Design of HIV-1 protease inhibitors active on multidrug-resistant virus.

abstract：:The increase in the incidence of both hospital- and community-acquired antibiotic-resistant infections is a major concern to the healthcare community. There have been only two new classes of antibiotics approved by the FDA over the past 40 years, and clearly there is a growing need for additional antimicrobial agents....

journal_title：Journal of medicinal chemistry

authors： Vooturi SK,Cheung CM,Rybak MJ,Firestine SM

更新日期：2009-08-27 00:00:00

abstract：:Inhibition of the cell cycle kinase, cyclin-dependent kinase-4 (Cdk4), is expected to provide an effective method for the treatment of proliferative diseases such as cancer. The pyrido[2,3-d]pyrimidin-7-one template has been identified previously as a privileged structure for the inhibition of ATP-dependent kinases, a...

journal_title：Journal of medicinal chemistry

authors： VanderWel SN,Harvey PJ,McNamara DJ,Repine JT,Keller PR,Quin J 3rd,Booth RJ,Elliott WL,Dobrusin EM,Fry DW,Toogood PL

更新日期：2005-04-07 00:00:00

abstract：:We have previously found that the 4-[4-(N-substituted carbamoyl)-1-piperazinyl]-6,7-dimethoxyquinazolines can function as potent and selective inhibitors of platelet-derived growth factor receptor (PDGFR) phosphorylation. A series of highly potent, specific, orally active, small molecule kinase inhibitors directed aga...

journal_title：Journal of medicinal chemistry

authors： Pandey A,Volkots DL,Seroogy JM,Rose JW,Yu JC,Lambing JL,Hutchaleelaha A,Hollenbach SJ,Abe K,Giese NA,Scarborough RM

更新日期：2002-08-15 00:00:00

abstract：:New analogues of human cholecystokinin in which the Tyr(SO3H) has been replaced by Phe(p-CH2SO3Na), methionines by norleucines, and tryptophan by 2-naphthylalanine([Phe(p-CH2- SO3Na)27,Nle28,31,Nal30]-CCK26-33 and [Phe(p-CH2SO3Na)27,Nle7,28,31,Nal30]-CCK-33) were synthesized by Fmoc solid phase methodology on two diff...

journal_title：Journal of medicinal chemistry

authors： Miranda MT,Liddle RA,Rivier JE

更新日期：1993-06-11 00:00:00

abstract：:Studies indicate that MAO-B is induced in peripheral inflammatory diseases. To target peripheral tissues using MAO-B inhibitors that do not permeate the blood-brain barrier (BBB) the MAO-B-selective inhibitor deprenyl was remodeled by replacing the terminal acetylene with a CO2H function, and incorporating a para-OCH2...

journal_title：Journal of medicinal chemistry

authors： Gealageas R,Devineau A,So PPL,Kim CMJ,Surendradoss J,Buchwalder C,Heller M,Goebeler V,Dullaghan EM,Grierson DS,Putnins EE

更新日期：2018-08-23 00:00:00

abstract：:The importance of steric factors in quantitative structure-activity relationships involving steroid hormones is discussed. a variety of steric parameters, such as parachlor, molecular volume, van der Waals volume, and including difference and squared steric terms, is explored in an attempt to find preferred forms for...

journal_title：Journal of medicinal chemistry

authors： Coburn RA,Solo AJ

更新日期：1976-06-01 00:00:00

abstract：:A novel class of therapeutic drug candidates for heart failure, highly potent and selective GRK2 inhibitors, exhibit potentiation of β-adrenergic signaling in vitro studies. Hydrazone derivative 5 and 1,2,4-triazole derivative 24a were identified as hit compounds by HTS. New scaffold generation and SAR studies of all ...

journal_title：Journal of medicinal chemistry

authors： Okawa T,Aramaki Y,Yamamoto M,Kobayashi T,Fukumoto S,Toyoda Y,Henta T,Hata A,Ikeda S,Kaneko M,Hoffman ID,Sang BC,Zou H,Kawamoto T

更新日期：2017-08-24 00:00:00

abstract：:Basic derivatives of 6,7-dihydroindolo[1,7-ab][1]benzazepine and 6H-indolo[7,1-cd][1,5]benzoxazepine incorporating the imipramine basic side chain were synthesized and screened for antidepressant activity in mice. With few exceptions, the compounds unsubstituted at C-2 antagonized reserpine-induced ptosis and hypother...

journal_title：Journal of medicinal chemistry

authors： Toscano L,Grisanti G,Fioriello G,Seghetti E,Bianchetti A,Bossoni G,Riva M

更新日期：1976-02-01 00:00:00

abstract：:Sepsis is characterized by a systemic inflammatory response syndrome. Derivatives of indole have been reported to exhibit diverse biological activities. This study reports on the design and synthesis of a new series of indole-2-carboxamide derivatives, which are screened for their anti-inflammatory activities in RAW 2...

journal_title：Journal of medicinal chemistry

authors： Liu Z,Tang L,Zhu H,Xu T,Qiu C,Zheng S,Gu Y,Feng J,Zhang Y,Liang G

更新日期：2016-05-26 00:00:00

abstract：:The thioredoxin system plays an important role in cancer cells. Inhibiting thioredoxin reductase (TrxR) has emerged as an effective strategy to selectively target cancer cells. Withangulatin A (WA), a natural product extracted from the whole herb of Physalis angulata L. (Solanaceae), exhibits potent anticancer activit...

journal_title：Journal of medicinal chemistry

authors： Wang C,Li S,Zhao J,Yang H,Yin F,Ding M,Luo J,Wang X,Kong L

更新日期：2020-10-08 00:00:00

abstract：:The synthesis, biological activity, and molecular modeling studies of C-ring-modified camptothecins are reported. A general synthetic protocol, based on "C-5 camptothecin (C-5-CPT) enolate chemistry", allows one to obtain various C5-substituted analogues. All new compounds, obtained as 1:1 epimeric mixtures, were test...

journal_title：Journal of medicinal chemistry

authors： Samorì C,Guerrini A,Varchi G,Fontana G,Bombardelli E,Tinelli S,Beretta GL,Basili S,Moro S,Zunino F,Battaglia A

更新日期：2009-02-26 00:00:00

abstract：:Acute lung injury (ALI) and idiopathic pulmonary fibrosis (IPF) are both serious public health problems with high incidence and mortality rate in adults, and with few drugs available for the efficient treatment in clinic. In this study, we identified that two known histone deacetylase (HDAC) inhibitors, suberanilohydr...

journal_title：Journal of medicinal chemistry

authors： Lu W,Yao X,Ouyang P,Dong N,Wu D,Jiang X,Wu Z,Zhang C,Xu Z,Tang Y,Zou S,Liu M,Li J,Zeng M,Lin P,Cheng F,Huang J

更新日期：2017-03-09 00:00:00

abstract：:In an effort to identify selective ligands for the estrogen receptor subtype ERbeta, a series of aryl benzthiophenes was synthesized. In a radioligand binding assay and reporter gene assays in HeLa and SH-SY5Y cells, compounds were characterized as ERbeta-selective agonists. By targeting ERbeta in the brain, these com...

journal_title：Journal of medicinal chemistry

authors： Schopfer U,Schoeffter P,Bischoff SF,Nozulak J,Feuerbach D,Floersheim P

更新日期：2002-03-28 00:00:00

abstract：:In this paper we report the systematic search for new, potent, and selective DPP II inhibitors. A study of the structure-activity relationship was conducted starting from aminoacyl pyrrolidides as lead compounds. Rational exploration of the P(1) and P(2) building blocks led to the discovery of some very potent DPP II ...

journal_title：Journal of medicinal chemistry

authors： Senten K,Van der Veken P,De Meester I,Lambeir AM,Scharpé S,Haemers A,Augustyns K

更新日期：2003-11-06 00:00:00

abstract：:Mechanism-based inhibitors of human cytomegalovirus (HCMV) protease have been designed based on the pyrrolidine-5,5-trans-lactam ring system. New routes to the beta-methyl-, desmethyl-, and alpha-methyl-pyrrolidine-5,5-trans-lactam templates have been developed from 2,4-diaminobutyric acid. ESI/MS studies have shown t...

journal_title：Journal of medicinal chemistry

authors： Borthwick AD,Angier SJ,Crame AJ,Exall AM,Haley TM,Hart GJ,Mason AM,Pennell AM,Weingarten GG

更新日期：2000-11-16 00:00:00

abstract：:We report the design, synthesis, and biological evaluation of heterocyclic-fused pyrimidines as tubulin polymerization inhibitors targeting the colchicine binding site with significantly improved therapeutic index. Additionally, for the first time, we report high-resolution X-ray crystal structures for the best compou...

journal_title：Journal of medicinal chemistry

authors： Banerjee S,Arnst KE,Wang Y,Kumar G,Deng S,Yang L,Li GB,Yang J,White SW,Li W,Miller DD

更新日期：2018-02-22 00:00:00

abstract：:The synthesis of hybrid "cationic metalloporphyrin-intercalator" molecules is reported. These molecules are based on 9-methoxyellipticine as intercalator and tris-(4-N-methylpyridiniumyl)metalloporphyrins having a 4-aminophenyl or a 4-hydroxyphenyl group for the attachment of the linker. The effect of the length of li...

journal_title：Journal of medicinal chemistry

authors： Ding L,Etemad-Moghadam G,Cros S,Auclair C,Meunier B

更新日期：1991-03-01 00:00:00

abstract：:A series of new HIV-1 protease inhibitors with the hydroxyethylamine core and different phenyloxazolidinone P2 ligands were designed and synthesized. Variation of phenyl substitutions at the P2 and P2' moieties significantly affected the binding affinity and antiviral potency of the inhibitors. In general, compounds w...

journal_title：Journal of medicinal chemistry

authors： Ali A,Reddy GS,Nalam MN,Anjum SG,Cao H,Schiffer CA,Rana TM

更新日期：2010-11-11 00:00:00

abstract：:The p7 protein is a small ion-channel-forming membrane polypeptide encoded by the hepatitis C virus which consists of two transmembrane alpha-helices, TM1 and TM2, and can be blocked by long-alkyl-chain iminosugar derivatives. The length of TM1 and TM2 was estimated by employing different secondary structure predictio...

journal_title：Journal of medicinal chemistry

authors： Patargias G,Zitzmann N,Dwek R,Fischer WB

更新日期：2006-01-26 00:00:00

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：:Every week, articles disclosing new antifungal leads reported as promising starting points for optimization projects are published. In many cases, the mechanism that accounts for their antifungal activity has not been fully elucidated. More significantly, the detrimental impact that could result from certain embedded ...

journal_title：Journal of medicinal chemistry

authors： Pouliot M,Jeanmart S

更新日期：2016-01-28 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：:A quantitative structure-activity relationship (QSAR) study was performed on a set of 49 negative allosteric modulators of AMPA receptor, acting as anticonvulsant agents, using multiple linear regression. The predictive ability of the resulting model was evaluated against a set of 12 compounds; the results showed good...

journal_title：Journal of medicinal chemistry

authors： Macchiarulo A,De Luca L,Costantino G,Barreca ML,Gitto R,Pellicciari R,Chimirri A

更新日期：2004-03-25 00:00:00

abstract：:The three dimers 3, 4, and 5 of mitomycin C (MC), a natural antibiotic and cancer chemotherapeutic agent, were synthesized in which two MC molecules were linked with -(CH(2))(4)-, -(CH(2))(12)-, and -(CH(2))(3)N(CH(3))(CH(2))(3)- tethers, respectively. The dimeric mitomycins were designed to react as polyfunctional DN...

journal_title：Journal of medicinal chemistry

authors： Paz MM,Kumar GS,Glover M,Waring MJ,Tomasz M

更新日期：2004-06-03 00:00:00

abstract：:The bradykinin B1 receptor is rapidly induced upon tissue injury and inflammation, stimulating the production of inflammatory mediators resulting in plasma extravasation, leukocyte trafficking, edema, and pain. We have previously reported on sulfonamide and sulfone-based B1 antagonists containing a privileged bicyclic...

journal_title：Journal of medicinal chemistry

authors： Biswas K,Peterkin TA,Bryan MC,Arik L,Lehto SG,Sun H,Hsieh FY,Xu C,Fremeau RT,Allen JR

更新日期：2011-10-27 00:00:00

abstract：:Generally, antipsychotic agents are dopamine receptor blocking agents that also block conditioned avoidance responding (CAR) in the rat. Recently, however, both (Q-methoxyphenyl)piperazine (OMPP, 1h) and (m-chlorophenyl)piperazine (MCPP, 1o) have been reported to block conditioned avoidance responding in the rat altho...

journal_title：Journal of medicinal chemistry

authors： Martin GE,Elgin RJ Jr,Mathiasen JR,Davis CB,Kesslick JM,Baldy WJ,Shank RP,DiStefano DL,Fedde CL,Scott MK

更新日期：1989-05-01 00:00:00

abstract：:Neuropeptide S (NPS) is the endogenous ligand of the previously orphan G-protein coupled receptor now named NPSR. The NPS-NPSR receptor system regulates important biological functions such as sleep/waking, locomotion, anxiety and food intake. Recently, exhaustive Ala scan and d-amino acid scan studies, together with s...

journal_title：Journal of medicinal chemistry

authors： Tancredi T,Guerrini R,Marzola E,Trapella C,Calo G,Regoli D,Reinscheid RK,Camarda V,Salvadori S,Temussi PA

更新日期：2007-09-06 00:00:00

abstract：:Glycogen synthase kinase 3beta (GSK-3beta) inhibition is expected to be a promising therapeutic approach for treating Alzheimer's disease. Previously we reported a series of 1,3,4-oxadiazole derivatives as potent and highly selective GSK-3beta inhibitors, however, the representative compounds 1a,b showed poor pharmaco...

journal_title：Journal of medicinal chemistry

authors： Saitoh M,Kunitomo J,Kimura E,Iwashita H,Uno Y,Onishi T,Uchiyama N,Kawamoto T,Tanaka T,Mol CD,Dougan DR,Textor GP,Snell GP,Takizawa M,Itoh F,Kori M

更新日期：2009-10-22 00:00:00

abstract：:A series of (8 beta)-6-methylergoline amide derivatives was synthesized with various alkyl substituents in the N1-position in order to evaluate their effectiveness in blocking vascular 5HT2 receptors. The influence of both the N1 substituent and amide derivative proved to be of great importance on binding affinities t...

journal_title：Journal of medicinal chemistry

authors： Misner JW,Garbrecht WL,Marzoni G,Whitten KR,Cohen ML

更新日期：1990-02-01 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