Synthesis of 6alpha-methyldigitoxigenin 3-acetate.

abstract：:Previously, we reported the thiourea antagonists 2a and 2b as potent and high affinity TRPV1 antagonists. For further optimization of the lead compounds, a series of their amide and alpha-substituted amide surrogates were investigated and novel chiral N-(2-benzyl-3-pivaloyloxypropyl) 2-[4-(methylsulfonylamino)phenyl]p...

journal_title：Journal of medicinal chemistry

authors： Ryu H,Jin MK,Kim SY,Choi HK,Kang SU,Kang DW,Lee J,Pearce LV,Pavlyukovets VA,Morgan MA,Tran R,Toth A,Lundberg DJ,Blumberg PM

更新日期：2008-01-10 00:00:00

abstract：:Photodynamic therapy uses a combination of light, oxygen, and a photosensitizer to induce the death of malignant cells. To improve the selectivity of a photosensitizer toward cancerous cells that express gonadotropin-releasing hormone (GnRH) receptors, protoporphyrin IX (PpIX) was conjugated to a GnRH agonist, [d-Lys6...

journal_title：Journal of medicinal chemistry

authors： Rahimipour S,Ben-Aroya N,Ziv K,Chen A,Fridkin M,Koch Y

更新日期：2003-09-11 00:00:00

abstract：:The heretofore unknown gamma-(m-carboxyanilide) and gamma-(m-boronoanillide) derivatives of methotrexate (MTX) and the gamma-(m-carboxyanilide) derivatives of aminopterin (AMT) were prepared and tested as inhibitors of dihydrofolate reductase (DHFR) and as inhibitors of cell growth in culture with the aim of comparing...

journal_title：Journal of medicinal chemistry

authors： Rosowsky A,Bader H,Freisheim JH

更新日期：1991-02-01 00:00:00

abstract：:A series of 7-(3-amino- or 3-aminomethyl-1-pyrrolidinyl)-1-cyclopropyl-6,8-difluoro-1,4-dihydro-4-o xo-3-quinolinecarboxylic acids was synthesized and tested for antibacterial activity. Unique to these quinolones was the presence of a methyl or phenyl group in the pyrrolidine ring. Although the in vitro activity of th...

journal_title：Journal of medicinal chemistry

authors： Hagen SE,Domagala JM,Heifetz CL,Sanchez JP,Solomon M

更新日期：1990-02-01 00:00:00

abstract：:A series of new amine cyanoborane derivatives were synthesized and exhibited antifungal activity. A long alkyl chain attached to the nitrogen of the amine cyanoboranes and carboxyboranes enhances antifungal activity. An enhanced activity was also obtained upon the halogenation of the amine cyanoboranes as well as in t...

journal_title：Journal of medicinal chemistry

authors： Takrouri K,Oren G,Polacheck I,Sionov E,Shalom E,Katzhendler J,Srebnik M

更新日期：2006-08-10 00:00:00

abstract：:The nature and the size of the benzylic substituent are shown to be the key to controlling receptor selectivity (CCR5 vs M1, M2) and potency in the title compounds. Optimization of the lead benzylic methyl compound 3 led to the methoxymethyl analogue 30, which had excellent receptor selectivity and oral bioavailabilit...

journal_title：Journal of medicinal chemistry

authors： Tagat JR,McCombie SW,Nazareno D,Labroli MA,Xiao Y,Steensma RW,Strizki JM,Baroudy BM,Cox K,Lachowicz J,Varty G,Watkins R

更新日期：2004-05-06 00:00:00

abstract：:Cathepsin B (CTB) is a cysteine protease believed to be an important therapeutic target or biomarker for several diseases including aggressive cancer, arthritis, and parasitic infections. The development of probes capable of assessing CTB activity in cell lysates, living cells, and animal models of disease are needed ...

journal_title：Journal of medicinal chemistry

authors： Chowdhury MA,Moya IA,Bhilocha S,McMillan CC,Vigliarolo BG,Zehbe I,Phenix CP

更新日期：2014-07-24 00:00:00

abstract：:Natural products (NPs) are a rich source of novel compound classes and new drugs. In the present study we have used the chemical space navigation tool ChemGPS-NP to evaluate the chemical space occupancy by NPs and bioactive medicinal chemistry compounds from the database WOMBAT. The two sets differ notably in coverage...

journal_title：Journal of medicinal chemistry

authors： Rosén J,Gottfries J,Muresan S,Backlund A,Oprea TI

更新日期：2009-04-09 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：:The cyclic AMP phosphodiesterase (cAMP PDE) inhibitor and cardiotonic agent lixazinone (N-cyclohexyl-N-methyl-4-[(1,2,3,5-tetrahydro-2- oxoimidazo[2,1-b]quinazolin-7-yl)oxy]butyramide, RS-82856, 1) and its acid and base addition salts were found to be insufficiently soluble in formulations suitable for intravenous adm...

journal_title：Journal of medicinal chemistry

authors： Venuti MC,Alvarez R,Bruno JJ,Strosberg AM,Gu L,Chiang HS,Massey IJ,Chu N,Fried JH

更新日期：1988-11-01 00:00:00

abstract：:The design and preparation of ortho-substituted benzofused macrocyclic lactams are described. The benzofused macrocyclic lactams were designed as neutral endopeptidase 24.11 (NEP) inhibitors. Docking studies were carried out in a model of thermolysin (TLN) using the MACROMODEL and QXP modeling programs to select suita...

journal_title：Journal of medicinal chemistry

authors： Ksander GM,de Jesus R,Yuan A,Ghai RD,Trapani A,McMartin C,Bohacek R

更新日期：1997-02-14 00:00:00

abstract：:RhoA is a member of Rho GTPases, a subgroup of the Ras superfamily of small GTP-binding proteins. RhoA, as an important regulator of diverse cellular signaling pathways, plays significant roles in cytoskeletal organization, transcription, and cell-cycle progression. The RhoA/ROCK inhibitors have emerged as a new promi...

journal_title：Journal of medicinal chemistry

authors： Deng J,Feng E,Ma S,Zhang Y,Liu X,Li H,Huang H,Zhu J,Zhu W,Shen X,Miao L,Liu H,Jiang H,Li J

更新日期：2011-07-14 00:00:00

abstract：:C5-unsubstituted-C6-aryl-1,4-dihydropyridines were prepared by a CAN-catalyzed multicomponent reaction from chalcones, β-dicarbonyl compounds, and ammonium acetate. These compounds were able to block Ca(2+) entry after a depolarizing stimulus and showed an improved Cav1.3/Cav1.2 selectivity in comparison with nifedipi...

journal_title：Journal of medicinal chemistry

authors： Tenti G,Parada E,León R,Egea J,Martínez-Revelles S,Briones AM,Sridharan V,López MG,Ramos MT,Menéndez JC

更新日期：2014-05-22 00:00:00

abstract：:Owing to the emergence of drug resistance and high morbidity and mortality, the need for novel anti-influenza A virus (IAV) drugs with divergent targets is highly sought after. Herein, we reveal the discovery of an anti-IAV agent as a dual inhibitor to block hemagglutinin-mediated adsorption and membrane fusion using ...

journal_title：Journal of medicinal chemistry

authors： Wu G,Yu G,Yu Y,Yang S,Duan Z,Wang W,Liu Y,Yu R,Li J,Zhu T,Gu Q,Li D

更新日期：2020-07-09 00:00:00

abstract：:The synthesis and antihypertensive activity of a series of novel 3-[(substituted-carbonyl)amino]-2H-1-benzopyran-4-ols, administered orally to spontaneously hypertensive rats, are described. Optimum activity in this series was observed for compounds with branched alkyl or branched alkylamino groups flanking the carbon...

journal_title：Journal of medicinal chemistry

authors： Cassidy F,Evans JM,Hadley MS,Haladij AH,Leach PE,Stemp G

更新日期：1992-05-01 00:00:00

abstract：:Tankyrases are poly(ADP-ribose) polymerases that have many cellular functions. They play pharmaceutically important roles, at least in telomere homeostasis and Wnt signaling, by covalently ADP-ribosylating target proteins and consequently regulating their functions. These features make tankyrases potential targets for...

journal_title：Journal of medicinal chemistry

authors： Narwal M,Venkannagari H,Lehtiö L

更新日期：2012-02-09 00:00:00

abstract：:Several esters of beta-carboline-3-carboxylic acid were synthesized and tested in respect to their affinity for the benzodiazepine receptor in bovine cortex membranes. Out of these derivatives, the methyl, ethyl, and n-propyl ester were clearly the most potent, while the n-butyl, benzyl, and 3-pyridylmethyl ester were...

journal_title：Journal of medicinal chemistry

authors： Lippke KP,Schunack WG,Wenning W,Müller WE

更新日期：1983-04-01 00:00:00

abstract：:A series of novel CCK tetrapeptide analogues of the general formula Boc-Trp-Lys(Tac)-N(R)-(CH2)nCON(R')Phe-NH2 (Tac = o-tolylaminocarbonyl), where R,R' = H or Me and n = 1-5, have been synthesized and tested. These analogues, which lack an acidic residue at the penultimate position, demonstrated surprisingly high CCK-...

journal_title：Journal of medicinal chemistry

authors： Elliott RL,Kopecka H,Tufano MD,Shue YK,Gauri AJ,Lin CW,Bianchi BR,Miller TR,Witte DG,Stashko MA

更新日期：1994-05-27 00:00:00

abstract：:Isosorbide-2-benzyl carbamate-5-benzoate is a highly potent and selective BuChE inhibitor. Meanwhile, isosorbide-2-aspirinate-5-salicylate is a highly effective aspirin prodrug that relies on the salicylate portion to interact productively with human BuChE. By integrating the salicylate group into the carbamate design...

journal_title：Journal of medicinal chemistry

authors： Carolan CG,Dillon GP,Khan D,Ryder SA,Gaynor JM,Reidy S,Marquez JF,Jones M,Holland V,Gilmer JF

更新日期：2010-02-11 00:00:00

abstract：:A conceptionally new 3D molecular descriptor type and methodology are deduced by simple statistical thermodynamic reasoning, based on the free energy change encountered during a transformation of a conformational ensemble of the ligand to an active conformation. The performance of the descriptor was first tested on 37...

journal_title：Journal of medicinal chemistry

authors： Martinek TA,Otvös F,Dervarics M,Tóth G,Fülöp F

更新日期：2005-05-05 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：:We synthesized 5-allyl-1-methyl-5-(m-trifluoromethyl-diazirynylphenyl)barbituric acid (14), a trifluoromethyldiazirine-containing derivative of general anesthetic mephobarbital, separated the racemic mixture into enantiomers by chiral chromatography, and determined the configuration of the (+)-enantiomer as S by X-ray...

journal_title：Journal of medicinal chemistry

authors： Savechenkov PY,Zhang X,Chiara DC,Stewart DS,Ge R,Zhou X,Raines DE,Cohen JB,Forman SA,Miller KW,Bruzik KS

更新日期：2012-07-26 00:00:00

abstract：:Analogues of captopril, enalaprilat, and the phosphinic acid [hydroxy(4-phenylbutyl)phosphinyl]acetyl]-L-proline incorporating 4-substituted proline derivatives have been synthesized and evaluated as inhibitors of angiotensin-converting enzyme (ACE) in vitro and in vivo. The 4-substituted prolines, incorporating alkyl...

journal_title：Journal of medicinal chemistry

authors： Krapcho J,Turk C,Cushman DW,Powell JR,DeForrest JM,Spitzmiller ER,Karanewsky DS,Duggan M,Rovnyak G,Schwartz J

更新日期：1988-06-01 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：:In a recent paper (Colotta et al. J. Med. Chem. 2000, 43, 1158-1164) we reported the synthesis and adenosine receptor binding activity of two sets of 2-aryl-1,2,4-triazolo[4,3-a]quinoxalines (A and B) some of which were potent and selective A(1) or A(3) antagonists. In this paper the synthesis of a set of 2-arylpyrazo...

journal_title：Journal of medicinal chemistry

authors： Colotta V,Catarzi D,Varano F,Cecchi L,Filacchioni G,Martini C,Trincavelli L,Lucacchini A

更新日期：2000-08-10 00:00:00

abstract：:A series of base- and amino acid modified analogues of S-aristeromycinyl-L-homocysteine, a carbocyclic nucleoside, were synthesized and evaluated as inhibitors of S-adenosyl-L-methionine-dependent methyltransferases, including catechol O-methyltransferase, phenylethanolamine N-methyltransferase, and histamine N-methyl...

journal_title：Journal of medicinal chemistry

authors： Houston DM,Matuszewska B,Borchardt RT

更新日期：1985-04-01 00:00:00

abstract：:The novel lead bis(1H-2-indolyl)methanone inhibits autophosphorylation of platelet-derived growth factor (PDGF) receptor tyrosine kinase in intact cells. Various substituents in the 5- or 6-position of one indole ring increase or preserve potency, whereas most modifications of the ring structures and of the methanone ...

journal_title：Journal of medicinal chemistry

authors： Mahboobi S,Teller S,Pongratz H,Hufsky H,Sellmer A,Botzki A,Uecker A,Beckers T,Baasner S,Schächtele C,Uberall F,Kassack MU,Dove S,Böhmer FD

更新日期：2002-02-28 00:00:00

abstract：:Novel tumor-targeting theranostic conjugates 1 and 2, bearing either a fluorine-labeled prosthetic as a potential (18)F-PET radiotracer (1) or a fluorescence probe (2) for internalization studies in vitro, were designed and synthesized. We confirmed efficient internalization of 2 in biotin-receptor positive (BR+) canc...

journal_title：Journal of medicinal chemistry

authors： Vineberg JG,Wang T,Zuniga ES,Ojima I

更新日期：2015-03-12 00:00:00

abstract：:The synthesis and antiviral activity of a number of 3'-C-difluoromethyl and 3'-deoxy-3'-C-fluoromethyl nucleosides are reported. The 3'-C-difluoromethyl nucleosides 26a and 26b were obtained by treatment of the corresponding 2',5'-di-O-protected-3'-C-formyl nucleosides 25a and 25b with (diethylamino)sulfur trifluoride...

journal_title：Journal of medicinal chemistry

authors： Bamford MJ,Coe PL,Walker RT

更新日期：1990-09-01 00:00:00

abstract：:Dihydrocodeinone oxime (1) under Beckmann rearrangement conditions gave a product (2) that facilitated the preparation of (-)-11 alpha-substituted 1,2,3,4,5,6-hexahydro-6 alpha,7-(methyleneoxy)-2,6-methano-3-benzazocines, a hitherto little-examined series of morphine partial structures. Compounds 7a and 12 gave good l...

journal_title：Journal of medicinal chemistry

authors： Cittern PA,Kapoor VK,Parfitt RT

更新日期：1986-10-01 00:00:00