93668-43-0Relevant articles and documents
Novel Aryl Substituted Pyrazoles as Small Molecule Inhibitors of Cytochrome P450 CYP121A1: Synthesis and Antimycobacterial Evaluation
Taban, Ismail M.,Elshihawy, Hosam E. A. E.,Torun, Beyza,Zucchini, Benedetta,Williamson, Clare J.,Altuwairigi, Dania,Ngu, Adeline S. T.,McLean, Kirsty J.,Levy, Colin W.,Sood, Sakshi,Marino, Leonardo B.,Munro, Andrew W.,De Carvalho, Luiz Pedro S.,Simons, Claire
, p. 10257 - 10267 (2018/01/10)
Three series of biarylpyrazole imidazole and triazoles are described, which vary in the linker between the biaryl pyrazole and imidazole/triazole group. The imidazole and triazole series with the short -CH2- linker displayed promising antimycobacterial activity, with the imidazole-CH2- series (7) showing low MIC values (6.25-25 μg/mL), which was also influenced by lipophilicity. Extending the linker to -C(O)NH(CH2)2- resulted in a loss of antimycobacterial activity. The binding affinity of the compounds with CYP121A1 was determined by UV-visible optical titrations with KD values of 2.63, 35.6, and 290 μM, respectively, for the tightest binding compounds 7e, 8b, and 13d from their respective series. Both binding affinity assays and docking studies of the CYP121A1 inhibitors suggest type II indirect binding through interstitial water molecules, with key binding residues Thr77, Val78, Val82, Val83, Met86, Ser237, Gln385, and Arg386, comparable with the binding interactions observed with fluconazole and the natural substrate dicyclotyrosine.
Imidazole-containing inhibitors of farnesyl protein transferase
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, (2008/06/13)
Inhibition of farnesyl transferase, which is an enzyme involved in ras oncogene expression, is effected by compounds of the formula their enantiomers, diastereomers, and pharmaceutically acceptable salts, prodrugs, and solvates, wherein:, G is G1 is G2 is or -NR10-CH(Q1)-;, J, K and L are each, independently, N, NR9, O, S or CR10 with the provisos that only one of the groups J, K and L can be O or S, and at least one of the groups J or L must be N, NR9, O or S to form a fused five-membered heteroring; the bond between J and K or K and L may also form one side of a phenyl ring fused to the fused five-membered heteroring;, Q is aryl;, Q1, A1 and A2 are each, independently, H, alkyl, substituted alkyl, phenyl or substituted phenyl;, G3 is R11, -C(O)OR11, -C(O)NR11R12, 5-tetrazolyl, -C(O)N(R13)OR11, -C(O)NHSO2R14 or -CH2OR11;, G4 is attached at the 1, 2, 4 or 5 position and optionally substituted, at any of the available position or positions on the ring, with halo, alkyl or substituted alkyl having 1 to 20 carbon atoms, alkoxy, aryl, aralkyl, hydroxy, alkanoyl, alkanoyloxy, amino, alkylamino, dialkylamino, alkanoylamino, thiol, alkylthio, alkylthiono, alkylsulfonyl, sulfonamido, nitro, cyano, carboxy, carbamyl, N-hydroxycarbamyl, N-alkylcarbamyl, N-dialkylcarbamyl, alkoxycarbonyl, phenyl, substituted phenyl, or a combinaton of these groups;, Y and Z are each, independently, -CH2- or -C(O)-;, R1 - R14 are each, independently, H or alkyl having 1 to 20 carbon atoms;, R7, R8 and R14 may also be aryl or aralkyl, and R3, R9, R11, R12 and R13 may also be aralkyl;, m, n and p are each, independently, 0 or an integer from 1 to 2;, q is 0 or an integer from 1 to 4; and, the dotted line represents an optional double bond.
Substituted N-[ω-(1H-imidazol-1-yl)alkyl]-amides
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, (2008/06/13)
This disclosure describes novel N-[ω-(1H-imidazol-1-yl)alkyl]amides which possess the property of inhibiting the enzyme thromboxane synthetase.
