当前位置： SCI文献检索 > JOURNAL OF MEDICINAL CHEMISTRY期刊下所有文献 > Novel heterocyclic analogues of the new potent class of calcium entry blockers: 1-[[4-(aminoalkoxy)phenyl]sulfonyl]indolizines.

Novel heterocyclic analogues of the new potent class of calcium entry blockers: 1-[[4-(aminoalkoxy)phenyl]sulfonyl]indolizines.

Abstract：

:Several heterocyclic analogues of the potent 1-[[4-(aminoalkoxy)phenyl]sulfonyl]indolizines were synthesized and evaluated for their antagonistic calcium activities in comparison with the 1-sulfonylindolizine SR 33557 and the usual calcium antagonist references verapamil, cis-(+)-diltiazem, and nifedipine. The bicyclic nine-membered rings were, in general, more potent than the bicyclic 10-membered or five-membered rings. Among the bicyclic nine-membered rings, the indole nucleus appeared to be extremely favorable to support the calcium antagonistic activity. In particular, compound 36, with an IC50 value for the inhibition of [3H]nitrendipine equal to 0.072 nM, is among the most potent calcium antagonist known. This compound has been selected for clinical development.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Gubin J,de Vogelaer H,Inion H,Houben C,Lucchetti J,Mahaux J,Rosseels G,Peiren M,Clinet M,Polster P

doi

10.1021/jm00062a015

subject

Has Abstract,Author List Incomplete

pub_date

1993-05-14 00:00:00

pages

1425-33

issue

10

eissn

0022-2623

issn

1520-4804

journal_volume

36

pub_type

杂志文章

相关文献

JOURNAL OF MEDICINAL CHEMISTRY文献大全
  • Amide, urea, and carbamate analogues of the muscarinic agent [4-[[N-(3-chlorophenyl)carbamoyl]oxy]-2-butynyl]trimethylammonium chloride.

    abstract：:A series of amide, urea, and carbamate analogues of the muscarinic (M1) ganglionic stimulant [4-[[N-(3-chlorophenyl)carbamoyl]oxy]-2-butynyl]trimethylammonium chloride (McN-A-343; 1) was prepared. The C1-methyl-substituted carbamates 8-11 were resolved into the enantiomers. In order to investigate the ganglionic stimu...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00093a011

    authors： Nilsson BM,Vargas HM,Hacksell U

    更新日期：1992-07-24 00:00:00

  • Novel tacrine-8-hydroxyquinoline hybrids as multifunctional agents for the treatment of Alzheimer's disease, with neuroprotective, cholinergic, antioxidant, and copper-complexing properties.

    abstract：:Tacrine and PBT2 (an 8-hydroxyquinoline derivative) are well-known drugs that inhibit cholinesterases and decrease beta-amyloid (Abeta) levels by complexation of redox-active metals, respectively. In this work, novel tacrine-8-hydroxyquinoline hybrids have been designed, synthesized, and evaluated as potential multifu...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm100329q

    authors： Fernández-Bachiller MI,Pérez C,González-Muñoz GC,Conde S,López MG,Villarroya M,García AG,Rodríguez-Franco MI

    更新日期：2010-07-08 00:00:00

  • Computational prediction of oral drug absorption based on absorption rate constants in humans.

    abstract：:Models for predicting oral drug absorption kinetics were developed by correlating absorption rate constants in humans (K(a)) with computational molecular descriptors. The K(a) values of a set of 22 passively absorbed drugs were derived from human plasma time-concentration profiles using a deconvolution approach. The K...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm051231p

    authors： Linnankoski J,Mäkelä JM,Ranta VP,Urtti A,Yliperttula M

    更新日期：2006-06-15 00:00:00

  • A click chemistry approach to pleuromutilin derivatives, part 2: conjugates with acyclic nucleosides and their ribosomal binding and antibacterial activity.

    abstract：:Pleuromutilin is an antibiotic that binds to bacterial ribosomes and thereby inhibit protein synthesis. A new series of semisynthetic pleuromutilin derivatives were synthesized by a click chemistry strategy. Pleuromutilin was conjugated by different linkers to a nucleobase, nucleoside, or phenyl group, as a side-chain...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm201266b

    authors： Dreier I,Kumar S,Søndergaard H,Rasmussen ML,Hansen LH,List NH,Kongsted J,Vester B,Nielsen P

    更新日期：2012-03-08 00:00:00

  • Potential antitumor agents. 39. Anilino ring geometry of amsacrine and derivatives: relationship to DNA binding and antitumor activity.

    abstract：:The clinical antileukemic drug amsacrine and analogues are thought to exert their biological activity by binding tightly but reversibly to DNA, with the acridine chromophore intercalated and the anilino group making additional binding contact in the minor groove of the double helix. In this binding model the steric en...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00365a014

    authors： Denny WA,Atwell GJ,Baguley BC

    更新日期：1983-11-01 00:00:00

  • Role of the glycopeptide framework in the antibacterial activity of hydrophobic derivatives of glycopeptide antibiotics.

    abstract：:The antibacterial properties of glycopeptide antibiotics are based on their interaction with the d-Ala-d-Ala containing pentapeptide of bacterial peptidoglycan. The hydrophobic amides of vancomycin (1), teicoplanin (2), teicoplanin aglycon (3), and eremomycin (4) were compared with similar amides of minimally or low a...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm020320o

    authors： Printsevskaya SS,Pavlov AY,Olsufyeva EN,Mirchink EP,Preobrazhenskaya MN

    更新日期：2003-03-27 00:00:00

  • Synthesis of some 1, 8- and 2, 8-disubstituted derivatives of adenosine cyclic 3', 5'-phosphate and their interaction with some enzymes of cAMP metabolism.

    abstract：:1, 8-Disubstituted derivatives of adenosine cyclic 3', 5'-phosphate (cAMP) were synthesized by N-oxidation or N-methylation of previously reported 8-substituted cAMP derivatives to yield 8-bromoadenosine cyclic 3', 5'-phosphate 1-oxide and 8-(benzylthio)-1-methyladenosine cyclic 3', 5'-phosphate. Substituents were int...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00225a017

    authors： Uno H,Meyer RB,Shuman DA,Robins RK,Simon LN,Miller JP

    更新日期：1976-03-01 00:00:00

  • Synthesis, cytostatic, antimicrobial, and anti-HCV activity of 6-substituted 7-(het)aryl-7-deazapurine ribonucleosides.

    abstract：:A series of 80 7-(het)aryl- and 7-ethynyl-7-deazapurine ribonucleosides bearing a methoxy, methylsulfanyl, methylamino, dimethylamino, methyl, or oxo group at position 6, or 2,6-disubstituted derivatives bearing a methyl or amino group at position 2, were prepared, and the biological activity of the compounds was stud...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm4018948

    authors： Nauš P,Caletková O,Konečný P,Džubák P,Bogdanová K,Kolář M,Vrbková J,Slavětínská L,Tloušt'ová E,Perlíková P,Hajdúch M,Hocek M

    更新日期：2014-02-13 00:00:00

  • The structural basis of camptothecin interactions with human serum albumin: impact on drug stability.

    abstract：:The intense intrinsic fluorescence emissions from several clinically relevant camptothecin drugs have been exploited in order to study the structural basis of drug binding to human serum albumin. Both HPLC and time-resolved fluorescence spectroscopic methodologies were employed to characterize the associations of camp...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00027a005

    authors： Burke TG,Mi Z

    更新日期：1994-01-07 00:00:00

  • 8-Substituted guanosine and 2'-deoxyguanosine derivatives as potential inducers of the differentiation of Friend erythroleukemia cells.

    abstract：:A variety of 8-substituted guanosine and 2'-deoxyguanosine derivatives were synthesized and tested as inducers of the differentiation of Friend murine erythroleukemia cells in culture. The most active agents in the guanosine series were 8-substituted-N(CH3)2, -NHCH3, -NH2, -OH, and -SO2CH3, which caused 68, 42, 34, 33...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00147a012

    authors： Lin TS,Cheng JC,Ishiguro K,Sartorelli AC

    更新日期：1985-09-01 00:00:00

  • Potent and selective farnesyl transferase inhibitors.

    abstract：:We recently described a novel series of CA(1)A(2)X peptidomimetics as farnesyl transferase inhibitors (FTIs). These compounds possess an N-(4-piperidinyl)benzamide scaffold mimicking A(1)A(2) residue. Extensive exploration of structure--activity relationships revealed that replacement of cysteine by substituted benzyl...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm030502y

    authors： Millet R,Domarkas J,Houssin R,Gilleron P,Goossens JF,Chavatte P,Logé C,Pommery N,Pommery J,Hénichart JP

    更新日期：2004-12-30 00:00:00

  • Potential antitumor agents. 40. Orally active 4,5-disubstituted derivatives of amsacrine.

    abstract：:The DNA-intercalating agent amsacrine is an effective drug for the treatment of human leukemias and lymphomas but has minimal solid tumor activity. As a first step in identifying analogues with a wider spectrum of activity, a comparison was made of the in vivo antileukemic (P-388) activity of amsacrine analogues given...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00369a021

    authors： Denny WA,Atwell GJ,Baguley BC

    更新日期：1984-03-01 00:00:00

  • From serendipity to rational antituberculosis drug discovery of mefloquine-isoxazole carboxylic acid esters.

    abstract：:Both in vitro and in vivo metabolism studies suggested that 5-(2,8-bis(trifluoromethyl)quinolin-4-yloxymethyl)isoxazole-3-carboxylic acid ethyl ester (compound 3) with previously reported antituberculosis activity is rapidly converted to two metabolites 3a and 3b. In order to improve the metabolic stability of this se...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm900340a

    authors： Mao J,Yuan H,Wang Y,Wan B,Pieroni M,Huang Q,van Breemen RB,Kozikowski AP,Franzblau SG

    更新日期：2009-11-26 00:00:00

  • Activity of aromatic substituted phenylpiperazines lacking affinity for dopamine binding sites in a preclinical test of antipsychotic efficacy.

    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

    pub_type： 杂志文章

    doi：10.1021/jm00125a020

    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

  • Design of novel chimeric melanotropin-deltorphin analogues. Discovery of the first potent human melanocortin 1 receptor antagonist.

    abstract：:A number of novel alpha-melanotropin (alpha-MSH) analogues have been designed, synthesized, and assayed for bioactivity at the melanocortin-1 (MC1) receptor from Xenopus frog skin, and selected potent analogues were examined at recombinant human MC1, MC3, and MC4 receptors expressed in human embryonic kidney (HEK) cel...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm020355o

    authors： Han G,Quillan JM,Carlson K,Sadée W,Hruby VJ

    更新日期：2003-02-27 00:00:00

  • Structure-activity studies of 5-[[4-(4,5-dihydro-2-oxazolyl) phenoxy]alkyl]-3-methylisoxazoles: inhibitors of picornavirus uncoating.

    abstract：:A series of substituted phenyl analogues of 5-[[4-(4,5-dihydro-2-oxazolyl) phenoxy]alkyl]-3-methylisoxazoles has been synthesized and evaluated in vitro against several human rhinovirus (HRV) serotypes. Substituents in the 2-position greatly enhanced activity when compared to the unsubstituted compound. Many of these ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00385a021

    authors： Diana GD,Oglesby RC,Akullian V,Carabateas PM,Cutcliffe D,Mallamo JP,Otto MJ,McKinlay MA,Maliski EG,Michalec SJ

    更新日期：1987-02-01 00:00:00

  • Cytotoxic activity of metal complexes of biogenic polyamines: polynuclear platinum(II) chelates.

    abstract：:Several polynuclear Pt(II) chelates with biogenic polyamines were synthesized and screened for their potential antiproliferative and cytotoxic activity in different human cancer cell lines. To gather information regarding the structure-activity relationships underlying their biological activity, the complexes studied ...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm0311238

    authors： Teixeira LJ,Seabra M,Reis E,da Cruz MT,de Lima MC,Pereira E,Miranda MA,Marques MP

    更新日期：2004-05-20 00:00:00

  • Structural insights into the ATP binding pocket of the anaplastic lymphoma kinase by site-directed mutagenesis, inhibitor binding analysis, and homology modeling.

    abstract：:Anaplastic lymphoma kinase (ALK) is a valid target for anticancer therapy; however, potent ALK inhibitors suitable for clinical use are lacking. Because the majority of described kinase inhibitors bind in the ATP pocket of the kinase domain, we have characterized this pocket in ALK using site-directed mutagenesis, inh...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm060380k

    authors： Gunby RH,Ahmed S,Sottocornola R,Gasser M,Redaelli S,Mologni L,Tartari CJ,Belloni V,Gambacorti-Passerini C,Scapozza L

    更新日期：2006-09-21 00:00:00

  • Non-natural macrocyclic inhibitors of histone deacetylases: design, synthesis, and activity.

    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

    pub_type： 杂志文章

    doi：10.1021/jm101092u

    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

  • Pharmacological chaperones as therapeutics for lysosomal storage diseases.

    abstract：:Lysosomal enzymes are responsible for the degradation of a wide variety of glycolipids, oligosaccharides, proteins, and glycoproteins. Inherited mutations in the genes that encode these proteins can lead to reduced stability of newly synthesized lysosomal enzymes. While often catalytically competent, the mutated enzym...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章,评审

    doi：10.1021/jm301557k

    authors： Boyd RE,Lee G,Rybczynski P,Benjamin ER,Khanna R,Wustman BA,Valenzano KJ

    更新日期：2013-04-11 00:00:00

  • Structure-activity relationship (SAR) optimization of 6-(indol-2-yl)pyridine-3-sulfonamides: identification of potent, selective, and orally bioavailable small molecules targeting hepatitis C (HCV) NS4B.

    abstract：:A novel, potent, and orally bioavailable inhibitor of hepatitis C RNA replication targeting NS4B, compound 4t (PTC725), has been identified through chemical optimization of the 6-(indol-2-yl)pyridine-3-sulfonamide 2 to improve DMPK and safety properties. The focus of the SAR investigations has been to identify the opt...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm401621g

    authors： Zhang N,Zhang X,Zhu J,Turpoff A,Chen G,Morrill C,Huang S,Lennox W,Kakarla R,Liu R,Li C,Ren H,Almstead N,Venkatraman S,Njoroge FG,Gu Z,Clausen V,Graci J,Jung SP,Zheng Y,Colacino JM,Lahser F,Sheedy J,Mollin A

    更新日期：2014-03-13 00:00:00

  • C-9 and N-substituted analogs of cis-(3aR)-(-)-2,3,3a,4,5,9b-hexahydro-3- propyl-1H-benz[e]indole-9-carboxamide: 5-HT1A receptor agonists with various degrees of metabolic stability.

    abstract：:Closely related analogs of the 5-HT1A receptor agonist cis-(3aR)-(-)-2,3,3a,4,5,9b-hexahydro-3-propyl-1H-benz[e]indole-9- carboxamide (1, U93385) were synthesized and pharmacologically evaluated. 9-Carboxamide analogs with varied nitrogen substitution (R2) were synthesized, and their serotonergic activity was evaluate...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00004a018

    authors： Haadsma-Svensson SR,Svensson K,Duncan N,Smith MW,Lin CH

    更新日期：1995-02-17 00:00:00

  • (E)-3-(4-Oxo-4H-quinazolin-3-yl)-2-propenoic acids, a new series of antiallergy agents.

    abstract：:A series of substituted (E)-3-(4-oxo-4H-quinazolin-3-yl)-2-propenoic acids was prepared and evaluated in the rat passive cutaneous anaphylaxis (PCA) test for antiallergic activity. Alkoxy, alkylthio, and isopropyl substituents at the 6- or 8-positions provided highly potent compounds. Conversion to the Z isomer, reduc...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00357a018

    authors： LeMahieu RA,Carson M,Nason WC,Parrish DR,Welton AF,Baruth HW,Yaremko B

    更新日期：1983-03-01 00:00:00

  • Synthesis and antiviral activity of certain 4-substituted and 2,4-disubstituted 7-[(2-hydroxyethoxy)methyl]pyrrolo[2,3-d]pyrimidines.

    abstract：:Treatment of the sodium salt of 4-chloro-2-(methylthio)pyrrolo[2,3-d]pyrimidine (2) with (2-acetoxyethoxy)methyl bromide (3) has provided 4-chloro-2-(methylthio)-7[(2-acetoxyethoxy)methyl]pyrrolo[2,3- d]pyrimidine (4). Ammonolysis of 4 at room temperature gave 4-chloro-2-(methylthio)-7-[(2-hydroxyethoxy)methyl]pyrrolo...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00403a005

    authors： Saxena NK,Hagenow BM,Genzlinger G,Turk SR,Drach JC,Townsend LB

    更新日期：1988-08-01 00:00:00

  • Antimalarial activity of yingzhaosu A analogues.

    abstract：:Iodonium ion mediated cyclization of unsaturated hydroperoxides 1 afforded the expected yingzhaosu A analogues 2. In some cases, however, the corresponding cyclic ethers 5 were formed competitively with the cyclic peroxides 2, the ratios of these two products being a marked function of the structure of the starting ma...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm020208q

    authors： Kim HS,Begum K,Ogura N,Wataya Y,Tokuyasu T,Masuyama A,Nojima M,McCullough KJ

    更新日期：2002-10-10 00:00:00

  • Methylation of Daptomycin Leading to the Discovery of Kynomycin, a Cyclic Lipodepsipeptide Active against Resistant Pathogens.

    abstract：:Increased usage of daptomycin to treat infections caused by Gram-positive bacterial pathogens has resulted in emergence of resistant mutants. In a search for more effective daptomycin analogues through medicinal chemistry studies, we found that methylation at the nonproteinogenic amino acid kynurenine in daptomycin co...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.9b01957

    authors： Chow HY,Po KHL,Gao P,Blasco P,Wang X,Li C,Ye L,Jin K,Chen K,Chan EWC,You X,Yi Tsun Kao R,Chen S,Li X

    更新日期：2020-03-26 00:00:00

  • Studies on the ATP Binding Site of Fyn Kinase for the Identification of New Inhibitors and Their Evaluation as Potential Agents against Tauopathies and Tumors.

    abstract：:Fyn is a member of the Src-family of nonreceptor protein-tyrosine kinases. Its abnormal activity has been shown to be related to various human cancers as well as to severe pathologies, such as Alzheimer's and Parkinson's diseases. Herein, a structure-based drug design protocol was employed aimed at identifying novel F...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/acs.jmedchem.5b00140

    authors： Tintori C,La Sala G,Vignaroli G,Botta L,Fallacara AL,Falchi F,Radi M,Zamperini C,Dreassi E,Dello Iacono L,Orioli D,Biamonti G,Garbelli M,Lossani A,Gasparrini F,Tuccinardi T,Laurenzana I,Angelucci A,Maga G,Schenone S

    更新日期：2015-06-11 00:00:00

  • Binding of indolylalkylamines at 5-HT2 serotonin receptors: examination of a hydrophobic binding region.

    abstract：:Taking advantage of a proposed hydrophobic region on 5-HT2 receptors previously identified by radioligand-binding studies utilizing various phenylisopropylamine derivatives, we prepared and evaluated several N1 - and/or C7-alkyl-substituted derivatives of alpha-methyltryptamine in order to improve its affinity and sel...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00172a016

    authors： Glennon RA,Chaurasia C,Titeler M

    更新日期：1990-10-01 00:00:00

  • Dibenztroponeacetic and -propionic acids. Potent new antiinflammatory agents.

    abstract：:The syntheses and antiinflammatory assays of some dibenztroponeacetic and -propionic acids and derivatives are described. The most potent compound, d-2-(5H-dibenzo[a,d]cyclohepten-5-on-2-yl)propionic acid, has a potency of ca, 70 times phenylbutazone in the rat carrageenan paw assay and two to three times indomethacin...

    journal_title：Journal of medicinal chemistry

    pub_type： 杂志文章

    doi：10.1021/jm00222a004

    authors： Dunn JP,Green DM,Nelson PH,Rooks WH 2nd,Tomolonis A,Untch KG

    更新日期：1977-12-01 00:00:00

  • Synthesis and structure-activity relationship studies of novel dihydropyridones as androgen receptor modulators.

    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

    pub_type： 杂志文章

    doi：10.1021/jm301714s

    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