Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Nitrogen containing other than solely as a nitrogen in an...
Reexamination Certificate
2002-07-30
2004-09-14
O'Sullivan, Peter (Department: 1621)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Nitrogen containing other than solely as a nitrogen in an...
C514S346000, C514S349000, C514S350000, C514S438000, C514S445000, C514S448000, C514S472000, C514S535000, C514S562000, C546S291000, C546S312000, C549S069000, C549S071000, C549S077000, C549S479000, C549S480000, C549S483000, C549S487000, C560S013000, C560S070000, C562S430000, C564S092000
Reexamination Certificate
active
06790866
ABSTRACT:
FIELD OF TECHNOLOGY
This invention relates to sulfonamide and carboamide derivatives. More particularly, this invention relates to
(1) the compounds of the formula (I):
(wherein all symbols are as hereinafter defined.),
(2) processes for preparing them and
(3) Prostaglandin E
2
(abbreviated as PGE
2
) antagonists or agonists which comprise them as an active ingredient.
BACKGROUND
PGE
2
has been known as metabolite in the arachidonate cascade. It has been known that PGE
2
causes uterine contraction, induction of pain, promotion of digestive peristalsis, awakening effect, vesica contraction, suppression of gastric acid secretion or reduction of blood pressure etc. The PGE
2
antagonist or PGE
2
agonist is expected to show the following actions.
To antagonize against PGE
2
means to suppress the effects above mentioned, so such an activity is linked to inhibition of uterine contraction, analgesic action, inhibition of digestive peristalsis, induction of sleep or increase of vesical capacity. Therefore, PGE
2
antagonists are considered to be useful for the prevention of abortion, as analgesics, as antidiarrheals, as sleep inducers or as agents for treating pollakiuria.
To show PGE
2
agonistic activity means to promote the effects above mentioned, so such an activity is linked to uterine contraction, promotion of digestive peristalsis, suppression of gastric acid secretion or reduction of blood pressure or diuresis. Therefore, PGE
2
agonists are considered to be useful as abortifacient, cathartic, antiulcer, anti-gastritis, antihypertensive or diuretic agents.
A lot of PGE
2
agonists including PGE
2
itself etc. have been known, but only a few compounds (PGE
2
antagonists) possessing the inhibition of activity of PGE
2
by antagonizing against PGE
2
have been known.
For example, the patent applications relating to PGE antagonists are as follows:
In the specification of WO-96/03380, it is disclosed that the compounds of the formula (A):
(wherein A is phenyl which may be substituted etc., B is ring system which may be substituted, D is ring system which may be substituted, R
1A
is carboxyl etc., R
2A
is H, C1-6 alkyl etc., R
3A
is H, C1-4 alkyl, R
4A
is H, C1-4 alkyl (as excerpt).) are active as PGE antagonists.
In the specification of WO-96/06822, it is disclosed that the compounds of the formula (B):
(wherein A is ring system which may be substituted, B is hetero aryl ring which may be substituted or phenyl which may be substituted, D is ring system which may be substituted, X
B
is (CHR
4B
)
nB
or (CHR
4B
)
p
CR
4B
═CR
4B
(CHR
4B
)
q
, R
1B
is carboxyl etc., R
3B
is H, C1-4 alkyl, R
4B
is H, C1-4 alkyl (as excerpt)) are active PGE antagonists.
In the specification of WO-96/11902, it is disclosed that the compounds of the formula (C):
(wherein A, B and D are various ring systems, R
1C
is carboxyl etc., R
3C
is H, C1-4 alkyl. Z is —(CH(R
5C
))
m
etc. (as excerpt)) are active as PGE antagonists.
On the other hand, some compounds having a similar structure to the present invention compounds have been known.
For example, the following compound is described in Justus Liebigs Ann. Chem. (1909), 367, 133:
(wherein R
D
is H or ethyl.)
The following compound is described in Khim. Geterotsikl. Soedin (1974), (6), 760:
(wherein R
E
is phenethyl, benzyl, hexadecyl, decyl, nonyl, butyl, propyl, ethyl, methyl.)
The following compound is described in Khim. Geterotsikl. Soedin (1972), (10), 1341:
(wherein R
F
is nitro or methoxy.)
The following compound is described in Khim. Geterotsikl. Soedin (1972), (5), 616:
The following compound is described in Khim. Geterotsikl. Soedin (1976), (5), 641:
The following compound is described in Khim. Geterotsikl. Soedin (1971), (7), 1028:
The following compound is described in Khim. Geterotsikl. Soedin (1970), (12), 1597:
(wherein each R
K
is Br or Cl.)
The compounds of the formula (A), (B) and (C) in the related arts possess the same pharmacological activity as the present invention compounds. But there is a difference in structure as follows: The present invention compounds have sulfonamide or carboamide as an essential element in their structure. On the other hand, the compounds described in such related arts have ether or alkylene in the corresponding part. So, it is not easy to predict the present invention compounds from the structure of these related arts.
In addition, the compounds of the formula (D) to (K) relate to the study for synthesis only. In these literature, there is no description on pharmacological activity. The carboxyl group in such compounds is connected at the ortho position, so the present invention compounds are different from such compounds in structure. Therefore, it is not easy to predict the present invention from such compounds possessing the different activity and structure.
THE DISCLOSURE OF THE INVENTION
The present invention relates to
(1) sulfonamide or carboamide derivatives of the formula (I)
(wherein
each, independently, is C5-15 carbocyclic ring or 5-7 membered heterocyclic ring containing one or two oxygen, sulfur or nitrogen atom(s),
Z
1
is
—COR
1
,
—C1-4 alkylene-COR
1
,
—CH═CH—COR
1
,
—C≡COR
1
, or
—O—C1-3 alkylene-COR
1
(wherein R
1
is hydroxy, C1-4 alkoxy or formula
NR
6
R
7
(wherein R
6
and R
7
each, independently, is H or C1-4 alkyl.).), or —C1-5 alkylene-OH,
Z
2
is H, C1-4 alkyl, C1-4 alkoxy, nitro, halogen, trifluoromethyl, trifluoromethoxy, hydroxy or COR
1
(wherein R
1
is as hereinbefore defined.),
Z
3
is single bond or C1-4 alkylene,
Z
4
is SO
2
or CO,
Z
5
is
(1) C1-8 alkyl, C2-8 alkenyl, or C2-8 alkynyl,
(2) phenyl, C3-7 cycloalkyl, or 5-7 membered heterocyclic ring containing one or two oxygen, sulfur or nitrogen atom(s), or
(3) C1-4 alkyl, C2-4 alkenyl or C2-4 alkynyl substituted by phenyl or C3-7 cycloalkyl
(phenyl, C3-7 cycloalkyl, and 5-7 membered heterocyclic ring containing one or two oxygen, sulfur or nitrogen atom(s) mentioned in the above (2) and (3) may be substituted by 1-5 of R
5
(wherein R
5
(if two or more R
5
, each independently) is H, C1-6 alkyl, C1-6 alkoxy, C1-6 alkylthio, nitro, halogen, tifluoromethyl, trifluoromethoxy or hydroxy.).),
R
2
is
CONR
8
,
NR
8
CO,
CONR
8
—C1-4 alkylene,
C1-4 alkylene-CONR
8
,
NR
8
CO—C1-4 alkylene,
C1-4 alkylene-NR
8
CO,
C1-3 alkylene-CONR
8
—C1-3 alkylene, or
C1-3 alkylene-NR
8
CO—C1-3 alkylene
(wherein each R
8
is H or C1-4 alkyl.),
O, S, NZ
6
(wherein Z
6
is H or C1-4 alkyl.),
Z
7
-C1-4 alkylene,
C1-4 alkylene-Z
7
, or
C1-3 alkylene-Z
7
-C1-3 alkylene
(wherein each Z
7
is O, S or NZ
6
(wherein Z
6
is as hereinbefore defined.).),
CO,
CO—C1-4 alkylene,
C1-4 alkylene-CO,
C1-3 alkylene-CO—C1-3 alkylene,
C2-4 alkylene,
C2-4 alkenylene, or
C2-4 alkynylene,
R
3
is H, C1-6 alkyl, C1-6 alkoxy, C1-6 alkylthio, nitro, halogen, trifluoromethyl, trifluoromethoxy, hydroxy or hydroxymethyl,
R
4
is
(1) H,
(2) C1-8 alkyl, C2-8 alkenyl, or C2-8 alkynyl,
(3) C1-6 alkyl substituted by one or two substituent(s) selected from the group consisting of COOZ
8
, CONZ
9
Z
10
, and OZ
8
(wherein Z
8
, Z
9
and Z
10
each, independently, is H or C1-4 alkyl.) and C1-4 alkoxy-C1-4 alkoxy,
(4) C3-7 cycloalkyl, or
(5) C1-4 alkyl, C2-4 alkenyl or C2-4 alkynyl substituted by phenyl or C3-7 cycloalkyl
(phenyl and C3-7 cycloalkyl mentioned in the above (4) and (5) may be substituted by 1-5 of R
5
(wherein R
5
is as hereinbefore defined.).), and n and teach, independently, is an integer of 1-4,
with the proviso that (1) R
2
and Z
3
should be connected at the 1- or 2-position of
is a benzene ring and (Z
2
)t is other than COR
1
, Z
1
should be connected at the 3- or 4-position of the benzene ring.), or a non-toxic salt thereof,
(2) processes for preparing them and
(3) PGE
2
antagonists or agonists which comprise them as an active ingredient.
REFERENCES:
patent: 3655693 (1972-04-01), Shen et al.
patent: 5397798 (1995-03-01), Fitch et al.
patent: 5916871 (1984-01-01), None
patent: 272150 (1990-03-01), None
patent: 9533461 (1995-12-01), None
patent: 9603380 (1996-02-01), None
patent: 9606822 (1996-03-01), None
Nagao Yuuki
Ohuchida Shuichi
O'Sullivan Peter
Ono Pharmaceutical Co. Ltd.
Stevens Davis Miller & Mosher L.L.P.
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