Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Reexamination Certificate
2000-04-27
2002-05-07
Raymond, Richard L. (Department: 1624)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
C514S255060, C514S252100, C514S256000, C514S354000, C514S617000
Reexamination Certificate
active
06384033
ABSTRACT:
TECHNICAL FIELD
The present invention relates to amide derivatives useful as a medicament. The amide derivatives of the present invention are useful as a medicament for treating retinal neurodegenerative disorders and the like.
BACKGROUND ART
N-t-Butyl-benzamide, N-t-butyl-4-bromobenzamide, N-t-butyl-4-nitrobenzamide, etc. are known to be useful as a medicament for treating neurodegenerative disorders such as Parkinson's disease, multiple sclerosis, Alzheimer's disease and the like (WO 95/28153, WO 96/31462). N-t-Butyl-3-chloro-2-pyridinecarboxamide, N-(2-hydroxy-1,1-dimethylethyl)-6-chloro-2-pyridinecarboxamide, etc. are known to be useful as a herbicide (JP 48-26918(A), JP 60-72803(A), JP 61-151174(A)).
It has been known that N-t-butyl-4-fluorobenzamide, N-t-butyl-2-fluorobenzamide, N-(2-hydroxy-1,1-dimethylethyl)-2,4,5-trifluorobenzamide, N-(2-hydroxy-1,1-dimethylethyl)-2,5-difluorobenzamide, N-(2-hydroxy-1,1-dimethylethyl)-2-fluorobenzamide, N-(2-hydroxy-1,1-dimethylethyl)-5-chloro-2-fluorobenzamide, N-(2-hydroxy-1,1-dimethylethyl)-2-fluoro-6-iodobenzamide, N-(2-hydroxy-1,1-dimethylethyl)-2,6-difluorobenzamide, N-(2-hydroxy-1,1-dimethylethyl)-2-chloro-4-fluorobenzamide, etc. were produced as synthetic intermediates (EP 511073, WO 89/06649, J. Org. Chem., 52, 713(1987), J. Org. Chem., 53, 345(1988), EP 538231, U.S. Pat. No. 3,985,889, etc.).
However, these documents do not disclose that the amide derivatives are effective for treating retinal neurodegenerative disorders.
DESCRIPTION OF THE INVENTION
The present invention is intended to provide a medicament for treating retinal neurodegenerative disorders and the like.
The inventors of the present invention have intensively carried out research, and found that amide derivatives are useful as a medicament for treating retinal degenerative disorders and the like. Thus, the present invention has been accomplished.
The present inventions are as follows:
[1] a medicament for treating retinal neurodegenerative disorder comprising a compound of the formula:
wherein
Ar is optionally substituted phenyl or optionally substituted aromatic heterocyclic group;
n is 0, 1 or 2;
R
1
is hydogen atom, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, alkoxycarbonyl, carbamoyl, alkanoyl or cyano; R
2
and R
3
are independently optionally substituted alkyl; or any two groups of R
1
, R
2
and R
3
may be taken together with the carbon atom adjacent thereto to form cycloalkane, or all of R
1
, R
2
and R
3
may be taken together with the carbon atom adjacent thereto to form bicycloalkane or tricycloalkane, wherein the cycloalkane, the bicycloalkane and the tricycloalkane may be substituted optionally;
R
4
and R
5
are independently hydrogen atom or optionally substituted alkyl;
R
6
is hydrogen atom, hydroxy or alkyl;
or a pharmaceutically acceptable salt thereof;
[2] a medicament comprising a compound of the formula:
wherein
Ar
1
is phenyl substituted by fluorine atom at the 2 or 4 position which may be substituted by further 1 or 2 halogen atoms, or optionally substituted 6-membered heteroaryl;
n, R
1
, R
2
, R
3
, R
4
, R
5
and R
6
are as defined above;
or a pharmaceutically acceptable salt thereof; and
[3] a compound of the formula:
wherein
Ar
2
is a group of the formula:
or 6-membered heteroaryl substituted by 1 to 3 halogen atoms;
n, R
1
, R
2
, R
3
and R
6
are as defined above; one of R
7
and R
8
is fluorine atom; the other is hydrogen atom or halogen atom;
R
9
is hydrogen atom or halogen atom; provided that the compound is not the following compound:
N-t-butyl-4-fluorobenzamide,
N-t-butyl-2-fluorobenzamide,
N-(2-hydroxy-1,1-dimethylethyl)-2,4,5-trifluorobenzamide,
N-(2-hydroxy-1,1-dimethylethyl)-2,5-difluorobenzamide,
N-(2-hydroxy-1,1-dimethylethyl)-2-fluorobenzamide,
N-(2-hydroxy-1,1-dimethylethyl)-5-chloro-2-fluorobenzamide,
N-(2-hydroxy-1,1-dimethylethyl)-2-fluoro-6-iodobenzamide,
N-(2-hydroxy-1,1-dimethylethyl)-2,6-difluorobenzamide,
N-(2-hydroxy-1,1-dimethylethyl)-2-chloro-4-fluorobenzamide,
N-t-Butyl-3-chloro-2-pyridinecarboxamide and
N-(2-hydroxy-1,1-dimethylethyl)-6-chloro-2-pyridinecarboxamide,
or a pharmaceutically acceptable salt thereof.
“Aromatic heterocyclic group” includes, for example, 5- or 6-membered aromatic heterocyclic group containing 1 to 3 atoms selected independently from the group consisting of nitrogen atoms, sulfur atoms and oxygen atoms, and the like. Nitrogen atom or sulfur atom constituting heteroaryl may be oxidized. 5-Membered aromatic heterocyclic group includes, for example, the 5-membered aromatic heterocyclic group containing 1 or 2 atoms selected independently from the group consisting of nitrogen atoms, sulfur atoms and oxygen atoms, such as pyrrolyl, thienyl, furyl, imidazolyl, pyrazolyl, isothiazolyl, isoxazolyl, thiazolyl, oxazolyl and the like, and the like. 6-Membered aromatic heterocyclic group includes, for example, the 6-membered aromatic heterocyclic group containing 1 to 3 nitrogen atoms, and the like. Typical examples are pyridyl, 1-oxido-pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, triazinyl and the like.
“Heterocyclic group” includes aromatic heterocyclic group, aliphatic heterocyclic group and the like. Aliphatic heterocyclic group includes, for example, 5- or 6-membered aliphatic heterocyclic group containing 1 to 3 atoms selected independently from the group consisting of nitrogen atoms, sulfur atoms and oxygen atoms, and the like. 5-Membered aliphatic heterocyclic group includes, for example, the 5-membered aliphatic heterocyclic group containing 1 or 2 atoms selected independently from the group consisting of nitrogen atoms, sulfur atoms and oxygen atoms, such as pyrrolidinyl, pyrrolinyl, imidazolidinyl, pyrazolidinyl, tetrahydrofuryl, tetrahydrothienyl, dioxolanyl and the like, and the like. 6-Membered aliphatic heterocyclic group includes, for example, the 6-membered aliphatic heterocyclic group containing 1 or 2 atoms selected independently from the group consisting of nitrogen atoms, sulfur atoms and oxygen atoms, such as piperidyl, piperazinyl, morpholinyl, tetrahydropyranyl, dioxanyl and the like, and the like.
The substituent of the substituted phenyl, the substituted aromatic heterocyclic group, the substituted 5-membered aromatic heterocyclic group and the substituted 6-membered aromatic heterocyclic group may be one or more and includes, for example, halogen atom, cyano, nitro, alkyl, alkyl substituted by halogen atom(s), alkoxy, alkoxy substituted by halogen atom(s), alkoxycarbonyl, alkanoylamino, amino, phenyl, alkyl aminocarbonylamino, alkoxycarbonylamino, alkylsulfonylamino, carbamoyl, carbamoyl substituted by alkyl(s) and the like.
Preferable substituents of the substituted phenyl include, for example, halogen atom, cyano, nitro, alkyl substituted by halogen atom(s), alkoxy substituted by halogen atom(s), alkoxycarbonyl, alkanoylamino, amino, phenyl, alkylaminocarbonylamino, alkoxycarbonylamino, alkylsulfonylamino, carbamoyl, carbamoyl substituted by alkyl(s) and the like. More preferable examples are the electron-withdrawing groups such as halogen atom, cyano, nitro, trifluoromethyl and the like. Furthermore, preferable is halogen atom, and the most preferable is fluorine atom.
Preferable substituents of the substituted aromatic heterocyclic group, the substituted 5-membered aromatic heterocyclic group and the substituted 6-membered aromatic heterocyclic group include, for example, halogen atom, cyano, nitro, alkyl, alkyl substituted by halogen atom(s), alkoxycarbonyl, alkanoylamino, amino, phenyl, alkylaminocarbonylamino, alkoxycarbonylamino, alkylsulfonylamino, carbamoyl, carbamoyl substituted by alkyl(s) and the like. Particularly preferable is halogen atom.
The number of substituents of the substituted phenyl may be 1, 2 or 3. Preferable examples are 1 and 2, and more preferable is 2. Preferable position of the substitution is the 4 position, and the positions are the 2 and 4 positions if the phenyl is substituted by multiple substituents
Fujibayashi Tatsuya
Ikeda Kazuhito
Nagata Ryu
Nishihara Toshio
Ogo Hiroki
Birch & Stewart Kolasch & Birch, LLP
Habte Kahsay
Sumitomo Pharmaceuticals Company Limited
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