Substituted tetracyclic tetrahydrofuran derivatives

Details Substituted tetracyclic tetrahydrofuran derivatives Substituted tetracyclic tetrahydrofuran derivatives

1998-10-06

2000-05-02

Kight, John

Organic compounds -- part of the class 532-570 series

Organic compounds

Unsubstituted hydrocarbyl chain between the ring and the -c-...

540587, 544359, 544375, 544380, 546192, 546195, 546197, 546202, 548517, 548454, 548525, 548526, 548527, 548528, 548529, 549 12, 549354, C07D22314, C07D33712, C07D31300, C07D21108, C07D40500

Patent

active

060574410

DESCRIPTION:

BRIEF SUMMARY
This invention concerns substituted tetracylic tetrahydrofuran derivatives having antipsychotic, cardiovascular and gastrokinetic activity and their preparations; it further relates to compositions comprising them, as well as their use as a medicine.
An article by Monkovic et al. (J. Med. Chem. (1973), 16(4), p. 403-407) describes the synthesis of (.+-.)-3,3a,8,12b-tetrahydro-N-methyl-2H-dibenzo[3,4:6,7]-cyclohepta[1,2-b ]furan-2-methanamine oxalic acid. Said compound was synthesized as potential antidepressant; however, it was found that this particular tetrahydrofurfurylamine derivative was inactive as antidepressant at a dose of 300 mg/kg. Compounds of similar structure are disclosed in U.S. Pat. No. 4,145,434, published on Mar. 20, 1979, and involve dibenzo(cyclohepta-, oxepino-, thiepino-) pyrrolidine derivatives as well as dibenzopyrrolidino azepine derivatives, having CNS-depressant, antihistamine and antiserotonin activities. The present compounds differ therefrom structurally by the presence of a tetrahydrofuran ring instead of a pyrrolidine ring, and are further distinguished by valuable pharmacological properties, in particular, they suppress mCPP (metachlorophenylpiperazine) induced effects in rats.
This invention concerns compounds of formula (I) ##STR2## the N-oxide forms, the pharmaceutically acceptable addition salts and the stereochemically isomeric forms thereof, wherein: C.sub.1-6 alkylcarbonyl;halomethylcarbonyl; C.sub.1-6 alkyl substituted with hydroxy, C.sub.1-6 alkyloxy, carboxyl, C.sub.1-6 alkylcarbonyloxy, C.sub.1-6 alkyloxycarbonyl or aryl; or R.sup.1 and R.sup.2 taken together with the nitrogen atom to which they are attached may form a morpholinyl ring or a radical of formula: ##STR3## wherein: R.sup.9, R.sup.10, R.sup.11 and R.sup.12 each independently are hydrogen, halo, halomethyl, or C.sub.1-6 alkyl; C.sub.1-6 alkyl, aryl or arylcarbonyl; or alkanediyl; halomethylcarbonyl; substituted with hydroxy, alkyloxycarbonyl or aryl; carboxyl, nitro, amino, mono- or di(C.sub.1-6 alkyl)amino, C.sub.1-6 alkylcarbonylamino, aminosulfonyl, mono- or di(C.sub.1-6 alkyl)aminosulfonyl, C.sub.1-6 alkyl, C.sub.1-6 alkyloxy, C.sub.1-6 alkylcarbonyl, C.sub.1-6 alkyloxycarbonyl; halomethoxy, carboxyl, nitro, amino, mono- or di(C.sub.1-6 alkyl)amino, C.sub.1-6 alkylcarbonylamino, aminosulfonyl, mono- or di(C.sub.1-6 alkyl)aminosulfonyl, C.sub.1-6 alkyl, C.sub.1-6 alkyloxy, C.sub.1-6 alkylcarbonyl, C.sub.1-6 alkyloxycarbonyl; wherein alkyl, halomethyl, C.sub.1-6 alkyloxy or R.sup.6 or R.sup.7 taken together may form methylene; mono- or di(cyano)methylene; a bivalent radical of formula --(CH.sub.2).sub.2 --, --(CH.sub.2).sub.3 --, --(CH.sub.2).sub.4 --, --(CH.sub.2).sub.5 --, --O--(CH.sub.2).sub.2 --O--, --O--(CH.sub.2).sub.3 --O--; or, together with the carbon atom to which they are attached, a carbonyl; arylcarbonyl, arylC.sub.1-6 alkylcarbonyl, C.sub.1-6 alkylsulfonyl, arylsulfonyl or arylC.sub.1-6 alkylsulfonyl; from halo, hydroxy, C.sub.1-6 alkyl and halomethyl; (.+-.)-3,3a,8,12b-tetrahydro-N-methyl-2H-dibenzo[3,4:6,7]-cyclohepta[1,2-b ]furan-2-methanamine oxalic acid.
In the foregoing definitions C.sub.1-6 alkyl defines straight and branch chained saturated hydrocarbon radicals having from 1 to 6 carbon atoms such as, for example, methyl, ethyl, propyl, butyl, 1-methylpropyl, 1,1-dimethylethyl, pentyl, hexyl; C.sub.4-5 alkanediyl defines bivalent straight and branch chained saturated hydrocarbon radicals having from 4 to 5 carbon atoms such as, for example, 1,4-butanediyl, 1,5-pentanediyl; halo is generic to fluoro, chloro, bromo and iodo. The term monocyanomethylene stands for a radical of formula .dbd.CHCN, and dicyanomethylene for a radical of formula .dbd.C(CN).sub.2. The term halomethyl is meant to include mono, di-, and trihalomethyl. Examples of halomethyl are fluoromethyl, difluoromethyl and particularly trifluoromethyl. In case R.sup.6 and R.sup.7 taken together form a bivalent radical of formula --(CH.sub.2).sub.2 --, --(CH.sub.2).sub.3 --, --(CH.sub.2).sub.4 --, --(CH.sub.2).sub.5 --

REFERENCES:
patent: 5089507 (1992-02-01), Vecchietti et al.
patent: 5286735 (1994-02-01), Bonnaud et al.
patent: 5310743 (1994-05-01), Schilling et al.
patent: 5541195 (1996-07-01), Schilling et al.
patent: 5646144 (1997-07-01), Schilling et al.
Goodman & Gilman's, The Pharmacological Basis of Therapeutics, ninth edition, McGraw-Hill, New York, Chapter 7:148-160 (1996).

Affiliated with

Also associated with

Rating

Substituted tetracyclic tetrahydrofuran derivatives does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Substituted tetracyclic tetrahydrofuran derivatives, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Substituted tetracyclic tetrahydrofuran derivatives will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-1594920