Identification of highly efficacious glucocorticoid receptor agonists with a potential for reduced clinical bone side effects.

abstract：:New carboxyalkyl compounds derived from Phe-Leu and Phe-Ala were synthesized and checked as inhibitors of "enkephalinase", a metalloendopeptidase cleaving the Gly3-Phe4 bond of enkephalins from mouse striatal membranes. Differential recognition of both brain enkephalinase and angiotensin-converting enzyme (ACE) cataly...

journal_title：Journal of medicinal chemistry

authors： Fournié-Zaluski MC,Chaillet P,Soroca-Lucas E,Marçais-Collado H,Costentin J,Roques BP

更新日期：1983-01-01 00:00:00

abstract：:Eucalyptin A (1), together with two known compounds 2 and 3 exhibiting potent inhibition on HGF/c-Met axis, was discovered from the fruits of Eucalyptus globulus. 1 possessed an unprecedented carbon framework of phloroglucinol-coupled sesquiterpenoid, and its structure was elucidated by spectroscopic method and ECD ca...

journal_title：Journal of medicinal chemistry

authors： Yang SP,Zhang XW,Ai J,Gan LS,Xu JB,Wang Y,Su ZS,Wang L,Ding J,Geng MY,Yue JM

更新日期：2012-09-27 00:00:00

abstract：:Exposure of dopamine to an excess of linoleic acid 13-hydroperoxide (13-hydroperoxyoctadecadienoic acid) in the presence of ferrous ions in Tris buffer, pH 7.4, resulted in a relatively fast, oxygen-independent reaction exhibiting first-order kinetics with respect to both catecholamine and metal concentrations. Produc...

journal_title：Journal of medicinal chemistry

authors： Pezzella A,d'Ischia M,Napolitano A,Misuraca G,Prota G

更新日期：1997-07-04 00:00:00

abstract：:Novel tetrahydro-2H-isoindoles have been prepared and evaluated as inhibitors of the COX-2 isoenzyme. A 1,3-diaryl substitution on the central polycyclic ring system and absence of a sulfonyl moiety are the two structural features of this chemical series. A short and easy synthetic pathway produced several derivatives...

journal_title：Journal of medicinal chemistry

authors： Portevin B,Tordjman C,Pastoureau P,Bonnet J,De Nanteuil G

更新日期：2000-11-30 00:00:00

abstract：:Results from previous studies indicate that rabbit liver microsomal cytochrome P-450 catalyzes the C-5' two-electron oxidation of (S)-nicotine stereoselectivity with preferential loss of the pro-(E)-hydrogen atom trans to the pyridine ring. We now have examined the regio- and stereochemical features of the oxidation o...

journal_title：Journal of medicinal chemistry

authors： Peterson LA,Castagnoli N Jr

更新日期：1988-03-01 00:00:00

abstract：:Replacing the 1alpha-OH group of the natural hormone 1alpha,25-dihydroxyvitamin D(3) (calcitriol) by a 1alpha-CHF(2) group and incorporating a potentiating side chain produced two new hybrid analogs 6 and 7. Both of these two hybrid analogs are as transcriptionally active as calcitriol and are strongly antiproliferati...

journal_title：Journal of medicinal chemistry

authors： Peleg S,Petersen KS,Suh BC,Dolan P,Agoston ES,Kensler TW,Posner GH

更新日期：2006-12-14 00:00:00

abstract：:We synthesized two series (7a-i and 8a-i) of 2,3,5-substituted [1,2,4]-thiadiazole analogues of SCH-202676 (7a, 2,3-diphenyl-5-N-methylimino-2H-[1,2,4]-thiadiazole) with emphasis on the N-imino substituent. Compounds 7a-g,i and 8a-g at a final concentration of 1 microM significantly inhibited [(3)H]CCPA (2-chloro-N(6)...

journal_title：Journal of medicinal chemistry

authors： Göblyös A,de Vries H,Brussee J,Ijzerman AP

更新日期：2005-02-24 00:00:00

abstract：:The mTOR protein is a master regulator of cell growth and proliferation, and inhibitors of its kinase activity have the potential to become new class of anticancer drugs. Starting from quinoline 1, which was identified in a biochemical mTOR assay, we developed a tricyclic benzonaphthyridinone inhibitor 37 (Torin1), wh...

journal_title：Journal of medicinal chemistry

authors： Liu Q,Chang JW,Wang J,Kang SA,Thoreen CC,Markhard A,Hur W,Zhang J,Sim T,Sabatini DM,Gray NS

更新日期：2010-10-14 00:00:00

abstract：:A series of transition-state analogues having heterocyclythio C-termini has been synthesized and evaluated for inhibition of human renin. Addition of mercaptoheterocycles to a chiral Boc-amino epoxide intermediate led, after several steps, to the target [(2R,3S)-3-(BocPheHis-amino)-4-cyclohexyl-2-hydroxy-1-butyl]thio ...

journal_title：Journal of medicinal chemistry

authors： Ashton WT,Cantone CL,Meurer LC,Tolman RL,Greenlee WJ,Patchett AA,Lynch RJ,Schorn TW,Strouse JF,Siegl PK

更新日期：1992-05-29 00:00:00

abstract：:The intracellular delivery of nucleic acid molecules is a complex process involving several distinct steps; among these the endosomal escape appeared to be of particular importance for an efficient protein production (or inhibition) into host cells. In the present study, a new series of ionizable vectors, derived from...

journal_title：Journal of medicinal chemistry

authors： Habrant D,Peuziat P,Colombani T,Dallet L,Gehin J,Goudeau E,Evrard B,Lambert O,Haudebourg T,Pitard B

更新日期：2016-04-14 00:00:00

abstract：:In 1869, Crum Brown discovered the first structure-activity link by showing that alkaloids, even convulsive ones, were converted by N-methylation to muscle relaxants resembling curarine (itself a quaternary amine). This led to an attempt to link every type of drug action to its own cluster of atoms. This quest was jol...

journal_title：Journal of medicinal chemistry

authors： Albert A

更新日期：1982-01-01 00:00:00

abstract：:Some small molecules, often hits from screening, form aggregates in solution that inhibit many enzymes. In contrast, drugs are thought to act specifically. To investigate this assumption, 50 unrelated drugs were tested for promiscuous inhibition via aggregation. Each drug was tested against three unrelated model enzym...

journal_title：Journal of medicinal chemistry

authors： Seidler J,McGovern SL,Doman TN,Shoichet BK

更新日期：2003-10-09 00:00:00

abstract：:Polyadenosine diphosphoribose glycohydrolase (PARG) catalyzes the intracellular hydrolysis of adenosine diphosphoribose polymers. Because structure-activity data are lacking for PARG, the specific inhibitor adenosine diphosphate (hydroxymethyl)pyrrolidinediol (ADP-HPD) was utilized to determine the effects of structur...

journal_title：Journal of medicinal chemistry

authors： Koh DW,Coyle DL,Mehta N,Ramsinghani S,Kim H,Slama JT,Jacobson MK

更新日期：2003-09-25 00:00:00

abstract：:In a study of nonsteroidal antiinflammatory and analgesic agents, a series of 1,3-dihydro-3-(substituted phenyl)imidazo[4,5-b]pyridin-2-ones-and 3-(substituted phenyl)triazolo[4,5-b]pyridines was prepared. Many of the imidazolones were alkylated on the free nitrogen. In a modified Randall-Selitto analgesic assay, the ...

journal_title：Journal of medicinal chemistry

authors： Clark RL,Pessolano AA,Shen TY,Jacobus DP,Jones H,Lotti VJ,Flataker LM

更新日期：1978-09-01 00:00:00

abstract：:The concept that polyamines may represent a universal template in the receptor recognition process is embodied in the design of new selective muscarinic ligands. Tetraamines 4-7 and 16-20 and diamine diamides 8-15 were synthesized, and their pharmacological profiles at muscarinic receptor subtypes were assessed by fun...

journal_title：Journal of medicinal chemistry

authors： Bolognesi ML,Minarini A,Budriesi R,Cacciaguerra S,Chiarini A,Spampinato S,Tumiatti V,Melchiorre C

更新日期：1998-10-08 00:00:00

abstract：:Di-tert-butyl (E)-4,4'-stilbenedicarboxylate and tert-butyl 4-vinylbenzoate were copolymerized with maleic anhydride and tert-butyl 4-maleimidobenzoate, individually and respectively. After conversion into polyanions, these four copolymers exhibited activity against four HIV-1 strains: IIIb, BaL, JR-CSF, and 92UG037. ...

journal_title：Journal of medicinal chemistry

authors： Savage AM,Li Y,Matolyak LE,Doncel GF,Turner SR,Gandour RD

更新日期：2014-08-14 00:00:00

abstract：:Avermectins A2a, B1a, and B2a (1, 2, and 3) were acetylated to give 4"- and 23-acetates 4 and 5 and 4",23-diacetate 6 from 1, the 4"-and 5-acetates 7 and 8 and 4",5-diacetate 9 from 2, and triacetate 10 from 3. Structure proof by 300-MHz 1H NMR and mass spectral fragmentation is discussed for 10. Forcing acetylation c...

journal_title：Journal of medicinal chemistry

authors： Mrozik H,Eskola P,Fisher MH,Egerton JR,Cifelli S,Ostlind DA

更新日期：1982-06-01 00:00:00

abstract：:A library of 3-hydroxy-2,3-dihydropyridones was synthesized, and their activities as antiandrogens were tested in the human prostate cancer cell line LNCaP. Structure-activity relationship (SAR) studies resulted in the identification of a potent compound whose activity is comparable to that of MDV3100. Homology modeli...

journal_title：Journal of medicinal chemistry

authors： Pepe A,Pamment M,Kim YS,Lee S,Lee MJ,Beebe K,Filikov A,Neckers L,Trepel JB,Malhotra SV

更新日期：2013-11-14 00:00:00

abstract：:Long chain fatty acid elongase 6 (ELOVL6) catalyzes the elongation of long chain fatty acyl-CoAs and is a potential target for the treatment of metabolic disorders. The ultrahigh throughput screen of our corporate chemical collections resulted in the identification of a novel 3-sulfonyl-8-azabicyclo[3.2.1]octane class...

journal_title：Journal of medicinal chemistry

authors： Nagase T,Takahashi T,Sasaki T,Nagumo A,Shimamura K,Miyamoto Y,Kitazawa H,Kanesaka M,Yoshimoto R,Aragane K,Tokita S,Sato N

更新日期：2009-07-23 00:00:00

abstract：:Previous work has shown that incorporation of either 1-aminocyclohexanecarboxylic acid (Ac6c) or alpha-methyl-p-phosphonophenylalanine ((alpha-Me)Ppp) in the phosphotyrosyl (pTyr) C-proximal position (pY + 1 residue) of Grb2 SH2 domain binding peptides confers high affinity. The tetralin-based (S)-2-amino-6-phosphonot...

journal_title：Journal of medicinal chemistry

authors： Oishi S,Karki RG,Kang SU,Wang X,Worthy KM,Bindu LK,Nicklaus MC,Fisher RJ,Burke TR Jr

更新日期：2005-02-10 00:00:00

abstract：:The kinase PIM-1 plays a pivotal role in cytokine signaling and is implicated in the development of a number of tumors. The three-dimensional structure of PIM-1 is characterized by an unique hinge region which lacks a second hydrogen bond donor and makes it particularly important to determine how inhibitors bind to th...

journal_title：Journal of medicinal chemistry

authors： Bullock AN,Debreczeni JE,Fedorov OY,Nelson A,Marsden BD,Knapp S

更新日期：2005-12-01 00:00:00

abstract：:C-terminal fragment analogues of the leech anticoagulant peptide hirudin represent a unique class of thrombin inhibitors that blocks thrombin's cleavage of fibrinogen but does not block the catalytic site of thrombin. In this paper, a series of synthetic peptides were prepared by solid-phase methodology to determine t...

journal_title：Journal of medicinal chemistry

authors： Owen TJ,Krstenansky JL,Yates MT,Mao SJ

更新日期：1988-05-01 00:00:00

abstract：:Dysregulation of translation initiation factor 4E (eIF4E) activity occurs in various cancers. Mitogen-activated protein kinase (MAPK) interacting kinases 1 and 2 (MNK1 and MNK2) play a fundamental role in activation of eIF4E. Structure-activity relationship-driven expansion of a fragment hit led to discovery of dual M...

journal_title：Journal of medicinal chemistry

authors： Kwiatkowski J,Liu B,Pang S,Ahmad NHB,Wang G,Poulsen A,Yang H,Poh YR,Tee DHY,Ong E,Retna P,Dinie N,Kwek P,Wee JLK,Manoharan V,Low CB,Seah PG,Pendharkar V,Sangthongpitag K,Joy J,Baburajendran N,Jansson AE,Nacro

更新日期：2020-01-23 00:00:00

abstract：:The design, synthesis, and biological profile of several indole melatonin analogues with a conformationally restricted C3 amidoethane side chain are presented. Examination of the accessible conformations of the melatonin side chain led us to explore some of its fully or partially restricted analogues, 2-12, the bindin...

journal_title：Journal of medicinal chemistry

authors： Spadoni G,Balsamini C,Diamantini G,Di Giacomo B,Tarzia G,Mor M,Plazzi PV,Rivara S,Lucini V,Nonno R,Pannacci M,Fraschini F,Stankov BM

更新日期：1997-06-20 00:00:00

abstract：:Novel N-substituted derivatives of acyclovir (1a) were synthesized and evaluated for their antiviral, antimetabolic, and antitumor cell properties in vitro. Monomethylation of 1a at positions 1, 7, and N-2 gave compounds 2-4, respectively. When positions 1 and N-2 were linked together by an isopropeno group, the tricy...

journal_title：Journal of medicinal chemistry

authors： Boryski J,Golankiewicz B,De Clercq E

更新日期：1988-07-01 00:00:00

abstract：:Although cyclooxygenase-1 (COX-1) inhibition is thought to be a major mechanism of gastric damage by nonsteroidal anti-inflammatory drugs (NSAIDs), some COX-1-selective inhibitors exhibit strong analgesic effects without causing gastric damage. However, it is not clear whether their analgesic effects are attributable ...

journal_title：Journal of medicinal chemistry

authors： Kakuta H,Zheng X,Oda H,Harada S,Sugimoto Y,Sasaki K,Tai A

更新日期：2008-04-24 00:00:00

abstract：:Largazole 4a and analogues with modifications at the C7 position, as well as 2,4'-bithiazole 5a, have been synthesized using an acyclic cross-metathesis of the corresponding depsipeptide structures assembled by N-C6(O) or C15(O)-N lactam formation. Similar to the parent system 4a, the series of largazole depsipeptides...

journal_title：Journal of medicinal chemistry

authors： Souto JA,Vaz E,Lepore I,Pöppler AC,Franci G,Alvarez R,Altucci L,de Lera AR

更新日期：2010-06-24 00:00:00

abstract：:We report, for the first time, the biological activities of four-carbon-atom bridged classical antifolates on dihydrofolate reductase (DHFR), thymidylate synthase (TS), and folylpolyglutamate synthetase (FPGS) as well as antitumor activity. Extension of the bridge homologation studies of classical two-carbon bridged a...

journal_title：Journal of medicinal chemistry

authors： Gangjee A,Zeng Y,McGuire JJ,Kisliuk RL

更新日期：2005-08-11 00:00:00

abstract：:Since the discovery of the serotonin 4 receptor (5-HT(4)R), a large number of receptor ligands have been studied. The safety concerns and the lack of market success of these ligands have mainly been attributed to their lack of selectivity. In this study we describe the discovery of N-[(4-piperidinyl)methyl]-1H-indazol...

journal_title：Journal of medicinal chemistry

authors： Furlotti G,Alisi MA,Apicella C,Capezzone de Joannon A,Cazzolla N,Costi R,Cuzzucoli Crucitti G,Garrone B,Iacovo A,Magarò G,Mangano G,Miele G,Ombrato R,Pescatori L,Polenzani L,Rosi F,Vitiello M,Di Santo R

更新日期：2012-11-26 00:00:00

abstract：:Members of a series of basic amide and ester derivatives of 2-substituted pyrido[2,1-b]quinazoline-8-carboxylic acids were prepared and evaluated for their ability to prevent slow-reacting substance of anaphylaxis (SRS-A) induced contractions of guinea pig ilea. The results indicate that the presence of a branched-cha...

journal_title：Journal of medicinal chemistry

authors： Tilley JW,Levitan P,Welton AF,Crowley HJ

更新日期：1983-11-01 00:00:00