Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1990-09-17
1991-09-24
Dentz, Bernard
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
546113, A61K 31435, C07D47104
Patent
active
050514121
DESCRIPTION:
BRIEF SUMMARY
BACKGROUND OF THE INVENTION
The present invention relates to certain pyrrolopyridines, methods of preparing such compounds, pharmaceutical compositions comprising such compounds, and the use of such compounds in treating obesity, depression, and disorders wherein aggression is a symptom (e.g., schizophrenia).
U.S. Pat. Nos. 4,232,031 and 4,278,677 refer to tetrahydropyridylindoles having antidepressive, antiemetic, antiparkinsonian and neuroleptic activity.
U.S. Pat. Nos. 3,993,764 and 4,196,209 refer to piperidylindoles having antidepressant, antiemetic and antiparkinsonian activity.
J. Guillaume et al., Eur. J. Med. Chem., 22, 33-43 (1987) refer to tetrahydropyridinylindoles having serotoninergic and anti-dopaminergic properties.
K. Freter, J. Org. Chem., 40, 2525-2529 (1975), refers to the react-ion of cyclic ketones and indoles to prepare 3-cycloalkenylindoles.
G. H. Kennet et al., European Journal of Pharmacology, 141, 429-435 (1987), C. Bendotti et al., Life Sciences, 41, 635-642 (1987), M. Carli et al., Psychopharmacology, 94, 359-364 (1988) and P. H. Hutson et al., Psychopharmacology, 95, 550-552 (1988), refer to the effects of RU 24969 (5-methoxy-3(1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole) as a 5-hydroxytryptamine agonist, its potential anxiolytic, and antidepressant effects and its effects on feeding.
SUMMARY OF THE INVENTION
The present invention relates to compounds of the formula ##STR2## wherein one of A, B, D and E is N and the remaining three atoms are C;
R.sup.1 and R.sup.2 are independently selected from hydrogen and C.sub.1 to C.sub.6 alkyl; and R.sup.3, R.sup.4, R.sup.5 and R.sup.6 are independently selected from hydrogen, halogen, hydroxy, C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.8 alkoxy, phenyl-C.sub.1 -C.sub.6 alkoxy, phenoxy, --NR.sup.7 R.sup.8 wherein R.sup.7 and R.sup.8 are independently selected from hydrogen, C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkanoyl, and COOR.sup.9 wherein R.sup.9 is hydrogen or C.sub.1 -C.sub.6 alkyl, cyano, COOR.sup.10 wherein R.sup.10 is hydrogen or C.sub.1 -C.sub.6 alkyl, and CONR.sup.11 R.sup.12 where R.sup.10 and R.sup.11 are independently selected from hydrogen and C.sub.1 -C.sub.6 alkyl, and the pharmaceutically acceptable salts thereof.
The pyrrolo[3,2-b]pyridines of the formula I wherein R.sup.1, R.sup.2, R.sup.5 and R.sup.6 are hydrogen, R.sup.3 is absent, R.sup.4 is as defined above, A is N, and B, D and E are C are preferred. Particularly preferred compounds are the foregoing compounds wherein R.sup.4 is hydrogen, C.sub.1 -C.sub.6 alkoxy (e.g., methoxy) or hydroxy.
Unless otherwise indicated, the alkyl groups referred to herein, as well as the alkyl moieties of other groups referred to herein (e.g., alkoxy and alkanoyl), may be linear or branched. They may also be cyclic or be linear or branched and contain cyclic moieties.
DETAILED DESCRIPTION OF THE INVENTION
The compounds of the formula I are prepared by reacting a compound of the formula ##STR3## wherein A, B, D, E, R.sup.2, R.sup.3, R.sup.4, R.sup.5 and R.sup.6 are as defined above, with a piperidone monohydrate hydrohalide (preferably, the hydrochloride) in the presence of a base. Suitable bases include sodium or potassium alkoxides and alkylmagnesium halides. A preferred base is sodium methoxide. The solvent should be an inert solvent. Suitable solvents include alcohols, dimethylformamide, and tetrahydrofuran. The preferred solvent is methanol. The reaction is conducted at a temperature of about 60.degree. to about 120.degree. C., preferably about 65.degree. to about 70.degree. C., most preferably at the reflux temperature of the solvent. The pressure is not critical. Generally, the reaction will be conducted at a pressure of about 0.5 to about 2 atmospheres, preferably at ambient pressure (about 1 atmosphere).
Compounds of the formula I may be converted into the salt of an inorganic or organic acid, preferably into a pharmaceutically acceptable salt, by reacting substantially stoichiometric amounts of the base and the acid. Examples of such salts are hydrochlorides, hydrobrom
REFERENCES:
patent: 4232031 (1980-11-01), Dumont et al.
patent: 4278677 (1981-07-01), Nedelec et al.
DeBenedictis Karen
Dentz Bernard
Ginsburg Paul H.
Pfizer Inc.
Richardson Peter C.
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