Mechanistic interpretation of the genotoxicity of nitrofurans (antibacterial agents) using quantitative structure-activity relationships and comparative molecular field analysis.

abstract：:A series of O-alkylated analogs of 5,6,7,8-tetrahydro-4H-isoxazolo[4,5-c]azepin-3-ol (THAO) were synthesized and characterized as ligands for muscarinic acetylcholine receptors (mAChRs). O-Methyl-THAO (4a), O-ethyl-THAO (4b), O-isopropyl-THAO (4c), and O-propargyl-THAO (4d) were shown to be potent inhibitors of the bi...

journal_title：Journal of medicinal chemistry

authors： Bräuner-Osborne H,Ebert B,Brann MR,Falch E,Krogsgaard-Larsen P

更新日期：1995-06-09 00:00:00

abstract：:Two series of indenoisoquinoline topoisomerase I inhibitors have been prepared to investigate optimal substituents on the indenone ring at the 9-position. The more exhaustive series was prepared using a nitrated isoquinoline ring that has been previously demonstrated to enhance biological activity. After preliminary b...

journal_title：Journal of medicinal chemistry

authors： Morrell A,Placzek M,Parmley S,Grella B,Antony S,Pommier Y,Cushman M

更新日期：2007-09-06 00:00:00

abstract：:A noninvasive topical ocular therapy for the treatment of neovascular or "wet" age-related macular degeneration would provide a patient administered alternative to the current standard of care, which requires physician administered intravitreal injections. This manuscript describes a novel strategy for the use of in v...

journal_title：Journal of medicinal chemistry

authors： Adams CM,Anderson K,Artman G 3rd,Bizec JC,Cepeda R,Elliott J,Fassbender E,Ghosh M,Hanks S,Hardegger LA,Hosagrahara VP,Jaffee B,Jendza K,Ji N,Johnson L,Lee W,Liu D,Liu F,Long D,Ma F,Mainolfi N,Meredith EL,Miran

更新日期：2018-02-22 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

abstract：:The perceived and actual burden of false positives in high-throughput screening has received considerable attention; however, few studies exist on the contributions of distinct mechanisms of nonspecific effects like chemical reactivity, assay signal interference, and colloidal aggregation. Here, we analyze the outcome...

journal_title：Journal of medicinal chemistry

authors： Jadhav A,Ferreira RS,Klumpp C,Mott BT,Austin CP,Inglese J,Thomas CJ,Maloney DJ,Shoichet BK,Simeonov A

更新日期：2010-01-14 00:00:00

abstract：:In a small range finding study a number of N-benzylpiperazino derivates of 3-nitro-4-hydroxycoumarin have been shown to combine potent H1-antihistamine activity with that of mast cell stabilization as demonstrated by their activity as antagonists of histamine on guinea pig ileum and by their inhibition of the release ...

journal_title：Journal of medicinal chemistry

authors： Buckle DR,Outred DJ,Smith H,Spicer BA

更新日期：1984-11-01 00:00:00

abstract：:A significant improvement in agonist activity of the previously described 2-aryloctahydrophenanthrene-2,3,7-triol series of dissociated glucocorticoid receptor agonists (DAGRs) was achieved by modifying the substitution at C3 from (S)-3-hydroxy to (R)-3-hydroxy-3-methyl. The IC50 of the prototype 13 in the efficacy as...

journal_title：Journal of medicinal chemistry

authors： Chantigny YA,Murray JC,Kleinman EF,Robinson RP,Plotkin MA,Reese MR,Buckbinder L,McNiff PA,Millham ML,Schaefer JF,Abramov YA,Bordner J

更新日期：2015-03-26 00:00:00

abstract：:Prostate-specific membrane antigen (PSMA) is an excellent biomarker for the early diagnosis of prostate cancer progression and metastasis. The most promising PSMA-targeted agents in the clinical phase are based on the Lys-urea-Glu motif, in which Lys and Glu are α-(l)-amino acids. In this study, we aimed to determine ...

journal_title：Journal of medicinal chemistry

authors： Kim K,Kwon H,Barinka C,Motlova L,Nam S,Choi D,Ha H,Nam H,Son SH,Minn I,Pomper MG,Yang X,Kutil Z,Byun Y

更新日期：2020-03-26 00:00:00

abstract：:Multidrug resistance-associated protein 1 (MRP1/ABCC1) is a very promiscuous transporter. Herein we used topological polar surface area (TPSA), a descriptor defined as the sum of surfaces of polar atoms in a molecule, to analyze drug transport by MRP1. We suggested that compounds with high TPSA are transported while t...

journal_title：Journal of medicinal chemistry

authors： Fernandes J,Gattass CR

更新日期：2009-02-26 00:00:00

abstract：:A comprehensive herbal medicine information system for cancer (CHMIS-C) has been developed. The current version of the database integrates information on more than 200 anticancer herbal recipes that have been used for the treatment of different types of cancer in clinic, 900 individual ingredients, and 8500 small orga...

journal_title：Journal of medicinal chemistry

authors： Fang X,Shao L,Zhang H,Wang S

更新日期：2005-03-10 00:00:00

abstract：:Substance P (Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Met-NH2) and the C-terminal partial sequences down to the tripeptide were synthesized by a solid-phase method. These peptides were assayed for vasodilator, spasmogenic, and venoconstrictor properties using three preparations, viz. the hind limb blood flow of the dog...

journal_title：Journal of medicinal chemistry

authors： Bury RW,Mashford ML

更新日期：1976-06-01 00:00:00

abstract：:A series of esters of 6beta-hydroxynortropane and the N-methyl analogue 6beta-tropanol were synthesized and screened versus binding of an antagonist (quinuclidinyl benzilate) and an agonist (oxotremorine-M) at sites on human m(1)-, m(2)-, m(3)-, and m(4)-muscarinic receptors in transfected cell membranes and on native...

journal_title：Journal of medicinal chemistry

authors： Daly JW,Gupta TH,Padgett WL,Pei XF

更新日期：2000-06-29 00:00:00

abstract：:We have previously described a cyclic tetrapeptide, 1, that displays μ opioid receptor (MOPr) agonist and δ opioid receptor (DOPr) antagonist activity, a profile associated with a reduced incidence of opioid tolerance and dependence. Like many peptides, 1 has poor bioavailability. We describe here an analogue of 1 wit...

journal_title：Journal of medicinal chemistry

authors： Mosberg HI,Yeomans L,Anand JP,Porter V,Sobczyk-Kojiro K,Traynor JR,Jutkiewicz EM

更新日期：2014-04-10 00:00:00

abstract：:An efficient modular synthesis of N(1)-substituted triamines containing different tether lengths between nitrogen centers was developed. A series of N(1)-(9-anthracenylmethyl)triamines were evaluated for biological activity in L1210 (murine leukemia), alpha-difluoromethylornithine (DFMO)-treated L1210, Chinese hamster...

journal_title：Journal of medicinal chemistry

authors： Wang C,Delcros JG,Biggerstaff J,Phanstiel O 4th

更新日期：2003-06-19 00:00:00

abstract：:Chagas disease, caused by the protozoan parasite Trypanosoma cruzi (T. cruzi), is an increasing threat to global health. Available medicines were introduced over 40 years ago, have undesirable side effects, and give equivocal results of cure in the chronic stage of the disease. We report the development of two compoun...

journal_title：Journal of medicinal chemistry

authors： Keenan M,Chaplin JH,Alexander PW,Abbott MJ,Best WM,Khong A,Botero A,Perez C,Cornwall S,Thompson RA,White KL,Shackleford DM,Koltun M,Chiu FC,Morizzi J,Ryan E,Campbell M,von Geldern TW,Scandale I,Chatelain E,Charman

更新日期：2013-12-27 00:00:00

abstract：:The linear interaction energy method with continuum electrostatics (LIECE) is evaluated in depth on five kinases. The two multiplicative coefficients for the van der Waals energy and electrostatic free energy are shown to be transferable among different kinases. Moreover, good enrichment factors are obtained for a lib...

journal_title：Journal of medicinal chemistry

authors： Kolb P,Huang D,Dey F,Caflisch A

更新日期：2008-03-13 00:00:00

abstract：:alpha-Fluoromethyl amino acids are enzyme-activated irreversible inhibitors of amino acid decarboxylases. Aromatic L-amino acid decarboxylase (AADC) is the enzyme responsible for the final step in the biosynthesis of both dopamine and serotonin via decarboxylation of L-dopa and 5-hydroxy-L-tryptophan, respectively. Ou...

journal_title：Journal of medicinal chemistry

authors： Zembower DE,Gilbert JA,Ames MM

更新日期：1993-02-05 00:00:00

abstract：:Polyadenosine diphosphoribose glycohydrolase (PARG) catalyzes the intracellular hydrolysis of adenosine diphosphoribose polymers. Because structure-activity data are lacking for PARG, the specific inhibitor adenosine diphosphate (hydroxymethyl)pyrrolidinediol (ADP-HPD) was utilized to determine the effects of structur...

journal_title：Journal of medicinal chemistry

authors： Koh DW,Coyle DL,Mehta N,Ramsinghani S,Kim H,Slama JT,Jacobson MK

更新日期：2003-09-25 00:00:00

abstract：:A three-dimensional structure of the complex of human renin and the scissile site P4 Pro to P1' Val of angiotensinogen was deduced in order to design potent human renin inhibitors rationally. On the basis of this structure, an orally potent human renin inhibitor (1a) was designed from the angiotensinogen transition st...

journal_title：Journal of medicinal chemistry

authors： Iizuka K,Kamijo T,Harada H,Akahane K,Kubota T,Umeyama H,Ishida T,Kiso Y

更新日期：1990-10-01 00:00:00

abstract：:We describe here the syntheses and the biological properties of new alkylaminooxysterols. Compounds were synthesized through the trans-diaxial aminolysis of 5,6-alpha-epoxysterols with various natural amines including histamine, putrescine, spermidine, or spermine. The regioselective synthesis of these 16 new 5alpha-h...

journal_title：Journal of medicinal chemistry

authors： de Medina P,Paillasse MR,Payré B,Silvente-Poirot S,Poirot M

更新日期：2009-12-10 00:00:00

abstract：:New, racemic, tricyclic trioxane alcohol 3 was designed and synthesized as a structurally simple analog of clinically useful, tetracyclic, antimalarial artemisinin. A series of 20 ester and ether derivatives of alcohol 3 were prepared easily, without destruction of the essential trioxane system. Chemical structure-ant...

journal_title：Journal of medicinal chemistry

authors： Posner GH,Oh CH,Gerena L,Milhous WK

更新日期：1992-06-26 00:00:00

abstract：:The cytotoxicity of oxysterols was systematically studied in tumor and normal cells. Synthetic strategies to prepare this library included oxidations at ring B and a new method to yield 6β-hemiphthalates directly from Δ(5)-steroids. Most oxysterols were cytotoxic and showed selectivity toward cancer cells, LAMA-84 cel...

journal_title：Journal of medicinal chemistry

authors： Carvalho JF,Silva MM,Moreira JN,Simões S,Sá e Melo ML

更新日期：2010-11-11 00:00:00

abstract：:The insertion of single 1,4-disubstituted 1,2,3-triazoles as metabolically stable bioisosteres of trans-amide bonds (triazole scan) was recently applied to the 177Lu-labeled tumor-targeting analog of minigastrin, [Nle15]MG11. The reported novel mono-triazolo-peptidomimetics of [Nle15]MG11 showed either improved resist...

journal_title：Journal of medicinal chemistry

authors： Grob NM,Schmid S,Schibli R,Behe M,Mindt TL

更新日期：2020-05-14 00:00:00

abstract：:Starting with 2,6-dichlorophenyl isothiocyanate, 1-(2-aminoethyl)-2-cyano-3-(2,6-dichlorophenyl)guanidine (2) was prepared in three steps. In contrast to the corresponding thiourea 1, this compound was essentially inactive as an antihypertensive agent. ...

journal_title：Journal of medicinal chemistry

authors： Tilley JW,Ramuz H,Hefti F,Gerold M

更新日期：1980-12-01 00:00:00

abstract：:The preparation of stable complexes between the N7-[2-(2-pyridyl)ethyl] and N7-(2-piperazinylethyl) derivatives of mitomycin C and metal ions such as Cu(II), Zn(II), and Pt(II) was accomplished. Mitomycin C did not form stable complexes, but it rearranged to a mitosene capable of complex formation. Some of these compl...

journal_title：Journal of medicinal chemistry

authors： Iyengar BS,Takahashi T,Remers WA,Bradner WT

更新日期：1986-01-01 00:00:00

abstract：:Effective and safe analgesics represent an unmet medical need for the treatment of acute and chronic pain. A series of N-cyclopropylmethyl-7α-phenyl-6,14-endoethanotetrahydronorthebaines were designed, synthesized, and assayed, leading to the discovery of a benzylamine derivative (compound 4, SLL-039) as a highly sele...

journal_title：Journal of medicinal chemistry

authors： Xiao L,Wang Y,Zhang M,Wu W,Kong L,Ma Y,Xu X,Liu X,He Q,Qian Y,Sun H,Wu H,Lin C,Huang H,Ye R,Jiang S,Ye RF,Yuan C,Fang S,Xue D,Yang X,Chen H,Zheng Y,Yu L,Xie Q,Zheng L,Fu W,Li W,Qiu Z,Liu J,Shao

更新日期：2019-12-26 00:00:00

abstract：:Mycobacterium abscessus (Mab) is a rapidly growing species of multidrug-resistant nontuberculous mycobacteria that has emerged as a growing threat to individuals with cystic fibrosis and other pre-existing chronic lung diseases. Mab pulmonary infections are difficult, or sometimes impossible, to treat and result in ac...

journal_title：Journal of medicinal chemistry

authors： Whitehouse AJ,Thomas SE,Brown KP,Fanourakis A,Chan DS,Libardo MDJ,Mendes V,Boshoff HIM,Floto RA,Abell C,Blundell TL,Coyne AG

更新日期：2019-08-08 00:00:00

abstract：:2'-Deoxy-2'-isocyano-1-beta-D-arabinofuranosylcytosine (8, NCDAC) has been synthesized as a potential antitumor antimetabolite from a corresponding 2'-azido-2'-deoxy-1-beta-D-arabinofuranosyluracil derivative 2a. Uracil and thymine analogues 6a and 6b of 8 were also prepared. Attempts to synthesize 2'-deoxy-2'-isocyan...

journal_title：Journal of medicinal chemistry

authors： Matsuda A,Dan A,Minakawa N,Tregear SJ,Okazaki S,Sugimoto Y,Sasaki T

更新日期：1993-12-24 00:00:00

abstract：:Dicarba analogues of the cyclic opioid peptides H-Tyr-c[d-Cys-Gly-Phe-d(or l)-Cys]NH2 were synthesized on solid phase by substituting allylglycines for the cysteines and cyclization by ring-closing metathesis between the side chains of the allylglycine residues. Mixtures of cis and trans isomers of the resulting olefi...

journal_title：Journal of medicinal chemistry

authors： Berezowska I,Chung NN,Lemieux C,Wilkes BC,Schiller PW

更新日期：2007-03-22 00:00:00

abstract：:Human neutrophil elastase (HNE) is an important therapeutic target for treatment of pulmonary diseases. Previously, we identified novel N-benzoylindazole derivatives as potent, competitive, and pseudoirreversible HNE inhibitors. Here, we report further development of these inhibitors with improved potency, protease se...

journal_title：Journal of medicinal chemistry

authors： Crocetti L,Schepetkin IA,Cilibrizzi A,Graziano A,Vergelli C,Giomi D,Khlebnikov AI,Quinn MT,Giovannoni MP

更新日期：2013-08-08 00:00:00