Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Reexamination Certificate
1999-02-26
2001-02-20
Kight, John (Department: 1612)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
C549S404000
Reexamination Certificate
active
06191164
ABSTRACT:
SUMMARY OF THE INVENTION
The invention relates to chromans of the formula I
in which:
R(1) and R(2) independently of one another are hydrogen, C
2
F
2p−1
, alkyl having 1,2,3,4,5 or 6 carbon atoms or phenyl,
which is unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF
3
, methyl, methoxy, sulfamoyl, methylsulfonylamino and methylsulfonyl;
p is 1,2 or 3;
or
R(1) and R(2) together are an alkylene chain having 2,3,4,5,6,7,8,9 or 10 carbon atoms;
R(3) is R(9)—C
n
H
2n
[NR(11)]
m
—:
R(9) is hydrogen or cycloalkyl having 3,4,5,6,7 or 8 carbon atoms;
n is zero, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10;
m is zero or 1;
R(11)is hydrogen or alkyl having 1, 2, 3, 4, 5 or 6 carbon atoms; or
R(11), together with R(9), is an alkylene group having from 1,2,3,4,5,6,7 or 8 carbon atoms:
where one CH
2
group of the group C
n
H
2n
can be replaced by —O—, —SO
q
or —NR(10);
q is zero, 1 or 2;
R(10) is hydrogen, methyl or ethyl;
R(4) is R(12)—C
r
H
2r
;
R(12) is hydrogen, cycloalkyl having 3, 4, 5, 6, 7 or 8 carbon atoms, piperidyl, 1-pyrrolidinyl, N-morpholine, N-methylpiperazino, C
p
F
2p+1
, pyridyl, thienyl, imidazolyl or phenyl,
which is unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF
3
, methyl, methoxy, sulfamoyl, methylsulfonyl and methylsulfonylamino;
r is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20;
where one CH
2
group of the group C
r
H
2r
can be replaced by —O—, —C═C—, —C≡C—, —CO—, —CO—O—, —SO
q
— or —NR(10)—;
q is zero, 1 or 2;
R(10) is hydrogen, methyl or ethyl;
R(5), R(6), R(7) and R(8) independently of one another are hydrogen, F, Cl, Br, I, alkyl having 1, 2, 3 or 4 carbon atoms, cycloalkyl having 3, 4, 5, 6, 7 or 8 carbon atoms, —CN, —CF
3
, —C
2
F
5
, —C
3
F
7
, —N
3
, —NO
2
, —NO
2
, —CONR(13)R(14), —COOR(15), R(16)—C
s
H
2s
—Y— or phenyl,
which is unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF
3
, methyl, methoxy, sulfamoyl and methylsulfonyl;
R(13) and R(14) independently of one another are hydrogen or alkyl having 1, 2 or 3 carbon atoms;
R(15) is hydrogen, methyl, ethyl, phenyl or —C
u
H
2u
—NR(13)R(14);
u is 2 or 3;
R(16) is hydrogen, cycloalkyl having 3, 4, 5, 6, 7 or 8 carbon atoms, —COOR(15), thienyl, imidazolyl, pyridyl, quinolyl, isoquinolyl, piperidyl, 1-pyrrolidinyl, N-morpholino, N-methylpiperazino, C
t
F
2t+1
or phenyl,
which is unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF
3
, methyl, methoxy, sulfamoyl or methylsulfonyl;
s is zero, 1, 2, 3, 4, 5 or
6
;
t is 1, 2 or 3;
Y is SO
q
, —CO—, —SO
2
—NR(10)—, —O—, —NR(10)— or —CO
13
NR(10);
but where R(6) cannot be —OCF
3
or —OC
2
F
5
;
and their physiologically tolerable salts.
Preferred compounds of the formula I are those in which:
R(1) and R(2) independently of one another are hydrogen, C
F3
, alkyl having 1, 2 or 3 carbon atoms, jointly an alkylene chain having 4 or 5 carbon atoms or phenyl,
which is unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF
3
, methyl, methoxy, sulfamoyl and methylsulfonyl;
R(3) is R(9)—C
n
H
2n
[NR(11)]
m
—;
R(9) is hydrogen;
n is zero, 1, 2, 3, 4, 5 or 6;
m is zero or 1;
R(11) is hydrogen or alkyl having 1, 2, 3 or 4 carbon atoms;
R(4) is R(121)—C
r
H
2r
;
R(12) is hydrogen, cycloalkyl having 5, 6, 7 or 8 carbon atoms, CF
3
, pyridyl or phenyl,
which is unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, CF
3
, sulfamoyl or methylsulfonyl;
r is 1,2,3,4,5,6,7,8,9 or 10;
where one CH
2
group of the group C
t
H
2t
can be replaced by —O—, —CO
13
, —CO—O— or —SO
q
—;
q is zero, 1 or 2;
R(5), R(6), R(7) and R(8) independently of one another are hydrogen, F, Cl, Br, I, alkyl having 1 or 2 carbon atoms, —CN, —CF
3
, —NO
2
, —CONR(13)R(14), —COOR(15), R(16)—C
s
H
2s
—Y— or phenyl,
which is unsubstituted or substituted by a substituent selected from the group consisting of F, Cl and CF
3
;
R(13) and R(14): independently of one another are hydrogen or alkyl having 1,2 or 3 carbon atoms;
R(15) is methyl, ethyl, phenyl or —C
u
H
2u
—NR(13)R(14);
u is 2 or 3;
R(16) is hydrogen, cycloalkyl having 5 or 6 carbon atoms, C
t
F
2t+1
or phenyl, which is unsubstituted or substituted by a substituent selected from the group consisting of F, Cl, Br, CF
3
, methyl, methoxy, sulfamoyl or methylsulfonyl;
t is 1, 2 or 3;
s is zero, 1, 2, 3 or 4;
Y is SO
q
, —CO—, —SO
2
—NR(10)—, —O—, —NR(10)— or —CO—NR(10);
q is zero, 1 or 2;
R(10) is hydrogen or methyl;
but where R(6) cannot be —OCF
3
or —OC
2
F
5
;
and their physiologically tolerable salts.
Particularly preferred compounds of the formula I are those in which:
R(1) and R(2) independently of one another are CF
3
, methyl or phenyl,
which is unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of F, Cl, Br, I, CF
3
, methyl, methoxy, sulfamoyl and methylsulfonyl;
R(3) is alkyl having 1, 2, 3 or 4 carbon atoms, dimethylamino or diethylamino;
R(4) is R(12)—C
r
H
2r
;
R(12) is hydrogen, cycloalkyl having 5 or 6 carbon atoms or CF
3
;
is 1, 2, 3, 4, 5, 6, 7 or 8;
where one CH
3
group of the group C
r
H
2r
can be replaced by —O—, —CO—, —CO—O— or —SO
q
—;
q is zero, 1 or 2;
R(5), R(6), R(7) and R(8) independently of one another are hydrogen, F, Cl, Br, I, alkyl having 1 or 2 carbon atoms, —CN —NO
2
, —COOR(15), R(16)—C
s
H
2s
—Y— or phenyl,
which is unsubstituted or substituted by a substituent selected from the group consisting of F or Cl;
R(15) is methyl, ethyl, phenyl or —C
u
H
2u
—NR(13)R(14);
u is 2 or 3;
R(13) and R(14) independently of one another are hydrogen or alkyl having 1, 2 or 3 carbon atoms;
R(16) is hydrogen, CF
3
or phenyl,
s is zero, 1, 2, 3 or 4;
y is SO
q
, —CO—, —SO
2
—NR(10)—, —NR(10)— or —CO—NR(10);
q is zero, 1 or 2;
R(10) is hydrogen or methyl;
but where R(6) cannot be —OCF
3
,
and their physiologically tolerable salts.
Very particularly preferred compounds of the formula I are the following:
4-(N-ethylsulfonyl-N-methyl)amino-6-fluoro-2,2-dimethylchroman,
6-cyano-4-(N-ethylsulfonyl-N-methyl)amino-2,2-dimethylchroman,
4-(N-ethylsulfonyl-N-methyl)amino-6-methoxycarbonyl-2,2-dimethyl-chroman,
6-cyano-4-[N-ethylsulfonyl-N-(4,4,4-trifluorobutyl)]amino-2,2-dimethyl-chroman,
4-(N-butyl-N-ethylsulfonyl)amino-6-cyano-2,2-dimethylchroman,
4-(N-ethylsulfonyl-N-methyl)amino-2,2,6-trimethylchroman,
7-chloro-4-(N-ethylsulfonyl-N-methyl)amino-6-flouro-2,2-dimethylchroman,
6,7-dichloro-4-(N-ethylsulfonyl-N-methyl)amino-2,2-dimethylchroman,
4-(N-butyl-N-ethylsulfonyl)amino-6-fluoro-2,2-dimethylchroman,
4-(N-ethylsulfonyl-N-methyl)amino-6-fluoro-2,2-tetramethylenechroman,
4[N-ethylsulfonyl-N-(4,4,4-trifluorobutyl)]amino-6-fluoro-2,2-dimethyl-chroman,
4-(N-ethylsulfonyl-N-hexyl)amino-6-fluoro-2,2-dimethylchroman,
6-ethyl-4-[N-ethylsulfonyl-N-(4,4,4-trifluorobutyl)]amino-2,2-dimethyl-chroman.
DETAILED DESCRIPTION OF THE INVENTION
The disclosures of German Application Nos. 19619614.0 filed May 15, 1996 and 19639462.7 filed Sep. 26, 1996 are hereby incorporated by reference.
If the compounds I contain an acidic or basic group or a basic heterocycle, the corresponding, pharmacologically and toxicologically tolerable salts are also a subject of the invention. Thus the compounds I which carry one or more —COOH groups, for example as alkali metal salts, can preferably be used as sodium or potassium salts. Compounds I which carry a basic, protonatable group or a basic heterocyclic radical can also be used in the form of their organic or inorganic, pharmacologically and toxicologically tolerable acid addition salts, for example as hydrochlorides, methanesulfonates, acetates, lactetes, maleates, fumarates, malates, gluconates etc. If the compounds I contain an acidic and basic group in the same molecule, the invention also includes, beside the salt forms described internal salts, so-called betain
Bohn Helmut
Brendel Joachim
Busch Andreas
Englert Henrich Christian
Gerlach Uwe
Covington Raymond
Finnegan Henderson Farabow Garrett & Dunner L.L.P.
Hoechst Aktiengesellschaft
Kight John
LandOfFree
Sulfonamide-substituted chromans, processes for their... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Sulfonamide-substituted chromans, processes for their..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Sulfonamide-substituted chromans, processes for their... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2566546