Back to results
US 2003/0114492 A1Published application
Method of using neurotrophic sulfonamide compounds
OwnerGregory S. Hamilton, Jia-He Li +1inventors
InventorsGregory S. Hamilton, Jia-He Li, Joseph P. Steiner
Life of this patent
Estimating the term…
Abstract
This invention relates to a method of using neurotrophic low molecular weight, small molecule sulfonamide compounds having an affinity for FKBP-type immunophilins, as inhibitors of the enzyme activity associated with immunophilin proteins, particularly peptidyl-prolyl isomerase, or rotamase, enzyme activity.
Claims20
A method of effecting a neuronal activity in an animal, comprising:
- administering to the animal a neurotrophically effective amount of a compound of formula I:
- 26
- or a pharmaceutically acceptable salt thereof, wherein:
- A is CH2, oxygen, NH or N-(C1-C4 alkyl);
- B and D are independently Ar, hydrogen, (C1-C6)-straight or branched alkyl, (C1-C6)-straight or branched alkenyl, (C1-C6)-straight or branched alkyl or alkenyl that is substituted with a (C5-C7)-cycloalkyl, (C1-C6)-straight or branched alkyl or alkenyl that is substituted with a (C5-C7)-cycloalkenyl, or Ar substituted (C1-C6)-straight or branched alkyl or alkenyl, wherein, in each case, one or two of the CH2 groups of the alkyl or alkenyl chains may contain 1-2 heteroatoms selected from the group consisting of oxygen, sulfur, SO and SO2 in chemically reasonable substitution patterns, or
- 27
- provided that both B and D are not hydrogen;
- Q is hydrogen, (C1-C6)-straight or branched alkyl or (C1-C6)-straight or branched alkenyl;
- T is Ar or substituted 5-7 membered cycloalkyl with substituents at positions 3 and 4 which are independently selected from the group consisting of hydrogen, hydroxyl, O-(C1-C4)-alkyl, O-(C1-C4)-alkenyl and carbonyl;
- Ar is selected from the group consisting of phenyl, 1-napthyl, 2-naphthyl, 2-furyl, 3-furyl, 2-thienyl, 3-thienyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, monocyclic and bicyclic heterocyclic ring systems with individual ring sizes being 5 or 6 which may contain in either or both rings a total of 1-4 heteroatoms independently selected from O, N and S;
- wherein Ar may contain one to three substituents which are independently selected from the group consisting of hydrogen, halo, hydroxyl, nitro, trifluoromethyl, trifluoromethoxy, (C1-C6)-straight or branched alkyl, (C2-C6)-straight or branched alkenyl, O-(C1-C4)-straight or branched alkyl, O-(C2-C4)-straight or branched alkenyl, O-benzyl, O-phenyl, 1,2-methylenedioxy, amino, carboxyl and phenyl;
- E is (C1-C6)-straight or branched alkyl, (C1-C6)-straight or branched alkenyl, (C5-C7)-cycloalkyl, (C5-C7)-cycloalkenyl substituted with (C1-C4)-straight or branched alkyl or (C1-C4)-straight or branched alkenyl, [(C2-C4)-alkyl or (C2-C4)-alkenyl)]-Ar or Ar;
- J is hydrogen or C1 or C2 alkyl or benzyl;
- K is (C1-C4)-straight or branched alkyl, benzyl or cyclohexylmethyl;
- or wherein J and K may be taken together to form a 5-7 membered heterocyclic ring which may contain an oxygen, sulfur, SO or SO2 substituent therein;
- n is 0 to 3;
- and
- the stereochemistry at carbon positions 1 and 2 are R or S.
15 more elements
A method of effecting a neuronal activity in an animal, comprising:
- administering to the animal a neurotrophically effective amount of a compound of formula III:
- 29
- or a pharmaceutically acceptable salt thereof, wherein:
- B and D are independently Ar, hydrogen, (C1-C6)-straight or branched alkyl, (C1-C6)-straight or branched alkenyl, (C1-C6)-straight or branched alkyl or alkenyl that is substituted with a (C5-C7)-cycloalkyl, (C1-C6)-straight or branched alkyl or alkenyl that is substituted with a (C5-C7)-cycloalkenyl, or Ar substituted (C1-C6)-straight or branched alkyl or alkenyl, wherein, in each case, one or two of the CH2 groups of the alkyl or alkenyl chains may contain 1-2 heteroatoms selected from the group consisting of oxygen, sulfur, SO and SO2 in chemically reasonable substitution patterns, or
- 30
- provided that both B and D are not hydrogen;
- Q is hydrogen, (C1-C6)-straight or branched alkyl or (C1-C6)-straight or branched alkenyl;
- T is Ar or substituted 5-7 membered cycloalkyl with substituents at positions 3 and 4 which are independently selected from the group consisting of hydrogen, hydroxyl, O-(C1-C4)-alkyl, O-(C1-C4)-alkenyl and carbonyl;
- Ar is selected from the group consisting of phenyl, 1-napthyl, 2-naphthyl, 2-furyl, 3-furyl, 2-thienyl, 3-thienyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, monocyclic and bicyclic heterocyclic ring systems with individual ring sizes being 5 or 6 which may contain in either or both rings a total of 1-4 heteroatoms independently selected from O, N and S;
- wherein Ar may contain one to three substituents which are independently selected from the group consisting of hydrogen, halo, hydroxyl, nitro, trifluoromethyl, trifluoromethoxy, (C1-C6)-straight or branched alkyl, (C2-C6)-straight or branched alkenyl, O-(C1-C4)-straight or branched alkyl, O-(C2-C4)-straight or branched alkenyl, O-benzyl, O-phenyl, 1, 2-methylenedioxy, amino, carboxyl and phenyl;
- E is (C1-C6)-straight or branched alkyl, (C1-C6)-straight or branched alkenyl, (C5-C7)-cycloalkyl, (C5-C7)-cycloalkenyl substituted with (C1-C4)-straight or branched alkyl or (C1-C4)-straight or branched alkenyl, [(C2-C4)-alkyl or (C2-C4)-alkenyl)]-Ar or Ar;
- and
- m is 0 to 3.
10 more elements
A method of effecting a neuronal activity in an animal, comprising:
- administering to the animal a neurotrophically effective amount of a compound of formula IV:
- 31
- or a pharmaceutically acceptable salt thereof, wherein:
- B and D are independently Ar, hydrogen, (C1-C6)-straight or branched alkyl, (C1-C6)-straight or branched alkenyl, (C1-C6)-straight or branched alkyl or alkenyl that is substituted with a (C5-C7)-cycloalkyl, (C1-C6)-straight or branched alkyl or alkenyl that is substituted with a (C5-C7)-cycloalkenyl, or Ar substituted (C1-C6)-straight or branched alkyl or alkenyl, wherein, in each case, one or two of the CH2 groups of the alkyl or alkenyl chains may contain 1-2 heteroatoms selected from the group consisting of oxygen, sulfur, SO and SO2 in chemically reasonable substitution patterns, or
- 32
- provided that both B and D are not hydrogen;
- Q is hydrogen, (C1-C6)-straight or branched alkyl or (C1-C6)-straight or branched alkenyl;
- T is Ar or substituted 5-7 membered cycloalkyl with substituents at positions 3 and 4 which are independently selected from the group consisting of hydrogen, hydroxyl, O-(C1-C4)-alkyl, O-(C1-C4)-alkenyl and carbonyl;
- Ar is selected from the group consisting of phenyl, 1-napthyl, 2-naphthyl, 2-furyl, 3-furyl, 2-thienyl, 3-thienyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, monocyclic and bicyclic heterocyclic ring systems with individual ring sizes being 5 or 6 which may contain in either or both rings a total of 1-4 heteroatoms independently selected from O, N and S;
- wherein Ar may contain one to three substituents which are independently selected from the group consisting of hydrogen, halo, hydroxyl, nitro, trifluoromethyl, trifluoromethoxy, (C1-C6)-straight or branched alkyl, (C2-C6)-straight or branched alkenyl, O-(C1-C4)-straight or branched alkyl, O-(C2-C4)-straight or branched alkenyl, O-benzyl, O-phenyl, 1, 2-methylenedioxy, amino, carboxyl and phenyl;
- E is (C1-C6)-straight or branched alkyl, (C1-C6)-straight or branched alkenyl, (C5-C7)-cycloalkyl, (C5-C7)-cycloalkenyl substituted with (C1-C4)-straight or branched alkyl or (C1-C4)-straight or branched alkenyl, [(C2-C4)-alkyl or (C2-C4)-alkenyl)]-Ar or Ar;
- and
- m is 0 to 3.
10 more elements
Dependencies are inferred from the claim text.