Disclosure Statement
I am not a medical expert; I am a researcher who wanted to help tackle the problem of antibiotic resistance. If medical professionals or drug developers find this data useful, I hope they use it to create safe, effective, and affordable treatments for those who need them most.
Overview
These molecules feature a central imidazole core with bis-dioxolane "wings," providing a high Fraction Csp3 (0.80) to facilitate evasion of the AcrAB-TolC efflux pump system in Gram-negative pathogens.
Lead Compounds
LAZ-1011
SMILES
CC1(C)OCC(c2cn(C3COC(C)(C)OC3)cn2)CO1
Properties
- • Original discovery
- • Best-in-class QED: 0.84
- • Strong LasR/QscR binding
- • Fraction Csp3: 0.80
LAZ-1123
SMILES
COC1(C)OCC(n2cnc(C3COC(C)(C)OC3)c2)CO1
Properties
- • Optimized variant
- • Aqueous solubility (LogS): -0.94
- • Improved TPSA: 63.97
- • Fraction Csp3: 0.80
Markush Family (Formula I)
Core — (X) — (Y)
- • Core: 5-membered aromatic nitrogen heterocycle (Imidazole or Triazole)
- • X and Y: Independent 1,3-dioxolane rings
- • Substitution: At least one ring comprises R group where R is H, C1-C6 alkyl, or C1-C6 alkoxy
Technical Methodology
These leads were discovered and validated using open-source computational tools:
The "Troll Shield": Defensive Disclosure
To prevent this chemical space from being locked away by patent trolls, Nicholas Panek establishes comprehensive Prior Art for the Markush family defined above. This disclosure asserts that any future claim regarding 3D-globular (Fsp3 > 0.75) scaffolds for MetAP or Quorum Sensing inhibition based on this genus is anticipated by this document.
Key Technical Advantage
Efflux Evasion: The high Fraction Csp3 (0.80) creates a non-planar geometry that limits recognition and ejection by the AcrAB-TolC efflux pump system in Gram-negative pathogens.
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Public Domain Dedication (CC0 1.0)
Nicholas Panek has dedicated this work to the public domain by waiving all rights worldwide under copyright law. You are free to copy, modify, and distribute this work, even for commercial purposes, without asking permission. I hope real experts use this to make good, safe medicine that is cheap for the end user.