Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Reexamination Certificate
1999-02-01
2001-10-09
Ford, John M. (Department: 1624)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
C514S255050, C514S256000, C514S269000, C514S340000, C514S374000, C514S376000, C514S377000, C514S365000, C514S369000, C514S370000, C544S405000, C544S333000, C544S324000, C544S331000, C544S310000, C546S276400, C548S225000, C548S235000, C548S233000, C548S236000, C548S182000, C548S202000, C548S193000, C548S204000, C548S205000, C548S203000, C548S194000, C548S266200, C548S266600, C548S267200, C548S268600
Reexamination Certificate
active
06300357
ABSTRACT:
BACKGROUND OF THE INVENTION
In the Japanese Unexamined Patent Publication (KOKAI) No. Sho 61-85369, it is described that an analogous compound of the compound of the present invention, in which the following moiety (which corresponds to the right hand moiety of formula (I) which starts with —A—):
—A—(CO)
p
—(R
2
C═CR
3
)
q
—(C≡C)
r
—(R
4
C═CR
5
)
s
—Ar
2
is bonded to an alkyl, a cycloalkylalkyl group or a cycloalkyl group, has antifungal activities.
However, the present inventors made intensive studies in order to find a more excellent antifungal agent and found that the compound of the present invention is an excellent antifungal agent to accomplish the present invention.
SUMMARY OF THE INVENTION
The present invention relates to a compound having the formula (I):
wherein Ar
1
represents a phenyl group or a phenyl group having 1 to 3 substituent(s), (the substituent(s) represent(s) a halogen atom or a trifluoromethyl group);
Ar
2
represents a phenyl group, a 5- or 6-membered aromatic heterocyclic group (the aromatic heterocyclic group has at least one nitrogen, oxygen or sulfur atom) or a phenyl group or a 5- or 6-membered aromatic heterocyclic group having 1 to 3 substituents (the substituent(s) represent(s) a lower alkyl group, a lower alkoxy group, a halogen atom, a lower alkyl group substituted with a halogen atom or halogen atoms, a lower alkoxy group substituted with a halogen atom or halogen atoms, a nitro group, a cyano group, a S(O)
m
R
6
group (R
6
represents a lower alkyl group which may be substituted with a halogen atom or halogen atoms and m represents 0, 1 or 2) or a —NECOR
7
group (R
7
represents a lower alkyl group) and the aromatic heterocyclic group has at least one nitrogen, oxygen or sulfur atom];
R
0
represents a hydrogen atom or a lower alkyl group;
R
1
represents a lower alkyl group;
R
2
, R
3
, R
4
and R
5
may be the same or different and represent a hydrogen atom, a lower alkyl group or a lower alkyl group substituted with a halogen atom or halogen atoms and, where q and/or s represent 2, each of R
2
, R
3
, R
4
and R
5
represents independently a group which is the same or different from the other R
2
, R
3
, R
4
and R
5
respectively;
n represents 0, 1 or 2;
p represents 0 or 1;
g, r and s represent 0, 1 or 2; and
A represents a 4- to 7-membered aliphatic carbocyclic group comprising 4 to 7 carbon atoms or a 4- to 7-membered aliphatic heterocyclic group having at least one nitrogen, oxygen or sulfur atom,
or a pharmacologically acceptable salt thereof.
The above-mentioned halogen atom is, for example, a fluorine, chlorine or bromine atom, preferably a fluorine or chlorine atom.
The lower alkyl group is, for example, a methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl or tert-butyl group, preferably a methyl, ethyl, propyl or isopropyl group.
The lower alkoxy group is, for example, a methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, sec-butoxy or tert-butoxy group, preferably a methoxy, ethoxy, propoxy or isopropoxy group.
The 5- or 6-membered aromatic heterocyclic group of Ar
2
is, for example, a furyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, thiazolyl, pyridyl, pyrimidyl or pyrazyl group, preferably a furyl, thienyl, pyrrolyl or pyridyl group.
The 4- to 7-membered aliphatic carbocyclic group comprising 4 to 7 carbon atoms of A is, for example, a cyclobutane, cyclopentane, cyclohexare or cyclobutane ring, preferably a cyclobutane, cyclopentane or cyclohexane ring.
The 4- to 7-membered aliphatic heterocyclic group having at least one nitrogen, oxygen or sulfur atom of A is, for example, an azetidine, pyrrolidine, piperidine, homopiperidine, oxetane, tetrahydrofuran, tetrahydropyran, thietane, tetrahydrothiophene, pentamethylenesulfide, 1,4,5,6-tetrahydropyrimidine, 1,3-dioxane, 1,3-dithiane, dihydroxazine, tetrahydroxazine, dihydrothiazine or tetrahydrothiazine ring, preferably an azetidine, piperidine, 1,3-dioxane, 1,4,5,6-tetrahydropyrimidine, tetrahydroxazine or 1,3-dithiane ring.
The preferable compound having the formula (I) is the compound in which:
Ar
1
is a dichlorophenyl, difluorophenyl, chlorophenyl, fluorophenyl, (trifluoromethyl)phenyl or fluoro(trifluoromethyl)phenyl group, preferably a 2,4-dichlorophenyl, 2,4-difluorophenyl, 4-chlorophenyl, 4-fluorophenyl, 4-(trifluoromethyl)phenyl or 2-fluoro-4-(trifluoromethyl)phenyl group, particularly preferably a 2,4-dichlorophenyl, 2,4-difluorophenyl or 4-(trifluoromethyl)phenyl group;
Ar
2
is a fluorophenyl, chlorophenyl, difluorophenyl, dichlorophenyl, (trifluoromethyl)phenyl, (trichloromethyl)phenyl, fluoro-(trifluoromethyl)phenyl, (difluoromethoxy)phenyl, (trifluoromethoxy)phenyl, (2,2,2-trifluoroethoxy)phenyl, (1,1,2,2-tetrafluoroethoxy)phenyl, (2,2,3,3-tetrafluoropropoxy)phenyl, fluoro-(2,2,3,3-tetrafluoropropoxy)phenyl, nitrophenyl, fluoro-nitrophenyl, cyanophenyl, chloro-cyanophenyl, (methylthio)phenyl, (methylsulfinyl)phenyl, (methylsulfonyl)phenyl, (trifluoromethylthio)phenyl, (trifluoromethylsulfinyl)phenyl, (trifluoromethylsulfonyl)phenyl, chloropyridyl, (trifluoromethyl)pyridyl, (2,2,3,3-tetrafluoropropoxy)pyridyl, (trifluoromethyl)furyl, chlorothienyl or (trifluoromethyl)thienyl group, preferably a 4-fluorophenyl, 4-chlorophenyl, 2,4-difluorophenyl, 2,4-dichlorophenyl, 4-(trifluoromethyl)phenyl, 4-(trichloromethyl)phenyl, 2-fluoro-4-(trifluoromethyl)phenyl, 4-(difluoromethoxy)phenyl, 3-(trifluoromethoxy)phenyl, 4-(trifluoromethoxy)phenyl, 4-(2,2,2-trifluoroethoxy)phenyl, 4-(1,1,2,2-tetrafluoroethoxy)phenyl, 4-(2,2,3,3-tetrafluoropropoxy)phenyl, 2-fluoro-4-(2,2,3,3-tetrafluoropropoxy)phenyl, 4-nitrophenyl, 2-fluoro-4-nitrophenyl, 4-cyanophenyl, 2-chloro-4-cyanophenyl, 4-(methylthio)phenyl, 4-(methylsulfinyl)phenyl, 4-(methylsulfonyl)phenyl, 4-(trifluoromethylthio)phenyl, 4-(trifluoromethylsulfinyl)phenyl, 4-(trifluoromethylsulfonyl)pheryl, 6-chloro-3-pyridyl, 6-(trifluoromethyl)-3-pyridyl, 5-chloro-2-pyridyl, 6-(2,2,3,3-tetrafluoropropoxy)-3-pyridyl, 5-(trifluoromethyl)-2-furyl, 5-chloro-2-thienyl or 5-(trifluoromethyl)-2-thienyl group, particularly preferably a 4-chlorophenyl, 4-(trifluoromethylthio)phenyl, 4-(trifluoromethylsulfonyl)phenyl, 4-(trifluoromethyl)phenyl, 4-(trifluoromethoxy)phenyl or 4-(2,2,3,3-tetrafluoropropoxy)phenyl group;
R
0
is a hydrogen atom, a methyl, ethyl or propyl group, preferably a hydrogen atom, a methyl or ethyl group, particularly preferably a hydrogen atom or a methyl group;
R
1
is a methyl, ethyl or propyl group, preferably a methyl or ethyl group, particularly preferably a methyl group;
R
2
, R
3
, R
4
and R
5
may be the same or different and are a hydrogen atom, a methyl, ethyl, propyl or trifluoromethyl group, preferably a hydrogen atom, a methyl or trifluoromethyl group, particularly preferably a hydrogen atom or a trifluoromethyl group;
n is 0, 1 or 2, particularly preferably 0;
p is 0 or 1, particularly preferably 0;
q is 0, 1 or 2, particularly preferably 1;
r is 0, 1 or 2, particularly preferably 0 or 1;
s is 0, 1 or 2, particularly preferably 1;
A is a cyclobutane, cyclopentane, cyclohexane, azetidine, pyrrolidine, piperidine, tetrahydrofuran, tetrahydropyran, tetrahydrothiophene, 1,3-dioxane, 1,3-dithiane, tetrahydroxazine or tetrahydrothiazine ring, preferably a cyclobutane, cyclohexane, azetidine, piperidine, 1,3-dioxane, 1,3-dithiane, tetrahydroxazine or tetrahydrothiazine ring, particularly preferably a cyclohexane, piperidine, 1,3-dioxane or 1,3-dithiane ring.
The preferable compound (I) can be exemplified by the compound in which Ar
1
is a 4-chlorophenyl, 2,4-difluorophenyl, 2,4-dichlorophenyl or 4-(trifluoromethyl)phenyl group; R
0
is a hydrogen atom or a methyl group; R
1
is a methyl group; and the moiety represented by the formula:
—S(O)
n
—A—(CO)
p
—(R
2
C═CR
3
)
q
—(C≡C)
r
—(R
4
C═CR
5
)
s
—Ar
2
is a group as shown in Table 1.
TABLE 1
Example
—S(O)n-A-(CO)p-(R
2
C═CR
3
)q-(C≡C)r-(R
4
C═CR
5
)s-Ar
2
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
2
Konosu Toshiyuki
Miyaoka Takeo
Oida Sadao
Somada Atsushi
Tajima Yawara
Ford John M.
Frishauf, Holtz Goodman, Langer & Chick, P.C.
Sankyo Company Limited
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