Product Design
Subject: Pharmacological Testing of Nicotine Analogues
Abstract
Lists all of the compounds which have been submitted for pharmacological testing. Lists name of compound and the catalogue number in parentheses. Notes that they have received complete data on only one-third of the compounds and requests that data be sent as soon as it is available, so that it might be determined earlier whether or not testing of a particular compound should be continued. Demonstrates interest in "assessing potential nicotine antagonism for at least some of our synthetic analogues, and establishment of some type of assay to determine competitive binding."
Fields
- Author
- Sanders, Edward B. (Ted), Ph.D. (PM Dir. of Chemical Research)Neuchatel, '99
- Recipient
- Osdene, Thomas Stefan, Ph.D. (Director of Science and Technology, Philip Morris [1986])Ph.D. in Organic Chemistry. Ten years of research when he started with PM in 1965. Worked in Chemical Research Division of PM 1965-66; Chemical and Biological Research Division 1966-69; Director of Research 1969-1984, also assumed independent position as Director of Research and Extramural Studies during these years; became Director of Science and Technology in 1984, reporting directly to Philip Morris USA Executive VP Mark Serrano. Involved with Center for Indoor Air Research (CIAR) 1988. Attended PM's Operation Downunder Conference in June, 1987. Retired 1993.
- Hypothesis
- Use of additivesModification of tobacco products through use of additives and measuring effects on dependence, behavior, and toxicity.
- Keyword
- "Frog posture" data
- LD50
- Nicotine antagonism
- Nicotinic responses
- Pharmacological testing
- LD50
- Smoke Constituent
- 1-methyl-2-(4-bromophenyl)pyrrolidine
- 1-methyl-2-(3-bromophenyl)pyrrolidine
- trans-5-carbomethoxynicotine
- trans-3-methylnicotine
- Nicotine-5-carboxamide
- l-nicotine
- l-n-methylanabasine
- l-anabasine
- l-6-methylnicotine
- d,l-nornicotine
- d,l-nicotine
- d,l-4-methylnicotine
- d,l-2-methylnicotine
- d,l-2,6-dimethylnicotine
- cis-5-methylnicotine
- Cis-5-carbomethyoxynicotine
- cis-3-methylnicotine
- 5-methylnicotine
- 5-cyanonicotine
- 1-methyl-2-phenylpyrrolidine
- 1-methyl-2-(4-trimethylsilylphenyl)pyrrolidine
- 1-methyl-2-(4-trifluoromethylphenyl)pyrrolidine
- 1-methyl-2-(4-methylphenyl)pyrrolidine
- 1-methyl-2-(4-fluorophenyl)pyrrolidine
- 1-methyl-2-(4-chlorophenyl)pyrrolidine
- Nornicotine
- 1-methyl-2-(3-chlorophenyl)pyrrolidine
- 1-methyl-2-(3-fluorophenyl)pyrrolidine
- 1-methyl-2-(3-methylphenyl)pyrrolidine
- 1-methyl-2-(3-methoxyphenyl)pyrrolidine
- 1-methyl-2-(3-trifluoromethylphenyl)pyrrolidine
- 1-methyl-2-(3-bromophenyl)pyrrolidine
- Subject
- nicotine analogues (Technology)
Document Images
To: Dr. T. S. Osdene
From: E. B. Sanders
Subject: Pharmacological Testing of Nicotine Analogues
Following is a list of all compounds submitted to date
for pharmacological testing:
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.
22.
23.
24.
25.
~ 26.
27.
28.
29.
30.
Nicotine-5'-carbosamide (CR-1271)
cis -5' -Carbomethoxynicot ine (CR-12 72A)
d,t,-Nornicotine (CR-1289)
d,LNicotine (CR-1290)
J-Nicotine (CR-1290A)
.,t-Anabas ine (CR-1315A)
,i-N' -Methylanabas ine (CR-1316A)
5'-Cyanonicotine (CR-1328)
cis-5'-Methylnicotine (CR-1336)
trans -5'-Carbomethoxynicotine (CR-1356)
d1-2-Methylnicotine (CR-1408)
d,J-2,6-Dimethylnicotine (CR-1461)
dJ-4-Methylnicotine (CR-1538)
R-6-Methylnicotine (CR-1542)
1-Methyl-2-13henylpyrrolidine (CR-1363)
1-Methyl-2-(4-chlorophenyl)pyrrolidine
(CR-1366)
1-Methyl-2-(4-bromophenyl)pyrrolidias (CR-1377)
1-Methyl-2-(3-chlorophenyl)pyrrolidine (CR-1385)
1-Methyl-2-(3-bromophenyl)pyrrolidine (CR-1392)
1-Methyl-2-(4-fluorophenyl)pyrrolidine (CR-1398)
1-Methyl-2-(3-fluorophenyl)pyrrolidine (CR-1399)
1-Methyl-2-(4-trifluoromethylphenyl)pyrrolidine (CR-1406)
1-Methyl-2-(3-trifluoromethylphenyl)pyrrolidine (CR-1407)
1-Methyl-2-(3-rnethoxyphenyl)pyrrolidine (CR-1445)
1-Methyl-2-(3-methylphenyl)pyrrolidine (CR-1449)
1-Methyl-2G(4-trimethylsilylphenyl)pyrrolidine (CR-1480)
1-Methyl-2-(4-methylphenyl)pyrrolidine (CR-1485)
cis-3'-Methylnicotine (CR-1494)
trans-3'-Methylnicotine (CR-1495)
5-Methylnicotine (CR-1523)
At this time we have received data for all test systems for
2.
compounds one through eleven, and partial data on compounds
twelve through fourteen. The data we have received have all been
in the form of simply average numbers, w ith the exception of
LD50 and "Frog Posture" data, where we have received full reports.
The Xa two reports we have received are magnificent. From
our point of x=x$hax view, the reports we haven't received
are of far,
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W e ore ote ial~ ~n erPrt tha the twn we h4v re e~ved.
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We realize tha thorough pharmac logical testing alces
considerable time. Nevertheless, it is difficult to proceed
with our program unless we have feedback. One suggestion which
might be profitable is for us to receive partial data on
compounds w e sen as fast as it b ecomes available. It is
possible that we might be able to determine from such data that
a given compound might be of less intesest than some others
and further testing g3o couldbe deferred. 21 I feel that
such an idea has merit.
Lastly, we have previously mentioned g bax$ our interest
in assessing potential nicotine antagonism for at least some
of our synthetic analogues, and establishment of some type
of assay to determine competitive binding at as pure a cholinergic
receptor site as is possible to convenientty to work with. W
Your comments on these two aspects would be greatly apxpx
appreciated.
