Author Topic: Replacing Benzene with Naphthalene -Nemesis  (Read 1110 times)

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Replacing Benzene with Naphthalene -Nemesis
« on: April 19, 2000, 08:44:00 AM »

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Author  Topic:   Replacing Benzene with Naphthalene 
Nemesis
Member   posted 11-08-1999 12:59 AM          
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ok I've been led to believe that this would bring out a new group of drugs. I've seen something similar in the phenethylamines with 2C-G-N (1,4-dimethoxynaphthyl-2-ethylamine) and G-N (1,4-dimethoxynaphthyl-2-isopropylamine). Now, there's another Naphthalene hallucinogen called 1,2,3,4-Tetrahydro-5,8-dimethoxy-6-methyl-2-naphthalenamine. I guess my question is what other noval phenethylamines or even tryptamines could be expected from this and how might one produce such a drug by replacing benzene or just adding another aromatic ring to an existing drug such as 2,5-DMA which would produce G-N, place it in the 3,4 or 4,5 positions of amphetamine, phenethylamine, or tryptamine. Also, any input on whether or not anyone thinks this is a very good idea or has any other ideas along the same line, please post. I hope that I am not off topic, I don't believe that I am since all of this is theoretical and only someone with advanced knowledge of chemistry could help me.
Laters, Nemesis


 
Nemesis
Member   posted 11-10-1999 02:16 AM          
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Nemesis
Member   posted 11-11-1999 01:08 AM          
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Something I found that I thought should be here:
TITLE: Substituted naphthofurans as hallucinogenic phenethylamine-ergoline hybrid molecules with unexpected muscarinic antagonist activity.
AUTHORS: Monte AP; Marona-Lewicka D; Lewis MM; Mailman RB; Wainscott DB; Nelson DL; Nichols DE
AUTHOR AFFILIATION: Department of Medicinal Chemistry and Molecular Pharmacology, School of Pharmacy, Purdue University, West Lafayette, Indiana 47907, USA.
SOURCE: J Med Chem 1998 Jun 4;41(12):2134-45
CITATION IDS: PMID: 9622555 UI: 98285679
ABSTRACT: A series of substituted racemic naphthofurans were synthesized as "hybrid" molecules of the two major prototypical hallucinogenic drug classes, the phenethylamines and the tryptamines/ergolines. Although it was hypothesized that these new agents might possess high affinity for the serotonin 5-HT2A/2C receptor subtypes, unexpected affinity for muscarinic receptors was observed. The compounds initially synthesized for this study were (+/-)-anti- and syn-4-amino-6-methoxy-2a,3,4,5- tetrahydro-2H-naphtho[1,8-bc]furan (4a,b), respectively, and their 8- bromo derivatives 4c,d, respectively. The brominated primary amines 4c,d were assayed initially for activity in the two-lever drug discrimination (DD) paradigm in rats trained to discriminate saline from LSD tartrate (0. 08 mg/kg). Also, 4c,d were evaluated for their ability to compete against agonist and antagonist radioligands at cloned human 5-HT2A, 5-HT2B, and 5-HT2C receptors. After the syn diastereomers were found to have the highest activity in these preliminary assays, the N-alkylated analogues syn-N,N-dimethyl-4-amino- 6-methoxy-2a,3,4, 5-tetrahydro-2H-naphtho[1,8-bc]furan (4e) and syn-N, N-dipropyl-4-amino-6-methoxy-2a,3,4,5-tetrahydro-2H-naphtho[1, 8- bc]furan (4f) were prepared and assayed for their affinities at [3H]ketanserin-labeled 5-HT2A and [3H]-8-OH-DPAT-labeled 5-HT1A sites. All of the molecules tested had relatively low affinity for serotonin receptors, yet a preliminary screen indicated that compound 4d had affinity for muscarinic receptors. Thus, 4b,d,e were evaluated for their affinity at muscarinic M1-M5 receptors and also assessed for their functional characteristics at the M1 and M2 isoforms. Compound 4d had affinities of 12-33 nM at all of the muscarinic sites, with 4b,e having much lower affinity. All three compounds fully antagonized the effects of carbachol at the M1 receptor, while only 4d completely antagonized carbachol at the M2 receptor. The fact that the naphthofurans lack LSD-like activity suggests that they do not bind to the serotonin receptor in a way such that the tricyclic naphthofuran nucleus is bioisosteric with, and directly superimposable upon, the A, B, and C rings of LSD. This also implies, therefore, that the hallucinogenic phenethylamines cannot be directly superimposed on LSD in a common binding orientation for these two chemical classes, contrary to previous hypotheses.
MAIN MESH HEADINGS: Ergolines/*chemistry
*Furans
*Hallucinogens
*Muscarinic Antagonists
Phenethylamines/*chemistry
*Tetrahydronaphthalenes
*Tetrahydronaphthalenes/chemistry
*Tetrahydronaphthalenes/chemical synthesis
*Tetrahydronaphthalenes/metabolism
*Tetrahydronaphthalenes/pharmacology
ADDITIONAL MESH HEADINGS: Animal
Binding, Competitive
Brain/metabolism
Cell Line
Discrimination Learning/drug effects
Furans/chemistry
Furans/chemical synthesis
Furans/metabolism
Furans/pharmacology
Hallucinogens/chemistry
Hallucinogens/chemical synthesis
Hallucinogens/metabolism
Hallucinogens/pharmacology
Hamsters
Human
Lysergic Acid Diethylamide/pharmacology
Male
Mice
Muscarinic Antagonists/chemistry
Muscarinic Antagonists/chemical synthesis
Muscarinic Antagonists/metabolism
Muscarinic Antagonists/pharmacology
Rats
Rats, Sprague-Dawley
Receptors, Muscarinic/metabolism
Receptors, Serotonin/metabolism
Recombinant Proteins/metabolism
Stereoisomerism
Structure-Activity Relationship
Support, U.S. Gov't, P.H.S.
PUBLICATION TYPES: JOURNAL ARTICLE
CAS REGISTRY NUMBERS: 0 (syn-4-amino-8-bromo-6-methoxy-2a,3,4,5-tetrahydro-2H-naphtho(1,8- bc)furan)
0 (Ergolines)
0 (Furans)
0 (Hallucinogens)
0 (Muscarinic Antagonists)
0 (Phenethylamines)
0 (Receptors, Muscarinic)
0 (Receptors, Serotonin)
0 (Recombinant Proteins)
0 (Tetrahydronaphthalenes)
50-37-3 (Lysergic Acid Diethylamide)
64-04-0 (phenethylamine)
LANGUAGES: Eng
GRANT/CONTRACT ID: DA02189/DA/NIDA
MH33127/MH/NIMH
HD03310/HD/NICHD
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