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US 2003/0153763 A1Published application
Pharmaceutically active compounds and methods of use
OwnerN. Laxma Reddy, Michael Maillard +3inventors
InventorsN. Laxma Reddy, Michael Maillard, David Berlove, Sharad Magar, Graham J. Durant
Life of this patent
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Abstract
The present invention relates to pharmaceutically acceptable compounds, including certain substituted indolinyl and derivatives thereof, 1,2,3,4-tetrahydroquinolinyl and derivatives thereof, 1,2,3,4-tetrahydroisoquinolinyl, benz[cd]indolinyl and 5,6-dihydrophenanthridinyl compounds, and methods of treatment and pharmaceutical compositions that utilize or comprise one or more such compounds. Compounds of the invention are particularly useful for the treatment or prophylaxis of neurological injury and neurodegenerative disorders.
Claims45
A compound of the following Formula I:
- 50
- wherein R and R1 are each independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkoxy, substituted or unsubstituted alkylthio, substituted or unsubstituted aminoalkyl, substituted or unsubstituted alkyls ulfinyl, substituted or unsubstituted alkylsulfonyl, substituted or unsubstituted carbocyclic aryl, or a substituted or unsubstituted heteroaromatic or heteroalicyclic group having from 1 to 3 rings, 3 to 8 ring members in each ring and from 1 to 3 hetero atoms, with at least one of R and R1 being other than hydrogen;
- each R2 and each R3 are each independently hydrogen, halogen, hydroxyl, azido, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkoxy, substituted or unsubstituted alkylthio, substituted or unsubstituted alkylsulfinyl, substituted or unsubstituted alkylsulfonyl, substituted or unsubstituted aminoalkyl, substituted or unsubstituted carbocyclic aryl, or substituted or unsubstituted aralkyl;
- X is substituted or substituted methylene, —S—, —O— or substituted or unsubstituted —N—;
- m is 0, 1 or 2;
- and n is 0, 1, 2, 3 or 4;
- with the exclusion of N-(m-ethylphenyl)-1-indolinylcarboximidamide;
- and pharmaceutically acceptable salts thereof.
5 more elements
A compound of the following Formula I″:
- 51
- wherein R and R1 are each independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkoxy, substituted or unsubstituted alkylthio, substituted or unsubstituted aminoalkyl, substituted or unsubstituted alkyls ulfinyl, substituted or unsubstituted alkylsulfonyl, substituted or unsubstituted carbocyclic aryl, or a substituted or unsubstituted heteroaromatic or heteroalicyclic group having from 1 to 3 rings, 3 to 8 ring members in each ring and from 1 to 3 hetero atoms, with at least one of R and R1 being other than hydrogen;
- each R2 and each R3 are each independently hydrogen, halogen, hydroxyl, azido, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkoxy, substituted or unsubstituted alkylthio, substituted or unsubstituted alkylsulfinyl, substituted or unsubstituted alkylsulfonyl, substituted or unsubstituted aminoalkyl, substituted or unsubstituted carbocyclic aryl, or substituted or unsubstituted aralkyl;
- X is —SO— or —SO2—;
- m is 0, 1 or 2;
- and n is 0, 1, 2, 3 or 4;
- and pharmaceutically acceptable salts thereof.
4 more elements
A compound of the following Formula II:
- 52
- wherein R and R1 are each independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkoxy, substituted or unsubstituted alkylthio, substituted or unsubstituted aminoalkyl, substituted or unsubstituted alkylsulfinyl or substituted or unsubstituted alkylsulfonyl, substituted or unsubstituted carbocyclic aryl, substituted or unsubstituted aralkyl, or a substituted or unsubstituted heteroaromatic or heteroalicyclic group having from 1 to 3 rings, 3 to 8 ring members in each ring and from 1 to 3 hetero atoms;
- each R2 and each R3 are each independently hydrogen, halogen, hydroxyl, azido, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkoxy, substituted or unsubstituted alkylthio, substituted or unsubstituted alkylsulfinyl, substituted or unsubstituted alkylsulfonyl, substituted or unsubstituted aminoalkyl, substituted or unsubstituted carbocyclic aryl, or substituted or unsubstituted aralkyl having at least about 6 ring carbon atoms;
- X is —O—, —S—, substituted or unsubstituted —N—, or substituted or unsubstituted methylene;
- m and n are each independently 0, 1, 2, 3 or 4;
- and pharmaceutically acceptable salts thereof.
3 more elements
A compound of the following Formula II″:
- 53
- wherein R and R1 are each independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkoxy, substituted or unsubstituted alkylthio, substituted or unsubstituted aminoalkyl, substituted or unsubstituted alkylsulfinyl or substituted or unsubstituted alkylsulfonyl, substituted or unsubstituted carbocyclic aryl, substituted or unsubstituted aralkyl, or a substituted or unsubstituted heteroaromatic or heteroalicyclic group having from 1 to 3 rings, 3 to 8 ring members in each ring and from 1 to 3 hetero atoms;
- each R2 and each R3 are each independently hydrogen, halogen, hydroxyl, azido, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkoxy, substituted or unsubstituted alkylthio, substituted or unsubstituted alkylsulfinyl, substituted or unsubstituted alkylsulfonyl, substituted or unsubstituted aminoalkyl, substituted or unsubstituted carbocyclic aryl, or substituted or unsubstituted aralkyl having at least about 6 ring carbon atoms;
- X is sulfinyl (—S(O)—) or sulfonyl (—S(O2)—);
- m and n are each independently 0, 1, 2, 3 or 4;
- and pharmaceutically acceptable salts thereof.
3 more elements
A compound of the following Formula III:
- 54
- wherein R and R1 are each independently hydrogen;
- substituted or unsubstituted alkyl having from 1 to about 20 carbon atoms;
- substituted or unsubstituted alkenyl having from 2 to about 20 carbon atoms;
- substituted or unsubstituted alkynyl having from 2 to about 20 carbon atoms;
- substituted or unsubstituted alkoxy having from 1 to about 20 carbon atoms;
- substituted or unsubstituted alkylthio having from 1 to about 20 carbon atoms;
- substituted or unsubstituted aminoalkyl having from 1 to about 20 carbon atoms;
- substituted or unsubstituted alkylsulfinyl having from 1 to about 20 carbon atoms;
- substituted or unsubstituted alkylsulfonyl having from 1 to about 20 carbon atoms;
- substituted or unsubstituted carbocyclic aryl having at least about 6 ring carbon atoms;
- or a substituted or unsubstituted heteroaromatic or heteroalicyclic group having from 1 to 3 rings, 3 to 8 ring members in each ring and from 1 to 3 hetero atoms;
- each R2 and each R3 are each independently hydrogen, halogen, hydroxyl, azido, substituted or unsubstituted alkyl having from 1 to about 20 carbon atoms, substituted or unsubstituted alkenyl having from 2 to about 20 carbon atoms, substituted or unsubstituted alkynyl having from 2 to about 20 carbon atoms, substituted or unsubstituted alkoxy having from 1 to about 20 carbon atoms, substituted or unsubstituted alkylthio having from 1 to about 20 carbon atoms, substituted or unsubstituted alkylsulfinyl having from 1 to about 20 carbon atoms, substituted or unsubstituted alkylsulfonyl having from 1 to about 20 carbon atoms, substituted or unsubstituted aminoalkyl having from 1 to about 20 carbon atoms, substituted or unsubstituted carbocyclic aryl having at least about 6 ring carbon atoms, or substituted or unsubstituted aralkyl having at least about 6 ring carbon atoms;
- m is 0, 1, 2, 3, 4, 5 or 6;
- n is 0, 1, 2, 3 or 4;
- and pharmaceutically acceptable salts thereof.
13 more elements
A compound of the following Formula IV:
- 55
- wherein R and R1 are each independently hydrogen;
- substituted or unsubstituted alkyl having from 1 to about 20 carbon atoms;
- substituted or unsubstituted alkenyl having from 2 to about 20 carbon atoms;
- substituted or unsubstituted alkynyl having from 2 to about 20 carbon atoms;
- substituted or unsubstituted alkoxy having from 1 to about 20 carbon atoms;
- substituted or unsubstituted alkylthio having from 1 to about 20 carbon atoms;
- substituted or unsubstituted aminoalkyl having from 1 to about 20 carbon atoms;
- substituted or unsubstituted alkylsulfinyl having 1 to about 20 carbon atoms;
- substituted or unsubstituted alkylsulfonly having 1 to about 20 carbon atoms;
- substituted or unsubstituted carbocyclic aryl having at least about 6 ring carbon atoms;
- or a substituted or unsubstituted heteroaromatic or heteroalicyclic group having from 1 to 3 rings, 3 to 8 ring members in each ring and from 1 to 3 hetero atoms, with at least one of R and R1 being other than hydrogen;
- each R2 and each R3 are each independently hydrogen, halogen, hydroxyl, azido, substituted or unsubstituted alkyl having from 1 to about 20 carbon atoms, substituted or unsubstituted alkenyl having from 2 to about 20 carbon atoms, substituted or unsubstituted alkynyl having from 2 to about 20 carbon atoms, substituted or unsubstituted alkoxy having from 1 to about 20 carbon atoms, substituted or unsubstituted alkylthio having 1 to about 20 carbon atoms, substituted or unsubstituted alkylsulfinyl having from 1 to about 20 carbon atoms, substituted or unsubstituted alkylsulfonyl having from 1 to about 20 carbon atoms, substituted or unsubstituted aminoalkyl having from 1 to about 20 carbon atoms, substituted or unsubstituted carbocyclic aryl having at least about 6 ring carbon atoms, or substituted or unsubstituted aralkyl having at least about 6 ring carbon atoms;
- m is 0, 1 or 2;
- and n is an integer of 0-6;
- and pharmaceutically acceptable salts thereof.
13 more elements
A compound of the following Formula V:
- 56
- wherein R and R1 are each independently hydrogen;
- substituted or unsubstituted alkyl having from 1 to about 20 carbon atoms;
- substituted or unsubstituted alkenyl having from 2 to about 20 carbon atoms;
- substituted or unsubstituted alkynyl having from 2 to about 20 carbon atoms;
- substituted or unsubstituted alkoxy having from 1 to about 20 carbon atoms;
- substituted or unsubstituted alkylthio having from 1 to about 20 carbon atoms;
- substituted or unsubstituted aminoalkyl having from 1 to about 20 carbon atoms;
- substituted or unsubstituted alkylsulfinyl having 1 to about 20 carbon atoms;
- substituted or unsubstituted alkylsulfonyl having 1 to about 20 carbon atoms;
- substituted or unsubstituted carbocyclic aryl having at least about 6 ring carbon atoms;
- or a substituted or unsubstituted heteroaromatic or heteroalicyclic group having from 1 to 3 rings, 3 to 8 members in each ring and from 1 to 3 hetero atoms, with at least one or R and R1 being other than hydrogen;
- each R2, each R3 and each R4 are each independently hydrogen, halogen, hydroxyl, azido, substituted or unsubstituted alkyl having from 1 to about 20 carbon atoms, substituted or unsubstituted alkenyl having from 2 to about 20 carbon atoms, substituted or unsubstituted alkynyl having from 2 to about 20 carbon atoms, substituted or unsubstituted alkoxy having from 1 to about 20 carbon atoms, substituted or unsubstituted alkylthio having 1 to about 20 carbon atoms, substituted or unsubstituted alkylsulfinyl having from 1 to about 20 carbon atoms, substituted or unsubstituted alkylsulfonyl having from about 1 to about 20 carbon atoms, substituted or unsubstituted aminoalkyl having from 1 to about 20 carbon atoms, substituted or unsubstituted carbocyclic aryl having at least about 6 ring carbon atoms, or substituted or unsubstituted aralkyl having at least about 6 ring carbon atoms;
- m is 0, 1 or 2;
- and n and r are each independently 0, 1, 2, 3 or 4;
- and
- pharmaceutically acceptable salts thereof.
14 more elements
A compound of the following formula VI:
- 57
- wherein R and R1 are each independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkoxy, substituted or unsubstituted alkylthio, substituted or unsubstituted aminoalkyl, substituted or unsubstituted alkylsulfinyl or substituted or unsubstituted alkylsulfonyl, substituted or unsubstituted carbocyclic aryl, substituted or unsubstituted aralkyl, or a substituted or unsubstituted heteroaromatic or heteroalicyclic group having from 1 to 3 rings, 3 to 8 ring members in each ring and from 1 to 3 hetero atoms;
- each R2 and each R3 are each independently hydrogen, halogen, hydroxyl, azido, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkoxy, substituted or unsubstituted alkylthio, substituted or unsubstituted alkylsulfinyl, substituted or unsubstituted alkylsulfonyl, substituted or unsubstituted aminoalkyl, substituted or unsubstituted carbocyclic aryl, or substituted or unsubstituted aralkyl having at least about 6 ring carbon atoms;
- X is —O—, —S—, sulfinyl (—S(O)—), sulfonyl (—S(O2)—), substituted or unsubstituted —N—, or substituted or unsubstituted methylene;
- m is 0, 1, 2, 3, 4, 5 or 6;
- n is 0, 1, 2, 3 or 4;
- and pharmaceutically acceptable salts thereof.
4 more elements
A compound of the following Formula VII:
- 58
- wherein R and R1 are each independently hydrogen;
- substituted or unsubstituted alkyl having from 1 to about 20 carbon atoms;
- substituted or unsubstituted alkenyl having from 2 to about 20 carbon atoms;
- substituted or unsubstituted alkynyl having from 2 to about 20 carbon atoms;
- substituted or unsubstituted alkoxy having from 1 to about 20 carbon atoms;
- substituted or unsubstituted alkylthio having from 1 to about 20 carbon atoms;
- substituted or unsubstituted aminoalkyl having from 1 to about 20 carbon atoms;
- substituted or unsubstituted alkylsulfinyl having 1 to about 20 carbon atoms;
- substituted or unsubstituted alkylsulfonyl having 1 to about 20 carbon atoms;
- substituted or unsubstituted carbocyclic aryl having at least about 6 ring carbon atoms;
- or a substituted or unsubstituted heteroaromatic or heteroalicyclic group having from 1 to 3 rings, 3 to 8 ring members in each ring and from 1 to 3 hetero atoms, with at least one of R and R1 being other than hydrogen;
- each R2 and each R3 are each independently hydrogen, halogen, hydroxyl, azido, substituted or unsubstituted alkyl having from 1 to about 20 carbon atoms, substituted or unsubstituted alkenyl having from 2 to about 20 carbon atoms, substituted or unsubstituted alkynyl having from 2 to about 20 carbon atoms, substituted or unsubstituted alkoxy having from 1 to about 20 carbon atoms, substituted or unsubstituted alkylthio having 1 to about 20 carbon atoms, substituted or unsubstituted alkylsulfinyl having from 1 to about 20 carbon atoms, substituted or unsubstituted alkylsulfonyl having from 1 to about 20 carbon atoms, substituted or unsubstituted aminoalkyl having from 1 to about 20 carbon atoms, substituted or unsubstituted carbocyclic aryl having at least about 6 ring carbon atoms, or substituted or unsubstituted aralkyl having at least about 6 ring carbon atoms;
- m is 0, 1 or 2;
- and n is an integer of 0-9;
- and pharmaceutically acceptable salts thereof.
13 more elements
A compound having the following Formula VIII:
- 59
- wherein R and R1 are each independently hydrogen;
- substituted or unsubstituted alkyl having from 1 to about 20 carbon atoms;
- substituted or unsubstituted alkenyl having from 2 to about 20 carbon atoms;
- substituted or unsubstituted alkynyl having from 2 to about 20 carbon atoms;
- substituted or unsubstituted alkoxy having from 1 to about 20 carbon atoms;
- substituted or unsubstituted alkylthio having from 1 to about 20 carbon atoms;
- substituted or unsubstituted aminoalkyl having from 1 to about 20 carbon atoms;
- substituted or unsubstituted alkylsulfinyl having 1 to about 20 carbon atoms;
- substituted or unsubstituted alkylsulfonyl having 1 to about 20 carbon atoms;
- substituted or unsubstituted carbocyclic aryl having at least about 6 ring carbon atoms;
- or a substituted or unsubstituted heteroaromatic or heteroalicyclic group having from 1 to 3 rings, 3 to 8 ring members in each ring and from 1 to 3 hetero atoms, preferably with at least one of R and R1 being other than hydrogen;
- each R2, each R3 and each R4 are each independently hydrogen, halogen, hydroxyl, azido, substituted or unsubstituted alkyl having from 1 to about 20 carbon atoms, substituted or unsubstituted alkenyl having from 2 to about 20 carbon atoms, substituted or unsubstituted alkynyl having from 2 to about 20 carbon atoms, substituted or unsubstituted alkoxy having from 1 to about 20 carbon atoms substituted or unsubstituted alkylthio having 1 to about 20 carbon atoms, substituted or unsubstituted alkylsulfinyl having from 1 to about 20 carbon atoms, substituted or unsubstituted alkylsulfonyl having from 1 to about 20 carbon atoms, substituted or unsubstituted aminoalkyl having from 1 to about 20 carbon atoms, substituted or unsubstituted carbocyclic aryl having at least about 6 ring carbon atoms, or substituted or unsubstituted aralkyl having at least about 6 ring carbon atoms;
- m is 0, 1, 2, 3 or 4;
- n and r are each independently 0, 1, 2, 3 or 4;
- the dotted line represents an optional carbon-carbon endocyclic double bond;
- and
- pharmaceutically acceptable salts thereof.
15 more elements
A compound of the following Formula IX:
- 60
- wherein R and R1 are each independently hydrogen, substituted or unsubstituted alkyl having from 1 to about 20 carbon atoms;
- substituted or unsubstituted alkenyl having from 2 to about 20 carbon atoms;
- substituted or unsubstituted alkynyl having from 2 to about 20 carbon atoms;
- substituted or unsubstituted alkoxy having from 1 to about 20 carbon atoms;
- substituted or unsubstituted alkylthio having from 1 to about 20 carbon atoms;
- substituted or unsubstituted aminoalkyl having from 1 to about 20 carbon atoms;
- substituted or unsubstituted alkylsulfinyl having 1 to about 20 carbon atoms;
- substituted or unsubstituted alkylsulfonyl having 1 to about 20 carbon atoms;
- substituted or unsubstituted carbocyclic aryl having at least about 6 ring carbon atoms;
- or a substituted or unsubstituted heteroaromatic or heteroalicyclic group having from 1 to 3 rings, 3 to 8 ring members in each ring and from 1 to 3 hetero atoms, preferably with at least one of R and R1 being other than hydrogen;
- each R2, each R3 and each R4 are each independently hydrogen, halogen, hydroxyl, azido, substituted or unsubstituted alkyl having from 1 to about 20 carbon atoms, substituted or unsubstituted alkenyl having from 2 to about 20 carbon atoms, substituted or unsubstituted alkynyl having from 2 to about 20 carbon atoms, substituted or unsubstituted alkoxy having from 1 to about 20 carbon atoms, substituted or unsubstituted alkylthio having 1 to about 20 carbon atoms, substituted or unsubstituted alkylsulfinyl having from 1 to about 20 carbon atoms, substituted or unsubstituted aminoalkyl having from 1 to about 20 carbon atoms, substituted or unsubstituted carbocyclic aryl having at least about 6 ring carbon atoms, or substituted or unsubstituted aralkyl having at least about 6 ring carbon atoms;
- m is 0, 1, 2, 3, 4, 5 or 6;
- and n and r are each independently 0, 1, 2, 3 or 4;
- and pharmaceutically acceptable salts thereof.
12 more elements
A compound of any of the preceding claims that is optically active.
Dependencies are inferred from the claim text.