Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Reexamination Certificate
2002-05-17
2004-04-06
Gerstl, Robert (Department: 1626)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
C514S367000, C548S178000, C548S217000
Reexamination Certificate
active
06716865
ABSTRACT:
The invention relates to benzoxa- and benzthiazole derivatives. It concerns a benzoxa- or benzthiazole substituted at the 2 position and carrying a sulfamic acid ester group bound via oxygen to the phenyl part of the ring structure, hereinafter briefly named “a compound of the invention”.
More specifically, it concerns a compound of formula I
wherein
X is O or S;
R
1
and R
2
either independently are hydrogen or alkyl, or one is hydrogen and the other is acyl or alkoxycarbonyl; and
R
3
is alkyl; alkenyl; alkinyl; cycloalkyl; cycloalkenyl; aryl; acyl; cycloalkylalkyl; cycloalkylalkenyl, including cycloalkanylidenealkyl; cycloalkenylalkyl; arylalkyl; arylalkenyl; arylalkinyl; alkoxycarbonylaminoalkyl; hydroxycycloalkylalkyl; cycloalkanylidenecycloalkanylidenalkyl; heteroaryl; or heteroarylalkyl;
in free form or salt form.
The sulfamoyloxy moiety in formula I is bound to the ring system in position 5 or 6, preferably 6.
Alkyl as a group R
1
or R
2
preferably is of 1 to 4 carbon atoms, it especially is methyl. Acyl as a group R
1
or R
2
preferably is formyl or alkylcarbonyl of altogether 2 to 5 carbon atoms, it especially is acetyl. Alkoxycarbonyl as a group R
1
or R
2
preferably is of altogether 2 to 5 carbon atoms, it especially is methoxycarbonyl.
In significance R
3
:
akyl as such or as part of a substituent such as cycloalkylalkyl includes (C
1-22
)alkyl, e.g. (C
1-16
)alkyl and (C
1-4
)alkyl;
alkenyl as such or as part of a substituent such as cycloalkylalkenyl includes (C
2-22
)alkenyl, e.g. (C
2-16
)alkenyl and (C
2-4
)alkenyl; when it is part of cycloalkanylidenealkyl the double bond is attached directly to the cycloalkyl moiety and thus the alkenyl part of such a cycloalkylalkenyl group is to be viewed as consisting of just one carbon atom;
alkinyl as such or as part of a substituent such as arylalkinyl includes (C
2-22
)alkinyl;
cycloalkyl as such or as part of a substituent such as cycloalkylalkyl or hydroxycycloalkylalkyl includes (C
4-12
)cycloalkyl, such as cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclododecanyl; it may be mono- or polycyclic, such as bridged cycloalkyl, as in adamantyl, hexahydro-2,5-methanopentalenyl; bicyclo[3.3.1]nonyl, or it may be cycloalkyl annexed to a second ring system, e.g. a second cycloalkyl, such as decalin (octahydronaphthyl), and includes spiro cycloalkyl, as in 1,4-dioxo-spiro[4.5]decyl or 1,5-dioxo-spiro[5.5]undecyl, whereby the cycloalkyl moiety and the annexed second ring system are unsubstituted or substituted with e.g up to 4, preferably one or two alkyl or alkoxy moieties of preferably 1 or 2 carbon atoms; when cycloalkyl is part of a substituent, there preferably is just one, but there may be up to two, mono- or polycyclic cycloalkyl moieties, as in e.g. dicyclohexylmethyl;
cycloalkenyl as such or as part of cycloalkenylalkyl includes (C
4-12
)cycloalkenyl, such as cyclohexenyl; it may be polycyclic, as in e.g. decahydrophenanthrenyl, and may be substituted, e.g. with 1 to 3 (C
1-4
)alkyl;
aryl as such or as part of arylalkyl, arylalkenyl or arylalkinyl includes (C
5-18
)aryl, e.g. (C
5-12
)aryl, e.g. phenyl or tetrahydronaphthalinyl, and may be substituted by e.g. alkyl; there may be up to 3, preferably 1 aryl moiety when aryl is part of a substituent, as in di- or triphenylmethyl;
aryl includes the residue of a carboxylic acid, in particular an alkyl, aralkyl or aryl carboxylic acid, e.g. an alkyl, aralkyl or aryl carbocyclic acid;
cycloalkylalkenyl includes e.g. a cycloalkanylidenalkyl group of formula i
wherein
R
4
is hydrogen or alkyl, e.g. (C
1-4
)alkenyl, especially methyl, and
R
5
and R
6
together with the carbon atom to which they are attached form cycloalkyl;
cycloalkenylalkyl is e.g. cyclohexenylmethyl;
alkoxycarbonylaminoalkyl is e.g. tert-butoxycarbonylamino-2,2-dimethylpropyl;
in hydroxycycloalkylalkyl the hydroxy group preferably is bound to the cycloalkyl part at the same carbon atom that is bound to the alkylene part of the hydroxycycloalkylalkyl moiety;
cycloalkanylidenecycloalkanylidenalkyl is e.g. bicyclobutylidenylidenemethyl;
heteroaryl as such or as part of heteroarylalkyl preferably is pyridyl or thienyl.
X preferably is oxygen, R
1
and R
2
preferably are hydrogen. R
3
preferably is alkyl; cycloalkylalkyl; cycloalkenylalkyl; alkoxycarbonylaminoalkyl; or cycloalkylalkenyl, e.g. a group of formula i as defined above.
A subgroup of compounds of the invention is the compounds of formula I wherein
X is as defined above;
R
1
and R
2
are hydrogen; and
R
3
is alkyl, alkenyl, cycloalkyl or cycloalkenyl,
in free form or salt form.
A further subgroup of compounds of the invention is the compounds of formula Is
wherein X, R
4
, R
5
and R
6
are as defined above; in free form or salt form.
A further subgroup of compounds of the invention is the compounds of formula It
wherein X, R
1
, R
2
and R
4
are as defined above; in free form or salt form; e.g. sulfamic acid 2-(adamantan-2-ylidenemethyl)benzoxazol-6-yl ester in free form or salt form.
A further subgroup of compounds of the invention is the compounds of formula I
p1
wherein
either R
1p
and R
2p
have the significances indicated above for R
1
and R
2
; and
R
3p1
is alkyl; alkenyl; alkinyl; cycloalkyl; acyl; cycloalkylalkyl; arylalkyl; arylalkenyl; arylalkinyl; heteroaryl; or heteroarylalkyl;
or R
1p
and R
2p
are hydrogen; and
R
3p1
is adamantan-2-ylidenemethyl;
in free form or salt form.
A further subgroup is the compounds of formula I
p2
wherein
R
1
and R
2
are as defined above; and
R
3p2
is alkyl; alkenyl; alkinyl; cycloalkyl; acyl; cycloalkylalkyl; adamantylalkenyl, including adamantanylidenalkyl; arylalkyl; arylalkenyl; arylalkinyl; heteroaryl; or heteroarylalkyl;
in free form or salt form.
A further subgroup is the compounds of formula Iq
wherein X is as defined above and
R
3q
is
(C
1-13
)alkyl;
(C
10-16
)alkenyl;
cycloalkyl selected from adamantyl and hexahydro-2-5-methano-pentalenyl;
the cycloalkenyl moiety 7-isopropyl-1,4a-dimethyl-1,2,3,4,4a,4b,5,6,10,10a-decahydrophenanthren-1-yl;
an aryl moiety 5,6,7,8-tetrahydronaphthalenyl;
cycloalkyl selected from adamantylalkyl of 1 to 4 carbon atoms in the alkylene part thereof and dicyclohexylmethyl;
cycloalkylalkenyl (including cycloalkanylidenalkyl) selected from:
adamantanyliden(C
1-4
)alkyl; (C
4-12
)cycloalkylidene(C
1-4
)alkyl; bicyclo[3.3.1]nonylidenemethyl; dimethylcyclohexylidenemethyl; (C
1-4
)alkoxycyclohexylidenemethyl; (C
1-4
)alkylcyclohexylidenemethyl; tetra(C
1-4
)alkylcyclohexylidenemethyl; 1,4-dioxaspiro[4.5]dec-8-ylidenemethyl; 3,3-dimethyl-1,5-dioxo-spiro[5.5]undec-9-ylidenemethyl; and octahydronaphthalylidenemethyl;
cyclohexenyl(C
1-4
)alkyl;
arylalkyl selected from di- or triphenyl(C
1-4
)alkyl;
(C
1-4
)alkoxycarbonylamino(C
1-6
)alkyl;
hydroxycycloalkylalkyl selected from: (2-hydroxyadamant-2-yl)(C
1-6
)alkyl; (9-hydroxybicyclo[3.3.1]non-9-yl(C
1-4
)alkyl; and
1-hydroxy-2,2-dimethylcyclohexyl(C
1-4
)alkyl; or
a cycloalkanylidenecycloalkanylidenalkyl moiety bicyclobutylidenylidenemethyl;
in free form or salt form.
A compound of the invention includes a compound in any form, e.g. in free form, in the form of a salt, in the form of a solvate and in the form of a solvated salt.
A salt of a compound of the invention includes a pharmaceutically acceptable salt, e.g. an acid addition salt. A compound of the invention in free form may be converted into a corresponding compound in the form of a salt and vice versa. A compound of the invention in the form of a solvate in free form or salt form may be converted into a corresponding compound in free form or salt form in unsolvated form and vice versa.
A compound of the invention may exist in the form of isomers and mixtures thereof; e.g. a compound of the invention may contain substituents exhibiting geometric isomerism and/or asymmetrically substituted carbon atoms and may thus exist in the form of isomers and/or diastereoisomers and mixtures thereof. Isomeric mixtures may be separated in conventional manner to obtain pure isomers
Billich Andreas
Schreiner Erwin Paul
Wolff-Winiski Barbara
Brouillette D. Gabrielle
Gerstl Robert
Loeschorn Carol
Novartis AG
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