Synthesis of potent and highly selective inhibitors of human tryptase

Slusarchyk, William A.; Bolton, Scott A.; Hartl, Karen S.; Huang, Ming‐Hsing; Jacobs, G. A.; Meng, Wei; Ogletree, Martin L.; Pi, Zulan; Schumacher, William A.; Seiler, Steven M.; Sutton, James; Treuner, U. D.; Zahler, Robert; Zhao, Guohua; Bisacchi, Gregory S.

doi:10.1016/s0960-894x(02)00689-3

Cited by 49 publications

(16 citation statements)

References 6 publications

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“…95 (2) Used as a building block in the synthesis of stereoisomers of antithrombotic nitpecotamides. 96,97 (3) Used as a building block in the oxidative C-arylation of free (NH)-heterocycles. 95 tively.…”

Section: Methods Numbermentioning

confidence: 99%

Enantiomeric impurities in chiral catalysts, auxiliaries, and synthons used in enantioselective syntheses. Part 4

Armstrong

Lee

Chang

2013

Tetrahedron: Asymmetry

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Section: Methods Numbermentioning

confidence: 99%

Enantiomeric impurities in chiral catalysts, auxiliaries, and synthons used in enantioselective syntheses. Part 4

Armstrong

Lee

Chang

2013

Tetrahedron: Asymmetry

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“…[86][87][88] More recently β-lactam research focused on modifications of the β-lactam ring in order to obtain compounds with very diverse pharmacological activities such as vasopressin V1a antagonist activity, cholesterol absorption inhibitory activity, thrombin and chymase inhibitory activity and antiparkinsonian, antidiabetic, antitubercular, anti-inflammatory and anti-HIV activity. [89][90][91][92] A related class of compounds concerns the γ-lactams; these systems appear in many natural products and bioactive derivatives. [93][94][95] Since β-and γ-lactams clearly represent biologically active scaffolds, they could serve as excellent motifs to include in hybrid molecules, where dual functionality could be beneficial for the overall activity.…”

Section: -Chloroquinoline-β/γ-lactam Hybridsmentioning

confidence: 99%

Quinoline-based antimalarial hybrid compounds

Vandekerckhove

D’hooghe

2015

Bioorganic & Medicinal Chemistry

196

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Quinoline-containing compounds, such as quinine and chloroquine, have a long-standing history as potent antimalarial agents. However, the increasing resistance of the Plasmodium parasite against these drugs and the lack of licensed malaria vaccines have forced chemists to develop synthetic strategies toward novel biologically active molecules. A strategy that has attracted considerable attention in current medicinal chemistry is based on the conjugation of two biologically active molecules into one hybrid compound. Since quinolines are considered to be privileged antimalarial building blocks, the synthesis of quinoline-containing antimalarial hybrids has been elaborated extensively in recent years. This review provides a literature overview of antimalarial hybrid molecules containing a quinoline core, covering publications between 2009 and 2014.

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“…32), was identified as a potent and selective tryptase inhibitor (IC 50 ¼ 4 nM) with a moderate to good selectivity profile except for trypsin, and having relatively good aqueous stability, which, when dosed intratracheally in ovalbumin-sensitized guinea pigs, reduced allergen-induced bronchoconstriction and inflammatory cell infiltration into the lung. Slusarchyk et al have described the synthesis and SAR study on a series of N1-activated-4-carboxy azetidinones [14]. SAR at N-1 and C-3 of the azetidinone nucleus of BMS-262084 has shown that conformationally constrained guanidinyl groups at C-3 and extended substituents appended to the piperazine at N-1 provide potent inhibitors of typtase with highly improved selectivity versus other serine proteases including trypsin.…”

Section: Tryptase and Chymase Inhibitory Activitymentioning

confidence: 99%