# US 4,395,416 A · 1-Spiro isobenzofuranic and 1-spiro isobenzothiophenic derivatives the process for preparing the same and their use in therapeutics > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 4,395,416 A - Document ID: US4395416A - Status: Granted - Kind: A - Application number: 06/341,415 - Filed: 1982-01-21 - Granted: 1983-07-26 - Earliest claimed: 1981-01-29 - Assignees: Delalande S.A. - Inventors: Michel Langlois; Bernard P. Bucher; Philippe L. Dostert; Alain P. Lacour; Gerard H. Moinet - Web page: https://patentgrep.com/patent/US4395416A ## CPC - C07D 491/10: Spiro-condensed systems - C07D 307/94: spiro-condensed with carbocyclic rings or ring systems, e.g. griseofulvins - C07D 495/10: Spiro-condensed systems - C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08) ## Abstract Derivatives of formula: ##STR1## in which Z< represents: either an amino group of struture >N-R.sub.1 where R.sub.1 represents a linear or branched alkyl group with 1 to 5 carbon atoms or a phenyl group possibly substituted by a chlorine atom, in which case: n=1 or 2, the pair (A, C X) assumes the following values: (S, C.dbd.O), (S, CH.sub.2), (O, CH.sub.2), (O, CH--C.sub.6 H.sub.5), and R represents a hydrogen or halogen atom, one or more methoxy groups or the butadiene-1,3 ylene chain ##STR2## fixed in position 5,6 of the phenyhl nucleus and thus forming with this latter a naphthyl nucleus; or a methylene group (--CH.sub.2 --), in which case: n=1 or 2, A represents the oxygen atom, >C X represents a carbonyl group (>C.dbd.O) or thiocarbonyl group (>C.dbd.S), and R has the same meanings as previously, as well as the mineral or organic acid addition salts thereof. The compounds exhibit anti-convulsion and analgesic activity. ## Claims ### Claim 1 A compound of the formula ##STR36## in which Z is >N--R.sub.1 or --CH.sub.2 --, wherein R.sub.1 is alkyl having 1 to 5 carbon atoms, phenyl or chlorophenyl, and in which 1. when Z is >N--R.sub.1, n is 1 or 2, the pair (A,>C X) is selected from the group consisting of (S, C.dbd.O), (S, CH.sub.2), (O, CH.sub.2) and (O, CH--C.sub.6 H.sub.5), and R is hydrogen, halogen, one or two methoxy groups or --CH.dbd.CH--CH.dbd.CH-- connected to the 5 and 6 positions of the phenyl nucleus whereby to form a naphthyl nucleus, and 2. when Z is --CH.sub.2 -- n is 1 or 2 A is oxygen, >C X is >C.dbd.O or >C.dbd.S, and R is the same as defined above, with the provisos that (a) when >C X is >C.dbd.O, R is not hydrogen, and (b) when the pair (>C X, n) is (>C.dbd.O, 2), R is not 5--Br, and the pharmacologically acceptable acid addition salts thereof when Z is >N--R.sub.1. ### Claim 2 (depends on 1) A compound as claimed in claim 1 in which Z is >N--R.sub.1, A is sulfur and >C X is >C.dbd.O. ### Claim 3 (depends on 2) A compound as claimed in claim 2, wherein the set (n, R, Z) is selected from the group consisting of: (1, H, NCH.sub.3), (2, H, NCH.sub.3), (1, H, NEt), (1, H, NC.sub.3 H.sub.7n), (1, 6--Cl, NCH.sub.3), (1, 5--Cl, NCH.sub.3), (1, 5--Cl, NEt), (1, 6--CH.sub.3 O, NCH.sub.3), (1, 5--CH.sub.3 O, NCH.sub.3), (1, 5,6-diCH.sub.3 O, NCH.sub.3), (1, 5--F, NCH.sub.3), (1, 6--F, NCH.sub.3), (1, H, N<), (2, 5--Cl, NCH.sub.3), (1, 4--Cl, NCH.sub.3), ##STR37## ### Claim 4 (depends on 1) A compound as claimed in claim 1 in which Z is --CH.sub.2 --. ### Claim 5 (depends on 4) A compound as claimed in claim 4 in which >C X is >C.dbd.S, n is 1 and R is hydrogen. ### Claim 6 (depends on 1) A compound as claimed in claim 1 in which Z is >N--R.sub.1, and the pair (A,>C X) is selected from the group consisting of (S,>CH.sub.2), (O,>CH.sub.2) and (O,>CH--C.sub.6 H.sub.5). ### Claim 7 (depends on 6) A compound as claimed in claim 6 in which the set (Z, n, R) is selected from the group consisting of (NCH.sub.3, 1, hydrogen) and (NCH.sub.3, 1, 5--Cl). ### Claim 8 A compound of the formula ##STR38## wherein n is 1 or 2, R.sub.1 is alkyl having 1 to 5 carbon atoms, phenyl or chlorophenyl, and R is hydrogen, halogen, one or two methoxy groups or --CH.dbd.CH--CH.dbd.CH-- connected to the 5 and 6 positions of the phenyl nucleus whereby to form a naphthyl nucleus. ### Claim 9 A process for preparing a compound of the formula ##STR39## in which R.sub.1 is alkyl having 1 to 5 carbon atoms, phenyl or chlorophenyl, n is 1 or 2, and R is hydrogen, halogen, one or two methoxy groups or --CH.dbd.CH--CH.dbd.CH-- connected to the 5 and 6 positions of the phenyl nucleus whereby to form a naphthyl nucleus, which comprises reacting a compound of the formula ##STR40## with phosphorus pentasulfide, in the presence of a base. ### Claim 10 A process for preparing a compound of the formula ##STR41## in which the pair (C X, A) is selected from the group consisting of (CH.sub.2, O), (CH--C.sub.6 H.sub.5, O) and (CH.sub.2, S), R.sub.1 is alkyl having 1 to 5 carbon atoms, phenyl or chlorophenyl, n is 1 or 2, and R is hydrogen, halogen, one or two methoxy groups or --CH.dbd.CH--CH.dbd.CH-- connected to the 5 and 6 positions of the phenyl nucleus whereby to form a naphthyl nucleus, which comprises condensing the lithium derivative of a compound of the formula ##STR42## in which R has the same meaning as defined above, and the pair (A, R.sub.2) is selected from the group consisting of (S, H), (O, H) and (O, C.sub.6 H.sub.5), with a compound of the formula ##STR43## in which R.sub.1 and n have the same meanings as defined above. ### Claim 11 A process for preparing a compound of the formula ##STR44## in which n is 1 or 2, and R is hydrogen, halogen, one or two methoxy groups, or --CH.dbd.CH--CH.dbd.CH-- connected to the 5 and 6 positions of the phenyl nucleus whereby to form a naphthyl nucleus, which comprises condensing the lithium derivative of a compound of the formula ##STR45## in which R has the same meaning as defined above, with a compound of the formula ##STR46## ### Claim 12 A process for preparing a compound of the formula ##STR47## in which n is 1 or 2, and R is hydrogen, halogen, one or two methoxy groups, or --CH.dbd.CH--CH.dbd.CH-- connected to the 5 and 6 positions of the phenyl nucleus whereby to form a naphthyl nucleus, which comprises reacting a compound of the formula ##STR48## in which n and R have the same meanings as defined above, with phosphorus pentasulfide. ### Claim 13 An analgesic or anticonvulsant composition comprising a therapeutically effective amount of a compound of the formula ##STR49## in which Z is >N--R.sub.1 or --CH.sub.2 --, wherein R.sub.1 is alkyl having 1 to 5 carbon atoms, phenyl or chlorophenyl, and in which 1. when Z is >N--R.sub.1, n is 1, or 2, the pair (A,>C X) is selected from the group consisting of (S, C.dbd.O), (S, CH.sub.2), (O, CH.sub.2) and (O, CH--C.sub.6 H.sub.5), and R is hydrogen, halogen, one or two methoxy groups or --CH.dbd.CH--CH.dbd.CH-- connected to the 5 and 6 positions of the phenyl nucleus whereby to form a naphthyl nucleus, and 2. when Z is --CH.sub.2 -- n is 1 or 2, A is oxygen, >C X is >C.dbd.O or >C.dbd.S, and R is the same as defined above, and the pharmacologically acceptable acid addition salts thereof when Z is >N--R.sub.1, in combination with a pharmaceutically acceptable vehicle.