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.


: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.


Bioorg Med Chem


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




Has Abstract


2008-12-01 00:00:00














  • SAR study of bisamides as cyclophilin a inhibitors for the development of host-targeting therapy for hepatitis C virus infection.

    abstract::The therapy of chronic hepatitis C virus infections has significantly improved with the development of direct-acting antivirals (DAAs), which contain NS3/4A protease, NS5A, and NS5B polymerase inhibitors. However, mutations in specific residues in these viral target genes are associated with resistance to the DAAs. Es...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Li X,Han J,Lee HW,Yoon YS,Jin Y,Khadka DB,Yang S,Kim M,Cho WJ

    更新日期:2020-10-01 00:00:00

  • Chemo-enzymatic synthesis of adenine substituted nicotinic acid adenine dinucleotide phosphate (NAADP) analogs.

    abstract::Nicotinamide adenine dinucleotide phosphate (NADP) is an indispensable metabolic co-substrate and nicotinic acid adenine dinucleotide phosphate (NAADP) is an important Ca2+ releasing intracellular second messenger. Exploration of the NADP and NAADP interactome often requires the synthesis of NADP derivatives substitut...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Su P,Bretz JD,Gunaratne GS,Marchant JS,Walseth TF,Slama JT

    更新日期:2021-01-15 00:00:00

  • Irreversibly inhibitory kinetics of 3,5-dihydroxyphenyl decanoate on mushroom (Agaricus bisporus) tyrosinase.

    abstract::3,5-Dihydroxyphenyl decanoate (DPD) is found to inhibit the diphenolase activity of tyrosinase from mushroom (Agaricus bisporus). The effects of DPD on the diphenolase activity of mushroom tyrosinase have been studied. The results show that the enzyme activity decreases very slowly with an increase in DPD concentratio...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Qiu L,Chen QX,Wang Q,Huang H,Song KK

    更新日期:2005-11-15 00:00:00

  • Arylcyanoacrylamides as inhibitors of the Dengue and West Nile virus proteases.

    abstract::The 3-aryl-2-cyanoacrylamide scaffold was designed as core pharmacophore for inhibitors of the Dengue and West Nile virus serine proteases (NS2B-NS3). A total of 86 analogs was prepared to study the structure-activity relationships in detail. Thereby, it turned out that the electron density of the aryl moiety and the ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Nitsche C,Steuer C,Klein CD

    更新日期:2011-12-15 00:00:00

  • Tylosema esculentum extractives and their bioactivity.

    abstract::The investigation of Tylosema esculentum (Morama) husks, cotyledons, and tuber yielded griffonilide 2, compound 1, griffonin 3, gallic acid 4, protocatechuic acid 5, β-sitosterol 6, behenic acid 7, oleic acid 8, sucrose 9, 2-O-ethyl-α-D-glucopyranoside 10, kaempferol 11 and kaempferol-3-O-β-D-glucopyranoside 12. The s...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Mazimba O,Majinda RR,Modibedi C,Masesane IB,Cencič A,Chingwaru W

    更新日期:2011-09-01 00:00:00

  • Dolastatin 11 conformations, analogues and pharmacophore.

    abstract::Twenty analogues of the natural antitumor agent dolastatin 11, including majusculamide C, were synthesized and tested for cytotoxicity against human cancer cells and stimulation of actin polymerization. Only analogues containing the 30-membered ring were active. Molecular modeling and NMR evidence showed the low-energ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Ali MA,Bates RB,Crane ZD,Dicus CW,Gramme MR,Hamel E,Marcischak J,Martinez DS,McClure KJ,Nakkiew P,Pettit GR,Stessman CC,Sufi BA,Yarick GV

    更新日期:2005-07-01 00:00:00

  • Structure-anticonvulsant activity studies in the group of (E)-N-cinnamoyl aminoalkanols derivatives monosubstituted in phenyl ring with 4-Cl, 4-CH3 or 2-CH3.

    abstract::A series of twenty two (E)-N-cinnamoyl aminoalkanols derivatives monosubstituted in phenyl ring with 4-Cl, 4-CH3 or 2-CH3 was designed, synthesized and evaluated for anticonvulsant activity in rodent models of seizures: maximal electroshock (MES) test, subcutaneous pentylenetetrazole (scPTZ) test, and 6-Hz test. There...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Gunia-Krzyżak A,Żelaszczyk D,Rapacz A,Żesławska E,Waszkielewicz AM,Pańczyk K,Słoczyńska K,Pękala E,Nitek W,Filipek B,Marona H

    更新日期:2017-01-15 00:00:00

  • Click synthesis of estradiol-cyclodextrin conjugates as cell compartment selective estrogens.

    abstract::Cyclodextrin (CD) is a well known drug carrier and excipient for enhancing aqueous solubility. CDs themselves are anticipated to have low membrane permeability because of relatively high hydrophilicity and molecular weight. CD derivatization with 17-beta estradiol (E(2)) was explored extensively using a number of diff...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Kim HY,Sohn J,Wijewickrama GT,Edirisinghe P,Gherezghiher T,Hemachandra M,Lu PY,Chandrasena RE,Molloy ME,Tonetti DA,Thatcher GR

    更新日期:2010-01-15 00:00:00

  • Substituted thiophene-anthranilamides as potent inhibitors of human factor Xa.

    abstract::A series of thiophene-containing non-amidine factor Xa inhibitors is described. Simple methyl-substituted thiophene analogs were relatively weak inhibitors. However, introduction of hydrophilic substituents at C-4 or C-5 of the thiophene afforded inhibitors with low nanomolar potency. Optimization of the thiophene sub...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Kochanny MJ,Adler M,Ewing J,Griedel BD,Ho E,Karanjawala R,Lee W,Lentz D,Liang AM,Morrissey MM,Phillips GB,Post J,Sacchi KL,Sakata ST,Subramanyam B,Vergona R,Walters J,White KA,Whitlow M,Ye B,Zhao Z,Shaw KJ

    更新日期:2007-03-01 00:00:00

  • Protein linear indices of the 'macromolecular pseudograph alpha-carbon atom adjacency matrix' in bioinformatics. Part 1: prediction of protein stability effects of a complete set of alanine substitutions in Arc repressor.

    abstract::A novel approach to bio-macromolecular design from a linear algebra point of view is introduced. A protein's total (whole protein) and local (one or more amino acid) linear indices are a new set of bio-macromolecular descriptors of relevance to protein QSAR/QSPR studies. These amino-acid level biochemical descriptors ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Marrero-Ponce Y,Medina-Marrero R,Castillo-Garit JA,Romero-Zaldivar V,Torrens F,Castro EA

    更新日期:2005-04-15 00:00:00

  • The evaluation of quinonoid compounds against Trypanosoma cruzi: synthesis of imidazolic anthraquinones, nor-beta-lapachone derivatives and beta-lapachone-based 1,2,3-triazoles.

    abstract::In continuing our screening program of naphthoquinone activity against Trypanosoma cruzi, the aetiological agent of Chagas' disease, new beta-lapachone-based 1,2,3-triazoles, 3-arylamino-nor-beta-lapachones, 3-alkoxy-nor-beta-lapachones and imidazole anthraquinones were synthesised and evaluated against bloodstream tr...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: da Silva EN Jr,Guimarães TT,Menna-Barreto RF,Pinto Mdo C,de Simone CA,Pessoa C,Cavalcanti BC,Sabino JR,Andrade CK,Goulart MO,de Castro SL,Pinto AV

    更新日期:2010-05-01 00:00:00

  • Tannic acid inhibited norovirus binding to HBGA receptors, a study of 50 Chinese medicinal herbs.

    abstract::Noroviruses (NoVs) are the leading cause of viral acute gastroenteritis affecting people of all ages worldwide. The disease is difficult to control due to its widespread nature and lack of an antiviral or vaccine. NoV infection relies on the interaction of the viruses with histo-blood group antigens (HBGAs) as host re...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Zhang XF,Dai YC,Zhong W,Tan M,Lv ZP,Zhou YC,Jiang X

    更新日期:2012-02-15 00:00:00

  • Click approach to the discovery of 1,2,3-triazolylsalicylamides as potent Aurora kinase inhibitors.

    abstract::A series of 1,2,3-triazolylsalicylamide derivatives has been developed from the antiproliferative agent 7 and was evaluated for their Aurora kinase inhibitory activity. The novel 1,2,3-triazolylsalicylamide scaffold could be readily assembled by Cu(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition, allowing rapid ac...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Song D,Park Y,Yoon J,Aman W,Hah JM,Ryu JS

    更新日期:2014-09-01 00:00:00

  • Investigating the activity of 2-substituted alkyl-6-(2,5-dioxopyrrolidin-1-yl)hexanoates as skin penetration enhancers.

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    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Brychtova K,Opatrilova R,Raich I,Kalinowski DS,Dvorakova L,Placek L,Csollei J,Richardson DR,Jampilek J

    更新日期:2010-12-15 00:00:00

  • Development of a cyclosporin A derivative with excellent anti-hepatitis C virus potency.

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    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Fu J,Becker C,Cao L,Capparelli M,Denay R,Fujimoto R,Gai Y,Gao Z,Guenat C,Karur S,Kim H,Li W,Li X,Li W,Lochmann T,Lu A,Lu P,Luneau A,Meier N,Mergo W,Ng S,Parker D,Peng Y,Riss B,Rivkin A,Roggo S,Schroede

    更新日期:2018-02-15 00:00:00

  • Inhibition of Helicobacter pylori aminoacyl-tRNA amidotransferase by chloramphenicol analogs.

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    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Balg C,De Mieri M,Huot JL,Blais SP,Lapointe J,Chênevert R

    更新日期:2010-11-15 00:00:00

  • An altered zinc-binding site confers resistance to a covalent inactivator of New Delhi metallo-beta-lactamase-1 (NDM-1) discovered by high-throughput screening.

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    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Thomas PW,Spicer T,Cammarata M,Brodbelt JS,Hodder P,Fast W

    更新日期:2013-06-01 00:00:00

  • d(G3T4G4) forms unusual dimeric G-quadruplex structure with the same general fold in the presence of K+, Na+ or NH4+ ions.

    abstract::We have recently communicated that DNA oligonucleotide d(G(3)T(4)G(4)) forms a dimeric G-quadruplex in the presence of K(+) ions [J. Am. Chem. Soc.2003, 125, 7866-7871]. The high-resolution NMR structure of d(G(3)T(4)G(4))(2) G-quadruplex exhibits G-quadruplex core consisting of three stacked G-quartets. The two overh...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Sket P,Crnugelj M,Plavec J

    更新日期:2004-11-15 00:00:00

  • Bisubstrate Inhibitors of the MYST HATs Esa1 and Tip60.

    abstract::Esa1 (essential Sas2-related acetyltransferase 1) and Tip60 (HIV-1 TAT-interactive protein, 60 kDa) are key members of the MYST family of histone acetyltransferases (HATs) and play important functions in many cellular processes. In this work, we designed, synthesized and evaluated a series of substrate-based analogs f...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Wu J,Xie N,Wu Z,Zhang Y,Zheng YG

    更新日期:2009-02-01 00:00:00

  • Novel leucine ureido derivatives as aminopeptidase N inhibitors using click chemistry.

    abstract::The over-expression of aminopeptidase N on diverse malignant cells is associated with the tumor angiogenesis and metastasis. In this report, one new series of leucine ureido derivatives containing the triazole moiety was designed, synthesized and evaluated as APN inhibitors. Among them, compound 13v showed the best AP...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Cao J,Ma C,Zang J,Gao S,Gao Q,Kong X,Yan Y,Liang X,Ding Q,Zhao C,Wang B,Xu W,Zhang Y

    更新日期:2018-07-23 00:00:00

  • Development of water-soluble 3,5-dinitrophenyl tetrazole and oxadiazole antitubercular agents.

    abstract::In this work, four series of tertiary amine-containing derivatives of 3,5-dinitrophenyl tetrazole and oxadiazole antitubercular agents were prepared, and their in vitro antimycobacterial effects were evaluated. We found that the studied compounds showed lipophilicity-dependent antimycobacterial activity. The N-benzylp...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Roh J,Karabanovich G,Vlčková H,Carazo A,Němeček J,Sychra P,Valášková L,Pavliš O,Stolaříková J,Klimešová V,Vávrová K,Pávek P,Hrabálek A

    更新日期:2017-10-15 00:00:00

  • Exploration of the nicotinamide-binding site of the tankyrases, identifying 3-arylisoquinolin-1-ones as potent and selective inhibitors in vitro.

    abstract::Tankyrases-1 and -2 (TNKS-1 and TNKS-2) have three cellular roles which make them important targets in cancer. Using NAD(+) as a substrate, they poly(ADP-ribosyl)ate TRF1 (regulating lengths of telomeres), NuMA (facilitating mitosis) and axin (in wnt/β-catenin signalling). Using molecular modelling and the structure o...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Paine HA,Nathubhai A,Woon EC,Sunderland PT,Wood PJ,Mahon MF,Lloyd MD,Thompson AS,Haikarainen T,Narwal M,Lehtiö L,Threadgill MD

    更新日期:2015-09-01 00:00:00

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    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Mowafy S,Galanis A,Doctor ZM,Paranal RM,Lasheen DS,Farag NA,Jänne PA,Abouzid KA

    更新日期:2016-08-15 00:00:00

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    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Pope SA,Burtin GE,Clayton PT,Madge DJ,Muller DP

    更新日期:2001-05-01 00:00:00

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    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Bremer RE,Szewczyk JW,Baird EE,Dervan PB

    更新日期:2000-08-01 00:00:00

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    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Lee M,Kim DH

    更新日期:2000-04-01 00:00:00

  • Synthesis, biological evaluation and molecular modeling study of 2-amino-3,5-disubstituted-pyrazines as Aurora kinases inhibitors.

    abstract::Serine/threonine protein kinases Aurora A, B, and C play essential roles in cell mitosis and cytokinesis, and a number of Aurora kinase inhibitors have been evaluated in the clinic. Herein we report the synthesis and their antiproliferation of 3,5-disubstituted-2-aminopyrazines as kinases inhibitors. Amongst, 4-((3-am...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Bo YX,Xiang R,Xu Y,Hao SY,Wang XR,Chen SW

    更新日期:2020-03-01 00:00:00

  • Thiophene bioisosteres of GluN2B selective NMDA receptor antagonists: Synthesis and pharmacological evaluation of [7]annuleno[b]thiophen-6-amines.

    abstract::Thiophene bioisosteres of potent GluN2B receptor negative allosteric modulators were prepared and evaluated pharmacologically. The five-step synthesis of 4,5,7,8-tetrahydro[7]annuleno[b]thiophen-6-one (10) was considerably improved by carboxylation of thiophene-3-carboxylic acid (8) in the first reaction step. Reducti...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Baumeister S,Schepmann D,Wünsch B

    更新日期:2020-01-15 00:00:00

  • Generation of highly potent DYRK1A-dependent inducers of human β-Cell replication via Multi-Dimensional compound optimization.

    abstract::Small molecule stimulation of β-cell regeneration has emerged as a promising therapeutic strategy for diabetes. Although chemical inhibition of dual specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A) is sufficient to enhance β-cell replication, current lead compounds have inadequate cellular potency for...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Allegretti PA,Horton TM,Abdolazimi Y,Moeller HP,Yeh B,Caffet M,Michel G,Smith M,Annes JP

    更新日期:2020-01-01 00:00:00

  • In-situ side-chain peptide cyclization as a breaker strategy against the amyloid aggregating peptide.

    abstract::Accumulation and deposition of misfolded amyloid β (Aβ) peptide outside the nerve cells are one of the major causes of Alzheimer's disease (AD). To date, one of the promising therapeutic strategies for AD is to block the early steps associated with the aggregation of Aβ peptide. We have developed synthetic breaker pep...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Ghosh N,Kundu LM

    更新日期:2021-01-16 00:00:00