here is an approach to generating hundreds of new pharmaceutically active compounds any thoughts are welcome
Creating hundreds or thousands of new physiologically active predrugs with the halogenated amplification of naturally ocurring plant plus organism concentrates
Finding fresh drug cores
The nifty way to find what new molecular cores are physiologically active is to use the way halogens like chlorine or fluorine amplify the physiological effect of a molecule hundreds or even (possibly) thousands of times Splenda is chlorosucrose 300 times more active at the receptor than sugar fluorocortisone is 700 times physiologically stronger than cortisone chloral hydrate is basically chloroethanol It is much more effective at causing sleep than ethyl alcohol
View these drug cores
Compare the middle of these two drugs one is estrogen which is basically a variation of cholesterol This new one which might have drug effects is based on hopanoid which is just cholesterol with more <=> I thought "I wonder if they have made hopanoid estrogen yet" just a few months from that thought there the first estronic hopanoid was created then characterized Just one there are possibly hundreds of popular molecules based on the cholesterol core
hopanoid.jpg 10.17KB
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Cholesterol.png 47.85KB
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Estriol.jpg 23.73KB
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What will be the effect of those hopanoid steroids as well as cortisol like chemicals Numerous new drugs may be produced with fresh molecular cores
Halogenation reactions on simple plant or organism concentrates
There is a published simple way to chlorinate naturally occuring organic molecules the tocopherol chlorination at http://www.ncbi.nlm....Pubmed_RVDocSum
Its pretty much dissolve concentrated material with rubber cement thinner then add bleach, swirl one to three minutes then crystallize from solvent or solvent aqueous extract (swirl liquid on water then crystallize what dissolves)
The idea here is just to make various plant as well as organism concentrates concentrate them with simple crystallization or solvent purification then chlorinate them then see if the chlorinated natural molecules haqve physiological effects now that many of them have been affinity amplified
Visualize a plant with 300 different molecules any of which is completely prior to any testing on c elegans to see effect Even if just two or three of those three hundred chemicals actually creates an amplified affinity form with chlorination then you have still created a new predrug that acts like 300 or 700 mg of purified material amidst nonactive versions which is sufficient to verify that the chloroversion of that material does something even with just a mg of material
The idea is to compare the known molecular cores of all the drugs at the pharmacopia with the new chloropredrugs that have any effect to see if new molecular drug cores have been found
From there we create variations on the new drug cores typically methylation or creating a =o from a -o- as well as the obvious thrill of the molecular model having a LUMO form where you could change groups to change affinities I dont know much about that buts computerwise its kind of like just clicking sample side groups to movie the orbital electron density around
Testing on c elegans or daphnia with multiwell plates
The 96 or larger multiwell plate that uses c elegans or possibly daphnia to detect physiological response is fairly recent I saw an award about it during 2008 or 2009 It permits the automated testing of physiological activy of perhaps 1100 chloropredrug compounds per hour if you are having a one c elegans one drug kind of afternoon (humor)
That might make sense as a different geographically distant researcher could duplicate your activity to control for oddities like lab lighting or group of sleepy c elegans I think intralab replication is much less statistically rigorous The different distant lab replication plus if you are actually screening 10,000 chloropredrugs every 24 hours on a multiwell plate machine the replication would be more numerically powerful as two separated labs validating
What to do with all those new physiologically active chemicals is the big thing
I noticed that things that seemed obvious to me like making chloroversions of some of the most prescribed medications awaits Niacin is a very common anticholesterol drug Halogenated niacin or versions where a P replaces the N on the molecule appear not to have been described or thats the way is seems with a very minimal online effort
If elemental as well as halovariations of highly popular drugs haven't had published research yet what do your possibly hundreds of new molecular drug cores do to become characterized sufficiently to become medications well much n vitro sampling on what are called cytopanels of cultured tissue is well known I think
Technology transfer may be assisted with this slightly novel protocol Different Universities have different cultures as well as contact groups Of the top 1000 universities most have technology transfer departments with similar standard forms
Basically you find two or three researchers at each university willing to be either an actual researcher or just of value a passthru (they get money if the IP work even absent effort) to that universitys technology transfer department The universities start the patent process on a few hundred of the better compounds This provides the University staff as a communications force as well as the professionally comfy way to bundle the new chemicals for private sector motivation
Then as each new chemical is transferred or sidelined you then systematically rotate the chemicals through the different universities The unused MIT IP goes to Stanford The unused Stanford IP goes to Michigan with a strong geographic rotation
Further the compounds can be rotated through various nations on those peculiar cultural events when other countries have standardized University private sector tech transfer deepartments Remembering each time to find a staff sponsor who may or may not actually further the research yet permits the passthru of the IP to that countrys private sector If MIT doesn't transfer it perhaps Cambridge or ETH has connection to a European company.
Heres a procedure that chlorinates naturally occuring plant or other material concentrates
Reaction of ã-Tocopherol with Hypochlorous Acid Quyen Nguyen1 and Peter T. Southwell-Keely Lipids. 2007 Mar;42(2):171-8
This is a study of the reactivity of ã-tocopherol with hypochlorous acid/hypochlorite Aqueous sodium hypochlorite (1.72 mmol; pH 7.4) was stirred with ã-tocopherol (0.12 mmol) in hexane for 2 min at room temperature. The following products were isolated: ã-tocopheryl quinone (0.6%), tocored (10%), 3-chloro-ã-tocopheryl quinone (14%), an ether dimer of 3-chloro-ã-tocopheryl quinone (0.4%), two isomers of 5-(5-ã-tocopheryl)-ã-tocopherol (3 and 2% respectively), 5-chloro-ã-tocopherol (14%) and two chlorinated dimers (14 and 24% respectively) which were identified as diastereomers of (3R,10R)-11a-chloro-2,3,9,10-tetrahydro-3,5,6,10,12,13-hexamethyl-3,10-bis[(4R,8R)-4,8,12-trimethyltridecyl]- 1H-pyrano(3,2a)-8H-pyrano(3,2g)-dibenzofuran-14(7aH)(14aH)-one. The chlorinated dimers, 5-chloro-ã-tocopherol, 3-chloro-ã-tocopheryl quinone and its ether dimer are new compounds
typical reaction, 1 (50 mg, 0.12 mmol) was dissolved in hexane (3 mL) and stirred with NaOCl (128 mg, 1.72 mmol) in water (3 mL, adjusted to pH 7.4 with HCl) for 2 min at room temperature. The hexane layer was washed with water until neutral, dried (Na2SO4), and the solvent removed in vacuo. The residue was chromatographed on thin layers of silica gel using light petroleum/ethyl acetate (19:1, v/v) as eluting solvent
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0 downloadsI've thought about simply getting everything from Kava to Cocoa at the grocery then chlorinating the concentrate with the rubber cement thinner plus bleach protocol described Then chlorinating it Cocoa has PEA The pharmaceutical 2CB is a halogenated Phenylethylamine perhaps chlorococoa is pleasant
Public domain copy then send to persons or public sites you think may actually create things Haloderivatives of unregulated natural products are to as far as I know legal
