Novel azalides derived from 16-membered macrolides. Part II: Isolation of the linear 9-formylcarboxylic acid and its sequential macrocyclization with an amino alcohol or an azidoamine.

Abstract:

:The design and synthesis of novel 14- to 16-membered 11-azalides starting from 16-membered macrolides are reported. A linear 9-formylcarboxylic acid was isolated via a mobile dialdehyde previously reported. Sequential macrocyclization of the formylcarboxylic acid with amino alcohol followed by deprotection afforded corresponding 14- to 16-membered azalides. On the other hand, reductive amination of the formylcarboxylic acid with an azidoamine followed by macrolactam formation with an amine generated from the azide gave 14- to 16-membered azalactams. Among these derivatives, 15-membered azalactams and 16-membered azalides exhibited characteristic in vitro antibacterial activities. Although optimization of 15-membered azalactams including demycarosyl analogues did not provide remarkably promising molecules, SAR studies of 16-membered azalides disclosed that substitution at the 15 position was very important for identification of a clinical candidate.

journal_name

Bioorg Med Chem

authors

Miura T,Kanemoto K,Natsume S,Atsumi K,Fushimi H,Yoshida T,Ajito K

doi

10.1016/j.bmc.2008.09.054

subject

Has Abstract

pub_date

2008-12-01 00:00:00

pages

10129-56

issue

23

eissn

0968-0896

issn

1464-3391

pii

S0968-0896(08)00905-X

journal_volume

16

pub_type

杂志文章
  • Synthesis of dihydronaphthofurandiones and dihydrofuroquinolinediones with trypanocidal activity and analysis of their stereoelectronic properties.

    abstract::The synthesis of dihydronaphthofurandione and dihydrofuroquinolinedione derivatives 4-11 was performed through Diels-Alder reactions of dihydrobenzofurandione 1 with several carbodienes and acrolein N,N-dimethylhydrazone. Then, the use of 5-bromobenzofurandione 2 toward 1,3-pentadiene and the 1-azadiene afforded quino...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2004.01.046

    authors: Tapia RA,Salas C,Morello A,Maya JD,Toro-Labbé A

    更新日期:2004-05-01 00:00:00

  • Fluoroalkene modification of mercaptoacetamide-based histone deacetylase inhibitors.

    abstract::Inhibitors of histone deacetylases (HDAC) are emerging as a promising class of anti-cancer agents. The mercaptoacetoamide-based inhibitors are reported to be less toxic than hydroxamate and are worthy of further consideration. Therefore, we have designed a series of analogs as potential inhibitors of HDACs, in which t...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2009.12.005

    authors: Osada S,Sano S,Ueyama M,Chuman Y,Kodama H,Sakaguchi K

    更新日期:2010-01-15 00:00:00

  • Analysis of the binding specificities of oligomannoside-binding proteins using methylated monosaccharides.

    abstract::The binding specificities of the closely related lectins from Canavalia ensiformis and Dioclea grandiflora were examined using specifically O-alkylated mono- and disaccharides. Both lectins accept any substitution at the monosaccharide C2 hydroxyl group. The binding energy of C2-alkylated ligands-concanavalin A comple...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/s0968-0896(96)00178-2

    authors: Chervenak MC,Toone EJ

    更新日期:1996-11-01 00:00:00

  • Synthesis of indomethacin analogues for evaluation as modulators of MRP activity.

    abstract::Synthesis of a range of indomethacin analogues, required for investigation in combination toxicity assays, bearing both N-benzyl and N-benzoyl groups, is described. ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/s0968-0896(00)00292-3

    authors: Maguire AR,Plunkett SJ,Papot S,Clynes M,O'Connor R,Touhey S

    更新日期:2001-03-01 00:00:00

  • Inhibition of thioredoxin reductase by a novel series of bis-1,2-benzisoselenazol-3(2H)-ones: Organoselenium compounds for cancer therapy.

    abstract::Thioredoxin reductase (TrxR) is critical for cellular redox regulation and is involved in tumor proliferation, apoptosis and metastasis. Its C-terminal redox-active center contains a cysteine (Cys497) and a unique selenocysteine (Sec498), which are exposed to solvent and easily accessible. Thus, it is becoming an impo...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2012.04.033

    authors: He J,Li D,Xiong K,Ge Y,Jin H,Zhang G,Hong M,Tian Y,Yin J,Zeng H

    更新日期:2012-06-15 00:00:00

  • Recreating ancient metabolic pathways before enzymes.

    abstract::The biochemistry of all living organisms uses complex, enzyme-catalyzed metabolic reaction networks. Yet, at life's origins, enzymes had not yet evolved. Therefore, it has been postulated that non-enzymatic metabolic pathways predated their enzymatic counterparts. In this account article, we describe our recent work t...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章,评审

    doi:10.1016/j.bmc.2019.03.012

    authors: Muchowska KB,Chevallot-Beroux E,Moran J

    更新日期:2019-06-15 00:00:00

  • Synthesis and antiviral evaluation of 9-(S)-[3-alkoxy-2-(phosphonomethoxy)propyl]nucleoside alkoxyalkyl esters: inhibitors of hepatitis C virus and HIV-1 replication.

    abstract::We reported previously that octadecyloxyethyl 9-(S)-[3-hydroxy-2-(phosphonomethoxy)-propyl]adenine (ODE-(S)-HPMPA) was active against genotype 1b and 2a hepatitis C virus (HCV) replicons. This is surprising because acyclic nucleoside phosphonates have been regarded as having antiviral activity only against double stra...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2011.06.009

    authors: Valiaeva N,Wyles DL,Schooley RT,Hwu JB,Beadle JR,Prichard MN,Hostetler KY

    更新日期:2011-08-01 00:00:00

  • Isolation of antiplasmodial anthraquinones from Kniphofia ensifolia, and synthesis and structure-activity relationships of related compounds.

    abstract::Bioassay-guided separation of the South African plant Kniphofia ensifolia for antiplasmodial activity led to the isolation of two new anthraquinones, named kniphofiones A and B (3 and 4), together with three known bioactive anthraquinone monomers (1, 2 and 5), and four known bisanthraquinones (6-9). The structures of ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2013.11.032

    authors: Dai Y,Harinantenaina L,Bowman JD,Da Fonseca IO,Brodie PJ,Goetz M,Cassera MB,Kingston DG

    更新日期:2014-01-01 00:00:00

  • Synthesis and evaluation of verticipyrone analogues as mitochondrial complex I inhibitors.

    abstract::Verticipyrone has recently been isolated from the culture broth of Verticillium sp. and shown to inhibit NADH fumarate reductase, as well as NADH oxidoreductase (complex I) of the mitochondrial electron transport chain. In order to assess the structural elements in verticipyrone essential for complex I inhibitor, 15 s...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2010.03.070

    authors: Leiris SJ,Khdour OM,Segerman ZJ,Tsosie KS,Chapuis JC,Hecht SM

    更新日期:2010-05-15 00:00:00

  • Synthesis and biological properties of 2-methylene-19-nor-25-dehydro-1alpha-hydroxyvitamin D(3)-26,23-lactones--weak agonists.

    abstract::In a continuing effort to explore the 2-methylene-1alpha-hydroxy-19-norvitamin D(3) class of pharmacologically important vitamin D compounds, two novel 2-methylene-19-nor-25-dehydro-1alpha-hydroxyvitamin D(3)-26,23-lactones, GC-3 and HLV, were synthesized and biologically tested. Based on reports of similarly structur...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2008.08.011

    authors: Chiellini G,Grzywacz P,Plum LA,Barycki R,Clagett-Dame M,DeLuca HF

    更新日期:2008-09-15 00:00:00

  • Novel 4-acetamide-2-alkylthio-N-acetanilides resembling nimesulide: Synthesis, cell viability evaluation and in silico studies.

    abstract::Since nimesulide, a nonsteroidal anti-inflammatory drug, is known to be a selective inhibitor of cyclooxygenase-2 and shows activity against cancer cells, there has been much interest in developing related molecules with enhanced anticancer properties. Taking in consideration structural features of nimesulide analogue...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2017.06.009

    authors: Catarro M,Serrano J,Cavalheiro E,Ramos S,Santos AO,Silvestre S,Almeida P

    更新日期:2017-08-15 00:00:00

  • Characterization and in vitro activity of a branched peptide boronic acid that interacts with HIV-1 RRE RNA.

    abstract::A branched peptide containing multiple boronic acids was found to bind RRE IIB selectively and inhibit HIV-1 p24 capsid production in a dose-dependent manner. Structure-activity relationship studies revealed that branching in the peptide is crucial for the low micromolar binding towards RRE IIB, and the peptide demons...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2016.04.009

    authors: Wynn JE,Zhang W,Tebit DM,Gray LR,Hammarskjold ML,Rekosh D,Santos WL

    更新日期:2016-09-01 00:00:00

  • Synthesis, biological evaluation and molecular docking studies of 1,3,4-oxadiazole derivatives as potential immunosuppressive agents.

    abstract::A series of 1,3,4-oxadiazole derivatives derived from 4-methoxysalicylic acid or 4-methylsalicylic acid (6a-6z) have been first synthesized for their potential immunosuppressive activity. Among them, compound 6z displayed the most potent biological activity against lymph node cells (inhibition=38.76% for lymph node ce...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2012.03.064

    authors: Zhang ZM,Zhang XW,Zhao ZZ,Yan R,Xu R,Gong HB,Zhu HL

    更新日期:2012-05-15 00:00:00

  • Design, synthesis and QSAR studies on N-aryl heteroarylisopropanolamines, a new class of non-peptidic HIV-1 protease inhibitors.

    abstract::A series of N-aryl heteroarylisopropanolamines in which an indole or a 3-arylpyrrole moiety was linked to an aryl group through an isopropanolamine linker, were designed and synthesized as potential anti-HIV-1-PR agents. Series was tested for their ability in blocking PR activity. As a rule, indole derivatives of clas...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/s0968-0896(02)00119-0

    authors: Di Santo R,Costi R,Artico M,Massa S,Ragno R,Marshall GR,La Colla P

    更新日期:2002-08-01 00:00:00

  • Novel tricyclic indeno[2,1-d]pyrimidines with dual antiangiogenic and cytotoxic activities as potent antitumor agents.

    abstract::We designed, synthesized and evaluated 13 novel tricyclic indeno[2,1-d]pyrimidines as RTK inhibitors. These analogues were synthesized via a Dieckmann condensation of 1,2-phenylenediacetonitrile followed by cyclocondensation with guanidine carbonate to afford the 2-amino-3,9-dihydro-indeno[2,1-d]pyrimidin-4-one. Sulfo...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2012.05.068

    authors: Gangjee A,Zhao Y,Ihnat MA,Thorpe JE,Bailey-Downs LC,Kisliuk RL

    更新日期:2012-07-15 00:00:00

  • Amide conjugates of ketoprofen and indole as inhibitors of Gli1-mediated transcription in the Hedgehog pathway.

    abstract::We have previously reported small-molecule inhibitors of Gli1-mediated transcription, an essential down-stream element of the Hh pathway. We created new derivatives of the previous compounds aiming to improve the druggable properties. The new compounds, amide conjugates of ketoprofen and indole, showed inhibitory acti...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2010.05.001

    authors: Mahindroo N,Connelly MC,Punchihewa C,Yang L,Yan B,Fujii N

    更新日期:2010-07-01 00:00:00

  • New cannabinoid receptor antagonists as pharmacological tool.

    abstract::Synthesis and pharmacological evaluation of a new series of cannabinoid receptor antagonists of indazole ether derivatives have been performed. Pharmacological evaluation includes radioligand binding assays with [3H]-CP55940 for CB1 and CB2 receptors and functional activity for cannabinoid receptors on isolated tissue...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2020.115672

    authors: González-Naranjo P,Pérez C,Girón R,Sánchez-Robles EM,Martín-Fontelles MI,Carrillo-López N,Martín-Vírgala J,Naves M,Campillo NE,Páez JA

    更新日期:2020-10-01 00:00:00

  • Chemical and microbial semi-synthesis of tetrahydroprotoberberines as inhibitors on tissue factor procoagulant activity.

    abstract::To discover new inhibitors on tissue factor procoagulant activity, 21 tetrahydroprotoberberines were screened on the model of human THP-1 cells stimulated by lipopolysaccharide. Among these tetrahydroprotoberberines, several unique compounds were synthesized through microbial transformation: compound 6 (l-corydalmine)...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2012.11.002

    authors: Ge HX,Zhang J,Chen L,Kou JP,Yu BY

    更新日期:2013-01-01 00:00:00

  • Discovery of platelet-type 12-human lipoxygenase selective inhibitors by high-throughput screening of structurally diverse libraries.

    abstract::Human lipoxygenases (hLO) have been implicated in a variety of diseases and cancers and each hLO isozyme appears to have distinct roles in cellular biology. This fact emphasizes the need for discovering selective hLO inhibitors for both understanding the role of specific lipoxygenases in the cell and developing pharma...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2007.08.015

    authors: Deschamps JD,Gautschi JT,Whitman S,Johnson TA,Gassner NC,Crews P,Holman TR

    更新日期:2007-11-15 00:00:00

  • Novel p-carborane-containing multitarget anticancer agents inspired by the metabolism of 17β-estradiol.

    abstract::The female hormone 17 β-estradiol (E2) is synthesized from estrone by steroid sulfatase (STS), and metabolized into 2-methoxyestradiol (2-ME), whereby the biological activity of the latter is substantially different from that of E2. Based on the metabolic pathways of E2, a carborane-containing 2-ME mimic (1c) and its ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2017.10.006

    authors: Kaise A,Ohta K,Endo Y

    更新日期:2017-12-15 00:00:00

  • Inhibitory activity of Brazilian green propolis components and their derivatives on the release of cys-leukotrienes.

    abstract::The effects of Brazilian green propolis ethanol extract on Cry j1-induced cys-leukotrienes and histamine release from peripheral leukocytes of patients with allergic rhinitis were investigated. One of the key mechanisms for the anti-allergic properties of the extract was revealed to be the suppression of cys-LTs relea...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2009.11.007

    authors: Tani H,Hasumi K,Tatefuji T,Hashimoto K,Koshino H,Takahashi S

    更新日期:2010-01-01 00:00:00

  • Drug design and synthesis of epsilon opioid receptor agonist: 17-(cyclopropylmethyl)-4,5alpha-epoxy-3,6beta-dihydroxy-6,14-endoethenomorphinan-7alpha-(N-methyl-N-phenethyl)carboxamide (TAN-821) inducing antinociception mediated by putative epsilon opioid

    abstract::Here we report the new drug design and synthesis of a series of 6,14-endoethenomorphinan-7-carboxamide derivatives as a putative epsilon opioid receptor agonist. One of these compounds, 17-(cyclopropylmethyl)-4,5alpha-epoxy-3,6beta-dihydroxy-6,14-endoethenomorphinan-7alpha-(N-methyl-N-phenethyl)carboxamide (TAN-821), ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2004.05.024

    authors: Fujii H,Narita M,Mizoguchi H,Murachi M,Tanaka T,Kawai K,Tseng LF,Nagase H

    更新日期:2004-08-01 00:00:00

  • N-substituted homopiperazine barbiturates as gelatinase inhibitors.

    abstract::Matrix metalloproteinases are implicated in a wide range of pathophysiological processes and potent selective inhibitors for these enzymes continue to be eagerly sought. 5,5-Disubstituted barbiturates hold promise as inhibitor types being stable in vivo and relatively selective for the gelatinases (MMP-2 and MMP-9). I...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2011.06.055

    authors: Wang J,Medina C,Radomski MW,Gilmer JF

    更新日期:2011-08-15 00:00:00

  • Design and synthesis of a cephalosporin-retinoic acid prodrug activated by a monoclonal antibody-beta-lactamase conjugate.

    abstract::Two novel series of all-trans-beta-retinoic acid derivatives were synthesized and found to possess anticancer activity. The first series, cephalosporin 3'-retinoic esters 6 and 7 were, respectively, obtained by the condensation of all-trans-beta-retinoic acid (2) with cephalosporins 4 and 5. The second series, 7-(reti...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/s0968-0896(01)00127-4

    authors: Hakimelahi GH,Ly TW,Yu SF,Zakerinia M,Khalafi-Nezhad A,Soltani MN,Gorgani MN,Chadegani AR,Moosavi-Movahedi AA

    更新日期:2001-08-01 00:00:00

  • Synthesis and biochemical activity of novel amidine derivatives as m1 muscarinic receptor agonists.

    abstract::As part of a continuing effort aimed at the development of selective, efficacious, and centrally active m1 muscarinic agonists for the treatment of Alzheimer's disease, a series of amide and hydrazide amidine derivatives (2a-e and 3b-d) was synthesized and examined for muscarinic agonist activity. Preliminary biochemi...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/0968-0896(96)00152-6

    authors: Ojo B,Dunbar PG,Durant GJ,Nagy PI,Huzl JJ 3rd,Periyasamy S,Ngur DO,el-Assadi AA,Hoss WP,Messer WS Jr

    更新日期:1996-10-01 00:00:00

  • Molecular determinants of recognition and activation at the cerebellar benzodiazepine receptor site.

    abstract::Semiempirical quantum mechanical and molecular mechanics calculations were carried out to identify and characterize the steric and electronic properties that modulate ligand recognition and activation of the cerebellar GABAA/benzodiazepine (BDZ) receptor. For this hypothesis development, thirteen compounds belonging t...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/s0968-0896(00)82053-2

    authors: Schove LT,Perez JJ,Loew GH

    更新日期:1994-10-01 00:00:00

  • 3D-chiral quadratic indices of the 'molecular pseudograph's atom adjacency matrix' and their application to central chirality codification: classification of ACE inhibitors and prediction of sigma-receptor antagonist activities.

    abstract::Quadratic indices of the 'molecular pseudograph's atom adjacency matrix' have been generalized to codify chemical structure information for chiral drugs. These 3D-chiral quadratic indices make use of a trigonometric 3D-chirality correction factor. These indices are nonsymmetric and reduced to classical (2D) descriptor...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2004.07.051

    authors: Ponce YM,Diaz HG,Zaldivar VR,Torrens F,Castro EA

    更新日期:2004-10-15 00:00:00

  • Novel benzimidazol-2-ylidene carbene precursors and their silver(I) complexes: Potential antimicrobial agents.

    abstract::Novel benzimidazolium salts were synthesized as N-heterocyclic carbene (NHC) precursors, these NHC precursors were metallated with Ag2O in dichloromethane at room temperature to give novel silver(I)-NHC complexes. Structures of these benzimidazolium salts and silver(I)-NHC complexes were characterized on the basis of ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2016.06.004

    authors: Kaloğlu M,Kaloğlu N,Özdemir İ,Günal S,Özdemir İ

    更新日期:2016-08-15 00:00:00

  • Solid phase synthesis and antiprotozoal evaluation of di- and trisubstituted 5'-carboxamidoadenosine analogues.

    abstract::The rapid increase of resistance to drugs commonly used in the treatment of tropical diseases such as malaria and African sleeping sickness calls for the prompt development of new safe and efficacious drugs. The pathogenic protozoan parasites lack the capability of synthesising purines de novo and they take up preform...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2005.10.011

    authors: Rodenko B,Detz RJ,Pinas VA,Lambertucci C,Brun R,Wanner MJ,Koomen GJ

    更新日期:2006-03-01 00:00:00

  • Bicyclic[4.1.0]heptanes as phenyl replacements for melanin concentrating hormone receptor antagonists.

    abstract::Melanin concentrating hormone (MCH) receptor antagonists have been proposed as potential treatments of obesity. MCH receptor antagonists with a biphenylamine subunit have been reported previously at Schering-Plough. Herein, we report the discovery of bicyclo[4.1.0]heptanes as replacements for the middle phenyl ring of...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2005.12.046

    authors: Xu R,Li S,Paruchova J,McBriar MD,Guzik H,Palani A,Clader JW,Cox K,Greenlee WJ,Hawes BE,Kowalski TJ,O'Neill K,Spar BD,Weig B,Weston DJ

    更新日期:2006-05-15 00:00:00