2-.beta.-substituted-6-alkylidene penicillanic acid...

C - Chemistry – Metallurgy – 07 – D

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C07D 499/87 (2006.01) A61K 31/43 (2006.01) C07D 499/00 (2006.01)

Patent

CA 2282461

Compounds of formula (I), wherein R1 and R2 are each independently hydrogen, (C1-C10)alkyl, (C3-C8)cycloalkyl, (C2-C10)alkenyl, (C2-C10)alkynyl, -COOR a, -CONR b R c, cyano, -C(-O)R d, -OR e, Image aryl, heteroaryl, oxazolidinyl, isoxazolidinyl, morpholinyl, -S(O)m R f, -NR g R h, azido, or halo; R3 is (C3-C10)alkyl, (C2-C10)alkenyl, (C2-C10)alkynyl, (C1-C10)alkanoyl, (C3-C8)cloalkyl, aryl, heteroaryl, aryl(C1-C10)alkyl, heteroaryl(C1-C10)alkyl, or -CH2R i, wherein Ri is halo, cyano, cyanato, -OR j, -NR k R l, azido, -SR m, or (C3-C8)cycloalkyl; R4 is hydrogen, (C1-C10)alkyl, (C3-C8)cycloalkyl, (C2-C10)alkenyl, (C2-C10)alkynyl, aryl, or heteroaryl; m and n are each independently 0, 1, or 2; and their pharmaceutically acceptable salts, are useful for inhibiting .beta.-lactamase enzymes, for enhancing the activity of .beta.-lactam antibiotics, and for treating .beta.-lactam resistant bacterial infections in a mammal. The invention also provides pharmaceutical compositions, processes for preparing compounds of formula (I), and novel intermediates useful for the synthesis of compounds of formula (I).

L'invention concerne des composés de formule I: (I) dans laquelle R<1> et R<2> représentent indépendamment hydrogène, alkyle(C1-C10), cycloalkyle(C3-C8), alkényle(C2-C10), alkynyle(C2-C10), -COORa, -CONRbRc, cyano, -C(=O)Rd, -ORe, aryle, hétéroaryle, oxazolidinyle, isoxazolidinyle, morpholinyle, -S(O)mRf, -NRgRh, azido, ou halo; R<3> représente alkyle(C3-C10), alkényle(C2-C10), alkynyle(C2-C10), alkanoyle(C1-C10), cycloalkyle(C3-C8), aryle, hétéroaryle, alkyle(C1-C10)aryle, alkyle(C1-C10) hétéroaryle, ou -CH2Ri, Ri représentant halo, cyano, cyanato, -ORj, -NRkRl, azido, -SRm, ou cycloalkyle(C3-C8); R<4> représente hydrogène, alkyle(C1-C10), cycloalkyle(C3-C8), alkényle(C2-C10), alkynyle(C2-C10), aryle, ou hétéroaryle; m et n sont indépendamment égaux à 0, 1, ou 2. L'invention concerne également les sels pharmaceutiquement acceptables de ces composés, qui sont utiles pour inhiber les enzymes bêta-lactamase, pour favoriser l'activité des bêta-lactamines, et pour traiter les infections bactériennes au bêta-lactame chez un mammifère. L'invention concerne en outre des compositions pharmaceutiques, des procédés de préparation des composés de formule I, et de nouveaux produits intermédiaires utiles à la synthèse desdits composés de formule I.

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