Indanylidenes. 2. Design and synthesis of (E)-2-(4-chloro-6-fluoro-1-indanylidene)-N-methylacetamide, a potent antiinflammatory and analgesic agent without centrally acting muscle relaxant activity.

abstract：:The discovery of selective endothelin (ET) receptor antagonists will facilitate identification of the physiological and pathological roles for ET and its isopeptides. Structure-activity studies of the C-terminal hexapeptide of ET have been carried out to elucidate those amino acids important for receptor binding and a...

journal_title：Journal of medicinal chemistry

authors： Doherty AM,Cody WL,DePue PL,He JX,Waite LA,Leonard DM,Leitz NL,Dudley DT,Rapundalo ST,Hingorani GP

更新日期：1993-09-03 00:00:00

abstract：:Pulmonary edema is a common ailment of heart failure patients and has remained an unmet medical need due to dose-limiting side effects associated with current treatments. Preclinical studies in rodents have suggested that inhibition of transient receptor potential vanilloid-4 (TRPV4) cation channels may offer an alter...

journal_title：Journal of medicinal chemistry

authors： Pero JE,Matthews JM,Behm DJ,Brnardic EJ,Brooks C,Budzik BW,Costell MH,Donatelli CA,Eisennagel SH,Erhard K,Fischer MC,Holt DA,Jolivette LJ,Li H,Li P,McAtee JJ,McCleland BW,Pendrak I,Posobiec LM,Rivera KLK,Rivero RA

更新日期：2018-12-27 00:00:00

abstract：:On the basis of our previous observation that N1-alkyl substituted chlorpropamide derivatives when administered to rats nonenzymatically eliminated n-propyl isocyanate, a known inhibitor of aldehyde dehydrogenase (AlDH), we have synthesized other latentiated n-propyl isocyanates as in vivo inhibitors of AlDH. N1-Allyl...

journal_title：Journal of medicinal chemistry

authors： Nagasawa HT,Elberling JA,Goon DJ,Shirota FN

更新日期：1994-11-25 00:00:00

abstract：:The recently described potent and selective GABAA antagonist SR 95531 (gabazine) is compared to six other GABAA antagonists: (+)-bicuculline, (-)-securinine, (+)-tubocurarine, iso-THAZ, R-5135, and pitrazepine. Starting from ab initio molecular orbital calculations performed on crystal atomic coordinates, attempts wer...

journal_title：Journal of medicinal chemistry

authors： Rognan D,Boulanger T,Hoffmann R,Vercauteren DP,Andre JM,Durant F,Wermuth CG

更新日期：1992-05-29 00:00:00

abstract：:Acyl carrier protein synthase (AcpS) catalyzes the transfer of the 4'-phosphopantetheinyl group from the coenzyme A to a serine residue in acyl carrier protein (ACP), thereby activating ACP, an important step in cell wall biosynthesis. The structure-based design of novel anthranilic acid inhibitors of AcpS, a potentia...

journal_title：Journal of medicinal chemistry

authors： Joseph-McCarthy D,Parris K,Huang A,Failli A,Quagliato D,Dushin EG,Novikova E,Severina E,Tuckman M,Petersen PJ,Dean C,Fritz CC,Meshulam T,DeCenzo M,Dick L,McFadyen IJ,Somers WS,Lovering F,Gilbert AM

更新日期：2005-12-15 00:00:00

abstract：:Here we describe the synthesis and structure-activity relationship for a class of pyrazoline-containing dihydroquinolone negative allosteric modulators of the NMDA receptor that show strong subunit selectivity for GluN2C- and GluN2D-containing receptors over GluN2A- and GluN2B-containing receptors. Several members of ...

journal_title：Journal of medicinal chemistry

authors： Acker TM,Khatri A,Vance KM,Slabber C,Bacsa J,Snyder JP,Traynelis SF,Liotta DC

更新日期：2013-08-22 00:00:00

abstract：:(+/-)-7-Aminosulfonyl-3-fluoromethyl-1,2,3,4-tetrahydroisoquinoline (7) is one of the most potent and selective inhibitors of phenylethanolamine N-methyltransferase (PNMT) reported to date, but a blood-brain barrier (BBB) model indicates that it cannot penetrate the BBB. To increase the lipophilicity of 7 by addition ...

journal_title：Journal of medicinal chemistry

authors： Romero FA,Vodonick SM,Criscione KR,McLeish MJ,Grunewald GL

更新日期：2004-08-26 00:00:00

abstract：:Conformational restriction of previously disclosed acyclic (diphenylethyl)diphenylacetamides led to the discovery of several potent inhibitors of acyl CoA:cholesterol acyltransferase (ACAT). cis-[2-(4-Hydroxyphenyl)-1-indanyl]diphenylacetamide (4a) was the most potent ACAT inhibitor identified (IC50 = 0.04 microM in a...

journal_title：Journal of medicinal chemistry

authors： Vaccaro W,Amore C,Berger J,Burrier R,Clader J,Davis H,Domalski M,Fevig T,Salisbury B,Sher R

更新日期：1996-04-12 00:00:00

abstract：:Non-nucleoside inhibitors of HIV reverse transcriptase (NNRTIs), albeit not the mainstays of HIV/AIDS treatment, have become increasingly important in highly active antiretroviral therapy (HAART) due to their unique mechanism of action. Several years ago our group identified the alkenyldiarylmethanes (ADAMs) as a pote...

journal_title：Journal of medicinal chemistry

authors： Cullen MD,Deng BL,Hartman TL,Watson KM,Buckheit RW Jr,Pannecouque C,Clercq ED,Cushman M

更新日期：2007-10-04 00:00:00

abstract：:The HIV-1 central nervous system infection leads to the onset of neurological impairments called AIDS dementia complex (ADC). PAF plays an important role in this pathology, as it is an HIV-1-induced neurotoxin produced by infected or activated macrophages and microglia, in the brain. We previously reported that PAF-an...

journal_title：Journal of medicinal chemistry

authors： Serradji N,Martin M,Bensaid O,Cisternino S,Rousselle C,Dereuddre-Bosquet N,Huet J,Redeuilh C,Lamouri A,Dong CZ,Clayette P,Scherrmann JM,Dormont D,Heymans F

更新日期：2004-12-02 00:00:00

abstract：:A variety of 2,3-disubstituted 5,7-dimethyl-1,8-naphthyridines was synthesized and tested in saline-loaded rats for their diuretic properties. The 2-amino-3-carbomethoxy and four 2-amino-3-N-alkylcarbamoyl compounds exhibited significant activity as measured by volume output; however, they were generally less potent t...

journal_title：Journal of medicinal chemistry

authors： Hawes EM,Gorecki DK,Gedir RG

更新日期：1977-06-01 00:00:00

abstract：:The mechanistic target of rapamycin (mTOR) plays a pivotal role in growth and tumor progression and is an attractive target for cancer treatment. ATP-competitive mTOR kinase inhibitors (TORKi) have the potential to overcome limitations of rapamycin derivatives in a wide range of malignancies. Herein, we exploit a conf...

journal_title：Journal of medicinal chemistry

authors： Borsari C,Rageot D,Dall'Asen A,Bohnacker T,Melone A,Sele AM,Jackson E,Langlois JB,Beaufils F,Hebeisen P,Fabbro D,Hillmann P,Wymann MP

更新日期：2019-09-26 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：: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：: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：:We previously reported that [[N-[3beta-hydroxyllup-20(29)-en-28-oyl]-7-aminoheptyl]carbamoyl]methane (A43D, 4) was a potent HIV-1 entry inhibitor. However, 4 was inactive against HIV-2 virus, suggesting the structural requirements for targeting these two retroviruses are different. In this study, a series of new betul...

journal_title：Journal of medicinal chemistry

authors： Dang Z,Lai W,Qian K,Ho P,Lee KH,Chen CH,Huang L

更新日期：2009-12-10 00:00:00

abstract：:Privileged structures are ligand substructures that are widely used to generate high-affinity ligands for more than one type of receptor. To explain this, we surmised that there must be some common feature in the target proteins. For a set of class A GPCRs, we found a good correlation between conservation patterns of ...

journal_title：Journal of medicinal chemistry

authors： Bondensgaard K,Ankersen M,Thøgersen H,Hansen BS,Wulff BS,Bywater RP

更新日期：2004-02-12 00:00:00

abstract：:A number of cycloalkyl substituents (from C-3 to C-8) have been introduced on the 6-amino group of adenosine, 1-deazaadenosine, and 2'-deoxyadenosine, bearing or not a chlorine atom at the 2-position, to evaluate the influence on the A(1) and A(2A) affinity of steric hindrance and lipophilicity. Furthermore, the guano...

journal_title：Journal of medicinal chemistry

authors： Vittori S,Lorenzen A,Stannek C,Costanzi S,Volpini R,IJzerman AP,Kunzel JK,Cristalli G

更新日期：2000-01-27 00:00:00

abstract：:Antibiotic resistance represents a worldwide concern, especially regarding the outbreak of methicillin-resistant Staphylococcus aureus, a common cause for serious skin and soft tissues infections. A major contributor to Staphylococcus aureus antibiotic resistance is the NorA efflux pump, which is able to extrude selec...

journal_title：Journal of medicinal chemistry

authors： Lepri S,Buonerba F,Goracci L,Velilla I,Ruzziconi R,Schindler BD,Seo SM,Kaatz GW,Cruciani G

更新日期：2016-02-11 00:00:00

abstract：:Progesterone receptors (PRs) are present in many breast tumors, and their levels are increased by certain endocrine therapies. We describe the synthesis and PR binding affinities of a series of bromine- and iodine-substituted 16alpha,17alpha-dioxolane progestins, some of which, when appropriately radiolabeled, are pot...

journal_title：Journal of medicinal chemistry

authors： Zhou D,Carlson KE,Katzenellenbogen JA,Welch MJ

更新日期：2006-07-27 00:00:00

abstract：:The cytotoxic complex, [PtCl(Am)2(ACRAMTU)](NO3)2 (1) ((Am)2 = ethane-1,2-diamine, en; ACRAMTU = 1-[2-(acridin-9-ylamino)ethyl]-1,3-dimethylthiourea), is a dual platinating/intercalating DNA binder that, unlike clinical platinum agents, does not induce DNA cross-links. Here, we demonstrate that substitution of the thi...

journal_title：Journal of medicinal chemistry

authors： Ma Z,Choudhury JR,Wright MW,Day CS,Saluta G,Kucera GL,Bierbach U

更新日期：2008-12-11 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 synthetic pentasaccharide (1) corresponding to the heparin sequence which binds to, and activates, antithrombin III (AT III) is a potent antithrombotic compound in several animal models of venous thrombosis. We describe here the preparation and the pharmacological properties of 34, an analogue of oligosaccharide 1...

journal_title：Journal of medicinal chemistry

authors： Petitou M,Duchaussoy P,Jaurand G,Gourvenec F,Lederman I,Strassel JM,Bârzu T,Crépon B,Hérault JP,Lormeau JC,Bernat A,Herbert JM

更新日期：1997-05-23 00:00:00

abstract：:FLT3 receptor tyrosine kinase is aberrantly active in many cases of acute myeloid leukemia (AML). Recently, bis(1H-indol-2-yl)methanones were found to inhibit FLT3 and PDGFR kinases. To optimize FLT3 activity and selectivity, 35 novel derivatives were synthesized and tested for inhibition of FLT3 and PDGFR autophospho...

journal_title：Journal of medicinal chemistry

authors： Mahboobi S,Uecker A,Sellmer A,Cénac C,Höcher H,Pongratz H,Eichhorn E,Hufsky H,Trümpler A,Sicker M,Heidel F,Fischer T,Stocking C,Elz S,Böhmer FD,Dove S

更新日期：2006-06-01 00:00:00

abstract：:Several derivatives of 4,5-disubstituted imidazole, 2,4,5-trisubstituted pyrimidine, 2-substituted purine, thiazolo[3,2-alpha]purine, [1,3]thiazino[3,2-alpha]purine, thiazolo[2,3-i]purine, [1,3]thiazino-[2,3-i]purine, and 6-substituted pyrazolo[3,4-d]pyrimidine were synthesized and tested as inhibitors of the xanthine...

journal_title：Journal of medicinal chemistry

authors： Biagi G,Costantini A,Costantino L,Giorgi I,Livi O,Pecorari P,Rinaldi M,Scartoni V

更新日期：1996-06-21 00:00:00

abstract：:The effect of incorporation of an eleostearoyl group into molecules of aralkylhydrazines on their monoamine oxidase inhibitory potency was investigated in vitro and in vivo. The results showed that on a molar basis the hydrazides possessed an in vitro potency lower than and an in vivo potency and acute toxicity compar...

journal_title：Journal of medicinal chemistry

authors： Hsu SY,Huang CL,Waters IW

更新日期：1975-01-01 00:00:00

abstract：:Antibiotic resistance is one of the biggest threats to public health, and new antibacterial agents hence are in an urgent need to combat infectious diseases caused by multidrug-resistant (MDR) pathogens. Utilizing dimerization strategy, we rationally designed and efficiently synthesized a new series of small molecule ...

journal_title：Journal of medicinal chemistry

authors： Niu Y,Wang M,Cao Y,Nimmagadda A,Hu J,Wu Y,Cai J,Ye XS

更新日期：2018-04-12 00:00:00

abstract：:Cell division cycle 25 (Cdc25) proteins are highly conserved dual specificity phosphatases that regulate cyclin-dependent kinases and represent attractive drug targets for anticancer therapies. To discover more potent and diverse inhibitors of Cdc25 biological activity, virtual screening was performed by docking 2.1 m...

journal_title：Journal of medicinal chemistry

authors： Lavecchia A,Di Giovanni C,Pesapane A,Montuori N,Ragno P,Martucci NM,Masullo M,De Vendittis E,Novellino E

更新日期：2012-05-10 00:00:00

abstract：:The conformation of the sodium salt of mycophenolic acid (MPA), a potent inhibitor of inosine monophosphate dehydrogenase (IMPD), derived from 1D DIFNOE and 2D ROESY experiments in water and molecular dynamics (MD) is described. The hexenoic acid side chain conformation consistent with the NMR data was similar to that...

journal_title：Journal of medicinal chemistry

authors： Makara GM,Keserû GM,Kajtár-Peredy M,Anderson WK

更新日期：1996-03-15 00:00:00

abstract：:Thyroid hormone analogues, polychlorinated biphenyls (PCBs), and their derivatives were shown to bind specifically to thyroxine-specific binding sites in rat liver nuclear extracts. The structure-binding relationship for thyroxine binding prealbumin was qualitatively similar to that for the nuclear receptor. In genera...

journal_title：Journal of medicinal chemistry

authors： McKinney J,Fannin R,Jordan S,Chae K,Rickenbacher U,Pedersen L

更新日期：1987-01-01 00:00:00