Novel potassium-channel openers: preparation and pharmacological evaluation of racemic and optically active N-(6-amino-3-pyridyl)-N'-bicycloalkyl-N"-cyanoguanidine derivatives.

abstract：:Brr2 is an RNA helicase belonging to the Ski2-like subfamily and an essential component of spliceosome. Brr2 catalyzes an ATP-dependent unwinding of the U4/U6 RNA duplex, which is a critical step for spliceosomal activation. An HTS campaign using an RNA-dependent ATPase assay and initial SAR study identified two diffe...

journal_title：Journal of medicinal chemistry

authors： Iwatani-Yoshihara M,Ito M,Klein MG,Yamamoto T,Yonemori K,Tanaka T,Miwa M,Morishita D,Endo S,Tjhen R,Qin L,Nakanishi A,Maezaki H,Kawamoto T

更新日期：2017-07-13 00:00:00

abstract：:Coactivator-associated arginine methyltransferase 1 (CARM1) represents a valuable target for hormone-dependent tumors such as prostate and breast cancers. Here we report the enzyme and cellular characterization of the 1-benzyl-3,5-bis(3-bromo-4-hydroxybenzylidene)piperidin-4-one (7g) and its analogues 8a-l. Among them...

journal_title：Journal of medicinal chemistry

authors： Cheng D,Valente S,Castellano S,Sbardella G,Di Santo R,Costi R,Bedford MT,Mai A

更新日期：2011-07-14 00:00:00

abstract：:A series of potent PDGFR inhibitors has been identified. The series was optimized for duration of action in the lung. A novel kinase occupancy assay was used to directly measure target occupancy after i.t. dosing. Compound 25 shows 24 h occupancy of the PDGFR kinase domain, after a single i.t. dose and has efficacy at...

journal_title：Journal of medicinal chemistry

authors： Shaw DE,Baig F,Bruce I,Chamoin S,Collingwood SP,Cross S,Dayal S,Drückes P,Furet P,Furminger V,Haggart D,Hussey M,Konstantinova I,Loren JC,Molteni V,Roberts S,Reilly J,Saunders AM,Stringer R,Sviridenko L,Thomas M,

更新日期：2016-09-08 00:00:00

abstract：:A series of biphenyl analogues of the new tuberculosis drug PA-824 was prepared, primarily by coupling the known (6S)-2-nitro-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazin-6-ol with iodobenzyl halides, followed by Suzuki coupling of these iodides with appropriate arylboronic acids or by assembly of the complete biaryl side...

journal_title：Journal of medicinal chemistry

authors： Palmer BD,Thompson AM,Sutherland HS,Blaser A,Kmentova I,Franzblau SG,Wan B,Wang Y,Ma Z,Denny WA

更新日期：2010-01-14 00:00:00

abstract：:Nonpeptidic chiral macrocycles were designed on the basis of an analogue of suberoylanilide hydroxamic acid (2) (SAHA, vorinostat) and evaluated against 11 histone deacetylase (HDAC) isoforms. The identification of critical amino acid residues highly conserved in the cap region of HDACs guided the design of the subero...

journal_title：Journal of medicinal chemistry

authors： Auzzas L,Larsson A,Matera R,Baraldi A,Deschênes-Simard B,Giannini G,Cabri W,Battistuzzi G,Gallo G,Ciacci A,Vesci L,Pisano C,Hanessian S

更新日期：2010-12-09 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 series of substituted chromone-2-carboxylic acids was synthesized and tested as antagonists of SRS-A induced contractions of isolated guinea pig ileum. This work led to the discovery of sodium 7-[3-(4-acetyl-3hydroxy-2-propylphenoxy)-2-hydroxypropoxy]-4-oxo-8-propyl-4H-1-benzopyran-2-carboxylate (FPL 55712) which is...

journal_title：Journal of medicinal chemistry

authors： Appleton RA,Bantick JR,Chamberlain TR,Hardern DN,Lee TB,Pratt AD

更新日期：1977-03-01 00:00:00

abstract：:A novel series of nonsteroidal progestins, 5-benzylidene-1, 2-dihydrochromeno[3,4-f]quinolines (2), was discovered, and a preliminary structure-activity relationship study around the 5-benzylidene ring generated several potent human progesterone receptor agonists (compounds 8, 16). These new progestins showed biologic...

journal_title：Journal of medicinal chemistry

authors： Tegley CM,Zhi L,Marschke KB,Gottardis MM,Yang Q,Jones TK

更新日期：1998-10-22 00:00:00

abstract：:A series of 6-(alkylamino)-9-alkylpurines was synthesized and evaluated for the property of antagonizing the behavioral effects in animals of the dopamine agonist apomorphine. This model for identifying potential antipsychotic agents is based on the hypothesis that agents that antagonize apomorphine-induced aggressive...

journal_title：Journal of medicinal chemistry

authors： Kelley JL,Bullock RM,Krochmal MP,McLean EW,Linn JA,Durcan MJ,Cooper BR

更新日期：1997-09-26 00:00:00

abstract：:Dimeric DNA cross-linking compounds have emerged as important new antitumor agents. We report the synthesis and biochemical evaluation of a select set of dimeric mitomycins in which the two mitomycin units are tethered at either the mitomycin C(7) amino or the aziridine N(1a) positions. Significantly, mitomycin C (1) ...

journal_title：Journal of medicinal chemistry

authors： Na Y,Li VS,Nakanishi Y,Bastow KF,Kohn H

更新日期：2001-10-11 00:00:00

abstract：:The effect of substitution of the pyrrolo- and indolo-N atoms in tetrahydronaltrindole (TNTI), tetrahydrooxymorphindole (TOMI), and 17-cyclopropylmethyl-3,14-dihydroxy-4,5-epoxy-4'-phenyl-6,7:2',3'-pyrrolomorphinan (4) is reported. In opioid functional assays 4 were potent deltaopioid receptor (DOR) antagonists while ...

journal_title：Journal of medicinal chemistry

authors： Srivastava SK,Shefali S,Miller CN,Aceto MD,Traynor JR,Lewis JW,Husbands SM

更新日期：2004-12-16 00:00:00

abstract：:Three analogs of luteinizing hormone-releasing hormone (LH-RH) of the structure less than Glu-His-Trp-Ser-Tyr-Gly-Gly-Leu-Arg-Pro-Gly-NH2, involving substitutions inpositions 1, 3, and 8 with nonprotein amino acids, have been synthesized by the solid-phase method. They are [pyro-L-alpha-(1-aminoadipic)]-LH-RH, [3-(2-n...

journal_title：Journal of medicinal chemistry

authors： Prasad KU,Roeske RW,Weitl FL,Vilchez-Martinez JA,Schally AV

更新日期：1976-04-01 00:00:00

abstract：:Although recognized in small molecules for quite some time, the implications of halogen bonding in biomolecular systems are only now coming to light. In this study, several systems of proteins in complex with halogenated ligands have been investigated by using a two-layer QM/MM ONIOM methodology. In all cases, the hal...

journal_title：Journal of medicinal chemistry

authors： Lu Y,Shi T,Wang Y,Yang H,Yan X,Luo X,Jiang H,Zhu W

更新日期：2009-05-14 00:00:00

abstract：:The diphenylsulfonyl sulfonamide scaffold represented by 1 (WAY-316606) are small molecule inhibitors of the secreted protein sFRP-1, an endogenous antagonist of the secreted glycoprotein Wnt. Modulators of the Wnt pathway have been proposed as anabolic agents for the treatment of osteoporosis or other bone-related di...

journal_title：Journal of medicinal chemistry

authors： Moore WJ,Kern JC,Bhat R,Commons TJ,Fukayama S,Goljer I,Krishnamurthy G,Magolda RL,Nogle L,Pitts K,Stauffer B,Trybulski EJ,Welmaker GS,Wilson M,Bodine PV

更新日期：2009-01-08 00:00:00

abstract：:A novel cytochrome P450, CYP53A15, was identified in the pathogenic filamentous ascomycete Cochliobolus lunatus. The protein, classified into the CYP53 family, was capable of para hydroxylation of benzoate. Benzoate is a key intermediate in the metabolism of aromatic compounds in fungi and yet basically toxic to the o...

journal_title：Journal of medicinal chemistry

authors： Podobnik B,Stojan J,Lah L,Krasevec N,Seliskar M,Rizner TL,Rozman D,Komel R

更新日期：2008-06-26 00:00:00

abstract：:Protecting enkephalins, endogenous opioid peptides released in response to nociceptive stimuli, is an innovative approach for acute and neuropathic pain alleviation. This is achieved by inhibition of their enzymatic degradation by two membrane-bound Zn-metallopeptidases, neprilysin (NEP, EC 3.4.24.11) and aminopeptida...

journal_title：Journal of medicinal chemistry

authors： Poras H,Bonnard E,Dangé E,Fournié-Zaluski MC,Roques BP

更新日期：2014-07-10 00:00:00

abstract：:(E)-Vinylphosphonate ((E)-VP), a metabolically stable phosphate mimic at the 5'-end of the antisense strand, enhances the in vivo potency of siRNA. Here we describe a straightforward synthetic approach to incorporate a nucleotide carrying a vinylphosphonate (VP) moiety at the 5'-end of oligonucleotides under standard ...

journal_title：Journal of medicinal chemistry

authors： Parmar RG,Brown CR,Matsuda S,Willoughby JLS,Theile CS,Charissé K,Foster DJ,Zlatev I,Jadhav V,Maier MA,Egli M,Manoharan M,Rajeev KG

更新日期：2018-02-08 00:00:00

abstract：:A family of analogues of des-AA(1,2,5)-[DTrp(8)/D2Nal(8)]-SRIF that contain a 4-(N-isopropyl)-aminomethylphenylalanine (IAmp) at position 9 was identified that has high affinity and selectivity for human somatostatin receptor subtype 1 (sst1). The binding affinities of des-AA(1,2,5)-[DTrp(8),IAmp(9)]-SRIF (c[H-Cys-Lys...

journal_title：Journal of medicinal chemistry

authors： Rivier JE,Hoeger C,Erchegyi J,Gulyas J,DeBoard R,Craig AG,Koerber SC,Wenger S,Waser B,Schaer JC,Reubi JC

更新日期：2001-06-21 00:00:00

abstract：:The syntheses of 2-amino-N-(2-benzoyl)-4-chlorophenyl)acetamides are reported. The pharmacological properties of these compounds were compared with data obtained from the corresponding cyclized products [5-(2,6-dichlorophenyl)-1,4-benzodiazepin-2-ones]. Evidence is presented which suggests that the central nervous sys...

journal_title：Journal of medicinal chemistry

authors： Fryer RI,Leimgruber W,Trybulski EJ

更新日期：1982-09-01 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：:Androgen receptors are present in most advanced prostate cancer specimens, having a critical role in development of this type of cancer. For correct prognosis of patient conditions and treatment monitoring, noninvasive imaging techniques have great advantages over surgical procedures. We developed synthetic methodolog...

journal_title：Journal of medicinal chemistry

authors： Marom H,Miller K,Bechor-Bar Y,Tsarfaty G,Satchi-Fainaro R,Gozin M

更新日期：2010-09-09 00:00:00

abstract：:Glycosylation of ethyl 3(5)-(bromomethyl)pyrazole-5(3)-carboxylate (3) and 3(5)-(bromomethyl)pyrazole-5(3)-carboxamide (4) with poly-O-acetylated sugars via an acid-catalyzed fusion method afforded the corresponding ethyl 3-(bromomethyl)pyrazole-5-carboxylate and 3-(bromomethyl)pyrazole-5-carboxamide substituted nucle...

journal_title：Journal of medicinal chemistry

authors： García-López MT,Herranz R,Alonso G

更新日期：1979-07-01 00:00:00

abstract：:Pyroptosis is a caspase-1-dependent pro-inflammatory form of programmed cell death implicated in the pathogenesis of autoinflammatory diseases as well as in disorders characterized by excessive cell death and inflammation. Activation of NLRP3 inflammasome is a key event in the pyroptotic cascade. In this study, we des...

journal_title：Journal of medicinal chemistry

authors： Cocco M,Garella D,Di Stilo A,Borretto E,Stevanato L,Giorgis M,Marini E,Fantozzi R,Miglio G,Bertinaria M

更新日期：2014-12-26 00:00:00

abstract：:1,3-Dipolar cycloaddition of benzyl azide or peracetylated glucopyranosyl azides to propargyl halides or 1,4-dihalobutynes yielded 1-benzyl- or 1-glycosyl(halomethyl)-1,2,3-triazoles. Alkylating chloromethyl- bromomethyl- and iodomethyl-1,2,3-triazoles were also obtained from the corresponding hydroxymethyl derivative...

journal_title：Journal of medicinal chemistry

authors： de las Heras FG,Alonso R,Alonso G

更新日期：1979-05-01 00:00:00

abstract：:As part of an ongoing effort to discover novel small-molecule antifolates combining the enzyme-binding species selectivity of trimethoprim (TMP) with the potency of piritrexim (PTX), 10 previously unreported 2,4-diamino-5-(2'-methoxy-5'-substituted)benzylpyrimidines (2-11) containing a carboxyl group at the distal end...

journal_title：Journal of medicinal chemistry

authors： Rosowsky A,Forsch RA,Queener SF

更新日期：2003-04-24 00:00:00

abstract：:Reaction of 1-(S)-[3-hydroxy-2-(phosphonomethoxy)propyl]-5-azacytosine (1) with dicyclohexylcarbodiimide and N,N,-dicyclohexyl-4-morpholinocarboxamidine in dimethylformamide at elevated temperature afforded the corresponding cyclic phosphonate 2, that is, 1-{[(5S)-2-hydroxy-2-oxido-1,4,2-dioxaphosphinan-5-yl]methyl}-5...

journal_title：Journal of medicinal chemistry

authors： Krecmerová M,Holý A,Pohl R,Masojídková M,Andrei G,Naesens L,Neyts J,Balzarini J,De Clercq E,Snoeck R

更新日期：2007-11-15 00:00:00

abstract：:Twenty N- and/or C-modified Dmt-Tic analogues yielded similar K(i) values with either [(3)H]DPDPE (delta(1) agonist) or [(3)H]N, N(Me)(2)-Dmt-Tic-OH (delta antagonist). N-Methylation enhanced delta antagonism while N-piperidine-1-yl, N-pyrrolidine-1-yl, and N-pyrrole-1-yl were detrimental. Dmt-Tic-X (X = -NHNH(2), -NH...

journal_title：Journal of medicinal chemistry

authors： Salvadori S,Guerrini R,Balboni G,Bianchi C,Bryant SD,Cooper PS,Lazarus LH

更新日期：1999-12-02 00:00:00

abstract：:Gamma9delta2T cells represent the most abundant population of human blood gammadeltaT lymphocytes. They produce and promote strong cytotoxic activity against many pathogens that are implicated in several human infectious diseases. Their activation requires their exposure to small phosphorus-containing antigens in the ...

journal_title：Journal of medicinal chemistry

authors： Zgani I,Menut C,Seman M,Gallois V,Laffont V,Liautard J,Liautard JP,Criton M,Montero JL

更新日期：2004-08-26 00:00:00

abstract：:A series of 3-(alkoxymethyl)-alpha-(N-substituted aminomethyl)-4-hydroxybenzyl alcohols was synthesized as potential bronchodilators. The ability to prevent effects against histamine-induced bronchoconstriction in guinea pigs was studied to determine their bronchodilating activity. Introduction of a methoxymethyl grou...

journal_title：Journal of medicinal chemistry

authors： Sohda S,Fujimoto M,Tamegai T,Hirose N

更新日期：1979-03-01 00:00:00

abstract：:We have identified RWJ-671818 (8) as a novel, low molecular weight, orally active inhibitor of human alpha-thrombin (K(i) = 1.3 nM) that is potentially useful for the acute and chronic treatment of venous and arterial thrombosis. In a rat deep venous thrombosis model used to assess antithrombotic efficacy, oral admini...

journal_title：Journal of medicinal chemistry

authors： Lu T,Markotan T,Ballentine SK,Giardino EC,Spurlino J,Crysler CS,Brown K,Maryanoff BE,Tomczuk BE,Damiano BP,Shukla U,End D,Andrade-Gordon P,Bone RF,Player MR

更新日期：2010-02-25 00:00:00