Water-soluble third generation antitumor platinum complexes, [2,2-bis (aminomethyl)-1,3-propanediol-N,N']-[1,1-cyclobutanedicarboxylato (2-)-O,O']platinum(II) and [1,1-cyclobutanedicarboxylato(2-)-O,O'] [tetrahydro-4H-pyran-4,4-dimethanamine-N,N']platinum

abstract：:A comparison of the effects of the 6-(2-chloro-6-fluorobenzyl)-2-(alkylthio)pyrimidin-4(3H)-ones (2-Cl-6-F-S-DABOs) 7-12 and the related 6-(2,6-difluorobenzyl) counterparts 13-15 in HIV-1 infected cells and in the HIV-1 reverse transcriptase (RT) assays is here described. The new 2-Cl-6-F-S-DABOs showed up to picomola...

journal_title：Journal of medicinal chemistry

authors： Rotili D,Tarantino D,Nawrozkij MB,Babushkin AS,Botta G,Marrocco B,Cirilli R,Menta S,Badia R,Crespan E,Ballante F,Ragno R,Esté JA,Maga G,Mai A

更新日期：2014-06-26 00:00:00

abstract：:Intrigued by the role of protein acetylation in hepatitis C virus (HCV) replication, we tested known histone deacetylase (HDAC) inhibitors and a focused library of structurally simple hydroxamic acids for inhibition of a HCV subgenomic replicon. While known HDAC inhibitors with varied inhibitory profiles proved to be ...

journal_title：Journal of medicinal chemistry

authors： Ai T,Xu Y,Qiu L,Geraghty RJ,Chen L

更新日期：2015-01-22 00:00:00

abstract：:Nonpeptidic chiral macrocycles were designed on the basis of an analogue of suberoylanilide hydroxamic acid (2) (SAHA, vorinostat) and evaluated against 11 histone deacetylase (HDAC) isoforms. The identification of critical amino acid residues highly conserved in the cap region of HDACs guided the design of the subero...

journal_title：Journal of medicinal chemistry

authors： Auzzas L,Larsson A,Matera R,Baraldi A,Deschênes-Simard B,Giannini G,Cabri W,Battistuzzi G,Gallo G,Ciacci A,Vesci L,Pisano C,Hanessian S

更新日期：2010-12-09 00:00:00

abstract：:Tumor necrosis factor α (TNFα) is a soluble cytokine that is directly involved in systemic inflammation through the regulation of the intracellular NF-κB and MAPK signaling pathways. The development of biologic drugs that inhibit TNFα has led to improved clinical outcomes for patients with rheumatoid arthritis and oth...

journal_title：Journal of medicinal chemistry

authors： Dietrich JD,Longenecker KL,Wilson NS,Goess C,Panchal SC,Swann SL,Petros AM,Hobson AD,Ihle D,Song D,Richardson P,Comess KM,Cox PB,Dombrowski A,Sarris K,Donnelly-Roberts DL,Duignan DB,Gomtsyan A,Jung P,Krueger AC,Ma

更新日期：2021-01-14 00:00:00

abstract：:A series of eight C5-substituted analogues of (+-)-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine (1) have been prepared by the directed lithiation-alkylation (and acylation) of its (+-)-N-tert-butylformamidinyl derivative 2 followed by formamidine solvolysis. An additional 10 analogues were prepared by elaborati...

journal_title：Journal of medicinal chemistry

authors： Monn JA,Thurkauf A,Mattson MV,Jacobson AE,Rice KC

更新日期：1990-03-01 00:00:00

abstract：:The labeling of proteins with ubiquitin/ubiquitin-like (Ubl) proteins is crucial for several physiological processes and in the onset of various diseases. Recently, targeting ubiquitin protein labeling has shifted toward the use of allosteric mechanisms over classical activity-based approaches. Allosteric enzyme regul...

journal_title：Journal of medicinal chemistry

authors： Paiva SL,da Silva SR,de Araujo ED,Gunning PT

更新日期：2018-01-25 00:00:00

abstract：:Forty-eight cationically substituted pentamidine congeners possessing benzofuran rings were synthesized by a copper mediated heteroannulation of substituted o-iodophenols with phenyl acetylenes. Activities of compounds 1-48 against Trypanosoma brucei rhodesiense, Plasmodium falciparum, and Leishmania donovani and cyto...

journal_title：Journal of medicinal chemistry

authors： Bakunov SA,Bakunova SM,Bridges AS,Wenzler T,Barszcz T,Werbovetz KA,Brun R,Tidwell RR

更新日期：2009-09-24 00:00:00

abstract：:In the present paper we describe the synthesis of some dermorphin and deltorphin analogues beta-O- and alpha-C-glycosylated on the C-terminal amino acid residue and report their opioid receptor affinity and selectivity as well as their analgesic potency after subcutaneous injection in mice. ...

journal_title：Journal of medicinal chemistry

authors： Negri L,Lattanzi R,Tabacco F,Orrù L,Severini C,Scolaro B,Rocchi R

更新日期：1999-02-11 00:00:00

abstract：:Botulinum neurotoxins (BoNT) are the most potent toxins known and a significant bioterrorist threat. Few small molecule compounds have been identified that are active in cell-based or animal models, potentially due to toxin enzyme plasticity. Here we screened commercially available quinolinols, as well as synthesized ...

journal_title：Journal of medicinal chemistry

authors： Caglič D,Krutein MC,Bompiani KM,Barlow DJ,Benoni G,Pelletier JC,Reitz AB,Lairson LL,Houseknecht KL,Smith GR,Dickerson TJ

更新日期：2014-02-13 00:00:00

abstract：:A series of 3-substituted [1,2,4]triazino[4,3-c]benzimidazoles V were prepared and tested at the central benzodiazepine receptor (BzR). These compounds were designed as rigid analogues of the previously described N-benzylindolylglyoxylylamide derivatives IV. The title compounds V showed an affinity which depended dire...

journal_title：Journal of medicinal chemistry

authors： Primofiore G,Da Settimo F,Taliani S,Marini AM,La Motta C,Novellino E,Greco G,Gesi M,Trincavelli L,Martini C

更新日期：2000-01-13 00:00:00

abstract：:Inhibition of the biosynthesis of proinflammatory cytokines such as tumor necrosis factor and interleukin-1 via p38 has been an approach toward the development of a disease modifying agent for the treatment of chronic inflammation and autoimmune diseases. The development of a new core structure of p38 inhibitors, 3-(4...

journal_title：Journal of medicinal chemistry

authors： Trejo A,Arzeno H,Browner M,Chanda S,Cheng S,Comer DD,Dalrymple SA,Dunten P,Lafargue J,Lovejoy B,Freire-Moar J,Lim J,Mcintosh J,Miller J,Papp E,Reuter D,Roberts R,Sanpablo F,Saunders J,Song K,Villasenor A,Warren

更新日期：2003-10-23 00:00:00

abstract：:Derivatives of N-[2-(dimethylamino)ethyl]-9-aminoacridine-4-carboxamide bearing a wide variety of different groups at the 5-position (and for comparative purposes at the 7-position) have been prepared, and their physicochemical properties and biological activities have been determined. Although both 5- and 7-substitut...

journal_title：Journal of medicinal chemistry

authors： Denny WA,Atwell GJ,Rewcastle GW,Baguley BC

更新日期：1987-04-01 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：:We recently described a novel series of CA(1)A(2)X peptidomimetics as farnesyl transferase inhibitors (FTIs). These compounds possess an N-(4-piperidinyl)benzamide scaffold mimicking A(1)A(2) residue. Extensive exploration of structure--activity relationships revealed that replacement of cysteine by substituted benzyl...

journal_title：Journal of medicinal chemistry

authors： Millet R,Domarkas J,Houssin R,Gilleron P,Goossens JF,Chavatte P,Logé C,Pommery N,Pommery J,Hénichart JP

更新日期：2004-12-30 00:00:00

abstract：:A series of both aliphatic and aromatic amides and aromatic amidines derived from 2-amino-1,10-phenanthroline (3) according to the Topliss scheme were synthesized and subsequently tested for antimycoplasmal potency. Although the compounds themselves showed no activity, in the presence of a nontoxic copper concentratio...

journal_title：Journal of medicinal chemistry

authors： de Zwart MA,Bastiaans HM,van der Goot H,Timmerman H

更新日期：1991-03-01 00:00:00

abstract：:The chemical synthesis of 2-[(2,6-dichloro-4-iodophenyl)imino]imidazolidine (PIC) and its radioiodinated analogue [125I]PIC is described. PIC was synthesized from 2,6-dichloroaniline in five synthetic steps. This agent displayed a high affinity for the alpha 2-adrenergic receptor (IC50 = 1.5 nM) in competitive binding...

journal_title：Journal of medicinal chemistry

authors： Van Dort M,Neubig R,Counsell RE

更新日期：1987-07-01 00:00:00

abstract：:The discovery of inhibitors of bromodomain and extra terminal domain (BET) has achieved great progress, and at least seven inhibitors have progressed into clinical trials for the treatment of cancer or inflammatory diseases. Here, we describe the identification, optimization, and evaluation of benzo[cd]indol-2(1H)-one...

journal_title：Journal of medicinal chemistry

authors： Xue X,Zhang Y,Liu Z,Song M,Xing Y,Xiang Q,Wang Z,Tu Z,Zhou Y,Ding K,Xu Y

更新日期：2016-02-25 00:00:00

abstract：:In colorectal cancer, adenomatous polyposis coli (APC) interacts with Rho guanine-nucleotide-exchange factor 4 (Asef), thereby stimulating aberrant colorectal-cancer-cell migration. Consequently, the APC-Asef interaction represents a promising therapeutic target for mitigating colorectal-cancer migration. In this stud...

journal_title：Journal of medicinal chemistry

authors： Yang X,Zhong J,Zhang Q,Qian J,Song K,Ruan C,Xu J,Ding K,Zhang J

更新日期：2018-09-13 00:00:00

abstract：:The compounds N6-allyl-, N6-isopropyl-, N6-propargyl-, and N6-(2-methylallyl)adenosine were prepared by reacting 6-chloropurine riboside with an excess of the corresponding amines in ethanol, in the presence of two acid acceptors resulting in virtually quantitative yields. The compounds showed biological activity in a...

journal_title：Journal of medicinal chemistry

authors： Fleysher MH,Bernacki RJ,Bullard GA

更新日期：1980-12-01 00:00:00

abstract：:Prodrug-mediated utilization of the cytochrome P450 (CYP) 1A1 to obtain the selective release of potent anticancer products within cancer tissues is a promising approach in chemotherapy. We herein report the rationale, preparation, biological evaluation, and mechanism of action of phenyl 4-(2-oxo-3-alkylimidazolidin-1...

journal_title：Journal of medicinal chemistry

authors： Fortin S,Charest-Morin X,Turcotte V,Lauvaux C,Lacroix J,Côté MF,Gobeil S,C-Gaudreault R

更新日期：2017-06-22 00:00:00

abstract：:The synthesis and biological evaluation of a novel paclitaxel photoaffinity probe is described. The synthesis involved the preparation of an azide-containing C13 side chain through a Staudinger cycloaddition followed by a lipase-mediated kinetic resolution to obtain the azetidinone in 99% ee. Coupling of the enantiopu...

journal_title：Journal of medicinal chemistry

authors： Spletstoser JT,Flaherty PT,Himes RH,Georg GI

更新日期：2004-12-16 00:00:00

abstract：:The synthesis of a series of 2-, 3-, and 4-substituted benzylamine derivatives is described. These compounds were studied for their effect on experimental cardiac arrhythmias. Many of the derivatives, but in particular 2-(p-methoxyphenylethynyl)benzylamine (3d), alpha,alpha-dimethyl-4y(phenylethynyl)benzylamine (7a), ...

journal_title：Journal of medicinal chemistry

authors： Remy DC,Van Saun WA Jr,Engelhardt EL

更新日期：1975-02-01 00:00:00

abstract：:Conformationally restricted 2'-spironucleosides and their prodrugs were synthesized as potential anti-HCV agents. Although the replicon activity of the new agents containing pyrimidine bases was modest, the triphosphate of a 2'-oxetane cytidine analogue demonstrated potent intrinsic biochemical activity against the NS...

journal_title：Journal of medicinal chemistry

authors： Du J,Chun BK,Mosley RT,Bansal S,Bao H,Espiritu C,Lam AM,Murakami E,Niu C,Micolochick Steuer HM,Furman PA,Sofia MJ

更新日期：2014-03-13 00:00:00

abstract：:ACTIBIND and its human homologue RNASET2 are T2 ribonucleases (RNases). RNases are ubiquitous and efficient enzymes that hydrolyze RNA to 3' mononucleotides and also possess antitumorigenic and antiangiogenic activities. Previously, we have shown that ACTIBIND and RNASET2 bind actin and interfere with the cytoskeletal...

journal_title：Journal of medicinal chemistry

authors： de Leeuw M,González A,Lanir A,Roiz L,Smirnoff P,Schwartz B,Shoseyov O,Almog O

更新日期：2012-02-09 00:00:00

abstract：:A series of natural epimers of alpha-homonojirimycin and its N-alkylated derivatives have been prepared to investigate the contribution of the different chiral centers and conformation of the specificity and potency of inhibition of glycosidases. These epimers and N-alkylated derivatives are alpha-homonojirimycin (1),...

journal_title：Journal of medicinal chemistry

authors： Asano N,Nishida M,Kato A,Kizu H,Matsui K,Shimada Y,Itoh T,Baba M,Watson AA,Nash RJ,Lilley PM,Watkin DJ,Fleet GW

更新日期：1998-07-02 00:00:00

abstract：:The endocannabinoid hydrolyzing enzyme FAAH uses a nonclassical catalytic triad (namely, Ser-Ser-Lys instead of Ser-Asp-His) to cleave its endogenous substrates. Because inhibiting FAAH has a clear therapeutic potential, we previously developed β-lactam-type inhibitors of hFAAH. Here, we report the synthesis of five n...

journal_title：Journal of medicinal chemistry

authors： Feledziak M,Muccioli GG,Lambert DM,Marchand-Brynaert J

更新日期：2011-10-13 00:00:00

abstract：:Protease activated receptors (PARs) or thrombin receptors constitute a class of G-protein-coupled receptors (GPCRs) implicated in the activation of many physiological mechanisms. Thus, thrombin activates many cell types such as vascular smooth muscle cells, leukocytes, endothelial cells, and platelets via activation o...

journal_title：Journal of medicinal chemistry

authors： Perez M,Lamothe M,Maraval C,Mirabel E,Loubat C,Planty B,Horn C,Michaux J,Marrot S,Letienne R,Pignier C,Bocquet A,Nadal-Wollbold F,Cussac D,de Vries L,Le Grand B

更新日期：2009-10-08 00:00:00

abstract：:Efforts were made to improve a series of potent dual ABL/SRC inhibitors based on a 7-azaindole core with the aim of developing compounds that demonstrate a wider activity on selected oncogenic kinases. Multi-targeted kinase inhibitors (MTKIs) were then derived, focusing on kinases involved in both angiogenesis and tum...

journal_title：Journal of medicinal chemistry

authors： Daydé-Cazals B,Fauvel B,Singer M,Feneyrolles C,Bestgen B,Gassiot F,Spenlinhauer A,Warnault P,Van Hijfte N,Borjini N,Chevé G,Yasri A

更新日期：2016-04-28 00:00:00

abstract：:Novel 3,5-bis(benzylidene)-1-[3-(2-hydroxyethylthio)propanoyl]piperidin-4-ones (3a-e) display potent cytotoxicity and a preferential lethality toward various neoplasms compared to some normal cells. The corresponding sulfonic acid analogues 5a-e and an isostere 4 demonstrated substantially lower activity. The leads 3d...

journal_title：Journal of medicinal chemistry

authors： Das U,Pati HN,Sakagami H,Hashimoto K,Kawase M,Balzarini J,De Clercq E,Dimmock JR

更新日期：2011-05-12 00:00:00

abstract：:A series of structurally related mono- and bis-1,3-disubstituted 2-[(hydroxyimino)methyl]imidazolium halides were evaluated in vitro for their ability to reactivate electric eel, bovine, and human erythrocyte (RBC) acetylcholinesterases (AChE) inhibited by ethyl p-nitrophenyl methylphosphonate (EPMP) and 3,3-dimethyl-...

journal_title：Journal of medicinal chemistry

authors： Bedford CD,Harris RN 3rd,Howd RA,Goff DA,Koolpe GA,Petesch M,Miller A,Nolen HW 3rd,Musallam HA,Pick RO

更新日期：1989-02-01 00:00:00