- Synthesis and radioligand binding studies of C-5- and C-8-substituted 1-(3,4-dimethoxybenzyl)-2,2-dimethyl-1,2,3,4-tetrahydroisoquinoliniums as SK channel blockers related to N-methyl-laudanosine and N-methyl-noscapine
-
The synthesis and the 125I-apamin binding studies of original C-5- and C-8-substituted 1-(3,4-dimethoxy-benzyl)-2,2-dimethyl-1,2,3,4- tetrahydroisoquinoliniums and 1-(3,4-dimethoxy-benzyl)-6,6-dimethyl-4,5,6,7- tetrahydrothieno[2,3-c]pyridiniums were performed in order to find a reversible and selective SK channel blocker structurally related to N-methyl-laudanosine and N-methyl-noscapine. A bulky alkyl substituent in the C-8 position of the tetrahydroisoquinoline produces a clear increase in the affinity for the apamin sensitive binding sites. The presence of an electron-withdrawing group in the C-5 and C-8 positions is not a suitable substitution for the affinity of drugs structurally related to N-methyl-laudanosine. Thiophenic analogues and 8-methoxy derivatives possess a poor affinity for the apamin sensitive binding sites. Electrophysiological studies performed with the most effective compound showed a blockade of the apamin sensitive afterhyperpolarization in rat dopaminergic neurons.
- Graulich, Amaury,Scuvée-Moreau, Jacqueline,Seutin, Vincent,Liégeois, Jean-Fran?ois
-
p. 4972 - 4982
(2007/10/03)
-
- AZACYCLIC COMPOUNDS AS INHIBITORS OF SENSORY NEURONE SPECIFIC CHANNELS
-
Compounds of the formula (I), and pharmaceutically acceptable salts thereof, are found to be antagonists of SNS sodium channels. They are therefore useful as analgesic and neuroprotective agents wherein: X is -N- or -CH-; n is from 0 to 3.
- -
-
-
- Studies on anti-Helicobacter pylori agents. Part 1: Benzyloxyisoquinoline derivatives
-
The synthesis and optimization of the anti-Helicobacter pylori activity of a novel series of benzyloxyisoquinoline derivatives that was discovered by a random screening process, are described. In the in vitro assay, compound 10c containing a 3-acetamido-2,6-dichlorobenzyl substituent was found to have extremely potent activity against H. pylori and no activity against other common bacteria. The anti-H. pylori activity of 10c was superior to that of amoxicillin (AMPC) (1) and clarithromycin (CAM) (2). However, 10c did not show in vivo efficacy in a mouse infection model; a feature attributed to the lack of strong bactericidal activity at short contact times. (C) 1999 Elsevier Science Ltd.
- Yoshida, Yoshiki,Barrett, David,Azami, Hidenori,Morinaga, Chizu,Matsumoto, Satoru,Matsumoto, Yoshimi,Takasugi, Hisashi
-
p. 2647 - 2666
(2011/05/18)
-
- Preparation of optically active 8,8′-disubstituted 1,1′-biisoquinoline
-
Synthesis of 1,1′-biisoquinolines having substituents in the 8,8′-positions and their resolution by hplc on a chiral column on a preparative scale are described.
- Hirao, Ken-Ichi,Tsuchiya, Ryuta,Yano, Yasuhiro,Tsue, Hirohito
-
p. 415 - 422
(2007/10/02)
-
- Synthesis of isoquinolines from indanones: Total synthesis of illudinine
-
Schmidt reaction of 5-methoxy or 7-methoxyindan-1-ones or their derivatives results exclusively in isocarbostyrils which are converted into 6-methoxy or 8-methoxyisoquinolines in good yields.This strategy has been extended to the total synthesis of illudinine methyl ester (1b) starting from methyl 8-methoxy-2,2-dimethyl-7-oxo-1,2,3,5,6,7-hexahydro-s-indacene-4-carboxylate (4).
- Shanker, P. Sathya,Rao, G. S. R. Subba
-
p. 1209 - 1213
(2007/10/02)
-
- Synthesis of 1,2,3,4-Tetrahydroisoquinolines
-
Several aspects of 1,2,3,4-tetrahydroisoquinoline synthesis have been examined.An improved synthesis of 2-(m-methoxyphenyl)ethylamine (4) is reported. m-Anisaldehyde (5) was treated with potassium cyanide and ethyl chloroformate to yield O-(ethoxycarbonyl)-3-methoxymandelonitrile (7).Hydrogenation afforded 2-(m-methoxyphenyl)ethylamine (4) in 87percent yield overall.Some observations have been made regarding the reduction of 3,4-dihydroisoquinolines derived from the Bischler-Napieralski reaction.Amides 3a and 3c were cyclized with phosphorus oxychloride, followed by reduction to the corresponding tetrahydroisoquinolines 1a and 1c.It was shown that 1a and 1c were contaminated with 4percent of 2a and 3percent of 2c, respectively.Both 2a and 2c were independently synthesized by routes with general applicability to 8-alkoxy-1,2,3,4-tetrahydroisoquinolines.
- Kashdan, David S.,Schwartz, John A.,Rapoport, Henry
-
p. 2638 - 2643
(2007/10/02)
-