Parallel synthesis of chiral pentaamines and pyrrolidine containing bis-heterocyclic libraries. Multiple scaffolds with multiple building blocks: a double diversity for the identification of new antitubercular compounds.
Combinatorial chemistry offers a unique opportunity for the synthesis and screening of large numbers of compounds and significantly enhances the prospect of finding new drugs. Collaborative efforts with the Tuberculosis Antimicrobial Acquisition & Coordinating Facility (TAACF), have led to the identification of submicromolar novel antitubercular hits. Chiral pentaamines and bis-heterocyclic compounds with 90-100% inhibition against Mycobacterium tuberculosis strain H(37)R(v) were identified. Some of the identified compounds are more active than the existing drug ethambutol.
Nefzi
Adel
A
Torrey Pines Institute for Molecular Studies, 3550 Genearl Atomocs Court, San Diego, CA 92121, USA. adeln@tpims.org
Appel
Jon
J
Arutyunyan
Sergey
S
Houghten
Richard A
RA
D000588:Amines / Q000737:chemistry*; D000995:Antitubercular Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D020650:Combinatorial Chemistry Techniques; D006571:Heterocyclic Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D011759:Pyrrolidines / Q000737:chemistry*; D054852:Small Molecule Libraries
D000588:Amines; D000995:Antitubercular Agents; D006571:Heterocyclic Compounds; D011759:Pyrrolidines; D054852:Small Molecule Libraries; C032519:pyrrolidine