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Aryl substituted tetrazole derivatives, and application thereof in therapeutics

Assignee: Synthelabo SA
•
Filing: 1989-05-25
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Granted: 1992-03-31
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Expires: 2009-05-25
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Abstract

Abstract Compounds for therapeutic use of formula: ##STR1## where the chain--W--V--N--represents--N═N--N--, --N--N═N--, --O--CO--N--, --O--CS--N--, --S--CO--N-- or --S--CS--N--; Ar is an aryl group; and A is a vinyl group or an alkylene chain terminated by CN, methoxy, ethoxy, OH, halogen or NH 2 which may possibly be substituted.

Inventors

  • 👤 Rene L. Milcent
  • 👤 Luc Lebreton
  • 👤 Fathi Mazouz
  • 👤 Claude Burstein
  • 👤 Salah Gueddari

Bibliographic Details

Application Number —
Jurisdiction US
Data Source google_patents
Last Synchronized 2026-11-09 03:11
CPC Classifications
C; C07; C07D; C07D257/00; C07D257/02; C07D257/04; A; A61; A61P; A61P25/00; A61P43/00; C07D271/00; C07D271/02; C07D271/10; C07D271/113; C07D285/00; C07D285/01; C07D285/02; C07D285/04; C07D285/12; C07D285/125; C07D285/13; C07D401/00; C07D401/02; C07D401/04; C07D403/00; C07D403/02; C07D403/06

Claims Analysis

Total Claims: 26
Claim 1
Independent Claim 238 words
Derivatives of formula: ##STR35## in which the chain ##STR36## represents 1) either the chain of structure: ##STR37## where A is: a) a vinyl group or a (CH 2 ) n --Z 1 group in which Z 1 represents a CN, methoxy or ethoxy group and n is an integer from 1 to 6, in which case Ar takes on the value Ar 1 which represents: a phenyl nucleus substituted by benzyloxy group of formula: ##STR38## where R 1 represents a hydrogen atom, one or two halogen atoms or a CN, NO 2 , NH 2 , CF 3 , C 1 -C 4 alkyl, C 1 -C 4 alkoxy or C 2 -C 4 acylamino group; or b) a group of formula (CH 2 ) m --Z 2 in which Z 2 represents an OH group, a halogen atom, an NH 2 , an NH 2 group substituted by one or two C 1 -C 4 alkyl groups, a C 2 -C 4 acylamino group or a phthalimido group and m is an integer from 2 to 6, in which case Ar takes on the value Ar 2 which represents: a phenyl nucleus substituted by a benzyloxy group of formula ##STR39## where R 1 has the same meaning as above; as well as the pharmaceutically acceptable acid addition salts of these derivatives (I) having a salifiable group, with the exclusion of 5-phenyl 2-tetrazole butyronitrile and 5-phenyl 2-tetrazole valeronitrile.
Claim 2
Dependent Claim 238 words
Derivatives of formula: ##STR35## in which the chain ##STR36## represents 1) either the chain of structure: ##STR37## where A is: a) a vinyl group or a (CH 2 ) n --Z 1 group in which Z 1 represents a CN, methoxy or ethoxy group and n is an integer from 1 to 6, in which case Ar takes on the value Ar 1 which represents: a phenyl nucleus substituted by benzyloxy group of formula: ##STR38## where R 1 represents a hydrogen atom, one or two halogen atoms or a CN, NO 2 , NH 2 , CF 3 , C 1 -C 4 alkyl, C 1 -C 4 alkoxy or C 2 -C 4 acylamino group; or b) a group of formula (CH 2 ) m --Z 2 in which Z 2 represents an OH group, a halogen atom, an NH 2 , an NH 2 group substituted by one or two C 1 -C 4 alkyl groups, a C 2 -C 4 acylamino group or a phthalimido group and m is an integer from 2 to 6, in which case Ar takes on the value Ar 2 which represents: a phenyl nucleus substituted by a benzyloxy group of formula ##STR39## where R 1 has the same meaning as above; as well as the pharmaceutically acceptable acid addition salts of these derivatives (I) having a salifiable group, with the exclusion of 5-phenyl 2-tetrazole butyronitrile and 5-phenyl 2-tetrazole valeronitrile.
Claim 3
Dependent Claim 61 words
Derivatives according to claim 1, of structure: ##STR40## where Z 1 =CN, n=1 or 2, Z 2 =OH, m=integer from 2 to 6 and Ar represents a phenyl nucleus para substituted by a benzyloxy group whose phenyl nucleus is possibly substituted by one or two halogen atoms or a C 1 -C 4 alkyl or C 1 -C 4 alkoxy group.
Claim 4
Dependent Claim 58 words
Compounds of formula: ##STR41## where Ar 1 represents: a phenyl nucleus substituted by benzyloxy group of formula: ##STR42## where R 1 represents a hydrogen atom, one or two halogen atoms or a CN, NO 2 , NH 2 , CF 3 , C 1 -C 4 alkyl, C 1 -C 4 alkoxy or C 2 -C 4 acylamino.
Claim 5
Dependent Claim 58 words
Compounds of formula: ##STR41## where Ar 1 represents: a phenyl nucleus substituted by benzyloxy group of formula: ##STR42## where R 1 represents a hydrogen atom, one or two halogen atoms or a CN, NO 2 , NH 2 , CF 3 , C 1 -C 4 alkyl, C 1 -C 4 alkoxy or C 2 -C 4 acylamino.
Claim 6
Dependent Claim 60 words
A compound of the formula ##STR43## in which Z 1 is CN or OH n is 1 or 2, and Ar 1 is ##STR44## wherein R 1 is H, one or two halogens, or CN, NO 2 , NH 2 , CF 3 , C 1 -C 4 alkyl, C 1 -C 4 alkoxy or C 2 -C 4 acylamino.
Claim 7
Dependent Claim 60 words
A compound of the formula ##STR43## in which Z 1 is CN or OH n is 1 or 2, and Ar 1 is ##STR44## wherein R 1 is H, one or two halogens, or CN, NO 2 , NH 2 , CF 3 , C 1 -C 4 alkyl, C 1 -C 4 alkoxy or C 2 -C 4 acylamino.
Claim 8
Dependent Claim 21 words
A compound as claimed in claim 4 in which Z 1 is CN, n is 2 and R 1 is hydrogen.
Claim 9
Dependent Claim 21 words
A compound as claimed in claim 4 in which Z 1 is OH, n is 2 and R 1 is hydrogen.
Claim 10
Dependent Claim 20 words
A compound as claimed in claim 4 in which Z is OH, n is 2 and R 1 is 2-Cl.
Claim 11
Dependent Claim 21 words
A compound as claimed in claim 4 in which Z 1 is OH, n is 2 and R 1 is 3-Cl.
Claim 12
Dependent Claim 21 words
A compound as claimed in claim 4 in which Z 1 is OH, n is 2 and R 1 is 4-Cl.
Claim 13
Dependent Claim 21 words
A compound as claimed in claim 4 in which Z 1 is OH, n is 2 and R 1 is 2,4-diCl.
Claim 14
Dependent Claim 21 words
A compound as claimed in claim 4 in which Z 1 is OH, n is 2 and R 1 is 2,6-diCl.
Claim 15
Dependent Claim 21 words
A compound as claimed in claim 4 in which Z 1 is OH, n is 2 and R 1 is 3,4-diCl.
Claim 16
Dependent Claim 58 words
A compound of the formula ##STR45## in which Z is CN or OH p is 1 or 2, and Ar is ##STR46## wherein R 1 is H, one or two halogens, or CN, NO 2 , NH 2 , CF 3 , C 1 -C 4 alkyl, C 1 -C 4 alkoxy or C 2 -C 4 acylamino.
Claim 17
Dependent Claim 58 words
A compound of the formula ##STR45## in which Z is CN or OH p is 1 or 2, and Ar is ##STR46## wherein R 1 is H, one or two halogens, or CN, NO 2 , NH 2 , CF 3 , C 1 -C 4 alkyl, C 1 -C 4 alkoxy or C 2 -C 4 acylamino.
Claim 18
Dependent Claim 22 words
A compound as claimed in claim 13 in which Z is CN, p is 1 and R 1 is 4-CH 3 .
Claim 19
Dependent Claim 22 words
A compound as claimed in claim 13 in which Z is OH, p is 2 and R 1 is 4-CH 3 .
Claim 20
Dependent Claim 20 words
A compound as claimed in claim 13 in which Z is OH, p is 2 and R 1 is 4-F.
Claim 21
Dependent Claim 167 words
A compound of the formula ##STR47## in which ##STR48## where A is either (a) vinyl or (CH 2 ) n --Z 1 in which Z 1 is CN, methoxy or ethoxy, and n is an integer of from 1 to 6 or (b) (CH 2 ) m --Z 2 , in which Z 2 is OH, halogen, NH 2 , NH 2 substituted with one or two C 1 -C 4 alkyls, C 2 -C 4 acylamino or phthalimido, and m is an integer from 2 to 6 with the proviso that when A is (a), Ar is phenyl substituted by ##STR49## in which R 1 is hydrogen, one or two halogens, or CN, NO 2 , NH 2 , CF 3 , C 1 -C 4 alkyl, C 1 -C 4 alkoxy or C 2 -C 4 acylamino, and when A is (b), Ar is phenyl substituted with C 1 -C 4 alkoxy or ##STR50## in which R 1 has the same meaning as defined above.
Claim 22
Dependent Claim 167 words
A compound of the formula ##STR47## in which ##STR48## where A is either (a) vinyl or (CH 2 ) n --Z 1 in which Z 1 is CN, methoxy or ethoxy, and n is an integer of from 1 to 6 or (b) (CH 2 ) m --Z 2 , in which Z 2 is OH, halogen, NH 2 , NH 2 substituted with one or two C 1 -C 4 alkyls, C 2 -C 4 acylamino or phthalimido, and m is an integer from 2 to 6 with the proviso that when A is (a), Ar is phenyl substituted by ##STR49## in which R 1 is hydrogen, one or two halogens, or CN, NO 2 , NH 2 , CF 3 , C 1 -C 4 alkyl, C 1 -C 4 alkoxy or C 2 -C 4 acylamino, and when A is (b), Ar is phenyl substituted with C 1 -C 4 alkoxy or ##STR50## in which R 1 has the same meaning as defined above.
Claim 23
Dependent Claim 245 words
A pharmaceutical composition comprising a therapeutically effective amount of a compound of formula (I): ##STR51## in which the chain ##STR52## represents either the chain of structure ##STR53## where A is a) a vinyl group or a (CH 2 ) n --Z 1 group in which Z 1 represents a CN, methoxy or ethoxy group and n is an integer from 1 to 6, in which case Ar takes on the value Ar 1 which represents a phenyl nucleus substituted by a benzyloxy group of formula ##STR54## where R 1 represents a halogen atom, one or two halogen atoms or a CN, NO 2 , NH 2 , CF 3 , C 1 -C 4 alkyl, C 1 -C 4 alkoxy or C 2 -C 4 acylamino group; or b) a group of formula (CH 2 ) m --Z 2 in which Z 2 represents an OH group, a halogen atom, an NH 2 group, an NH 2 group substituted by one or two C 1 -C 4 alkyl groups, a C 2 -C 4 acylamino group or a phthalimido group and m is an integer from 2 to 6, in which case Ar takes on the value Ar 2 which represents a phenyl nucleus substituted by a benzyloxy group of formula ##STR55## where R 1 has the same meaning as above, or a pharmaceutically acceptable salt thereof, with the exclusion of 5-phenyl-2-tetrazole butyronitrile or and 5-phenyl-2-tetrazole valeronitrile, combined with a pharmaceutically acceptable carrier or excipient.
Claim 24
Dependent Claim 245 words
A pharmaceutical composition comprising a therapeutically effective amount of a compound of formula (I): ##STR51## in which the chain ##STR52## represents either the chain of structure ##STR53## where A is a) a vinyl group or a (CH 2 ) n --Z 1 group in which Z 1 represents a CN, methoxy or ethoxy group and n is an integer from 1 to 6, in which case Ar takes on the value Ar 1 which represents a phenyl nucleus substituted by a benzyloxy group of formula ##STR54## where R 1 represents a halogen atom, one or two halogen atoms or a CN, NO 2 , NH 2 , CF 3 , C 1 -C 4 alkyl, C 1 -C 4 alkoxy or C 2 -C 4 acylamino group; or b) a group of formula (CH 2 ) m --Z 2 in which Z 2 represents an OH group, a halogen atom, an NH 2 group, an NH 2 group substituted by one or two C 1 -C 4 alkyl groups, a C 2 -C 4 acylamino group or a phthalimido group and m is an integer from 2 to 6, in which case Ar takes on the value Ar 2 which represents a phenyl nucleus substituted by a benzyloxy group of formula ##STR55## where R 1 has the same meaning as above, or a pharmaceutically acceptable salt thereof, with the exclusion of 5-phenyl-2-tetrazole butyronitrile or and 5-phenyl-2-tetrazole valeronitrile, combined with a pharmaceutically acceptable carrier or excipient.
Claim 25
Independent Claim 274 words
A method of treating a patient to inhibit type B monoamine oxidase which comprises administering to the patient a therapeutically effective amount of a compound of formula (I) ##STR56## in which the chain ##STR57## 1) either the chain of structure ##STR58## where A is a) a vinyl group or a (CH 2 ) n --Z 1 group in which Z 1 represents a CN, methoxy or ethoxy group and n is an integer from 1 to 6, in which case Ar takes on the value Ar 1 which represents a phenyl nucleus; a phenyl nucleus substituted by one or two halogen atoms or an NO 2 , methyl, ethyl, methoxy, ethoxy, phenyl or benzyloxy group of formula ##STR59## where R 1 represents a hydrogen atom, one or two halogen atoms or a CN, NO 2 , CF 3 , C 1 -C 4 alkyl, C 1 -C 4 alkoxy or C 2 -C 4 acylamino group; or b) a group of formula (CH 2 ) m --Z 2 in which Z 2 represents an OH group, a halogen atom, an NH 2 , an NH 2 group substituted by one or two C 1 -C 4 alkyl groups, a C 2 -C 4 acylamino group or a phthalimido group and m is an integer from 2 to 6, in which case Ar takes on the value Ar 2 which represents a phenyl nucleus substituted by a C 1 -C 4 alkoxy group or a benzyloxy group of formula ##STR60## where R 1 has the same meaning as above; or a pharmaceutically acceptable salt thereof with exclusion of 5-phenyl 2-tetrazole butyronitrile and 5-phenyl 2-tetrazole valeronitrile.
Claim 26
Independent Claim 274 words
A method of treating a patient to inhibit type B monoamine oxidase which comprises administering to the patient a therapeutically effective amount of a compound of formula (I) ##STR56## in which the chain ##STR57## 1) either the chain of structure ##STR58## where A is a) a vinyl group or a (CH 2 ) n --Z 1 group in which Z 1 represents a CN, methoxy or ethoxy group and n is an integer from 1 to 6, in which case Ar takes on the value Ar 1 which represents a phenyl nucleus; a phenyl nucleus substituted by one or two halogen atoms or an NO 2 , methyl, ethyl, methoxy, ethoxy, phenyl or benzyloxy group of formula ##STR59## where R 1 represents a hydrogen atom, one or two halogen atoms or a CN, NO 2 , CF 3 , C 1 -C 4 alkyl, C 1 -C 4 alkoxy or C 2 -C 4 acylamino group; or b) a group of formula (CH 2 ) m --Z 2 in which Z 2 represents an OH group, a halogen atom, an NH 2 , an NH 2 group substituted by one or two C 1 -C 4 alkyl groups, a C 2 -C 4 acylamino group or a phthalimido group and m is an integer from 2 to 6, in which case Ar takes on the value Ar 2 which represents a phenyl nucleus substituted by a C 1 -C 4 alkoxy group or a benzyloxy group of formula ##STR60## where R 1 has the same meaning as above; or a pharmaceutically acceptable salt thereof with exclusion of 5-phenyl 2-tetrazole butyronitrile and 5-phenyl 2-tetrazole valeronitrile.

References Cited (Backward Citations)

FR1084633A Cited
GB1163355A Cited
US3509153A Cited
US3453285A Cited
US3865570A Cited
EP0028305A1 Cited

USPTO Annuity & Maintenance Windows

Annuity Stage Window Opens Payment Deadline Surcharge Period Until Estimated Fee Status
3.5 Years (Year 4) 1995-03-31 1995-09-30 1996-03-31 $2000.00 Window Closed / Lapsed
7.5 Years (Year 8) 1999-03-31 1999-09-30 2000-03-31 $3760.00 Window Closed / Lapsed
11.5 Years (Year 12) 2003-03-31 2003-09-30 2004-03-31 $7700.00 Window Closed / Lapsed

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