3251-56-7Relevant articles and documents
Photochemical Methoxide Exchange in Some Nitromethoxybenzenes. The Role of the Nitro Group in SN2Ar* Reactions
Riel, H. C. H. A. van,Lodder, G.,Havinga, E.
, p. 7257 - 7262 (1981)
Photoinduced methoxide exchange has been measured for o-, m-, and p-nitromethoxybenzene as well as for the methoxy-labeled 4-nitroveratroles.In these reactions (of the SN23Ar* type), where the substituting and leaving groups are the same, the origin of the meta activation found cannot be otherwise than in the steps leading to the symmetrical ? complex.Next to considerations on the basis of charge distributions of the excited aromatic compounds and of electron densities in the HOMO and LUMO, a rationalization for the regioselectivity and activation is offered on the basis of the energy gap between the ground-state and the excited-state surfaces.Since the level of the ground-state ? complex corresponding to meta substitution as compared to that for ortho/para substitution is highest in energy and since the trajectory from the (triplet) excited state leading to the ? complex for meta substitution is lowest in energy, the energy gap between the excited-state and ground-state hypersurface is considerable smaller for the geometry that leads to the meta ? complex and thus to meta substitution.Meta direction and activation of photosubstitutions will therefore be outspoken in the case of a substituent that gives difficult or no substitution at the meta position in the ground state and brings with it low triplet energy.The NO2 group conforms nicely to these criteria.
Synthesis and Antileishmanial Evaluation of Arylimidamide-Azole Hybrids Containing a Phenoxyalkyl Linker
Abdelhameed, Ahmed,Feng, Mei,Joice, April C.,Zywot, Emilia M.,Jin, Yiru,La Rosa, Chris,Liao, Xiaoping,Meeds, Heidi L.,Kim, Yena,Li, Junan,McElroy, Craig A.,Wang, Michael Zhuo,Werbovetz, Karl A.
, p. 1901 - 1922 (2021/02/22)
Due to the limitations of existing medications, there is a critical need for new drugs to treat visceral leishmaniasis. Since arylimidamides and antifungal azoles both show oral activity in murine visceral leishmaniasis models, a molecular hybridization approach was employed where arylimidamide and azole groups were separated by phenoxyalkyl linkers in an attempt to capitalize on the favorable antileishmanial properties of both series. Among the target compounds synthesized, a greater antileishmanial potency against intracellular Leishmania donovani was observed as the linker length increased from two to eight carbons and when an imidazole ring was employed as the terminal group compared to a 1,2,4-triazole group. Compound 24c (N-(4-((8-(1H-imidazol-1-yl)octyl)oxy)-2-isopropoxyphenyl) picolinimidamide) displayed activity against L. donovani intracellular amastigotes with an IC50 value of 0.53 μM. When tested in a murine visceral leishmaniasis model, compound 24c at a dose of 75 mg/kg/day p.o. for five consecutive days resulted in a modest 33% decrease in liver parasitemia compared to the control group, indicating that further optimization of these molecules is needed. While potent hybrid compounds bearing an imidazole terminal group were also strong inhibitors of recombinant CYP51 from L. donovani, as assessed by a fluorescence-based assay, additional targets are likely to play an important role in the antileishmanial action of these compounds.
ANTI-PARASITIC COMPOUNDS
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Paragraph 00124, (2018/03/25)
Provided are compounds, methods, and pharmaceutical compositions useful for treatment of parasites, e.g., Leishmania. For example, the compound may he represented by Ar—C(=NR1)NR2—A—X—Y—Het2, and pharmaceutically acceptable salts thereof. Ar may be an optionally substituted, aryl or nitrogen-containing heteroaryl. R1 and R2 may independently represent H, optionally substituted C1-C6 alkyl, or optionally substituted C3-C6 cycloalkyl. A may be a bond or an optionally substituted linking moiety comprising 1, 2, or 3 rings. Each ring in the optionally substituted linking moiety may independently be one of: aryl, cycloalkyl, heterocycloalkyl, and heteroaryl. X may be O, S, amide, or a bond. Y may be optionally substituted C1-C14 alkyl or optionally substituted C2-C14 alkenyl. Het2 may be an optionally substituted five-membered nitrogen-containing heteroaromatic ring comprising 1, 2, or 3 ring heteroatoms.
Reactions of aryl 5-substituted-2-thiophenecarboxylates promoted by 4-Z-C6H4O-/4-Z-C6H4OH in 20 mol % DMSO(aq). Effect of nucleophile on acyl-transfer reaction
Pyun, Sang Yong,Paik, Kyu Cheol,Han, Man So,Cho, Bong Rae
, p. 2810 - 2814 (2016/02/05)
Nucleophilic substitution reactions of 5-XC4H2(S)C(O)OC6H3-2-Y-4-NO2 (1) promoted by 4-Z-C6H4O-/4-Z-C6H4OH in 20 mol % dimethyl sulfoxide (DMSO)(aq) have been studied kinetically. The reactions exhibited second-order kinetics with βacyl = -2.52 to -2.83, ρ(x) = 2.81-3.16, βnuc = 0.88-0.04 and βlg = -0.94, respectively. The results have been interpreted with an addition-elimination mechanism in which the nucleophilic attack occurs in the rate-determining step. Comparison with existing data reveals that the ratedetermining step changes from the second to the first step by the change in the nucleophile from R2NH/R2NH2+ to 4-Z-C6H4O-/4-Z-C6H4OH.
