Replacement of imidazolyl by pyridyl in biphenylmethylenes results in selective CYP17 and dual CYP17/CYP11B1 inhibitors for the treatment of prostate cancer.

abstract：:Three novel, N-acyl-pro-pyrrolidine-type, inhibitors of prolyl oligopeptidase (POP) with nanomolar activities were synthesized and their binding analyzed to the host enzyme in the light of X-ray diffraction and molecular modeling studies. We were interested in the alteration in the binding affinity at the S3 site as a...

journal_title：Journal of medicinal chemistry

authors： Kánai K,Arányi P,Böcskei Z,Ferenczy G,Harmat V,Simon K,Bátori S,Náray-Szabo G,Hermecz I

更新日期：2008-12-11 00:00:00

abstract：:[4-Threonine, 7-glycine]oxytocin and [1-(L-2-hydroxy-3-mercaptopropanoic acid), 4-threonine, 7-glycine]oxytocin (hydroxy[Thr4, Gly7]oxytocin) were synthesized by a combination of solid-phase and classical methods of peptide synthesis. A protected octapeptide was synthesized by the solid-phase method and following ammo...

journal_title：Journal of medicinal chemistry

authors： Lowbridge J,Manning M,Haldar J,Sawyer WH

更新日期：1977-01-01 00:00:00

abstract：:Fifteen anthracene-9,10-dione ("anthraquinone") derivatives with (omega-aminoalkyl)carboxamido substituents at the 1-, 2-, 1,4-, or 2, 6-ring positions were tested for bacterial mutagenicity in reverse-mutation assays using Salmonella typhimurium frameshift strains TA1538, TA98, and TA97a, in the presence and absence ...

journal_title：Journal of medicinal chemistry

authors： Venitt S,Crofton-Sleigh C,Agbandje M,Jenkins TC,Neidle S

更新日期：1998-09-10 00:00:00

abstract：:Drug-resistant bacterial infections and lack of available antibacterial agents in clinical practice are becoming serious risks to public health. We synthesized a new class of haloemodins by modifying a traditional Chinese medicine component, emodin. The novel haloemodin exerts strong inhibitory activity on bacterial t...

journal_title：Journal of medicinal chemistry

authors： Duan F,Li X,Cai S,Xin G,Wang Y,Du D,He S,Huang B,Guo X,Zhao H,Zhang R,Ma L,Liu Y,Du Q,Wei Z,Xing Z,Liang Y,Wu X,Fan C,Ji C,Zeng D,Chen Q,He Y,Liu X,Huang W

更新日期：2014-05-08 00:00:00

abstract：:The preparation of 6-chloro-5-(cyclopentylmethyl)indan-1-carboxylic acid is described. This acid has good anti-inflammatory and analgesic activities without producing irritation in the gastrointestinal tract up to the highest tested dose. ...

journal_title：Journal of medicinal chemistry

authors： Boettcher I,Elger W,Kirsch G,Siegmund F,Wachtel H

更新日期：1984-03-01 00:00:00

abstract：:A variety of N-(aminoalkanoyl)-S-acylcysteamine and N,N'-bis(aminoalkanoyl)cystamine salt derivatives were synthesized. Toxicity and radioprotective activity (as the dose reduction factor DRF) were determined in vivo on mice and compared to WR 2721 and S-acetylcysteamine hydrochloride. One of the most interesting comp...

journal_title：Journal of medicinal chemistry

authors： Oiry J,Pue JY,Imbach JL,Fatome M,Sentenac-Roumanou H,Lion C

更新日期：1986-11-01 00:00:00

abstract：:The recently discovered nicotinic agonist pyrido[3,4-b]norhomotropane [corrected] (PHT) as well as its N-methyl and 2'-methyl derivatives (syntheses reported herein) were compared with nicotine, nornicotine, and anatoxin a in a series of in vitro and in vivo assays. The results reveal that PHT possesses activity compa...

journal_title：Journal of medicinal chemistry

authors： Kanne DB,Abood LG

更新日期：1988-03-01 00:00:00

abstract：:2,4-Diaminoquinazoline antifolates with a lipophilic side chain at the 5-position, and in one case with a classical (p-aminobenzoyl)-L-glutamate side chain, were synthesized as potentially selective inhibitors of a site-directed mutant of human dihydrofolate reductase (DHFR) containing phenylalanine instead of leucine...

journal_title：Journal of medicinal chemistry

authors： Rosowsky A,Mota CE,Queener SF,Waltham M,Ercikan-Abali E,Bertino JR

更新日期：1995-03-03 00:00:00

abstract：:CXCL12 binds to CXCR4, promoting both chemotaxis of lymphocytes and metastasis of cancer cells. We previously identified small molecule ligands that bind CXCL12 and block CXCR4-mediated chemotaxis. We now report a 1.9 Å resolution X-ray structure of CXCL12 bound by such a molecule at a site normally bound by sY21 of C...

journal_title：Journal of medicinal chemistry

authors： Smith EW,Liu Y,Getschman AE,Peterson FC,Ziarek JJ,Li R,Volkman BF,Chen Y

更新日期：2014-11-26 00:00:00

abstract：:Malaria is still a leading cause of mortality among children in the developing world, and despite the immense progress made in reducing the global burden, further efforts are needed if eradication is to be achieved. In this context, targeting transmission is widely recognized as a necessary intervention toward that go...

journal_title：Journal of medicinal chemistry

authors： Rueda-Zubiaurre A,Yahiya S,Fischer OJ,Hu X,Saunders CN,Sharma S,Straschil U,Shen J,Tate EW,Delves MJ,Baum J,Barnard A,Fuchter MJ

更新日期：2020-03-12 00:00:00

abstract：:A new class of substituted 1-phenyl-3-piperazinyl-2-propanones with antimuscarinic activity is reported. As part of a structure-activity relationship study of this class, various structural modifications, particularly ones involving substitution of position 1 and the terminal piperazine nitrogen, were investigated. Th...

journal_title：Journal of medicinal chemistry

authors： Kaiser C,Audia VH,Carter JP,McPherson DW,Waid PP,Lowe VC,Noronha-Blob L

更新日期：1993-03-05 00:00:00

abstract：:Adrenomedullin (AM) is a peptide hormone implicated in blood pressure regulation and in the pathophysiology of several diseases such as hypertension, cancer, diabetes, and renal disorders, becoming an interesting new target for the development of drugs. In a recent high-throughput screening study, a positive modulator...

journal_title：Journal of medicinal chemistry

authors： García MA,Martín-Santamaría S,Cacho M,de la Llave FM,Julián M,Martínez A,de Pascual-Teresa B,Ramos A

更新日期：2005-06-16 00:00:00

abstract：:In lead optimization, open, solvent-exposed protein pockets are often disregarded as prospective binding sites. Because of bulk-solvent proximity, researchers are instead enticed to attach charged polar groups at inhibitor scaffolds to improve solubility and pharmacokinetic properties. It is rarely considered that sol...

journal_title：Journal of medicinal chemistry

authors： Cramer J,Krimmer SG,Heine A,Klebe G

更新日期：2017-07-13 00:00:00

abstract：:Overexpression of myeloid cell leukemia-1 (Mcl-1) in cancers correlates with high tumor grade and poor survival. Additionally, Mcl-1 drives intrinsic and acquired resistance to many cancer therapeutics, including B cell lymphoma 2 family inhibitors, proteasome inhibitors, and antitubulins. Therefore, Mcl-1 inhibition ...

journal_title：Journal of medicinal chemistry

authors： Lee T,Christov PP,Shaw S,Tarr JC,Zhao B,Veerasamy N,Jeon KO,Mills JJ,Bian Z,Sensintaffar JL,Arnold AL,Fogarty SA,Perry E,Ramsey HE,Cook RS,Hollingshead M,Davis Millin M,Lee KM,Koss B,Budhraja A,Opferman JT,Kim K

更新日期：2019-04-25 00:00:00

abstract：:The synthesis of a series of N-phosphonalkyl dipeptides 6 is described. Syntheses were devised that allowed the preparation of single diastereoisomers and the assignment of stereochemistry. The compounds were evaluated in vitro for their ability to inhibit the degradation of radiolabeled collagen by purified human lun...

journal_title：Journal of medicinal chemistry

authors： Bird J,De Mello RC,Harper GP,Hunter DJ,Karran EH,Markwell RE,Miles-Williams AJ,Rahman SS,Ward RW

更新日期：1994-01-07 00:00:00

abstract：:The synthesis of diversely substituted 3-isopropoxy-, 3-isopropylsulfanyl-, 3-isopropylsulfinyl-, and 3-isobutyl-4H-1,2,4-benzothiadiazine 1,1-dioxides is described. Their activity on pancreatic β-cells (inhibitory effect on the insulin releasing process) and on vascular and uterine smooth muscle tissues (myorelaxant ...

journal_title：Journal of medicinal chemistry

authors： Pirotte B,de Tullio P,Boverie S,Michaux C,Lebrun P

更新日期：2011-05-12 00:00:00

abstract：:A novel series of ligands with substitutions at the 5-position on phenyl ring A and at the 4'-position on phenyl ring B of 2-(2'-((dimethylamino)methyl)-4'-(fluoroalkoxy)phenylthio)benzenamine (4'-2-fluoroethoxy derivatives 28-31 and 4'-3-fluoropropoxy derivatives 40-42) were prepared and tested as serotonin transport...

journal_title：Journal of medicinal chemistry

authors： Parhi AK,Wang JL,Oya S,Choi SR,Kung MP,Kung HF

更新日期：2007-12-27 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：: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：: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：:Structure-based strategy was employed to design flavonoid compounds to mimic the Bim BH3 peptide as a new class of inhibitors of the anti-apoptotic Bcl-2 proteins. The most potent compound, 4 (BI-33), binds to Bcl-2 and Mcl-1 with Ki values of 17 and 18 nM, respectively. Compound 4 inhibits cell growth in the MDA-MB-2...

journal_title：Journal of medicinal chemistry

authors： Tang G,Ding K,Nikolovska-Coleska Z,Yang CY,Qiu S,Shangary S,Wang R,Guo J,Gao W,Meagher J,Stuckey J,Krajewski K,Jiang S,Roller PP,Wang S

更新日期：2007-07-12 00:00:00

abstract：:The structure-based design, chemical synthesis, and biological evaluation of peptide-derived human rhinovirus (HRV) 3C protease (3CP) inhibitors are described. These compounds incorporate various Michael acceptor moieties and are shown to irreversibly bind to HRV serotype 14 3CP with inhibition activities (kobs/[I]) r...

journal_title：Journal of medicinal chemistry

authors： Dragovich PS,Webber SE,Babine RE,Fuhrman SA,Patick AK,Matthews DA,Lee CA,Reich SH,Prins TJ,Marakovits JT,Littlefield ES,Zhou R,Tikhe J,Ford CE,Wallace MB,Meador JW 3rd,Ferre RA,Brown EL,Binford SL,Harr JE,DeLisle

更新日期：1998-07-16 00:00:00

abstract：:4,6,6a,7,8,12b-Hexahydroindolo[4,3-ab]phenanthridines ("benzergolines") was the first structural class of potent and selective dopamine D1 agonists lacking a catechol group. In order to determine the enantioselectivity of the 7-methyl derivative in the adenylate cyclase assay, its 5,5a-dihydro precursor was resolved a...

journal_title：Journal of medicinal chemistry

authors： Seiler MP,Floersheim P,Markstein R,Widmer A

更新日期：1993-04-16 00:00:00

abstract：:A series of nitrocoumarin and nitrochromene derivatives have been prepared and shown to inhibit the phosphatidylinositol-specific phospholipase C(PLC)(IC50 < 10 micrograms/mL) isolated from human melanoma. The inhibition of PLC by nitrocoumarin 4a was time-dependent and irreversible. The inhibition of PLC was shown to...

journal_title：Journal of medicinal chemistry

authors： Perrella FW,Chen SF,Behrens DL,Kaltenbach RF 3rd,Seitz SP

更新日期：1994-07-08 00:00:00

abstract：:(4-Methoyx-2,3,6-trimethylphenyl)nonatetraenoic acids, esters, and amides (analogues of retinoic acid) bearing a fluorine atom(s) or a trifluoromethyl group on the polyene side chain were synthesized. The biological activities of these compounds and of 10-, 12-, and 14-fluororetinoic acid esters were evaluated in vivo...

journal_title：Journal of medicinal chemistry

authors： Pawson BA,Chan KK,DeNoble J,Han RJ,Piermattie V,Specian AC,Srisethnil S,Trown PW,Bohoslawec O,Machlin LJ,Gabriel E

更新日期：1979-09-01 00:00:00

abstract：:2,9beta-Dimethyl-2'-hydroxy-6,7-benzomorphan (18) has been synthesized from m-methoxyphenylacetone (6a) or m-methoxyphenylacetonitrile (1) via bromo-alpha-tetralone (10). Isomeric bromo-alpha-tetralone 9, instead of undergoing cyclization to a 6,7-benzomorphan, gave aromatization product 12. The structures and stereoc...

journal_title：Journal of medicinal chemistry

authors： Inoue H,O-ishi T,May EL

更新日期：1975-08-01 00:00:00

abstract：:In the present investigation, the last two possible modes of generating conformationally semirigid diacylglycerol (DAG) analogues embedded into five-membered ring lactones as templates III and IV are investigated. The first two templates studied in previous investigations corresponded to 2-deoxyribonolactone (template...

journal_title：Journal of medicinal chemistry

authors： Lee J,Lewin NE,Acs P,Blumberg PM,Marquez VE

更新日期：1996-12-06 00:00:00

abstract：:An enzymatically activated liposome-based drug-delivery concept involving masked antitumor ether lipids (AELs) has been investigated. This concept takes advantage of the cytotoxic properties of AEL drugs as well as the membrane permeability enhancing properties of these molecules, which can lead to enhanced drug diffu...

journal_title：Journal of medicinal chemistry

authors： Andresen TL,Davidsen J,Begtrup M,Mouritsen OG,Jørgensen K

更新日期：2004-03-25 00:00:00

abstract：:Resistance to β-lactam antibiotics can be mediated by metallo-β-lactamase enzymes (MBLs). An MBL inhibitor could restore the effectiveness of β-lactams. We report on the evaluation of approved thiol-containing drugs as inhibitors of NDM-1, VIM-1, and IMP-7. Drugs were assessed by a novel assay using a purchasable fluo...

journal_title：Journal of medicinal chemistry

authors： Klingler FM,Wichelhaus TA,Frank D,Cuesta-Bernal J,El-Delik J,Müller HF,Sjuts H,Göttig S,Koenigs A,Pos KM,Pogoryelov D,Proschak E

更新日期：2015-04-23 00:00:00

abstract：:The relative binding affinities to human dihydrofolate reductase of four new potential antifolates, containing ester linkages between the two aromatic systems, were estimated by free energy perturbation simulations. The ester analogue, predicted to exhibit the highest binding affinity to human dihydrofolate reductase,...

journal_title：Journal of medicinal chemistry

authors： Graffner-Nordberg M,Marelius J,Ohlsson S,Persson A,Swedberg G,Andersson P,Andersson SE,Aqvist J,Hallberg A

更新日期：2000-10-19 00:00:00