US 6,281,211 B1 · Substituted semicarbazides and the use thereof

Abstract

This invention is related to substituted semicarbazides represented by Formula (I) or a pharmaceutically acceptable salt or prodrug thereof, wherein: R1 and R2 are independently hydrogen, alkyl, cycloalkyl, alkenyl, alkynyl, haloalkyl, aryl, aminoalkyl, hydroxyalkyl, alkoxyalkyl or carboxyalkyl; R3, R4, R5 and R6 are independently hydrogen, alkyl, cycloalkyl, alkenyl, alkynyl, haloalkyl, aryl, aminoalkyl, hydroxyalkyl, alkoxyalkyl or carboxyalkyl, or R3 and R4 is defined as above, and R5 and R6 together with the nitrogen atom to which they are attached form a heterocycle, including piperidine, piperazine, morpholine; A1 and A2 are independently aryl, heteroaryl, saturated or partially unsaturated carbocycle or saturated or partially unsaturated heterocycle, any of which is optionally substituted; X is one of O, S, NR7, CH2, C(O), NR7C(O), C(O)NR7, SO, SO2 or a covalent bond; where R7 is hydrogen, alkyl, cycloalkyl, alkenyl, alkynyl, haloalkyl, aryl, aminoalkyl, hydroxyalkyl, alkoxyalkyl or carboxyalkyl; n is 0, 1, 2 or 3. m is 0, 1, 2 or 3. The invention also is directed to the use of substituted semi-carbazides for the treatment of neuronal damage following global and focal ischemia, for the treatment or prevention of neurodegenerative conditions such as amyotrophic lateral sclerosis (ALS), and for the treatment, prevention or amelioration of both acute or chronic pain, as anticonvulsants, and as antimanic depressants, as anti-nigraine agents, as local anesthetics, as antiarrhythmics and for the treatment or prevention of diabetic neuropathy.

Claims21

Dependent claims

A compound having the Formula I:

or a pharmaceutically acceptable salt or prodrug thereof, wherein:
R1 and R2 are independently hydrogen, alkyl, cycloalkyl, alkenyl, alkynyl, haloalkyl, aryl, aminoalkyl, hydroxyalkyl, alkoxyalkyl or carboxyalkyl;
R3, R4, R5 and R6 are independently hydrogen, alkyl, cycloalkyl, alkenyl, alkynyl, haloalkyl, aryl, aminoalkyl, hydroxyalkyl, alkoxyalkyl or carboxyalkyl, or R3 and R4 are defined as above, and R5 and R6 together with the nitrogen atom to which they are attached form a heterocycle
A1 and A2 are independently aryl, heteroaryl, saturated or partially unsaturated cycloalky or saturated or partially unsaturated heterocycle, any of which is optionally substituted;
X is one of O, S, NR7, CH2, C(O), NR7C(O), C(O)NR7, SO, SO2 or a covalent bond;
where
R7 is hydrogen, alkyl, cycloalkyl, alkenyl, alkynyl, haloalkyl, aryl, aminoalkyl, hydroxyalkyl, alkoxyalkyl or carboxyalkyl;
n is 0, 1, 2or 3;
and
m is 0, 1, 2, or 3.

7 more elements

A method of treating a disorder responsive to the blockade of sodium channels in a mammal suffering therefrom, comprising administering to a mammal in need of such treatment an effective amount of a compound having the Formula I:

or a pharmaceutically acceptable salt or prodrug thereof, wherein:
R1 and R2 are independently hydrogen, alkyl, cycloalkyl, alkenyl, alkynyl, haloalkyl, aryl, aminoalkyl, hydroxyalkyl, alkoxyalkyl or carboxyalkyl;
R3, R4, R5 and R6 are independently hydrogen, alkyl, cycloalkyl, alkenyl, alkynyl, haloalkyl, aryl, aminoalkyl, hydroxyalkyl, alkoxyalkyl or carboxyalkyl, or R3 and R4 is defined as above, and R5 and R6 together with the nitrogen atom to which they are attached form a heterocycle;
A1 and A2 are independently aryl, heteroaryl, saturated or partially unsaturated cycloalkyl or saturated or partially unsaturated heterocycle, any of which is optionally substituted;
X is one of O, S, NR7, CH2, C(O), NR7C(O), C(O)NR7, SO, SO2 or a covalent bond;
where
R7 is hydrogen, alkyl, cycloalkyl, alkenyl, alkynyl, haloalkyl, aryl, aminoalkyl, hydroxyalkyl, alkoxyalkyl or carboxyalkyl;
n is 0, 1, 2 or 3;
and
m is 0, 1, 2, or 3.

7 more elements

A method for treating, preventing or ameliorating neuronal loss following global and focal ischemia;

treating, preventing or ameliorating neurodegenerative conditions;
treating, preventing or ameliorating pain;
treating, preventing or ameliorating manic depression;
providing local anesthesia;
or treating arrhythmias, or treating convulsions, comprising administering to a mammal in need of such treatment an effective amount of a compound having the Formula I:
or a pharmaceutically acceptable salt or prodrug thereof, wherein:
R1 and R2 are independently hydrogen, alkyl, cycloalkyl, alkenyl, alkynyl, haloalkyl, aryl, aminoalkyl, hydroxyalkyl, alkoxyalkyl or carboxyalkyl;
R3, R4, R5 and R6 are independently hydrogen, alkyl, cycloalkyl, alkenyl, alkynyl, haloalkyl, aryl, aminoalkyl, hydroxyalkyl, alkoxyalkyl or carboxyalkyl, or R3 and R4 is defined as above, and R5 and R6 together with the nitrogen atom to which they are attached form a heterocycle;
A1 and A2 are independently aryl, heteroaryl, saturated or partially unsaturated cycloalkyl or saturated or partially unsaturated heterocycle, any of which is optionally substituted;
X is one of O, S, NR7, CH2, C(O), NR7C(O), C(O)NR7, SO, SO2 or a covalent bond;
where
R7 is hydrogen, alkyl, cycloalkyl, alkenyl, alkynyl, haloalkyl, aryl, aminoalkyl, hydroxyalkyl, alkoxyalkyl or carboxyalkyl;
n is 0, 1, 2 or 3;
and
m is 0, 1, 2, or 3.

12 more elements

Dependencies are inferred from the claim text.

Substituted semicarbazides and the use thereof

Life of this patent

Substituted semicarbazides and the use thereof

Life of this patent

Abstract

Claims21