SH2-directed ligands of the Lck tyrosine kinase.

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：:In order to investigate the structural requirements for gastroprotective activity in 6-[[1(S)-(3(S),4-dihydro-8- hydroxy-1-oxo-1H-2-benzopyran-3-yl)-3-methylbutyl]amino]-4(S),5(S)-dihydroxy 6-oxo-3(S)-ammoniohexanoate [AI-77-B, 1], a product of Bacillus pumilus AI-77, nine derivatives were prepared and then tested for...

journal_title：Journal of medicinal chemistry

authors： Shimojima Y,Hayashi H

更新日期：1983-10-01 00:00:00

abstract：:The principle of bioisosterism-similarly shaped molecules are more likely to share biological properties than are other molecules-has long helped to guide drug discovery. An algorithmic implementation of this principle, based on shape comparisons of a single rule-generated "topomer" conformation per molecule, had been...

journal_title：Journal of medicinal chemistry

authors： Cramer RD,Poss MA,Hermsmeier MA,Caulfield TJ,Kowala MC,Valentine MT

更新日期：1999-09-23 00:00:00

abstract：:Cyclin-dependent kinases (cdk) have recently raised considerable interest in view of their essential role in the regulation of the cell division cycle. The structure-activity relationships of cdk inhibition showed that the 1, 3; and 7 positions of the purine ring must remain free, probably for a direct interaction, in...

journal_title：Journal of medicinal chemistry

authors： Havlícek L,Hanus J,Veselý J,Leclerc S,Meijer L,Shaw G,Strnad M

更新日期：1997-02-14 00:00:00

abstract：:We have reported that [methyl- (11)C] (3 R,5 R)-5-(3-methoxyphenyl)-3-[(R)-1-phenylethylamino]-1-(4-trifluoromethylphenyl)pyrrolidin-2-one ([(11)C] 8, [(11)C]MePPEP) binds with high selectivity to cannabinoid type-1 (CB 1) receptors in monkey brain in vivo. We now describe the synthesis of 8 and four analogues, namely...

journal_title：Journal of medicinal chemistry

authors： Donohue SR,Krushinski JH,Pike VW,Chernet E,Phebus L,Chesterfield AK,Felder CC,Halldin C,Schaus JM

更新日期：2008-09-25 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：:The in vivo antitumor activity and in vitro metabolic dealkylation have been measured for an homologous series of 3-alkyl-1-(4-carbamoylphenyl)-3-methyltriazenes and have been compared with their partition coefficients. This investigation has shown that the extent of oxidative metabolism in vitro and the antitumor act...

journal_title：Journal of medicinal chemistry

authors： Wilman DE,Cox PJ,Goddard PM,Hart LI,Merai K,Newell DR

更新日期：1984-07-01 00:00:00

abstract：:We have previously reported a series of μ-opioid receptor (MOR) agonist/δ-opioid receptor (DOR) antagonist ligands to serve as potential nonaddictive opioid analgesics. These ligands have been shown to be active in vivo, do not manifest withdrawal syndromes or reward behavior in conditioned-place preference assays in ...

journal_title：Journal of medicinal chemistry

authors： Henry SP,Fernandez TJ,Anand JP,Griggs NW,Traynor JR,Mosberg HI

更新日期：2019-04-25 00:00:00

abstract：:A series of cis- and trans-6,6a,7,8,9,10,10a,11-octahydro-11- oxodibenzo[b,e]thiepinacetic acids (6-9) and -oxepinacetic acids (10-13) were prepared and their antiinflammatory activity was examined in the rat carrageenan hind paw edema test. The antiinflammatory activity of these compounds depended on their stereochem...

journal_title：Journal of medicinal chemistry

authors： Kurokawa M,Uno H,Nakamura H,Sato F,Naruto S

更新日期：1990-02-01 00:00:00

abstract：:A series of 2-substituted methyl 2,3-dihydroimidazo[1, 2-c]quinazolin-5(6H)-ones (4), 3-substituted methyl 2, 3-dihydroimidazo[1,2-c]quinazolin-5(6H)-ones (5), 3-substituted methyl 2,3-dihydro-5H-thiazolo[2,3-b]quinazolin-5-ones (15a,b), 3-substituted methyl 2,3-dihydroimidazo[2,1-b]quinazolin-5(1H)-ones (16a,b), 3-su...

journal_title：Journal of medicinal chemistry

authors： Chern JW,Tao PL,Wang KC,Gutcait A,Liu SW,Yen MH,Chien SL,Rong JK

更新日期：1998-08-13 00:00:00

abstract：:Twenty-nine novel 3'-substituted derivatives of the thyroid hormone 3,3',5-triiodo-L-thyronine (T3) have been synthesized by using established methods and by a new route involving manipulation of a 3'-formyl intermediate. In vitro hormone receptor binding (to intact nuclei) and in vivo thyromimetic activity (induction...

journal_title：Journal of medicinal chemistry

authors： Leeson PD,Ellis D,Emmett JC,Shah VP,Showell GA,Underwood AH

更新日期：1988-01-01 00:00:00

abstract：:The concept of molecular hybridization led us to discover a novel series of coumarin-dihydropyridine hybrids that have potent osteoblastic bone formation in vitro and that prevent ovariectomy-induced bone loss in vivo. In this context, among all the compounds screened for alkaline phosphatase activity, four compounds ...

journal_title：Journal of medicinal chemistry

authors： Sashidhara KV,Kumar M,Khedgikar V,Kushwaha P,Modukuri RK,Kumar A,Gautam J,Singh D,Sridhar B,Trivedi R

更新日期：2013-01-10 00:00:00

abstract：:The in vitro pharmacological properties and conformational features of analogs of the delta opioid receptor selective tetrapeptide Tyr-c[D-Cys-Phe-D-Pen]OH (JOM-13) in which the Phe3 residue was replaced by each of the four stereoisomers of beta-methylphenylalanine (beta-MePhe) were investigated. Both analogs in which...

journal_title：Journal of medicinal chemistry

authors： Mosberg HI,Omnaas JR,Lomize A,Heyl DL,Nordan I,Mousigian C,Davis P,Porreca F

更新日期：1994-12-09 00:00:00

abstract：:The synthesis and testing of potential multisubstrate inhibitors of tyrosine-specific protein kinases are described. One of the substrates, ATP, was mimicked by the known kinase inhibitor 5'-[4-(fluorosulfonyl)benzoyl]adenosine, which was covalently linked via the sulfonyl moiety to tyrosine mimics. The resulting mult...

journal_title：Journal of medicinal chemistry

authors： Kruse CH,Holden KG,Pritchard ML,Feild JA,Rieman DJ,Greig RG,Poste G

更新日期：1988-09-01 00:00:00

abstract：:The IAPs are key regulators of the apoptotic pathways and are commonly overexpressed in many cancer cells. IAPs contain one to three BIR domains that are crucial for their inhibitory function. The pro-survival properties of XIAP come from binding of the BIR domains to the pro-apoptotic caspases. The BIR3 domain of XIA...

journal_title：Journal of medicinal chemistry

authors： Kester RF,Donnell AF,Lou Y,Remiszewski SW,Lombardo LJ,Chen S,Le NT,Lo J,Moliterni JA,Han X,Hogg JH,Liang W,Michoud C,Rupert KC,Mischke S,Le K,Weisel M,Janson CA,Lukacs CM,Fretland AJ,Hong K,Polonskaia A,Gao L

更新日期：2013-10-24 00:00:00

abstract：:Series of N-alkylated derivatives of 2-amino-4,6-dihydroxyindan 3 and 6-amino-1,3-dihydroxybenzocycloheptene 2 were prepared for pharmacological testing as congeners of 2-amino-5,7-dihydroxytetralin, which elicits dopaminergic effects in a variety of assays. All of the subject compounds demonstrated a lower order of d...

journal_title：Journal of medicinal chemistry

authors： Cannon JG,Pease JP,Hamer RL,Ilhan M,Bhatnagar RK,Long JP

更新日期：1984-02-01 00:00:00

abstract：:A pair of enantiomeric Pt(II) complexes, [Pt(R-ahaz)Cl2] and [Pt(S-ahaz)Cl2] (ahaz = 3-aminohexahydroazepine), has been investigated for their ability to bind enantioselectively to DNA. Improved synthetic procedures were developed for preparing both the ligands and the Pt complexes. The structure of the complex of the...

journal_title：Journal of medicinal chemistry

authors： Fenton RR,Easdale WJ,Er HM,O'Mara SM,McKeage MJ,Russell PJ,Hambley TW

更新日期：1997-03-28 00:00:00

abstract：:The 6-aminoglucosamine ring of the aminoglycoside antibiotic neomycin B (ring II) was conjugated to a 16-mer peptide nucleic acid (PNA) targeting HIV-1 TAR RNA. For this purpose, we prepared the aminoglucosamine monomer 15 and attached it to the protected PNA prior to its cleavage from the solid support. We found that...

journal_title：Journal of medicinal chemistry

authors： Das I,Désiré J,Manvar D,Baussanne I,Pandey VN,Décout JL

更新日期：2012-07-12 00:00:00

abstract：:Among the small peptides 2-31, (H)Gly-Gly-Phe-Leu(OMe) (30) reduced prostaglandin production of COX-2 with an IC50 of 60 nM relative to 6000 nM for COX-1. The 5 mg kg(-1) dose of compound 30 rescued albino mice by 80% from capsaicin-induced paw licking and recovered it by 60% from carrageenan-induced inflammation. The...

journal_title：Journal of medicinal chemistry

authors： Singh P,Kaur S,Kaur J,Singh G,Bhatti R

更新日期：2016-04-28 00:00:00

abstract：:The endocannabinoid 2-arachidonoylglycerol (2-AG) plays a major role in many physiological processes, and its action is quickly terminated via enzymatic hydrolysis catalyzed by monoglyceride lipase (MGL). Regulating its endogenous level could offer therapeutic opportunities; however, few selective MGL inhibitors have ...

journal_title：Journal of medicinal chemistry

authors： Matuszak N,Muccioli GG,Labar G,Lambert DM

更新日期：2009-12-10 00:00:00

abstract：:A study of the structure-activity relationships (SAR) of 2f (OL-135), a potent inhibitor of fatty acid amide hydrolase (FAAH), is detailed, targeting the 5-position of the oxazole. Examination of a series of substituted benzene derivatives (12-14) revealed that the optimal position for substitution was the meta-positi...

journal_title：Journal of medicinal chemistry

authors： Romero FA,Du W,Hwang I,Rayl TJ,Kimball FS,Leung D,Hoover HS,Apodaca RL,Breitenbucher JG,Cravatt BF,Boger DL

更新日期：2007-03-08 00:00:00

abstract：:The antineoplastic constituents of Combretum caffrum (Eckl. and Zeyh) Kuntze (Combretaceae family), a species indigenous to South Africa, have been investigated. Subsequently we isolated a series of closely related bibenzyls, stilbenes, and phenanthrenes from C. caffrum. Some of the stilbenes proved to be potent antim...

journal_title：Journal of medicinal chemistry

authors： Pettit GR,Singh SB,Boyd MR,Hamel E,Pettit RK,Schmidt JM,Hogan F

更新日期：1995-05-12 00:00:00

abstract：:We report here the optimization of an HldE kinase inhibitor to low nanomolar potency, which resulted in the identification of the first reported compounds active on selected E. coli strains. One of the most interesting candidates, compound 86, was shown to inhibit specifically bacterial LPS heptosylation on efflux pum...

journal_title：Journal of medicinal chemistry

authors： Desroy N,Denis A,Oliveira C,Atamanyuk D,Briet S,Faivre F,LeFralliec G,Bonvin Y,Oxoby M,Escaich S,Floquet S,Drocourt E,Vongsouthi V,Durant L,Moreau F,Verhey TB,Lee TW,Junop MS,Gerusz V

更新日期：2013-02-28 00:00:00

abstract：:A series of tetrazole amide derivatives of (+/-)-2-dodecyl-alpha-phenyl-N-(2,4,6-trimethoxyphenyl)-2H-tetrazole-5- acetamide (1) was prepared and evaluated for their ability to inhibit acyl-CoA: cholesterol O-acyltransferase (ACAT) in vitro and to lower plasma total cholesterol in vivo. For this series of compounds, o...

journal_title：Journal of medicinal chemistry

authors： O'Brien PM,Sliskovic DR,Picard JA,Lee HT,Purchase CF 2nd,Roth BD,White AD,Anderson M,Mueller SB,Bocan T,Bousley R,Hamelehle KL,Homan R,Lee P,Krause BR,Reindel JF,Stanfield RL,Turluck D

更新日期：1996-06-07 00:00:00

abstract：:The novel lead bis(1H-2-indolyl)methanone inhibits autophosphorylation of platelet-derived growth factor (PDGF) receptor tyrosine kinase in intact cells. Various substituents in the 5- or 6-position of one indole ring increase or preserve potency, whereas most modifications of the ring structures and of the methanone ...

journal_title：Journal of medicinal chemistry

authors： Mahboobi S,Teller S,Pongratz H,Hufsky H,Sellmer A,Botzki A,Uecker A,Beckers T,Baasner S,Schächtele C,Uberall F,Kassack MU,Dove S,Böhmer FD

更新日期：2002-02-28 00:00:00

abstract：:2-, 6-, And 8-alkylated (methyl, ethyl, and vinyl) adenosine analogues were synthesized by a palladium-catalyzed cross-coupling of a tetraalkyltin with the halogenated purine nucleosides. The synthesis of the 8-substituted analogues was accomplished using a transient protection procedure. The 6-alkylated-9-beta-D-ribo...

journal_title：Journal of medicinal chemistry

authors： Van Aerschot AA,Mamos P,Weyns NJ,Ikeda S,De Clercq E,Herdewijn PA

更新日期：1993-10-01 00:00:00

abstract：:N-Methyl-d-aspartate (NMDA) receptor dysfunction has been linked to several neuropsychiatric disorders, including Alzheimer's disease, epilepsy, drug addiction, and schizophrenia. A radioligand that could be used with PET to image and quantify human brain NMDA receptors in the activated "open channel" state would be u...

journal_title：Journal of medicinal chemistry

authors： Naumiec GR,Jenko KJ,Zoghbi SS,Innis RB,Cai L,Pike VW

更新日期：2015-12-24 00:00:00

abstract：:Several substance P analogues containing various D-amino acid modifications have been synthesized by the solid-phase procedure, detached from the solid support by ammonolysis, and purified by gel filtration combined with reversed-phase chromatography. Three compounds were fair to very potent competitive antagonists of...

journal_title：Journal of medicinal chemistry

authors： Caranikas S,Mizrahi J,Escher E,Regoli D

更新日期：1982-11-01 00:00:00

abstract：:5-fluorouracil (5-FU) seco-nucleosdies having as the "sugar" moiety a two-carbon (C2) side chain carrying a N-(2-chloroethyl)-N-nitrosourea group were designed as molecular combinations of antimetabolite and alkylating agent, but hydrolytic release of free 5-FU was not fast enough for significant contribution to the h...

journal_title：Journal of medicinal chemistry

authors： McElhinney RS,McCormick JE,Bibby MC,Double JA,Radacic M,Dumont P

更新日期：1996-03-29 00:00:00

abstract：:To find Delta(8)-Delta(7) sterol isomerase (EBP) selective ligands, various arylpiperazines previously studied and structurally related to some sigma receptors ligands were preliminarily screened. Consequently, a novel series of 2- or 2,6-disubstituted (CH(3), CH(3)O, Cl, F) cis- and trans-4-(4-aryl)cyclohexyl-1-(2-py...

journal_title：Journal of medicinal chemistry

authors： Berardi F,Abate C,Ferorelli S,de Robertis AF,Leopoldo M,Colabufo NA,Niso M,Perrone R

更新日期：2008-12-11 00:00:00