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Design and synthesis of novel antileishmanial compounds.

Loedige M - Int J Med Chem (2015)

Bottom Line: According to the WHO, infectious diseases, and in particular neglected tropical diseases in poor developing countries, still play a significant role in a vast number of deaths reported worldwide.This synthetic approach allows for rapid access to new active antileishmanial drug templates and their first derivatives in moderate to very good yields.Although the compounds reported here are bioactive, the detailed biological results are part of a more comprehensive study and will be reported separately by our collaborators.

View Article: PubMed Central - PubMed

Affiliation: Institute of Organic Chemistry, University of Würzburg, Am Hubland, 97074 Würzburg, Germany.

ABSTRACT
According to the WHO, infectious diseases, and in particular neglected tropical diseases in poor developing countries, still play a significant role in a vast number of deaths reported worldwide. Among them, leishmaniasis occurs as a complex and clinically diverse illness caused by protozoan Leishmania species which are transmitted through the bite of sandflies. They develop through a complex life cycle, from promastigotes in sandflies to amastigotes in humans. The severity of disease is determined by the type of infecting Leishmania species and also depends strongly on whether the parasite infection leads to a systemic involvement or not. Since the sensitivity towards diverse medicaments highly differs among the Leishmania species, it is advantageous to treat leishmaniasis with species-specific drugs. Towards this goal we report a synthetic methodology and characterization of novel small molecular agents active against both forms of L. major. This synthetic approach allows for rapid access to new active antileishmanial drug templates and their first derivatives in moderate to very good yields. Although the compounds reported here are bioactive, the detailed biological results are part of a more comprehensive study and will be reported separately by our collaborators.

No MeSH data available.


Related in: MedlinePlus

Synthesized analogs (31 to 35) of the assumed pharmacophore moiety. Reagents and conditions: (a) 3,3-dimethylbutanoylchloride, NEt3, DCM (dry), 0–25°C; (b) (rac)-1,4-dibromopentane, NaH, DMF (dry), 0–25°C; (c) NaN3, DMF (dry), 25°C; (d) PPh3, MeOH (dry), 25°C.
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sch7: Synthesized analogs (31 to 35) of the assumed pharmacophore moiety. Reagents and conditions: (a) 3,3-dimethylbutanoylchloride, NEt3, DCM (dry), 0–25°C; (b) (rac)-1,4-dibromopentane, NaH, DMF (dry), 0–25°C; (c) NaN3, DMF (dry), 25°C; (d) PPh3, MeOH (dry), 25°C.

Mentions: In order to investigate which functional groups of the assumed pharmacophore were required for activity, analogs with diverse terminal functional groups in position B were synthesized. The original tert-butyloxycarbonylbenzylamino group was replaced by a N-benzyl-3,3-dimethylbutanamide (Scheme 7) functionality as well as by a phthalimide group (Scheme 8).


Design and synthesis of novel antileishmanial compounds.

Loedige M - Int J Med Chem (2015)

Synthesized analogs (31 to 35) of the assumed pharmacophore moiety. Reagents and conditions: (a) 3,3-dimethylbutanoylchloride, NEt3, DCM (dry), 0–25°C; (b) (rac)-1,4-dibromopentane, NaH, DMF (dry), 0–25°C; (c) NaN3, DMF (dry), 25°C; (d) PPh3, MeOH (dry), 25°C.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4320803&req=5

sch7: Synthesized analogs (31 to 35) of the assumed pharmacophore moiety. Reagents and conditions: (a) 3,3-dimethylbutanoylchloride, NEt3, DCM (dry), 0–25°C; (b) (rac)-1,4-dibromopentane, NaH, DMF (dry), 0–25°C; (c) NaN3, DMF (dry), 25°C; (d) PPh3, MeOH (dry), 25°C.
Mentions: In order to investigate which functional groups of the assumed pharmacophore were required for activity, analogs with diverse terminal functional groups in position B were synthesized. The original tert-butyloxycarbonylbenzylamino group was replaced by a N-benzyl-3,3-dimethylbutanamide (Scheme 7) functionality as well as by a phthalimide group (Scheme 8).

Bottom Line: According to the WHO, infectious diseases, and in particular neglected tropical diseases in poor developing countries, still play a significant role in a vast number of deaths reported worldwide.This synthetic approach allows for rapid access to new active antileishmanial drug templates and their first derivatives in moderate to very good yields.Although the compounds reported here are bioactive, the detailed biological results are part of a more comprehensive study and will be reported separately by our collaborators.

View Article: PubMed Central - PubMed

Affiliation: Institute of Organic Chemistry, University of Würzburg, Am Hubland, 97074 Würzburg, Germany.

ABSTRACT
According to the WHO, infectious diseases, and in particular neglected tropical diseases in poor developing countries, still play a significant role in a vast number of deaths reported worldwide. Among them, leishmaniasis occurs as a complex and clinically diverse illness caused by protozoan Leishmania species which are transmitted through the bite of sandflies. They develop through a complex life cycle, from promastigotes in sandflies to amastigotes in humans. The severity of disease is determined by the type of infecting Leishmania species and also depends strongly on whether the parasite infection leads to a systemic involvement or not. Since the sensitivity towards diverse medicaments highly differs among the Leishmania species, it is advantageous to treat leishmaniasis with species-specific drugs. Towards this goal we report a synthetic methodology and characterization of novel small molecular agents active against both forms of L. major. This synthetic approach allows for rapid access to new active antileishmanial drug templates and their first derivatives in moderate to very good yields. Although the compounds reported here are bioactive, the detailed biological results are part of a more comprehensive study and will be reported separately by our collaborators.

No MeSH data available.


Related in: MedlinePlus