemistry

authors： Saitoh M,Kunitomo J,Kimura E,Iwashita H,Uno Y,Onishi T,Uchiyama N,Kawamoto T,Tanaka T,Mol CD,Dougan DR,Textor GP,Snell GP,Takizawa M,Itoh F,Kori M

更新日期：2009-10-22 00:00:00

abstract：:Three derivatives of angelicin (1) [4'-methyl-, 4,4'-dimethyl-, and 4',5-dimethylangelicin (2a-c)] have been prepared with the aim of obtaining new agents for the photochemotherapy of psoriasis. These compounds form a complex in the dark with DNA that shows an affinity for the macromolecule higher than that of the par...

journal_title：Journal of medicinal chemistry

authors： Dall'Acqua F,Vedaldi D,Bordin F,Baccichetti F,Carlassare F,Tamaro M,Rodighiero P,Pastorini G,Guiotto A,Recchia G,Cristofolini M

更新日期：1983-06-01 00:00:00

abstract：:Two prototype N-methyl-4-thio-substituted cyclophosphamide (CP) derivatives (5 and 6), prodrugs of 4-hydroxycyclophosphamide (4-HO-CP), were designed to undergo oxidative N-demethylation to release the active alkylating agent. These prodrugs were chemically stable until oxidatively N-demethylated in the presence of he...

journal_title：Journal of medicinal chemistry

authors： Moon KY,Shirota FN,Baturay N,Kwon CH

更新日期：1995-03-03 00:00:00

abstract：:4-[4-(N-Substituted (thio)carbamoyl)-1-piperazinyl]-6,7-dimethoxyquinazoline derivatives such as KN1022 are potent inhibitors of the phosphorylation of platelet derived growth factor receptor (PDGFR). Structure activity relationships in the (thio)urea moiety, the phenyl ring itself, the linker between these two moieti...

journal_title：Journal of medicinal chemistry

authors： Matsuno K,Nakajima T,Ichimura M,Giese NA,Yu JC,Lokker NA,Ushiki J,Ide S,Oda S,Nomoto Y

更新日期：2002-09-26 00:00:00

abstract：:Recently we have described the antitumor activities of 2-benzoxazolylhydrazones derived from 2-formyl and 2-acetylpyridines. In search of a more efficacious analogue, compounds in which the 2-acetylpyridine moiety has been replaced by 2-acylpyridine and alpha-(N)-acetyldiazine/quinoline groups have been synthesized. T...

journal_title：Journal of medicinal chemistry

authors： Easmon J,Pürstinger G,Thies KS,Heinisch G,Hofmann J

更新日期：2006-10-19 00:00:00

abstract：:New acetamidines structurally related to N-(3-(aminomethyl)benzyl)acetamidine (1, W1400) were designed as inhibitors of inducible nitric oxide synthase (iNOS). Six compounds were found to be selective for iNOS over endothelial nitric oxide synthase (eNOS), and among them, the most active and selective compound was the...

journal_title：Journal of medicinal chemistry

authors： Maccallini C,Patruno A,Besker N,Alì JI,Ammazzalorso A,De Filippis B,Franceschelli S,Giampietro L,Pesce M,Reale M,Tricca ML,Re N,Felaco M,Amoroso R

更新日期：2009-03-12 00:00:00

abstract：:Adenosine (ADO) is an endogenous homeostatic inhibitory neuromodulator that reduces cellular excitability at sites of tissue injury and inflammation. Inhibition of adenosine kinase (AK), the primary metabolic enzyme for ADO, selectively increases ADO concentrations at sites of tissue trauma and enhances the analgesic ...

journal_title：Journal of medicinal chemistry

authors： Lee CH,Jiang M,Cowart M,Gfesser G,Perner R,Kim KH,Gu YG,Williams M,Jarvis MF,Kowaluk EA,Stewart AO,Bhagwat SS

更新日期：2001-06-21 00:00:00

abstract：:Synthesis, biological testing, structure-activity relationships (SARs), and selectivity of novel disubstituted dibenzosuberone derivatives as p38 MAP kinase inhibitors are described. Hydrophilic moieties were introduced at the 7-, 8-, and 9-position of the 2-phenylamino-dibenzosuberones, improving physicochemical prop...

journal_title：Journal of medicinal chemistry

authors： Koeberle SC,Fischer S,Schollmeyer D,Schattel V,Grütter C,Rauh D,Laufer SA

更新日期：2012-06-28 00:00:00

abstract：:Indoleamine 2,3-dioxygenase 1 (IDO1) catalyzes the rate-limiting step in the kynurenine pathway of tryptophan metabolism, which is involved in immunity, neuronal function, and aging. Its implication in pathologies such as cancer and neurodegenerative diseases has stimulated the development of IDO1 inhibitors. However,...

journal_title：Journal of medicinal chemistry

authors： Röhrig UF,Reynaud A,Majjigapu SR,Vogel P,Pojer F,Zoete V

更新日期：2019-10-10 00:00:00

abstract：:Thirty compounds related to the selective dopamine-autoreceptor agonist 3-(3-hydroxyphenyl)-N-n-propylpiperidine have been synthesized and tested for central dopamine-autoreceptor stimulating activity. The 3-(3-hydroxyphenyl)piperidine moiety seems indispensable for high potency and selectivity. Introduction of an add...

journal_title：Journal of medicinal chemistry

authors： Hacksell U,Arvidsson LE,Svensson U,Nilsson JL,Sanchez D,Wikström H,Lindberg P,Hjorth S,Carlsson A

更新日期：1981-12-01 00:00:00

abstract：:Models for predicting oral drug absorption kinetics were developed by correlating absorption rate constants in humans (K(a)) with computational molecular descriptors. The K(a) values of a set of 22 passively absorbed drugs were derived from human plasma time-concentration profiles using a deconvolution approach. The K...

journal_title：Journal of medicinal chemistry

authors： Linnankoski J,Mäkelä JM,Ranta VP,Urtti A,Yliperttula M

更新日期：2006-06-15 00:00:00

abstract：:Insulin secretion by pancreatic β-cells in response to glucose or other secretagogues is tightly coupled to membrane potential. Various studies have highlighted the prospect of enhancing insulin secretion in a glucose-dependent manner by blocking voltage-gated potassium channels (K(v)) and calcium-activated potassium ...

journal_title：Journal of medicinal chemistry

authors： Nguyen TT,Folch B,Létourneau M,Truong NH,Doucet N,Fournier A,Chatenet D

更新日期：2014-03-27 00:00:00

abstract：:Class IIb bacteriocins are ribosomally synthesized antimicrobial peptides comprising two different peptides synergistically acting in equal amounts for optimal potency. In this study, we demonstrate for the first time potent (nanomolar) antimicrobial activity of a representative class IIb bacteriocin, plantaricin S (P...

journal_title：Journal of medicinal chemistry

authors： Soliman W,Wang L,Bhattacharjee S,Kaur K

更新日期：2011-04-14 00:00:00

abstract：:A series of 2-aryl-4-benzoyl-imidazoles (ABI) was synthesized as a result of structural modifications based on the previous set of 2-aryl-imidazole-4-carboxylic amide (AICA) derivatives and 4-substituted methoxylbenzoyl-aryl-thiazoles (SMART). The average IC(50) of the most active compound (5da) was 15.7 nM. ABI analo...

journal_title：Journal of medicinal chemistry

authors： Chen J,Wang Z,Li CM,Lu Y,Vaddady PK,Meibohm B,Dalton JT,Miller DD,Li W

更新日期：2010-10-28 00:00:00

abstract：:We describe here the design, synthesis, molecular modeling, and biological evaluation of a series of small molecule, nonpeptide inhibitors of SARS-CoV PLpro. Our initial lead compound was identified via high-throughput screening of a diverse chemical library. We subsequently carried out structure-activity relationship...

journal_title：Journal of medicinal chemistry

authors： Ghosh AK,Takayama J,Aubin Y,Ratia K,Chaudhuri R,Baez Y,Sleeman K,Coughlin M,Nichols DB,Mulhearn DC,Prabhakar BS,Baker SC,Johnson ME,Mesecar AD

更新日期：2009-08-27 00:00:00

abstract：:Mutant epidermal growth factor receptor (EGFR) is a major driver of non-small-cell lung cancer (NSCLC). Marketed first generation inhibitors, such as erlotinib, effect a transient beneficial response in EGFR mutant NSCLC patients before resistance mechanisms render these inhibitors ineffective. Secondary oncogenic EGF...

journal_title：Journal of medicinal chemistry

authors： Planken S,Behenna DC,Nair SK,Johnson TO,Nagata A,Almaden C,Bailey S,Ballard TE,Bernier L,Cheng H,Cho-Schultz S,Dalvie D,Deal JG,Dinh DM,Edwards MP,Ferre RA,Gajiwala KS,Hemkens M,Kania RS,Kath JC,Matthews J,Murra

更新日期：2017-04-13 00:00:00