Structure-activity relationship within a series of pyrazolidinone antibacterial agents. 2. Effect of side-chain modification on in vitro activity and pharmacokinetic parameters

Ternansky, Robert J.; Draheim, Susan E.; Pike, Andrew; Counter, F. T.; Eudaly, J. A.; Kasher, Jeffrey S.

doi:10.1021/jm00074a002

Cited by 66 publications

(24 citation statements)

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“…[8] Next, av ariety of allylic acetals 2b-2g was employed in the reaction with 1a under the optimized reaction conditions, and the results are shown in Table 3. It should be noted that this reaction is not limited to only hetero(aryl) azomethine imines.…”

Section: Angewandte Chemiementioning

confidence: 99%

Allylic Acetals as Acrolein Oxonium Precursors in Tandem C−H Allylation and [3+2] Dipolar Cycloaddition

et al. 2019

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The ruthenium(II)-catalyzed C À Hfunctionalization of (hetero)aryl azomethine imines with allylic acetals is described.The initial formation of allylidene-(methyl)oxoniums from allylic acetals could trigger C(sp 2 )À Ha llylation, and subsequent endo-type [3+ +2] dipolar cycloaddition of polar azomethine fragments to deliver valuable indenopyrazolopyrazolones.T he utility of this method is showcased by the late-stage functionalization of bioactive molecules such as estrone and celecoxib.C ombined experimental and computational investigations elucidate ap lausible mechanism of this new tandem reaction. Notably,the reductive transformation of synthesized compounds into biologically relevant diazocine frameworks highlights the importance of the developed methodology.Inrecent decades,g reat advances in transition-metal-catalyzed CÀHf unctionalization have been achieved due to its remarkable advantage in atom economy and environmental sustainability. [1] Thec ombination of C À Hf unctionalization and annulation with various p-unsaturated reactants has been recognized as avaluable strategy for the efficient construction of carbocyclic and heterocyclicc ompounds. [2] Significant progress in this direction has been realized by av ariety of transition-metal catalysts.I np articular, ruthenium catalysts have been employed due to their low cost, high efficiency, broad substrate scope,a nd good functional group tolerance under relatively mild conditions. [3] Azomethine imines have been widely employed in cycloaddition reactions with various coupling partners such as alkenes,a lkynes,a nd allenoates. [4] Recently,L ie tal. has reported the C(sp 2 ) À Hf unctionalization of azomethine imines under Rh III catalysis to provide 1,2-dihydrophthalazi-nes [5a] and bridged benzoxazepines. [5b] Alkenes have been intensively studied for the formation of heterocyclic compounds in CÀHf unctionalization event involving the nucleophilic addition of directing groups to olefinic moieties or the electrophilic addition of directing groups to M À Ci ntermediates.V ery recently,our group disclosed the Rh III -catalyzed C À Hf unctionalization and in situ annulation reaction using Morita-Baylis-Hillman adducts to afford 2-benzazepines, [6a] bridged benzoxazepines, [6b] and 2-naphthols. [6c] In these transformations,weobserved that the ester functionality on MBH adducts can lower the energy barrier of the migratory insertion step,h ence enhancing the catalytic cycle.O nt he other hand, allyl acetate was inactive under the identical reaction condition, which was supported by DFT calculations. [6a] These results indicate that the electron density on olefin moiety is crucial for the success of the reaction. In this regard, we envisioned that we might overcome this issue if ah igher inductive effect at the allylic position can be produced. Owing to their equilibrium under metal catalysis, [7] allylic acetals might serve as highly activated acrolein oxonium precursors for cross-coupling reactions (Scheme 1A). Interestingly,w ed iscovered in the...

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Section: Angewandte Chemiementioning

confidence: 99%

Allylic Acetals as Acrolein Oxonium Precursors in Tandem C−H Allylation and [3+2] Dipolar Cycloaddition

et al. 2019

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“…The applicability of 40 for the preparation of biologically active peptide mimetics was successfully demonstrated by researchers at Eli Lilly almost three decades ago. [19][20][21][22] Strangely enough, very few other examples of 40-derived compounds have been reported since 1990, meaning that 40 is a practically unexplored scaffold with reasonable applicative potential. The most general and straightforward synthetic approach towards derivatives of 40 includes stereoselective 1,3-dipolar cycloaddition as the key-step and starting from 4-acylamino-3-pyrazolidinones, which in turn are easily available by simple treatment of α,β-dehydro-α-amino acid derivatives with excess hydrazine hydrate.…”

Section: Pyrazolo[12-a]pyrazolesmentioning

confidence: 99%

“…16,17 Bicyclic pyrazolidinones are used, among others, as drugs to relieve Alzheimer's disease 18 and as antibacterial agents. [19][20][21][22][23] Some important 3-pyrazolidinones are presented in (Figure 1). Due to their applicability and biological activity, pyrazolidin-3-one derivatives, both monoand bi-cyclic, remain attractive synthetic targets.…”

Section: Introductionmentioning

confidence: 99%

Recent advances in the synthesis of polysubstituted 3-pyrazolidinones

Grošelj¹,

Svete²

2015

Arkivoc

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An account of recent developments in the field of 3-pyrazolidinone chemistry is given with special focus on the synthesis and transformations of 5-substituted 4-benzyloxycarbonylamino-3-pyrazolidinones, pyrazolo[1,2-a]pyrazole-based peptide analogues, and tetrahydropyrazolo-[1,5-c]pyrimidine-2,7-diones. In terms of practical application, polyfunctionalized 3-pyrazolidinones as 'aza-deoxa' analogues of cycloserine, peptide mimetics based on 3-amino-2-oxo-1,5-diazabicyclo[3.3.0]octane-7-carboxylic acid, and 1,6-disubstituted tetrahydropyrazolo[1,5-c]-pyrimidine-2,7-diones as the first representatives of a novel saturated heterocyclic system were prepared by these newly developed synthetic methods.

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“…Among bicyclic analogues, perhydropyrazolo[1,2-a]pyrazolones belong to azabicycloalkane amino acids, which are U-shaped conformationally constrained heterocyclic analogues of peptides that simulate β-turn structures. 9,10 Consequently, bicyclic pyrazolidinones are used as drugs to relieve Alzheimer's disease 11 and as antibacterial (Eli-Lilly's γ-lactam antibiotics), 12 and antitrypanosomal agents. 13 Synthetic applications of 3-pyrazolidinones comprise their use as chiral auxiliaries, [14][15][16][17][18][19] as templates in asymmetric Diels-Alder cycloadditions, [20][21][22] and as a new scaffold in organocatalysis.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Novel 3D-Rich α-Amino Acid-Derived 3-Pyrazolidinones

Glavač¹,

Dahmann²,

Požgan³

et al. 2017

ACSi

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Synthetic approaches towards novel 3-pyrazolidinone derivatives functionalized at positions N(1) and/or C(5) were studied. 5-Aminoalkyl-3-pyrazolidinones were prepared in four steps from N-protected glycines via Masamune-Claisen homologation, reduction, O-mesylation, and cyclisation with a hydrazine derivative. The free amines were prepared by acidolytic deprotection. Title compound was also prepared by 'ring switching' transformation of N-Boc-pyrrolin-2(5H)-one with hydrazine hydrate. Hydrogenolytic deprotection of 5-(N-alkyl-N-Cbz-aminomethyl)pyrazolidine-3-ones followed by cyclisation with 1,1'-carbonyldiimidazole (CDI) gave two novel representatives of perhydroimidazo [1,5-b] pyrazole, which is an almost unexplored heterocyclic system. Amidation of 3-oxopyrazolidine-5-carboxylic acid gave the corresponding carboxamides in moderate yields. Diastereomeric non-racemic carboxamides obtained from (S)-AlaOMe and (S)-ProOMe were separated by MPLC.

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Structure-activity relationship within a series of pyrazolidinone antibacterial agents. 2. Effect of side-chain modification on in vitro activity and pharmacokinetic parameters

Cited by 66 publications

References 1 publication

Allylic Acetals as Acrolein Oxonium Precursors in Tandem C−H Allylation and [3+2] Dipolar Cycloaddition

Allylic Acetals as Acrolein Oxonium Precursors in Tandem C−H Allylation and [3+2] Dipolar Cycloaddition

Recent advances in the synthesis of polysubstituted 3-pyrazolidinones

Synthesis of Novel 3D-Rich α-Amino Acid-Derived 3-Pyrazolidinones

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