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Daniel Lednicer

Dan Lednicer said:
You must admit that "Who is Daniel Lednicer?" is a rather attention-grabbing hit!!
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Note that this thread is the 4th hit on Google for "Daniel Lednicer".

Glad to see you here, sir :) I hope you don't think it rude that I posted your email addresss - I certainly wouldn't have done it if it wasn't publicly available (on PubMed).
 
I wonder if Lednicer knows that someone is adding every synthesis schema in his series to Wikipedia and in many cases also copying his text word for word.
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It could be the OP- In fact, these days I've read where he brags about how well he knows him, has worked with him.

That's why old threads by banned members shouldn't be resurrected.
 
A Chat with Dan

Dr Daniel Lednicer has lost his wife between now and last Christmas. He told me as a passing phrase - he's still mourning. Anyone who has a connection to Daniel are better not to mention it. He heard it was my birthday and what did I want. So, winging it's way to me is a signed & framed sketch of MDPC (the p-Me analogue that they forgot to test in the original work (facepalm).

I've sent him a copy of the paper 'Design, Synthesis and Biological Evaluation of 3-Amino-3-phenylpropionamide Derivatives as Novel Opioid Receptor Ligands'
Bioorganic & Medicinal Chemistry Letters 10 (2000) 523±526

Interesting that the O in the amide acts like the -OH in MDPC. The 2 compounds closely overlay except the one above has a secondary amine. Dan's going to look through all his papers to see if any MDPC derivatives displayed kappa activity.

I mention the above because it uses the dimethyl moiety to fix conformal isomerism... and the strongest overlays BDPC, It could be a kappa antagonist, for all I know.
 
People SHOULD contact the great chemists while there is time to do so. Paul Janssen passed away 12 years ago, Kenneth Bentley 8 years ago. If there is someone YOU would like to ask, they are retired now, but a REAL medicinal chemist has an element of single-mindedness and a polite E-mail or letter has never, in my experience, gone ignored. Danial Lednicer is easy to find. He paints miniatures which he sells. I don't think he charges a fortune for a commission and who wouldn't like a painting of BDPC or as I am going to ask him. 4 minatures. 1 with BDPC, 1 with etorphine, 1 with OHMEfentanyl and one with the strong etonitazene derivatives (wiki page includes references to compound x4 more potent).



As for the paper I mentione above - it's on the net and overlays MDPC (and BDPC) VERY well. As I have pointed out, ALL of the very potent opioids have 2 aromatics and that alkene (as seen in allylprodine) is certainly important. Check out the relative potencies from the patent. If anyone can point to other examples, I would be very grateful.
 
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clubcard said:
the strong etonitazene derivatives (wiki page includes references to compound x4 more potent).
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Can you elaborate on this? None of the compounds in the references listed on the wikipedia page are more potent than etonitazene. The referenced patent is about carbamoyl derivatives, so I am guessing the compound you are referring to belongs to that class. The carbamoyl derivative of clonitazene (marked as #4 in the other reference, from the journal Experentia) was about as potent as clonitazene (marked as #8 ). They didn't specifically test the carbamoyl derivative of etonitazene, but my copy of the book "Opioid Analgesics" states on p. 387 that the carbamoyl derivative of etonitazene is only 1/5 as potent as etonitazene.
 
Yes, the x4 potency modification is mentioned, When initially contacting a chemist, you have to ask a serious chemical question - then they are happy to talk and be friends. How do you think Dr. Dave gets some of his work from? Independent chemists E-mailing results.

It IS sad Seiko, they were together for more than 50 years. I got a christmas card from both but with one thing and another, I never got around to talking to him ;-( When such a good friend is in pain, but 4000 miles away, its difficult to know what to do so I am writing me a letter. I insisted on reciprocating the gift so he told me to donate to Planned Parenthood. Have you seen how many books he has written? Talking with younger chemists is good for him - makes him feel useful (and being one of the 20th centuries greatest chemists, he is!).

FREEDOM OF SPEECH
 
clubcard said:
Yes, the x4 potency modification is mentioned,
FREEDOM OF SPEECH
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Your reply was not very helpful. If I could find where they mentioned the compound in the article then I wouldn't have asked you to elaborate. None of the 14 compounds in the table were more potent than etonitazene.
 
The 3rd & 4th line with the references? I just find them - I'm not an artist. I have all of the papers and spent a long time finding WHY adding a -CONH2 worked. Yhey tried ketones and alcohols but the amide is a hydrogen-bond acceptor. The research on pharmocores identify an aromatic, 2 hydrogen-bond acceptors and a positively ionized function. I think I've made it clear that ALL of the high-potency compounds from N-phenylethyl nor-levorphanol to W-18, BDPC and the fentanyls have a second aromatic. Then their is the rare alkene - trying to find sufficient compounds for a training set will be tricky.

I don't wish to MAKE any of these compounds - I want to build the BEST pharmocore known to medicine so rational design can find more compounds. The ORL1 & mu are successfully mated in the etonitazene derivatives - could prote to be an alternative to the mu + NMDA compounds seemingly every country has (USA - levorphanol, UK - Diconal, Netherlands/Belgium - piritramide, Ketobemidone - Scandinavia and so on).

FREEDOM OF SPEECH
 
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I'm referencing the wikipedia article you cited, specifically references 3 and 4 that you said described a compound 4x etonitazene. I'm asking for you to please specify where I should look in reference 4 to find a description of this compound (the compound #, or the page and paragraph). Because I don't see anything in the article about the compound you are talking about. There are 14 compounds listed in the Experentia article (reference 4), and none of them was found to be more potent then etonitazene.

Reference 3 (a patent) doesn't list potency data, so that can't be what you are referring to.

I am confused because in reference 4, they are saying that adding a -CONH2 did not increase potency over the parent compound. In the case of etonitazene, other papers have shown that a -CONH2 causes potency to drop by 80%.
 
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You need to read reference 4-the one in German; they CLEARLY state that potency is x4 - based on the fact that etonitazene is only x60 morphine in mammals. LOTS of opioids show HUGE potency in rodents; ratatonia is a fact of life. They discuss x200+. I don''t think the Straub test or affinity values were common Anyway, getting back to Dr. Lendicer. I think the work I'm doing on pharmocores are of interest - he wants a copy of the paper... of course, GETTING the paper published in a GOOD periodicals might need his help. I would never ask him, nor would he ever support a work that wasn't professional.

Put simply - why do a set of totally different compounds exhibit SUCH affinity? I don't know but using the methodology of 'Insights into subtype selectivity of opioid agonists by ligand-based and structure-based methods' is a modern, accepted methodology. If I know Dan, he will edit, work to get it published and then leave his name off - he's a VERY generous man. As the only newer work is by Schmidhammer who is excellent (although avoiding NaH is among my wish-list) but is very formal in communications. You have to limit yourself to specific steps or compounds.
 
I read reference 4 in German. You are totally misstating the potency. If etonitazene is significantly less potent in mammals vs. mice/dogs, then you can't compare etonitazene potency in mammals vs. etonitazene-CONH2 data from mice and dogs. The problem with doing that is that if mammals are less sensitive to etonitazene then they would most likely also be less sensitive to etonitazene-CONH2. The only way to know that a compound is more potent than etonitazene is if both compounds were tested in the same species using the same assay.
 
OK, heres the FULL set

US Patents 294002,2944062,2980690,300890
Some Branched-chain Analogues of Analgesically Active I -(2-Aminoeth'yl)-
2-benzyl benzimidazole Derivatives' By A. F. Casy and J. Wright
Benzimidazol-Derivate und verwandte Heterocyclen VI l) Synthese von Phenyl-[l-aminoalkyl-benzimidazolyl-(2)]-essigsaureesternund -amiden von A. Hunger, J. Kebrle, A. Rossi und K. Hoffmann

plus the ones I marked on Wiki. The QSAR has been researched a LOT!

FREEDOM OF SPEECH
 
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