Nitrone compounds, pharmaceutical compositions containing the same and methods for treating inflammation and neuropathic pain
AssigneeRenovis, Inc.
InventorsM. Amin Khan, Ravindra B. Upasani, Paul L. Wood
Life of this patent
Estimating the term…
Abstract
Disclosed are nitrone compounds and pharmaceutical compositions containing such compounds. The nitrone compounds have one to six additional carbons bridging between the nitrone functionality and the nitrone aryl ring. The disclosed compositions are useful as therapeutics for inflammation-related conditions and analgesia in mammals, such as arthritis, and for neuropathic pain and traumatic injuries such as traumatic brain injury and acute spinal cord injury.
Claims62
A compound of formula 1
- wherein:
- (i) n is an integer with a value ranging from two to six;
- (ii) each R1 is independently selected from:
- hydrogen,
- alkyl, alkenyl, alkynyl. cycloalkyl, cycloalkenyl, aryl, alkaryl, aralkyl, aralkenyl, aralkynyl,
- halo, haloalkyl,
- hydroxyl, alkoxyl, hydroxyalkyl, alkoxyalkoxyl, acyl, carboxylate, carboxyl, alkanoyloxy,
- nitrate, nitrite, nitrile, cyanate, isocyanate, primary amino, secondary amino, tertiary amino, azido, carboxamido, acylamino,
- thiol, sulfonyl, alkyl sulfonate, aryl sulfonate, sulfonamide, thioaryloxy, thioalkoxy,
- oxygen heterocycles, nitogen heterocycles and sulfur heterocycles;
- (iii) R2, R3 and R5 are each independently selected from hydrogen, alkyl and cycloalkyl;
- and
- (iv) R4 is selected from alkyl, cycloalkyl, cycloalkylalkylene, cycloalkenyl, aryl and aralkyl,
- provided that:
- not all R1s are hydrogen.
A nitrone compound having at least a Ph-Z-C(H)═N(═O)—R4 where Ph represents a substituted aryl moiety, Z is a saturated aliphatic carbon chain of two to six carbon atoms in length, and R4 is selected from alkyl, cycloalkyl, cycloalkylalkylene, cycloalkenyl, and aralkyl.
A pharmaceutical composition comprising a pharmaceutically acceptable carrier and one or more compounds of formula I as active ingredients.
- wherein:
- (i) n is an integer with a value ranging from two to six;
- (ii) each R1 is independently selected from:
- hydrogen,
- alkyl, alkenyl, alkynyl. cycloalkyl, cycloalkenyl, aryl, alkaryl, aralkyl, aralkenyl, aralkynyl,
- halo, haloalkyl,
- hydroxyl, alkoxyl, hydroxyalkyl, alkoxyalkoxyl, acyl, carboxylate, carboxyl, alkanoyloxy,
- nitrate, nitrite, nitrite, cyanate, isocyanate, primary amino, secondary amino, tertiary amino, azido, carboxamido, acylamino,
- thiol, sulfonyl, alkyl sulfonate, aryl sulfonate, sulfonamide, thioaryloxy, thioalkoxy,
- oxygen heterocycles, nitogen heterocycles and sulfur heterocycles;
- (iii) R2, R3 and R5 are each independently selected from hydrogen, alkyl and cycloalkyl;
- and
- (iv) R4 is selected from alkyl, cycloalkyl, cycloalkylalkylene, cycloalkenyl, aryl and aralkyl
- provided that:
- not all R1s are hydrogen.
A pharmaceutical composition comprising a pharmaceutically-acceptable carrier and as active ingredients one or more compounds selected from the group consisting of:
- Compound 1
- N-tert-butyl-C-(2-phenylethyl) nitrone
- Compound 2
- N-tert-butyl-C-{2-[4-(methoxymethoxy)phenyl]ethyl} nitrone
- Compound 3
- N-tert-butyl-C-[2-(4-hydroxyphenyl]ethyl nitrone
- Compound 4
- N-tert-butyl-C-[2-(4-methoxyphenyl)ethyl] nitrone
- Compound 6
- N-tert-butyl-C-[2-(4-isopropoxyphenyl)ethyl] nitrone
- Compound 7
- N-tert-butyl-C-[2-(4-ethoxyphenyl)ethyl] nitrone
- Compound 8
- N-tert-butyl-C-[2-(4-benzenesulfonyloxy)phenyl]ethyl] nitrone
- Compound 9
- N-tert-butyl-C-[2-(4-acetamidophenyl)ethyl] nitrone
- Compound 10
- N-tert-butyl-C-[2-(4-benzenesulfonamidophenyl)ethyl] nitrone
- Compound 11
- N-tert-butyl-C-[2-(4-N,N Dibenzenesulfimidophenyl)ethyl] nitrone
- Compound 13
- N-tert-butyl-C-[2-(4-isopropylphenyl)-1-methyethyl] nitrone
- Compound 15
- N-tert-butyl-C-[1-(4-tert-butyl benzyl)-ethyl] nitrone
- Compound 16
- N-tert-butyl-C-[1-methyl-2-(4-methoxyphenyl)ethyl] nitrone
- Compound 17
- N-tert-butyl-C phenylmethyl nitrone
- Compound 20
- N-tert-butyl-C-[1-(phenyl)ethyl] nitrone
- Compound 21
- N-tert-butyl-C-[2-(3,5-di-tert-butyl-4-hydroxyphenyl)ethyl] nitrone
- Compound 23
- N-tert-butyl-C-[4-methoxy-phenyl)propyl] nitrone, and pharmaceutically
- acceptable salts thereof.
A pharmaceutical composition comprising a pharmaceutical carrier and, as an active ingredient at least one nitrone compound, the nitrone compound having a formula Ph-Z-C(H)═N(═O)—R4 where Ph represents a substituted aryl moiety, and Z is a saturated aliphatic carbon chain of two to six carbon atoms in length, and R4 is selected from alkyl, cycloalkyl, cycloalkylalkylene, cycloalkenyl, and aralky.
A pharmaceutical composition for treating inflammation, neuropathic pain, neurodegenerative disease, pain associated with arthritis or traumatic injury to the brain or spinal cord of a mammal comprising a pharmaceutically acceptable carrier and one or more compounds of formula I as active ingredients
- wherein:
- (i) n is an integer with a value ranging from one to six;
- (ii) each R1 is independently selected from:
- hydrogen,
- alkyl, alkenyl, alkynyl. cycloalkyl, cycloalkenyl, aryl, alkaryl, aralkyl, aralkenyl, aralkynyl,
- halo, haloalkyl,
- hydroxyl, alkoxyl, hydroxyalkyl, alkoxyalkoxyl, acyl, carboxylate, carboxyl, alkanoyloxy,
- nitrate, nitrite, nitrile, cyanate, isocyanate, primary amino, secondary amino, tertiary amino, azido, carboxamido, acylamino,
- thiol, sulfonyl, alkyl sulfonate, aryl sulfonate, sulfonamide, thioaryloxy, thioalkoxy,
- oxygen heterocycles, nitogen heterocycles and sulfur heterocycles;
- (iii) R2, R3 and R5 are each independently selected from hydrogen, alkyl and cycloalkyl;
- and
- (iv) R4 is selected from alkyl, cycloalkyl, cycloalkylalkylene, cycloalkenyl, aryl and aralkyl.
A pharmaceutical composition comprising a pharmaceutically-acceptable carrier and as active ingredients one or more compounds selected from the group consisting of:
- Compound 1
- N-tert-butyl-C-(2-phenylethyl) nitrone
- Compound 2
- N-tert-butyl-C-{2-[4-(methoxymethoxy)phenyl]ethyl} nitrone
- Compound 3
- N-tert-butyl-C-[2-(4-hydroxyphenyl]ethyl nitrone
- Compound 4
- N-tert-butyl-C-[2-(4-methoxyphenyl)ethyl] nitrone
- Compound 5
- N-tert-butyl-C-[4-(tetrahydropyran-2-yloxy) phenyl] nitrone
- Compound 6
- N-tert-butyl-C-[2-(4-isopropoxyphenyl)ethyl] nitrone
- Compound 7
- N-tert-butyl-C-[2-(4-ethoxyphenyl)ethyl] nitrone
- Compound 8
- N-tert-butyl-C-[2-(4-benzenesulfonyloxy)phenyl]ethyl] nitrone
- Compound 9
- N-tert-butyl-C-[2-(4-acetamidophenyl)ethyl] nitrone
- Compound 10
- N-tert-butyl-C-[2-(4-benzenesulfonamidophenyl)ethyl] nitrone
- Compound 11
- N-tert-butyl-C-[2-(4-N,N-Dibenzenesulfimidophenyl)ethyl] nitrone
- Compound 12
- N-tert-butyl-C-(5-phenylpentyl) nitrone
- Compound 13
- N-tert-butyl-C-[2-(4-isopropylphenyl)-1-methyethyl] nitrone
- Compound 14
- N-tert-butyl-C-(4-phenylpropyl) nitrone
- Compound 15
- N-tert-butyl-C-[1-(4-tert-butyl benzyl)-ethyl] nitrone
- Compound 16
- N-tert-butyl-C-[1-methyl-2-(4-methoxyphenyl)ethyl] nitrone
- Compound 17
- N-tert-butyl-C phenylmethyl nitrone
- Compound 18
- N-cyclohexyl-C-(2-phenylethyl) nitrone
- Compound 19
- N-tert-butyl-C-[4-phenylbutyl] nitrone
- Compound 20
- N-tert-butyl-C-[1-(phenyl)ethyl] nitrone
- Compound 21
- N-tert-butyl-C-[2-(3,5-di-tert-butyl-4-hydroxyphenyl)ethyl] nitrone
- Compound 22
- N-tert-butyl-C-[2-(3,5-di-tert-butyl-4-hydroxyphenyl)methyl] nitrone
- Compound 23
- N-tert-butyl-C-[4-methoxy-phenyl)propyl] nitrone, and pharmaceutically
- acceptable salts thereof.
A pharmaceutical composition conprising a pharmaceutical carrier and, as are active ingredient at least one nitrone compound, the nitrone compound comprising at least a Ph-Z-C(H)═N(═O)— where Ph represents a substituted or unsubstituted aryl moiety, and Z is a saturated aliphatic carbon chain of one to six carbon atoms in length covalently bonded intermediate the aryl moiety and the nitrone carbon.
Dependencies are inferred from the claim text.