Claims
- 1. A compound of formula (I) or a pharmaceutically acceptable salt or N-oxide thereof: ##STR9## in which R is a substituted lactam ring of formula (i): ##STR10## where Z is oxygen or sulphur; p is 1; and
- P is a substituted or unsubstituted bicyclic ring containing one or two heteroatoms; or P is an unsubstituted or substituted 5- to 7-membered saturated ring containing one or two heteroatoms;
- R.sup.4 and R.sup.5 are independently hydrogen halogen C.sub.1-6 alkyl, C.sub.3-6 cycloalkyl, C.sub.3-6 cycloalkenyl, C.sub.1-6 alkoxy, hydroxyC.sub.1-6 alkyl, C.sub.1-6 alkylOC.sub.1-6 alkyl, acyl, aryl, acyloxy, hydroxy, nitro, trifluoromethyl, cyano, CO.sub.2 R.sup.11, CONR.sup.12 R.sup.13, NR.sup.12 R.sup.13 where R.sup.11, R.sup.12 and R.sup.13 are independently hydrogen or C.sub.1-6 alkyl, or R.sup.4 and R.sup.5 together form a group --(CH.sub.2).sub.r --R.sup.14 --(C.sub.2).sub.s -- where R.sup.14 is O, S, CH.sub.2 or NR.sup.15 where R.sup.15 is hydrogen or C.sub.1-6 alkyl and r and s are independently 0, 1 or 2;
- B is oxygen or sulphur;
- D is nitrogen;
- R.sup.6 together with R.sup.7 forms a group --A-- where A is (CR.sup.16 R.sup.17).sub.t where t is 2 and R.sup.16 and R.sup.17 are independently hydrogen or C.sub.1-6 alkyl;
- R.sup.8 is hydrogen, C.sub.1-6 alkyl, C.sub.3-6 cycloalkyl, C.sub.2-6 alkenyl or C.sub.1-6 alkyIC.sub.3-6 cycloalkyl;
- R.sup.9 and R.sup.10 are independently hydrogen or C.sub.1-6 alkyl;
- E is oxygen;
- G is (CR.sup.21 R.sup.22).sub.n where R.sup.21 and R.sup.22 are independently hydrogen or C.sub.1-6 alkyl and n is 1;
- X and Y are independently CR.sup.9 R.sup.10 where R.sup.9 and R.sup.10 are as defined above; and
- m is 2.
- 2. A compound according to claim 1 in which R.sup.4 is C.sub.1-6 alkyl.
- 3. A compound according to claim 1 in which R.sup.5 is hydrogen.
- 4. A compound according to claim 1 in which E is oxygen and G is CH.sub.2.
- 5. A compound according to claim 1 in which X and Y are both CH.sub.2.
- 6. A compound according to claim 1 in which R.sup.9 and R.sup.10 are both hydrogen.
- 7. A compound according to claim 1 which is:
- 1'-methyl-5-[2'-methyl-4'-(2-oxo-1-piperidinyl)biphenyl-4-carbonyl]-2,3,6,7-tetrahydrospiro [furo[2,3-f]indole-3,4'-piperidine],
- 5-[4'-(4,5-dihydro-2-oxooxazol-3-yl)-2'-methylbiphenyl-4-carbonyl]-1'-methyl-2,3,6,7-tetrahydrospiro[furo[2,3-f]indole-3,4'-piperidine],
- 5-(4'-acetamido-2'-methylbiphenyl-4-carbonyl)-1'-metbyl-2,3,6,7-tetrahydrospiro[furo[2,3-f]indole-3,4'-piperidine],
- 1'-methyl-5-[2'-methyl-4'-(2-thioxo-1-pyrrolidinyl)biphenyl-4-carbonyl]-2,3,6,7-tetrahydrospiro[furo[2,3-f]indole-3,4'-piperidine],
- 5-[4'-(1,1-dioxo-2,3,4,5-tetrahydroisothiazol-2-yl)-2'-methylbiphenyl-4-carbonyl]-1-'-methyl-2,3,6,7-tetrahydrospiro[furo[2,3-f]indole-3,4'-piperidine],
- 5-[4'-(4,5-dihydro-2-oxoimidazol-1-yl)-2'-methylbiphenyl-4-carbonyl]-1'-methyl-2,3,6,7-tetrahydrospiro[furo[2,3-f]indole-3,4'-piperidine],
- 5-[4'-(4,5-dihydro-3-methyl-2-oxoimidazol-1-yl)-2'-methylbiphenyl-4-carbonyl]-1'-methyl-2,3,6,7-tetrahydrospiro[furo[2,3-f]indole-3,4'-piperidine],
- 1'-methyl-5-[2'-methyl-4'-(3-methyl-2-oxopyrrolidin-1-yl)biphenyl-4-carbonyl]-2,3,6,7-tetrahydrospiro[furo[2,3-f]indole-3,4'-piperidine],
- 5-[4'-(3,3-dimethyl-2-oxopyrrolidin-1-yl)-2'-methylbiphenyl-4-carbonyl]-1'-methyl-2,3,6,7-tetrahydrospiro[furo[2,3-f]indole-3,4'-piperidine],
- 5-[4'-(2,3-dihydro-1-oxoisoindol-2-yl)-2'-methylbiphenyl-4-carbonyl]-1'-methyl-2,3,6,7-tetrahydrospiro[furo[2,3-f]indole-3,4'-piperidine],
- 5-[2,3 7-dimethyl4'-(2-oxopyrrolidin-1-yl)biphenyl-4-carbonyl]-1-methyl-2,3,6,7-tetrahydrospiro[furo[2,3-f]indole-3,4'-piperidine],
- 1'-methyl-5-[4'-(2-oxo-1-pyrrolidinyl)-2'-trifluoromethylbiphenyl-4-carbonyl]-2,3,6,7-tetrahydrospiro[furo[2,3-f]indole-3,4'-piperidine],
- 5-[2'-chloro-4'-(2-oxo-1-pyrrolidinyl)biphenyl-4-carbonyl]-1'-methyl-2,3,6,7-tetrahydrospiro[furo[2,3-f]indole-3,4'-piperidine],
- 5-[4-(1-acetyl-1,2,3,4-tetrahydroqainolin-6-yl)-3-methylbenzoyl]-1'-methyl-2,3,6,7-tetrahydrospiro[furo [2,3-f]indole-3,4'-piperidine],
- 5-4-(1-acetyl-2,3-dihydroindol-5-yl)-3-methylbenzoyl]-1'-methyl-2,3,6,7-tetrahydrospiro [furo[2,3-f]indole-3,4'-piperidine],
- 1'-methyl-5-(2'-methyl-4'-(2-oxo-1H-pyrazin-1-yl)biphenyl-4-carbonyl)-2,3,6,7-tetrahydrospiro [furo[2,3-f]indole-3,4'-piperidine],
- 5-[2'-methyl-4'-(2-oxopyrrolidin-1-yl)biphenyl-4-carbonyl]-2,3,6,7-tetrahydrospiro[furo[2,3-f]indole-3,4-piperidine],
- 1'-ethyl-5-(2'-methyl-4'-(2-oxopyrrolidin-1-yl)biphenyl-4-carbonyl]-2,3,6,7-tetrabydrospiro[furo[2,3-f]indole-3,4'-piperidire],
- 5-2'-methyl-4'-(2-oxopyrrolidin-1-yl)biphenyl-4-carbonyl]-1'-n-propyl-2,3,6,7-tetrabydrospiro[furo[2,3-f]indole-3,4'-piperidine],
- 1'-isopropyl-5-[2'-methyl-4'-(2-oxopyrrolidin-1-yl)biphenyl-4-carbonyl]-2,3,6,7-tetrahydrospiro[furo[2,3-f]indole-3,4'-piperidine],
- 1'-n-butyl-5-[2'-methyl-4'-(2-oxopyrrolidin-1-yl)biphenyl-4-carbonyl]-2,3 6,7-tetrahydrospiro[furo[2,3-f]indole-3,4'-piperidine],
- 1'-cyclopropylmethyl-5-[2'-methyl-4'(2-oxopyrrolidin-1-yl)biphenyl-4-carbonyl]-2,3,6,7-tetrahydrospiro[furo[2,3-f]indole-3,4'-piperidine],
- 1'-allyl-5-[2'-methyl-4'-(2-oxopyrrolidin-1-yl)biphenyl-4-carbonyl]-2,3,6,7-tetrahydrospiro[furo[2,3-f]indole-3,4'-piperidine],
- 1'-cyclopentyl-5-[2'-methyl-4'-(2-oxopyrrolidin-1-yl)biphenyl-4-carbonyl]-2,3,6,7-tetrahydrospiro[furo[2,3-f]indole-3 4'-piperidine],
- 5-[2'-methoxycarbonyl-4'-(2-oxopyrrolidin-1-yl)biphenyl-4-carbonyl]-1'-methyl-2,3,6,7-tetrahydrospiro[furo[2,3,f]indole-3,4'-piperidine],
- 5-2'-hydroxymethyl-4'-(2-oxopyrrolidin-1-yl)biphenyl-4-carbonyl]-1'-methyl-2,3,6,7-tetrahydrospiro[furo[2,3-f]indole-3,4'-piperidine],
- 5-[2'-methoxymethyl-4'-(2-oxopyrrolidin-1-yl)biphenyl4-carbonyl]-1'-methyl-2,3,6,7-tetrahydrospiro[furo[2,3-f]indole-3,4'-piperidine],
- 1'-tert-butyl-5-[2'-methyl-4'-(2-oxopyrrolidin-1-yl)biphenyl-4-carbonyl]-2,3,6,7-tetrahydrospiro[furo[2,3-f]indole-3,4'-piperidine],
- or a pharmaceutically acceptable salt or N-oxides thereof.
- 8. A compound according to claim 1 which is:
- 5-[2'-methyl4'-(2-oxo-1-pyrrolidinyl)biphenyl-4-carbonyl]-1'-methyl-2,3,6,7-tetrahydrospiro[furo[2,3-f]indole-3,4'-piperidine],
- 1'-methyl-5-[2'-methyl-4'-(3-methyl-2-oxopyrrolidin-1-yl)biphenyl-4-carbonyl]-2,3,6,7-tetrahydrospiro[furo[2,3-f]indole-3,4'-piperidine],
- 1'-isopropyl-5-[2'-methyl-4'-(2-oxopyrrolidin-1-yl)biphenyl-4-carbonyl]-2,3,6,7-tetrahydrospiro[furo[2,3-f]indole-3,4'-piperidine],
- or a pharmaceutically acceptable salt thereof.
- 9. A pharmaceutical composition which comprises a compound according to claim 1 in association with a pharmaceutically acceptable carrier or excipient.
- 10. A method of treating depression, seasonal effective disorder, dysthymia, anxiety, panic disorder, agoraphobia, social phobia, obsessive compulsive disorder, post-traumatic stress disorder, dementia, amnesia, age-associated memory impairment, anorexia nervosa, bulimia nervosa, Parkinson's disease, dementia in Parkinson's disease, neuroleptic-induced Parkinsonism, tardive dyskinesias which method involves treating a patient in need thereof with a therapeutically effective amount of a compound of claim 1.
- 11. A method of treating hyperprolactinaemia, vasospasm, hypertension, hypothermia and sexual dysfunction which method involves treating a patient in need thereof with a therapeutically effective amount of a compound of claim 1.
- 12. A process for the preparation of a compound of formula (I) which comprises:
- (a) for compounds of formula (I) where D is nitrogen reaction of a compound of formula (II): ##STR11## in which R, R.sup.3, R.sup.4 and R.sup.5 are groups as defined in formula (I) or protected derivatives thereof and L is a leaving group with a compound of formula (III): ##STR12## wherein R.sup.6, R.sup.7, R.sup.8, R.sup.9, R.sup.10, E, G, X, Y, and m are groups as defined in formula (I) or protected derivatives thereof, or
- (b) for compounds of formula (I) where D is carbon, B is oxygen and R.sup.6 /R.sup.7 is .dbd.CR.sup.16 O, .dbd.CR.sup.16 S or .dbd.CR.sup.16 --NR.sup.17 reaction of a compound of formula (II) as defined above where L is chloro with a compound of formula (IV): ##STR13## wherein R.sup.6, R.sup.7, R.sup.8, R.sup.9, R.sup.10, E, G, X, Y, and m are groups as defined in formula (I) or protected derivatives thereof and V is NR.sup.17, O or S, and optionally after (a) or (b) in any order, removing any protecting groups, converting a compound of formula (I) into another compound of formula (I), forming a pharmaceutically acceptable salt.
Priority Claims (1)
Number |
Date |
Country |
Kind |
9605883 |
Mar 1996 |
GBX |
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Parent Case Info
This is a 371 of International Application PCT/EP97/01404, filed Mar. 19, 1997.
PCT Information
Filing Document |
Filing Date |
Country |
Kind |
102e Date |
371c Date |
PCT/EP97/01404 |
3/19/1997 |
|
|
9/18/1998 |
9/18/1998 |
Publishing Document |
Publishing Date |
Country |
Kind |
WO97/34901 |
9/25/1997 |
|
|
US Referenced Citations (1)
Number |
Name |
Date |
Kind |
5591849 |
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Jan 1997 |
|
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