当前位置： SCI文献检索 > JOURNAL OF MEDICINAL CHEMISTRY期刊下所有文献 > N2-substituted O6-cyclohexylmethylguanine derivatives: potent inhibitors of cyclin-dependent kinases 1 and 2.

N2-substituted O6-cyclohexylmethylguanine derivatives: potent inhibitors of cyclin-dependent kinases 1 and 2.

Abstract：

:The adenosine 5'-triphosphate (ATP) competitive cyclin-dependent kinase inhibitor O(6)-cyclohexylmethylguanine (NU2058, 1) has been employed as the lead in a structure-based drug discovery program resulting in the discovery of the potent CDK1 and -2 inhibitor NU6102 (3, IC(50) = 9.5 nM and 5.4 nM vs CDK1/cyclinB and CDK2/cyclinA3, respectively). The SAR for this series have been explored further by the synthesis and evaluation of 45 N(2)-substituted analogues of NU2058. These studies have confirmed the requirement for the hydrogen bonding N(2)-NH group and the requirement for an aromatic N(2)-substituent to confer potency in the series. Additional potency is conferred by the presence of a group capable of donating a hydrogen bond at the 4'-position, for example, the 4'-hydroxy derivative (25, IC(50) = 94 nM and 69 nM vs CDK1/cyclinB and CDK2/cyclinA3, respectively), 4'-monomethylsulfonamide derivative (28, IC(50) = 9 nM and 7.0 nM vs CDK1/cyclinB and CDK2/cyclinA3, respectively), and 4'-carboxamide derivative (34, IC(50) = 67 nM and 64 nM vs CDK1/cyclinB and CDK2/cyclinA3, respectively). X-ray crystal structures have been obtained for key compounds and have been used to explain the observed trends in activity.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Hardcastle IR,Arris CE,Bentley J,Boyle FT,Chen Y,Curtin NJ,Endicott JA,Gibson AE,Golding BT,Griffin RJ,Jewsbury P,Menyerol J,Mesguiche V,Newell DR,Noble ME,Pratt DJ,Wang LZ,Whitfield HJ

doi

10.1021/jm0311442

keywords:

subject

Has Abstract

pub_date

2004-07-15 00:00:00

pages

3710-22

issue

15

eissn

0022-2623

issn

1520-4804

journal_volume

47

pub_type

杂志文章

相关文献

JOURNAL OF MEDICINAL CHEMISTRY文献大全
  • Synthesis and preliminary in vitro investigation of bivalent ligands containing homo- and heterodimeric pharmacophores at mu, delta, and kappa opioid receptors.

    abstract：:A series of homo- and heterodimeric ligands containing kappa agonist and mu agonist/antagonist pharmacophores joined by a linker chain of varying lengths was synthesized and evaluated in vitro by their binding affinity at mu, delta, and kappa opioid receptors. The functional activities of these compounds were measured...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm050577x

    authors： Peng X,Knapp BI,Bidlack JM,Neumeyer JL

    更新日期：2006-01-12 00:00:00

  • Microwave-assisted ring opening of epoxides: a general route to the synthesis of 1-aminopropan-2-ols with anti malaria parasite activities.

    abstract：:A series of 1-aminopropan-2-ols were synthesized and evaluated against two strains of malaria, Plasmodium falciparum FCR3 (chloroquine-resistant) and 3D7 (chloroquine-sensitive). Microwave-assisted ring opening of epoxides (aryl and alkyl glycidyl ethers, glycidol, epichlorohydrin) with various amines without catalyst...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm070553l

    authors： Robin A,Brown F,Bahamontes-Rosa N,Wu B,Beitz E,Kun JF,Flitsch SL

    更新日期：2007-08-23 00:00:00

  • Antifilarial agents. 3-Aminopyrrolidine and 1,4-diazabicyclo[3.2.1]octane derivatives as analogues of diethylcarbamazine.

    abstract：:3-Aminopyrrolidines bearing acyl substituents on either nitrogen and N-acylated 1,4-diazabicyclo[3.2.1]octanes are potent microfilaricides in the Litomosoides carinii gerbil test system but have no effect on adult worms. The high activity of the pyrrolidine derivatives establishes that diethylcarbamazine (DEC) like an...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00220a021

    authors： Sturm P,Cory M,Henry DW

    更新日期：1977-10-01 00:00:00

  • New orally active dual enkephalinase inhibitors (DENKIs) for central and peripheral pain treatment.

    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

    pub_type： 杂志文章

    doi：10.1021/jm500602h

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

    更新日期：2014-07-10 00:00:00

  • Discovery of N-[2-[2-[[3-methoxy-4-(5-oxazolyl)phenyl]amino]-5-oxazolyl]phenyl]-N-methyl-4- morpholineacetamide as a novel and potent inhibitor of inosine monophosphate dehydrogenase with excellent in vivo activity.

    abstract：:Inosine monophosphate dehydrogenase (IMPDH) is a key enzyme that is involved in the de novo synthesis of purine nucleotides. Novel 2-aminooxazoles were synthesized and tested for inhibition of IMPDH catalytic activity. Multiple analogues based on this chemotype were found to inhibit IMPDH with low nanomolar potency. O...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm0105777

    authors： Dhar TG,Shen Z,Guo J,Liu C,Watterson SH,Gu HH,Pitts WJ,Fleener CA,Rouleau KA,Sherbina NZ,McIntyre KW,Shuster DJ,Witmer MR,Tredup JA,Chen BC,Zhao R,Bednarz MS,Cheney DL,MacMaster JF,Miller LM,Berry KK,Harper TW,

    更新日期：2002-05-23 00:00:00

  • 1,3-Dialkyl-8-(p-sulfophenyl)xanthines: potent water-soluble antagonists for A1- and A2-adenosine receptors.

    abstract：:A series of 8-(substituted phenyl) derivatives of theophylline and other 1,3-dialkylxanthines were evaluated for potency and selectivity as antagonists at A1- and A2-adenosine receptors in brain tissue. Theophylline has a similar potency (Ki = 14 microM) at both A1 and A2 receptors. 8-Phenyltheophylline is 25-35-fold ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00382a018

    authors： Daly JW,Padgett W,Shamim MT,Butts-Lamb P,Waters J

    更新日期：1985-04-01 00:00:00

  • Kynurenic acid derivatives inhibit the binding of nerve growth factor (NGF) to the low-affinity p75 NGF receptor.

    abstract：:The ability of a series of substituted kynurenic acids, thienopyridinonecarboxylic acids, and related compounds to inhibit the binding of nerve growth factor (NGF) to the p75 NGF receptor (NGFR) was evaluated in a radioligand binding assay that utilized a biotinylated derivative of the extracellular domain of p75 NGFR...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00022a008

    authors： Jaen JC,Laborde E,Bucsh RA,Caprathe BW,Sorenson RJ,Fergus J,Spiegel K,Marks J,Dickerson MR,Davis RE

    更新日期：1995-10-27 00:00:00

  • Antitumor agents. 123. Synthesis and human DNA topoisomerase II inhibitory activity of 2'-chloro derivatives of etoposide and 4 beta-(arylamino)-4'-O-demethylpodophyllotoxins.

    abstract：:The 2'-chloro derivatives of etoposide and 4 beta-(arylamino)-4'-O-demethylpodophyllotoxins have been synthesized and evaluated for their inhibitory activity against the human DNA topoisomerase II as well as for their activity in causing cellular protein-linked DNA breakage. The results showed that none of the compoun...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00083a009

    authors： Hu H,Wang ZQ,Liu SY,Cheng YC,Lee KH

    更新日期：1992-03-06 00:00:00

  • Synthesis and biological activity of several amino analogues of thymidine.

    abstract：:3',5'-Diamino-3',5'-dideoxythymidine (7) was synthesized via a nine-step synthesis from thymidine in good overall yield. 3'-Amino-3'-deoxythymidine (8) and 5'-amino-5'-deoxythymidine (12) were prepared with a minor modification of the procedure reported by Horwitz and co-workers. Although the 5'-amino analogue 12 had ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：

    authors： Lin TS,Prusoff WH

    更新日期：1978-01-01 00:00:00

  • Pharmacological Characterization of Low-to-Moderate Affinity Opioid Receptor Agonists and Brain Imaging with 18F-Labeled Derivatives in Rats.

    abstract：:The 3,4-dichloro-N-(1-(dimethylamino)cyclohexyl)methyl benzamide scaffold was studied as a template for 18F-positron emission tomography (18F-PET) radiotracer development emphasizing sensitivity to changes in opioid receptor (OR) occupancy over high affinity. Agonist potency, binding affinity, and relevant pharmacolog...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.0c00683

    authors： Ott J,Spilhaug MM,Maschauer S,Rafique W,Jakobsson JE,Hartvig K,Hübner H,Gmeiner P,Prante O,Riss PJ

    更新日期：2020-09-10 00:00:00

  • Design, synthesis, and physicochemical and biological characterization of a new iron chelator of the family of hydroxychromenes.

    abstract：:Increasing evidence suggests that iron plays an important role in tissue damage both during chronic iron overload diseases (i.e., hemochromatosis) and when, in the absence of actual tissue iron overload, iron is delocalized from specific carriers or intracellular sites (inflammation, neurodegenerative diseases, postis...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm021022u

    authors： Ferrali M,Bambagioni S,Ceccanti A,Donati D,Giorgi G,Fontani M,Laschi F,Zanello P,Casolaro M,Pietrangelo A

    更新日期：2002-12-19 00:00:00

  • Dual-action cephalosporins: cephalosporin 3'-quinolone carbamates.

    abstract：:A series of cephalosporins has been prepared in which the 3'-position was linked to the nitrogen of the antibacterial quinolone ciprofloxacin through a carbamate function. Like the ester-linked and quaternary-linked dual-action cephalosporins reported earlier, these carbamate-linked compounds exhibited a broad antibac...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00113a026

    authors： Albrecht HA,Beskid G,Christenson JG,Georgopapadakou NH,Keith DD,Konzelmann FM,Pruess DL,Rossman PL,Wei CC

    更新日期：1991-09-01 00:00:00

  • Design and synthesis of 4-azaindoles as inhibitors of p38 MAP kinase.

    abstract：:Inhibition of the biosynthesis of proinflammatory cytokines such as tumor necrosis factor and interleukin-1 via p38 has been an approach toward the development of a disease modifying agent for the treatment of chronic inflammation and autoimmune diseases. The development of a new core structure of p38 inhibitors, 3-(4...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm0301787

    authors： Trejo A,Arzeno H,Browner M,Chanda S,Cheng S,Comer DD,Dalrymple SA,Dunten P,Lafargue J,Lovejoy B,Freire-Moar J,Lim J,Mcintosh J,Miller J,Papp E,Reuter D,Roberts R,Sanpablo F,Saunders J,Song K,Villasenor A,Warren

    更新日期：2003-10-23 00:00:00

  • Cyclopentadienyl-ruthenium(II) and iron(II) organometallic compounds with carbohydrate derivative ligands as good colorectal anticancer agents.

    abstract：:New ruthenium(II) and iron(II) organometallic compounds of general formula [(η(5)-C5H5)M(PP)Lc][PF6], bearing carbohydrate derivative ligands (Lc), were prepared and fully characterized and the crystal structures of five of those compounds were determined by X-ray diffraction studies. Cell viability of colon cancer HC...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.5b00403

    authors： Florindo PR,Pereira DM,Borralho PM,Rodrigues CM,Piedade MF,Fernandes AC

    更新日期：2015-05-28 00:00:00

  • Synthesis and biological evaluation of analogues of Pro-Leu-Gly-NH2 modified at the leucyl residue.

    abstract：:A series of analogues of Pro-Leu-Gly-NH2 (PLG) in which the leucine residue has been replaced with the aliphatic amino acids L-isoleucine, L-2-aminohexanoic acid (Ahx), L-2-aminopentanoic acid, and L-2-aminobutanoic acid and the aromatic amino acids L-phenylalanine, L-phenylglycine, L- and D-2-amino-4-phenylbutanoic a...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00168a045

    authors： Johnson RL,Bontems RJ,Yang KE,Mishra RK

    更新日期：1990-06-01 00:00:00

  • Generation of ligand-based pharmacophore model and virtual screening for identification of novel tubulin inhibitors with potent anticancer activity.

    abstract：:A pharmacophore model, Hypo1, was built on the basis of 21 training-set indole compounds with varying levels of antiproliferative activity. Hypo1 possessed important chemical features required for the inhibitors and demonstrated good predictive ability for biological activity, with high correlation coefficients of 0.9...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm801649y

    authors： Chiang YK,Kuo CC,Wu YS,Chen CT,Coumar MS,Wu JS,Hsieh HP,Chang CY,Jseng HY,Wu MH,Leou JS,Song JS,Chang JY,Lyu PC,Chao YS,Wu SY

    更新日期：2009-07-23 00:00:00

  • Synthesis of spiro[isobenzofuran-1(3H),4'-piperidines] as potential central nervous system agents. 6. Synthesis, 13C NMR, and biological evaluation of cis- and trans-4-amino-3'-arylspiro[cyclohexane-1,1'(3'H)-isobenzofuran] derivatives.

    abstract：:4-(Dimethylamino)- and 4-(methylamino)-3'-arylspiro[cyclohexane-1,1'(3'H)-isobenzofuran] derivatives were prepared as analogues of previously reported 3-arylspiro[isobenzofuran-1(3H),4'-piperidines]. Metalation of benzanilide with n-butyllithium, addition of 4-(dimethylamino)cyclohexanone, and acidification afforded a...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00137a025

    authors： Martin LL,Worm M,Agnew MN,Kruse H,Wilker JC,Geyer HM 3rd

    更新日期：1981-05-01 00:00:00

  • Heterocyclic Quinones. 4. A new highly cytotoxic drug: 6,7-bis(1-aziridinyl)-5,8-quinazolinedione.

    abstract：:With the aim of obtaining new antitumoral agents, a series of 5,8-quinazolinediones was prepared. 5-Amino-6-methoxyquinazoline was oxidized by Fremy's salt to give 6-methoxy-5,8-quinazolinedione. Nucleophilic substitution reaction at C6, electrophilic substitution at C7, and synthesis of 7-amino-6-methoxy-5,8-quinazol...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00366a011

    authors： Renault J,Giorgi-Renault S,Baron M,Mailliet P,Paoletti C,Cros S,Voisin E

    更新日期：1983-12-01 00:00:00

  • 2,4-diaminopyrimidine derivatives as potent growth hormone secretagogue receptor antagonists.

    abstract：:Ghrelin, a gut-derived orexigenic hormone, is an endogenous ligand of the growth hormone secretagogue receptor (GHS-R). Centrally administered ghrelin has been shown to cause hunger and increase food intake in rodents. Inhibition of ghrelin actions with ghrelin antibody, peptidyl GHS-R antagonists, and antisense oligo...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm0510934

    authors： Serby MD,Zhao H,Szczepankiewicz BG,Kosogof C,Xin Z,Liu B,Liu M,Nelson LT,Kaszubska W,Falls HD,Schaefer V,Bush EN,Shapiro R,Droz BA,Knourek-Segel VE,Fey TA,Brune ME,Beno DW,Turner TM,Collins CA,Jacobson PB,Sham H

    更新日期：2006-04-20 00:00:00

  • Optimization of benzodiazepinones as selective inhibitors of the X-linked inhibitor of apoptosis protein (XIAP) second baculovirus IAP repeat (BIR2) domain.

    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

    pub_type： 杂志文章

    doi：10.1021/jm400732v

    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

  • Total synthesis and biological properties of novel antineoplastic (chloromethyl)furanoindolines: an asymmetric hydroboration mediated synthesis of the alkylation subunits.

    abstract：:1,2-Dihydro-1-(chloromethyl)-5-hydroxy-8-methyl-3H-furano[3,2-e]in dole (CFI) as a novel replacement of the cyclopropylpyrroloindoline (CPI) alkylation subunit of CC-1065, U-71184, and U-73975 (adozelesin) has been synthesized and incorporated into a series of efficacious antineoplastic agents. A partial solution to a...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00028a005

    authors： Mohamadi F,Spees MM,Staten GS,Marder P,Kipka JK,Johnson DA,Boger DL,Zarrinmayeh H

    更新日期：1994-01-21 00:00:00

  • A thymidine phosphorylase-stable analogue of BVDU with significant antiviral activity.

    abstract：:(E)-5-(2-Bromovinyl)isodideoxyuridine (BVisoDDU), synthesized on the basis of molecular modeling, is selectively active against HSV-1 (three different strains) but inactive against HSV-2. Unlike BVDU, BVisoDDU is completely resistant to cleavage by thymidine phosphorylase. BVisoDDU is also the first nucleoside analogu...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm025569k

    authors： Guenther S,Balzarini J,De Clercq E,Nair V

    更新日期：2002-12-05 00:00:00

  • Comparative structure-activity relationships of antifolate triazines inhibiting murine tumor cells sensitive and resistant to methotrexate.

    abstract：:The inhibitory effect of 108 4,6-diamino-1,2-dihydro-2,2-dimethyl-1-(substituted-phenyl)-s-triazines on murine L5178Y tumor cells, resistant and sensitive to methotrexate (MTX), has been studied. From the pI50 values, quantitative structure-activity relationships have been formulated which show that the lipophilic tri...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00369a019

    authors： Selassie CD,Hansch C,Khwaja TA,Dias CB,Pentecost S

    更新日期：1984-03-01 00:00:00

  • Tetracyclic pyridazines as potential psychopharmacological agents.

    abstract：:Since the Z isomer of chlorprothixene (1) is far more active than its E counterpart, it was of interest to develop a stereoselective synthesis for this class of compounds. Insertion of a benzenesulfonamido group at the peri position of a chlorprothixene precursor did affect the stereochemistry of side-chain olefin for...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00145a005

    authors： Ross BS,Wiley RA

    更新日期：1985-07-01 00:00:00

  • Single point D-substituted corticotropin-releasing factor analogues: effects on potency and physicochemical characteristics.

    abstract：:In an attempt to determine which conformational parameters are important for the biological activity of ovine corticotropin-releasing factor (oCRF), we have synthesized in significant amounts (50-200 mg) and characterized chemically, structurally (CD), and biologically, oCRF analogues with substitution of each amino a...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00072a003

    authors： Rivier J,Rivier C,Galyean R,Miranda A,Miller C,Craig AG,Yamamoto G,Brown M,Vale W

    更新日期：1993-10-01 00:00:00

  • Discovery of 1-(3'-aminobenzisoxazol-5'-yl)-3-trifluoromethyl-N-[2-fluoro-4- [(2'-dimethylaminomethyl)imidazol-1-yl]phenyl]-1H-pyrazole-5-carboxyamide hydrochloride (razaxaban), a highly potent, selective, and orally bioavailable factor Xa inhibitor.

    abstract：:Modification of a series of pyrazole factor Xa inhibitors to incorporate an aminobenzisoxazole as the P(1) ligand resulted in compounds with improved selectivity for factor Xa relative to trypsin and plasma kallikrein. Further optimization of the P(4) moiety led to compounds with enhanced permeability and reduced prot...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm0497949

    authors： Quan ML,Lam PY,Han Q,Pinto DJ,He MY,Li R,Ellis CD,Clark CG,Teleha CA,Sun JH,Alexander RS,Bai S,Luettgen JM,Knabb RM,Wong PC,Wexler RR

    更新日期：2005-03-24 00:00:00

  • Improved delivery through biological membranes. 1. Synthesis and properties of 1-methyl-1,6-dihydropyridine-2-carbaldoxime, a pro-drug of N-methylpyridinium-2-carbaldoxime chloride.

    abstract：:A dihydropyridine-pyridine type redox pro-drug system was developed for delivering quaternary pyridinium salts through biological membranes. As a first application, the dihydropyridine derivative of N-methylpyridinium-2-carbaldoxime chloride (2-PAM) was synthesized using a reduction-addition-elimination sequence. The ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00223a017

    authors： Bodor N,Shek E,Higuchi T

    更新日期：1976-01-01 00:00:00

  • Discovery of Novel 15-Lipoxygenase Activators To Shift the Human Arachidonic Acid Metabolic Network toward Inflammation Resolution.

    abstract：:For disease network intervention, up-regulating enzyme activities is equally as important as down-regulating activities. However, the design of enzyme activators presents a challenging route for drug discovery. Previous studies have suggested that activating 15-lipoxygenase (15-LOX) is a promising strategy to interven...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.5b01011

    authors： Meng H,McClendon CL,Dai Z,Li K,Zhang X,He S,Shang E,Liu Y,Lai L

    更新日期：2016-05-12 00:00:00

  • Discovery of Potent and Selective PI3Kγ Inhibitors.

    abstract：:The selective inhibition of the lipid signaling enzyme PI3Kγ constitutes an opportunity to mediate immunosuppression and inflammation within the tumor microenvironment but is difficult to achieve due to the high sequence homology across the class I PI3K isoforms. Here, we describe the design of a novel series of poten...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.0c01203

    authors： Drew SL,Thomas-Tran R,Beatty JW,Fournier J,Lawson KV,Miles DH,Mata G,Sharif EU,Yan X,Mailyan AK,Ginn E,Chen J,Wong K,Soni D,Dhanota P,Chen PY,Shaqfeh SG,Meleza C,Pham AT,Chen A,Zhao X,Banuelos J,Jin L,Schind

    更新日期：2020-10-08 00:00:00

  • 6-Benzoxazinylpyridazin-3-ones: potent, long-acting positive inotrope and peripheral vasodilator agents.

    abstract：:A series of 6-benzoxazinylpyridazin-3-ones was prepared and evaluated for inhibition of cardiac phosphodiesterase (PDE) fraction III in vitro and for positive inotropic activity in vivo. 6-[3,4-Dihydro-3-oxo-1,4(2H)-benzoxazin-7-yl]-2,3,4,5-tetrahydro-5 - methylpyridazin-3-one (bemoradan) was found to be an extremely ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00163a061

    authors： Combs DW,Rampulla MS,Bell SC,Klaubert DH,Tobia AJ,Falotico R,Haertlein B,Lakas-Weiss C,Moore JB

    更新日期：1990-01-01 00:00:00