Structure-Activity Relationship of the Antimalarial Ozonide Artefenomel (OZ439).

Abstract:

:Building on insights gained from the discovery of the antimalarial ozonide arterolane (OZ277), we now describe the structure-activity relationship (SAR) of the antimalarial ozonide artefenomel (OZ439). Primary and secondary amino ozonides had higher metabolic stabilities than tertiary amino ozonides, consistent with their higher pKa and lower log D7.4 values. For primary amino ozonides, addition of polar functional groups decreased in vivo antimalarial efficacy. For secondary amino ozonides, additional functional groups had variable effects on metabolic stability and efficacy, but the most effective members of this series also had the highest log D7.4 values. For tertiary amino ozonides, addition of polar functional groups with H-bond donors increased metabolic stability but decreased in vivo antimalarial efficacy. Primary and tertiary amino ozonides with cycloalkyl and heterocycle substructures were superior to their acyclic counterparts. The high curative efficacy of these ozonides was most often associated with high and prolonged plasma exposure, but exposure on its own did not explain the presence or absence of either curative efficacy or in vivo toxicity.

journal_name

J Med Chem

authors

Dong Y,Wang X,Kamaraj S,Bulbule VJ,Chiu FC,Chollet J,Dhanasekaran M,Hein CD,Papastogiannidis P,Morizzi J,Shackleford DM,Barker H,Ryan E,Scheurer C,Tang Y,Zhao Q,Zhou L,White KL,Urwyler H,Charman WN,Matile H,Witt

doi

10.1021/acs.jmedchem.6b01586

subject

Has Abstract

pub_date

2017-04-13 00:00:00

pages

2654-2668

issue

7

eissn

0022-2623

issn

1520-4804

journal_volume

60

pub_type

杂志文章
  • Nuclear magnetic resonance and molecular modeling study on mycophenolic acid: implications for binding to inosine monophosphate dehydrogenase.

    abstract::The conformation of the sodium salt of mycophenolic acid (MPA), a potent inhibitor of inosine monophosphate dehydrogenase (IMPD), derived from 1D DIFNOE and 2D ROESY experiments in water and molecular dynamics (MD) is described. The hexenoic acid side chain conformation consistent with the NMR data was similar to that...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/jm950600m

    authors: Makara GM,Keserû GM,Kajtár-Peredy M,Anderson WK

    更新日期:1996-03-15 00:00:00

  • Discovery and early clinical development of 2-{6-[2-(3,5-dichloro-4-pyridyl)acetyl]-2,3-dimethoxyphenoxy}-N-propylacetamide (LEO 29102), a soft-drug inhibitor of phosphodiesterase 4 for topical treatment of atopic dermatitis.

    abstract::Development of orally available phosphodiesterase 4 (PDE4) inhibitors as anti-inflammatory drugs has been going on for decades. However, only roflumilast has received FDA approval. One key challenge has been the low therapeutic window observed in the clinic for PDE4 inhibitors, primarily due to PDE4 mediated side effe...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章,评审

    doi:10.1021/jm500378a

    authors: Felding J,Sørensen MD,Poulsen TD,Larsen J,Andersson C,Refer P,Engell K,Ladefoged LG,Thormann T,Vinggaard AM,Hegardt P,Søhoel A,Nielsen SF

    更新日期:2014-07-24 00:00:00

  • DL-threo-beta-Fluoroaspartate and DL-threo-beta-fluoroasparagine: selective cytotoxic agents for mammalian cells in culture.

    abstract::Absolute configuration assignments have been made for the diastereomers of DL-beta-fluoroaspartate by X-ray analysis. The cytotoxicity of these isomers against various mammalian cells was examined. DL-threo-beta-Fluoroaspartate shows selective cytotoxicity. Growth of the most sensitive cells is completely inhibited by...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/jm00347a013

    authors: Stern AM,Foxman BM,Tashjian AH Jr,Abeles RH

    更新日期:1982-05-01 00:00:00

  • A Developability-Focused Optimization Approach Allows Identification of in Vivo Fast-Acting Antimalarials: N-[3-[(Benzimidazol-2-yl)amino]propyl]amides.

    abstract::Malaria continues to be a major global health problem, being particularly devastating in the African population under the age of five. Artemisinin-based combination therapies (ACTs) are the first-line treatment recommended by the WHO to treat Plasmodium falciparum malaria, but clinical resistance against them has alre...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/acs.jmedchem.5b00114

    authors: Keurulainen L,Vahermo M,Puente-Felipe M,Sandoval-Izquierdo E,Crespo-Fernández B,Guijarro-López L,Huertas-Valentín L,de las Heras-Dueña L,Leino TO,Siiskonen A,Ballell-Pages L,Sanz LM,Castañeda-Casado P,Jiménez-Díaz MB,Martínez

    更新日期:2015-06-11 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 relationships of cyclic lactam analogues of alpha-melanocyte-stimulating hormone (alpha-MSH) targeting the human melanocortin-3 receptor.

    abstract::A variety of dicarboxylic acid linkers introduced between the alpha-amino group of Pro(6) and the -amino group of Lys(10) of the cyclic lactam alpha-melanocyte-stimulating hormone (alpha-MSH)-derived Pro(6)-D-Phe(7)/D-Nal(2')(7)-Arg(8)-Trp(9)-Lys(10)-NH2 pentapeptide template lead to nanomolar range and selective hMC3...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/jm070461w

    authors: Mayorov AV,Cai M,Palmer ES,Dedek MM,Cain JP,Van Scoy AR,Tan B,Vagner J,Trivedi D,Hruby VJ

    更新日期:2008-01-24 00:00:00

  • Spirovesamicols: conformationally restricted analogs of 2-(4-phenylpiperidino)cyclohexanol (vesamicol, AH5183) as potential modulators of presynaptic cholinergic function.

    abstract::In an effort to develop selective inhibitors of vesicular acetylcholine storage, we have synthesized a series of semirigid vesamicol receptor ligands based on the structure of 2-(4-phenylpiperidino)-cyclohexanol (vesamicol, AH5183, 1). In these compounds, the planes of the phenyl and piperidyl moieties of the parent l...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/jm00042a010

    authors: Efange SM,Khare AB,Foulon C,Akella SK,Parsons SM

    更新日期:1994-08-05 00:00:00

  • Metal complexes of mitomycins.

    abstract::The preparation of stable complexes between the N7-[2-(2-pyridyl)ethyl] and N7-(2-piperazinylethyl) derivatives of mitomycin C and metal ions such as Cu(II), Zn(II), and Pt(II) was accomplished. Mitomycin C did not form stable complexes, but it rearranged to a mitosene capable of complex formation. Some of these compl...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/jm00151a023

    authors: Iyengar BS,Takahashi T,Remers WA,Bradner WT

    更新日期:1986-01-01 00:00:00

  • Synthesis of a methylenebis(phosphonate) analogue of mycophenolic adenine dinucleotide: a glucuronidation-resistant MAD analogue of NAD.

    abstract::Mycophenolic alcohol (MPAlc), obtained by reduction of the carboxylic group of mycophenolic acid (MPA), was coupled with 2',3'-O-isopropylideneadenosine 5'-methylenebis(phosphonate) (4) in the presence of diisopropylcarbodiimide (DIC) to give P1-(2',3'-O-isopropylideneadenosin-5'-yl)-P2-(mycophenolic alcohol-6'-yl)met...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/jm970705k

    authors: Lesiak K,Watanabe KA,Majumdar A,Powell J,Seidman M,Vanderveen K,Goldstein BM,Pankiewicz KW

    更新日期:1998-02-12 00:00:00

  • Nonlinear quantitative structure-activity relationship for the inhibition of dihydrofolate reductase by pyrimidines.

    abstract::A novel method for quantitative structure-activity relationship (QSAR) analysis is presented. The method, which does not assume any particular functional form for the QSAR, develops nonlinear relationships between parameters describing a set of molecules and the activity of the molecules. For the QSAR of the inhibitio...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/jm960197z

    authors: Hirst JD

    更新日期:1996-08-30 00:00:00

  • Potent and selective fluoroketone inhibitors of group VIA calcium-independent phospholipase A2.

    abstract::Group VIA calcium-independent phospholipase A(2) (GVIA iPLA(2)) has recently emerged as a novel pharmaceutical target. We have now explored the structure-activity relationship between fluoroketones and GVIA iPLA(2) inhibition. The presence of a naphthyl group proved to be of paramount importance. 1,1,1-Trifluoro-6-(na...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/jm901872v

    authors: Kokotos G,Hsu YH,Burke JE,Baskakis C,Kokotos CG,Magrioti V,Dennis EA

    更新日期:2010-05-13 00:00:00

  • Dimeric 1,3-phenylene-bis(piperazinyl benzimidazole)s: synthesis and structure-activity investigations on their binding with human telomeric G-quadruplex DNA and telomerase inhibition properties.

    abstract::Ligand-induced stabilization of G-quadruplex structures formed by the human telomeric DNA is an active area of research. The compounds which stabilize the G-quadruplexes often lead to telomerase inhibition. Herein we present the results of interaction of new monomeric and dimeric ligands having 1,3-phenylene-bis(piper...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/jm200860b

    authors: Jain AK,Paul A,Maji B,Muniyappa K,Bhattacharya S

    更新日期:2012-04-12 00:00:00

  • Identification of Mineralocorticoid Receptor Modulators with Low Impact on Electrolyte Homeostasis but Maintained Organ Protection.

    abstract::The mechanism-based risk for hyperkalemia has limited the use of mineralocorticoid receptor antagonists (MRAs) like eplerenone in cardio-renal diseases. Here, we describe the structure and property-driven lead generation and optimization, which resulted in identification of MR modulators ( S)-1 and ( S)-33. Both compo...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/acs.jmedchem.8b01523

    authors: Granberg KL,Yuan ZQ,Lindmark B,Edman K,Kajanus J,Hogner A,Malmgren M,O'Mahony G,Nordqvist A,Lindberg J,Tångefjord S,Kossenjans M,Löfberg C,Brånalt J,Liu D,Selmi N,Nikitidis G,Nordberg P,Hayen A,Aagaard A,Hansson E

    更新日期:2019-02-14 00:00:00

  • Synthesis and in vitro biological profile of all four isomers of the potent muscarinic agonist 3-(3-methyl-1,2,4-oxadiazol-5-yl)-1-azabicyclo[2.2.1]heptane.

    abstract::The four stereoisomers of the muscarinic agonist 7 have been synthesized from enantiomerically pure exo-azanorbornane esters (13a,b). The esters were obtained in optically active form by separation of the carboxamide diastereomers 12a,b, formed from the borane complex of exo-azanorbornane-3-carboxylate 10 and a chiral...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/jm00083a016

    authors: Showell GA,Baker R,Davis J,Hargreaves R,Freedman SB,Hoogsteen K,Patel S,Snow RJ

    更新日期:1992-03-06 00:00:00

  • Structure-based exploration of cyclic dipeptide chitinase inhibitors.

    abstract::Family 18 chitinases play an essential role in a range of pathogens and pests. Several inhibitors are known, including the potent inhibitors argadin and allosamidin, and the structures of these in complex with chitinases have been elucidated. Recent structural analysis has revealed that CI-4 [cyclo-(L-Arg-D-Pro)] inhi...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/jm049940a

    authors: Houston DR,Synstad B,Eijsink VG,Stark MJ,Eggleston IM,van Aalten DM

    更新日期:2004-11-04 00:00:00

  • High-affinity, non-peptide agonists for the ORL1 (orphanin FQ/nociceptin) receptor.

    abstract::The discovery of 8-(5,8-dichloro-1,2,3,4-tetrahydro-naphthalen-2-yl)-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one, 1a, as a high-affinity ligand for the human ORL1 (orphanin FQ/nociceptin) receptor led to the synthesis of a series of optimized ligands. These compounds exhibit high affinity for the human ORL1 receptor, e...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/jm991129q

    authors: Röver S,Adam G,Cesura AM,Galley G,Jenck F,Monsma FJ Jr,Wichmann J,Dautzenberg FM

    更新日期:2000-04-06 00:00:00

  • Structure and molecular modeling of GABAA receptor antagonists.

    abstract::The recently described potent and selective GABAA antagonist SR 95531 (gabazine) is compared to six other GABAA antagonists: (+)-bicuculline, (-)-securinine, (+)-tubocurarine, iso-THAZ, R-5135, and pitrazepine. Starting from ab initio molecular orbital calculations performed on crystal atomic coordinates, attempts wer...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/jm00089a005

    authors: Rognan D,Boulanger T,Hoffmann R,Vercauteren DP,Andre JM,Durant F,Wermuth CG

    更新日期:1992-05-29 00:00:00

  • Bicyclic Helical Peptides as Dual Inhibitors Selective for Bcl2A1 and Mcl-1 Proteins.

    abstract::A 26-residue peptide BimBH3 binds indiscriminately to multiple oncogenic Bcl2 proteins that regulate apoptosis of cancer cells. Specific inhibition of the BimBH3-Bcl2A1 protein-protein interaction was obtained in vitro and in cancer cells by shortening the peptide to 14 residues, inserting two cyclization constraints ...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/acs.jmedchem.8b00010

    authors: D de Araujo A,Lim J,Wu KC,Xiang Y,Good AC,Skerlj R,Fairlie DP

    更新日期:2018-04-12 00:00:00

  • Synthesis and Pharmacological Evaluation of Triazolopyrimidinone Derivatives as Noncompetitive, Intracellular Antagonists for CC Chemokine Receptors 2 and 5.

    abstract::CC chemokine receptors 2 (CCR2) and 5 (CCR5) are involved in many inflammatory diseases; however, most CCR2 and CCR5 clinical candidates have been unsuccessful. (Pre)clinical evidence suggests that dual CCR2/CCR5 inhibition might be more effective in the treatment of such multifactorial diseases. In this regard, the h...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/acs.jmedchem.9b00742

    authors: Ortiz Zacarías NV,van Veldhoven JPD,den Hollander LS,Dogan B,Openy J,Hsiao YY,Lenselink EB,Heitman LH,IJzerman AP

    更新日期:2019-12-26 00:00:00

  • α2-adrenoceptor antagonists: synthesis, pharmacological evaluation, and molecular modeling investigation of pyridinoguanidine, pyridino-2-aminoimidazoline and their derivatives.

    abstract::We have previously identified phenylguanidine and phenyl-2-aminoimidazoline compounds as high affinity ligands with conflicting functional activity at the α2-adrenoceptor, a G-protein-coupled receptor with relevance in several neuropsychiatric conditions. In this paper we describe the design, synthesis, and pharmacolo...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/jm501635e

    authors: Kelly B,McMullan M,Muguruza C,Ortega JE,Meana JJ,Callado LF,Rozas I

    更新日期:2015-01-22 00:00:00

  • Structure-based discovery of small molecule inhibitors targeted to protein tyrosine phosphatase 1B.

    abstract::Protein tyrosine phosphatases (PTPases) are involved in the control of tyrosine phosphorylation levels in the cell and are believed to be crucial for the regulation of a multitude of cellular functions. A detailed understanding of the role played by PTPases in various signaling pathways has not yet been achieved, and ...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/jm990329z

    authors: Sarmiento M,Wu L,Keng YF,Song L,Luo Z,Huang Z,Wu GZ,Yuan AK,Zhang ZY

    更新日期:2000-01-27 00:00:00

  • 3-Oxoisoindoline-1-carboxamides: potent, state-dependent blockers of voltage-gated sodium channel Na(V)1.7 with efficacy in rat pain models.

    abstract::The voltage-gated sodium channel Na(V)1.7 is believed to be a critical mediator of pain sensation based on clinical genetic studies and pharmacological results. Clinical utility of nonselective sodium channel blockers is limited due to serious adverse drug effects. Here, we present the optimization, structure-activity...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/jm300623u

    authors: Macsari I,Besidski Y,Csjernyik G,Nilsson LI,Sandberg L,Yngve U,Ahlin K,Bueters T,Eriksson AB,Lund PE,Venyike E,Oerther S,Hygge Blakeman K,Luo L,Arvidsson PI

    更新日期:2012-08-09 00:00:00

  • 1-Aryl-3,5-dihydro-4H-2,3-benzodiazepin-4-ones: novel AMPA receptor antagonists.

    abstract::Our previous publication (Eur. J. Pharmacol. 1995, 294, 411-422) reported preliminary chemical and biological studies of some 2,3-benzodiazepines, analogues of 1-(4-aminophenyl)-4-methyl-7,8-(methylenedioxy)-5H-2,3-benzodiazepine (1, GYKI 52466), which have been shown to possess significant anticonvulsant activity. Th...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/jm960506l

    authors: Chimirri A,De Sarro G,De Sarro A,Gitto R,Grasso S,Quartarone S,Zappalà M,Giusti P,Libri V,Constanti A,Chapman AG

    更新日期:1997-04-11 00:00:00

  • N-(2-{3-[3,5-bis(trifluoromethyl)phenyl]ureido}ethyl)-glycyrrhetinamide (6b): a novel anticancer glycyrrhetinic acid derivative that targets the proteasome and displays anti-kinase activity.

    abstract::18-β-Glycyrrhetinic acid (GA; 1) and many of its derivatives are cytotoxic in cancer cells. The current study aims to characterize the anticancer effects of 17 novel 1 derivatives. On the basis of these studies, N-(2-{3-[3,5-bis(trifluoromethyl)phenyl]ureido}ethyl)-glycyrrhetinamide (6b) appeared to be the most potent...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/jm200285z

    authors: Lallemand B,Chaix F,Bury M,Bruyère C,Ghostin J,Becker JP,Delporte C,Gelbcke M,Mathieu V,Dubois J,Prévost M,Jabin I,Kiss R

    更新日期:2011-10-13 00:00:00

  • Radioiodinated p-iodoclonidine: a high-affinity probe for the alpha 2-adrenergic receptor.

    abstract::The chemical synthesis of 2-[(2,6-dichloro-4-iodophenyl)imino]imidazolidine (PIC) and its radioiodinated analogue [125I]PIC is described. PIC was synthesized from 2,6-dichloroaniline in five synthetic steps. This agent displayed a high affinity for the alpha 2-adrenergic receptor (IC50 = 1.5 nM) in competitive binding...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/jm00390a021

    authors: Van Dort M,Neubig R,Counsell RE

    更新日期:1987-07-01 00:00:00

  • Determinants of retinoid X receptor transcriptional antagonism.

    abstract::The synthesis and bioactivity of the retinoid X receptor (RXR) antagonist 4-[(3'-n-butyl-5',6',7',8'-tetrahydro-5',5',8',8'-tetramethyl-2'-naphthalenyl)(cyclopropylidene)methyl]benzoic acid and several heteroatom-substituted analogues are described. Ligand design was based on the scaffold of the 3'-methyl RXR-selectiv...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/jm030651g

    authors: Cavasotto CN,Liu G,James SY,Hobbs PD,Peterson VJ,Bhattacharya AA,Kolluri SK,Zhang XK,Leid M,Abagyan R,Liddington RC,Dawson MI

    更新日期:2004-08-26 00:00:00

  • Synthesis, Biological Activities, and X-ray Crystal Structural Analysis of 25-Hydroxy-25(or 26)-adamantyl-17-[20(22),23-diynyl]-21-norvitamin D Compounds.

    abstract::Novel 19-norvitamin D analogues (ADYW1-4, 5a-d) in which an adamantyl diyne side chain is attached directly to the 17-position of the D ring are designed and stereoselectively synthesized. The adamantane ring of these analogues was expected to interfere with helix 12 (H12, activation function 2) of the vitamin D recep...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/acs.jmedchem.5b00792

    authors: Watarai Y,Ishizawa M,Ikura T,Zacconi FC,Uno S,Ito N,Mouriño A,Tokiwa H,Makishima M,Yamada S

    更新日期:2015-12-24 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

  • A Novel Pyrazolopyridine with in Vivo Activity in Plasmodium berghei- and Plasmodium falciparum-Infected Mouse Models from Structure-Activity Relationship Studies around the Core of Recently Identified Antimalarial Imidazopyridazines.

    abstract::Toward improving pharmacokinetics, in vivo efficacy, and selectivity over hERG, structure-activity relationship studies around the central core of antimalarial imidazopyridazines were conducted. This study led to the identification of potent pyrazolopyridines, which showed good in vivo efficacy and pharmacokinetics pr...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/acs.jmedchem.5b01605

    authors: Le Manach C,Paquet T,Brunschwig C,Njoroge M,Han Z,Gonzàlez Cabrera D,Bashyam S,Dhinakaran R,Taylor D,Reader J,Botha M,Churchyard A,Lauterbach S,Coetzer TL,Birkholtz LM,Meister S,Winzeler EA,Waterson D,Witty MJ,Wittl

    更新日期:2015-11-12 00:00:00

  • Cephalosporins to carbapenems: 1-oxygenated carbapenems and carbapenams.

    abstract::The photo "Wolff" rearrangement of readily available 2-diazoceph-3-em oxides (1) directly affords carbapen-2-ems, allowing a facile entry into a ring system previously accessible only by total synthesis, lengthly semisynthesis or fermentation. The chirality of the cephalosporin is accurately translated into the corres...

    journal_title:Journal of medicinal chemistry

    pub_type: 杂志文章

    doi:10.1021/jm00163a048

    authors: Rosati RL,Kapili LV,Morrissey P,Retsema JA

    更新日期:1990-01-01 00:00:00