| Sonstiges: |
- Nachgewiesen in: USPTO Patent Grants
- Sprachen: English
- Patent Number: 7,375,219
- Publication Date: May 20, 2008
- Appl. No: 11/404267
- Application Filed: April 13, 2006
- Assignees: NeurAxon, Inc. (Toronto, Ontario, CA)
- Claim: 1. A compound having the formula: [chemical expression included] (I), or a pharmaceutically acceptable salt or prodrug thereof, wherein, R 1 is H, optionally substituted C 1-6 alkyl, optionally substituted C 1-4 alkaryl, or optionally substituted C 1-4 alkheterocyclyl; R 2 is (CH 2) m2 X 2 , wherein X 2 is selected from the group consisting of: [chemical expression included] wherein each of R 2A and R 2B is, independently, H, optionally substituted C 1-6 alkyl, optionally substituted C 3-8 cycloalkyl, optionally substituted C 6-10 aryl, optionally substituted C 1-4 alkaryl, C 2-9 heterocyclyl, or optionally substituted C 1-4 alkheterocyclyl; each of R 2C and R 1D is, independently, H, OH, CO 2 R 2E , or NR 2F R 2G , wherein each of R 2E , R 2F , and R 2G is, independently, H, optionally substituted C 1-6 alkyl, optionally substituted C 3-8 cycloalkyl, optionally substituted C 6-10 aryl, optionally substituted C 1-4 alkaryl, C 2-9 heterocyclyl, or optionally substituted C 1-4 alkheterocyclyl, or R 2C and R 2D together with the carbon they are bonded to are C═O; Z 2 is NR 2H , NC(O)R 2H , NC(O)OR 2H , NC(O)NHR 2H , NC(S)R 2H , NC(S)NHR 2H , NS(O) 2 R 2H , O, S, S(O), or S(O) 2 , wherein R 2H is H, optionally substituted C 1-6 alkyl, optionally substituted C 3-8 cycloalkyl, optionally substituted C 6-10 aryl, optionally substituted C 1-4 alkaryl, C 2-9 heterocyclyl, or optionally substituted C 1-4 alkheterocyclyl; m2 is an integer of 0 to 6; n2 is an integer of 1 to 4; p2 is an integer of 0 to 2; and q2 is an integer of 0 to 5; R 3 is H, Hal, optionally substituted C 1-6 alkyl, optionally substituted C 6-10 aryl, optionally substituted C 1-4 alkaryl, optionally substituted C 2-9 bridged heterocyclyl, optionally substituted C 1-4 bridged alkheterocyclyl, optionally substituted C 2-9 heterocyclyl, or optionally substituted C 1-4 alkheterocyclyl; each of R 4 and R 7 is, independently, H, F, C 1-6 alkyl, or C 1-6 alkoxy; R 5 is H, R 5A C(NH)NH(CH 2) r5 or R 5A NHC(S)NH(CH 2) r5 , wherein r5 is an integer from 0 to 2, R 5A is optionally substituted C 1-6 alkyl, optionally substituted C 6-10 aryl, optionally substituted C 1-4 alkaryl, optionally substituted C 2-9 heterocyclyl, optionally substituted C 1-4 alkheterocyclyl, optionally substituted C 1-6 thioalkoxy, optionally substituted C 1-4 thioalkaryl, optionally substituted aryloyl, or optionally substituted C 1-4 thioalkheterocyclyl; and R 6 is H or R 6A C(NH)NH(CH 2) r6 or R 6A NHC(S)NH(CH 2) r6 , wherein r6 is an integer from 0 to 2, R 6A is optionally substituted C 1-6 alkyl, optionally substituted C 6-10 aryl, optionally substituted C 1-4 alkaryl, optionally substituted C 2-9 heterocyclyl, optionally substituted C 1-4 alkheterocyclyl, optionally substituted C 1-6 thioalkoxy, optionally substituted C 1-4 thioalkaryl, optionally substituted aryloyl, or optionally substituted C 1-4 thioalkheterocyclyl; wherein one, but not both, of R 5 and R 6 is H.
- Claim: 2. A compound having the formula: [chemical expression included] or a pharmaceutically acceptable salt or prodrug thereof, wherein, R 1 is (CH 2) m3 X 1 , wherein X 1 is selected from the group consisting of: [chemical expression included] wherein each of R 3C and R 3D is, independently, H, OH, CO 2 R 3E , or NR 3F R 3G , wherein each of R 3E , R 3F , and R 3G is, independently, H, optionally substituted C 1-6 alkyl, optionally substituted C 3-8 cycloalkyl, optionally substituted C 6-20 aryl, optionally substituted C 1-4 alkaryl, C 2-9 heterocyclyl, or optionally substituted C 1-4 alkheterocyclyl, or R 3C and R 3D together with the carbon they are bonded to are C═O; Z 3 is NC(NH)R 3H , wherein R 3H is H, optionally substituted C 1-6 alkyl, optionally substituted C 3-8 cycloalkyl, optionally substituted C 6-10 aryl, optionally substituted C 1-4 alkaryl, C 2-9 heterocyclyl, or optionally substituted C 1-4 alkheterocyclyl; m 3 is an integer of 0 to 6; n 3 is an integer of 1 to 4; p 3 is an integer of 0 to 2; and q 3 is an integer of 0 to 5; each of R 2 and R 3 is, independently, H, Hal, optionally substituted C 1-6 alkyl, optionally substituted C 6-10 aryl, optionally substituted C 1-4 alkaryl, optionally substituted C 2-9 bridged heterocyclyl, optionally substituted C 1-4 bridged alkheterocyclyl, optionally substituted C 2-9 heterocyclyl, or optionally substituted C 1-4 alkheterocyclyl; each of R 4 and R 7 is, independently, H, F, C 1-6 alkyl, or C 1-6 alkoxy; R 5 is H, R 5A C(NH)NH(CH 2) r5 or R 5A NHC(S)NH(CH 2) r5 , wherein r5 is an integer from 0 to 2, R 5A is optionally substituted C 1-6 alkyl, optionally substituted C 6-10 aryl, optionally substituted C 1-4 alkaryl, optionally substituted C 2-9 heterocyclyl, optionally substituted C 1-4 alkheterocyclyl, optionally substituted C 1-6 thioalkoxy, optionally substituted C 1-4 thioalkaryl, optionally substituted aryloyl, or optionally substituted C 1-4 thioalkheterocyclyl; and R 6 is H or R 6A C(NH)NH(CH 2) r6 or R 6A NHC(S)NH(CH 2) r6 , wherein r6 is an integer from 0 to 2, R 6A is optionally substituted C 1-6 alkyl, optionally substituted C 6-10 aryl, optionally substituted C 1-4 alkaryl, optionally substituted C 2-9 heterocyclyl, optionally substituted C 1-4 alkheterocyclyl, optionally substituted C 1-6 thioalkoxy, optionally substituted C 1-4 thioalkaryl, optionally substituted aryloyl, or optionally substituted C 1-4 thioalkheterocyclyl; wherein one, but not both, of R 5 and R 6 is H.
- Claim: 3. A compound having the formula: [chemical expression included] (I), or a pharmaceutically acceptable salt or prodrug thereof, wherein, R 1 is H, optionally substituted C 1-6 alkyl, optionally substituted C 1-4 alkaryl, or optionally substituted C 1-4 alkheterocyclyl; R 2 is (CH 2) m3 X 2 , wherein X 2 is selected from the group consisting of: [chemical expression included] wherein each of R 3C and R 3D is, independently, H, OH, CO 2 R 3E or NR 3F R 3G , wherein each of R 3E , R 3F , and R 3G is, independently, H, optionally substituted C 1-6 alkyl, optionally substituted C 3-8 cycloalkyl, optionally substituted C 6-10 aryl, optionally substituted C 1-4 alkaryl, C 2-9 heterocyclyl, or optionally substituted C 1-4 alkheterocyclyl, or R 3C and R 3D together with the carbon they are bonded to are C═O; Z 3 is NC(NH)R 3H , wherein R 3H is H, optionally substituted C 1-6 alkyl, optionally substituted C 3-8 cycloalkyl, optionally substituted C 6-10 aryl, optionally substituted C 1-4 alkaryl, C 2-9 heterocyclyl, or optionally substituted C 1-4 alkheterocyclyl; m 3 is an integer of 0 to 6; n 3 is an integer of 1 to 4; p 3 is an integer of 0 to 2; and q 3 is an integer of 0 to5; R 3 is H, Hal, optionally substituted C 1-6 alkyl, optionally substituted C 6-10 aryl, optionally substituted C 1-4 alkaryl, optionally substituted C 2-9 bridged heterocyclyl, optionally substituted C 1-4 bridged alkheterocyclyl, optionally substituted C 2-9 heterocyclyl, or optionally substituted C 1-4 alkheterocyclyl; each of R 4 and R 7 is, independently, H, F, C 1-6 alkyl, or C 1-6 alkoxy; R 5 is H, R 5A C(NH)NH(CH 2) r5 or R 5A NHC(S)NH(CH 2) r5 , wherein r5 is an integer from 0 to 2, R 5A is optionally substituted C 1-6 alkyl, optionally substituted C 6-10 aryl, optionally substituted C 1-4 alkaryl, optionally substituted C 2-9 heterocyclyl, optionally substituted C 1-4 alkheterocyclyl, optionally substituted C 1-6 thioalkoxy, optionally substituted C 1-4 thioalkaryl, optionally substituted aryloyl, or optionally substituted C 1-4 thioalkheterocyclyl; and R 6 is H or R 6A C(NH)NH(CH 2) r6 or R 6A NHC(S)NH(CH 2) r6 , wherein r6 is an integer from 0 to 2, R 6A is optionally substituted C 1-6 alkyl, optionally substituted C 6-10 aryl, optionally substituted C 1-4 alkaryl, optionally substituted C 2-9 heterocyclyl, optionally substituted C 1-4 alkheterocyclyl, optionally substituted C 1-6 thioalkoxy, optionally substituted C 1-4 thioalkaryl, optionally substituted aryloyl, or optionally substituted C 1-4 thioalkheterocyclyl; wherein one, but not both, of R 5 and R 6 is H.
- Claim: 4. A compound having the formula: [chemical expression included] (I), or a pharmaceutically acceptable salt or prodrug thereof, wherein, R 1 is H, optionally substituted C 1-6 alkyl, optionally substituted C 1-4 alkaryl, or optionally substituted C 1-4 alkheterocyclyl; R 2 is H, Hal, optionally substituted C 1-6 alkyl, optionally substituted C 6-10 aryl, optionally substituted C 1-4 alkaryl, optionally substituted C 2-9 bridged heterocyclyl, optionally substituted C 1-4 bridged alkheterocyclyl, optionally substituted C 2-9 heterocyclyl, or optionally substituted C 1-4 alkheterocyclyl; R 3 is (CH 2) m3 X 3 , wherein X 3 is selected from the group consisting of: [chemical expression included] wherein each of R 3C and R 3D is, independently, H, OH, CO 2 R 3E , or NR 3F R 3G , wherein each of R 3E , R 3F and R 3G is, independently, H, optionally substituted C 1-6 alkyl, optionally substituted C 3-8 cycloalkyl, optionally substituted C 6-10 aryl, optionally substituted C 1-4 alkaryl, C 2-9 heterocyclyl, or optionally substituted C 1-4 alkheterocyclyl, or R 3c and R 3D together with the carbon they are bonded to are C═O; Z 3 is NC(NH)R 3H , wherein R 3H is H, optionally substituted C 1-6 alkyl, optionally substituted C 3-8 cycloalkyl, optionally substituted C 6-10 aryl, optionally substituted C 1-4 alkaryl, C 2-9 heterocyclyl, or optionally substituted C 1-4 alkheterocyclyl; m 3 is an integer of 0 to 6; n 3 is an integer of 1 to 4; p 3 is an integer of 0 to 2; and q 3 is an integer of 0 to 5; each of R 4 and R 7 is, independently, H, F, C 1-6 alkyl, or C 1-6 alkoxy; R 5 is H, R 5A C(NH)NH(CH 2) r5 or R 5A NHC(S)NH(CH 2) r5 , wherein r5 is an integer from 0 to 2, R 5A is optionally substituted C 1-6 alkyl, optionally substituted C 6-10 aryl, optionally substituted C 1-4 alkaryl, optionally substituted C 2-9 heterocyclyl, optionally substituted C 1-4 alkheterocyclyl, optionally substituted C 1-6 thioalkoxy, optionally substituted C 1-4 thioalkaryl, optionally substituted aryloyl, or optionally substituted C 1-4 thioalkheterocyclyl; and R 6 is H or R 6A C(NH)NH(CH 2) r6 or R 6A NHC(S)NH(CH 2) r6 , wherein r6 is an integer from 0 to 2, R 6A is optionally substituted C 1-6 alkyl, optionally substituted C 6-10 aryl, optionally substituted C 1-4 alkaryl, optionally substituted C 2-9 heterocyclyl, optionally substituted C 1-4 alkheterocyclyl, optionally substituted C 1-6 thioalkoxy, optionally substituted C 1-4 thioalkaryl, optionally substituted aryloyl, or optionally substituted C 1-4 thioalkheterocyclyl; wherein one, but not both, of R 5 and R 6 is H.
- Claim: 5. A compound having the formula: [chemical expression included] (I), or a pharmaceutically acceptable salt or prodrug thereof, wherein, R 1 is (CH 2) m1 X 1 , wherein X 1 is selected from the group consisting of: [chemical expression included] wherein each of R 1A and R 1B is, independently, H, optionally substituted C 1-6 alkyl, optionally substituted C 3-8 cycloalkyl, optionally substituted C 6-10 aryl, optionally substituted C 1-4 alkaryl, C 2-9 heterocyclyl, or optionally substituted C 1-4 alkheterocyclyl; each of R 1C and R 1D is, independently, H, OH, COR 1E , or NR 1F R 1G , wherein each of R 1E , R 1F , and R 1G is, independently, H, optionally substituted C 1-6 alkyl, optionally substituted C 3-8 cycloalkyl, optionally substituted C 6-10 aryl, optionally substituted C 1-4 alkaryl, C 2-9 heterocyclyl, or optionally substituted C 1-4 alkheterocyclyl, or R 1C and R 1D together with the carbon they are bonded to are C═O; Z 1 is NR 1H , NC(O)R 1H , NC(O)OR 1H , NC(O)NHR 1H , NC(S)R 1H , NC(S)NHR 1H , NS(O) 2 R 1H , O, S, S(O), or S(O) 2 , wherein R 1H is H, optionally substituted C 1-6 alkyl, optionally substituted C 3-8 cycloalkyl, optionally substituted C 6-10 aryl, optionally substituted C 1-4 alkaryl, C 2-9 heterocyclyl, or optionally substituted C 1-4 alkheterocyclyl; m1 is an integer of 2 to 6; n1 is an integer of 1 to 4; p1 is an integer of 0 to 2; and q1 is an integer of 0 to 5; R 2 is [chemical expression included] wherein each of R 2J2 , R 2J3 , R 2J4 , R 2J5 , and R 26J is, independently, C 1-6 alkyl; OH; C 1-6 alkoxy; SH; C 1-6 thioalkoxy; Halo; NO 2 ; CN; CF 3 ; OCF 3 ; NR 2Ja R 2Jb , where each of R 2Ja and R 2Jb is, independently, H or C 1-6 alkyl; C(O)R 2Jc , where R 2Jc is H or C 1-6 alkyl; CO 2 R 2Jd , where R 2Jd is H or C 1-6 alkyl; tetrazolyl; C(O)NR 2Je R 2Jf , where each of R 2Je and R 2Jf is, independently, H or C 1-6 alkyl; OC(O)R 2Jg , where R 2Jg is C 1-6 alkyl; NHC(O)R 2Jh , where R 2Jh is H or C 1-6 alkyl; SO 3 H; S(O) 2 NR 2Ji R 2Ji , where each of R 2Ji and R 2Ji is, independently, H or C 1-6 alkyl; S(O)R 2Jk , where R 2Jk is C 1-6 alkyl; and S(O) 2 R 2Jl , where R 2Jl is C 1-6 alkyl; R 3 is H, Hal, optionally substituted C 1-6 alkyl, optionally substituted C 6-10 aryl, optionally substituted C 1-4 alkaryl, optionally substituted C 2-9 bridged heterocyclyl, optionally substituted C 1-4 bridged alkheterocyclyl, optionally substituted C 1-9 heterocyclyl, or optionally substituted C 1-4 alkheterocyclyl; each of R 4 and R 7 is, independently, H, F, C 1-6 alkyl, or C 1-6 alkoxy; R 5 is H, R 5A C(NH)NH(CH 2) r5 or R 5A NHC(S)NH(CH 2) r5 , wherein r5 is an integer from 0 to 2, R 5A is optionally substituted C 1-6 alkyl, optionally substituted C 6-10 aryl, optionally substituted C 1-4 alkaryl, optionally substituted C 2-9 heterocyclyl, optionally substituted C 1-4 alkheterocyclyl, optionally substituted C 1-6 thioalkoxy, optionally substituted C 1-4 thioalkaryl, optionally substituted aryloyl, or optionally substituted C 1-4 thioalkheterocyclyl; and R 6 is H or R 6A C(NH)NH(CH 2) r6 or R 6H NHC(S)NH(CH 2) r6 , wherein r6 is an integer from 0 to 2, R 6A is optionally substituted C 1-6 alkyl, optionally substituted C 6-10 aryl, optionally substituted C 1-4 alkaryl, optionally substituted C 1-9 heterocyclyl, optionally substituted C 1-4 alkheterocyclyl, optionally substituted C 1-6 thioalkoxy, optionally substituted C 1-4 thioalkaryl, optionally substituted aryloyl, or optionally substituted C 1-4 thioalkheterocyclyl; wherein one, but not both, of R 5 and R 6 is H.
- Claim: 6. A compound having the formula: [chemical expression included] (I), or a pharmaceutically acceptable salt or prodrug thereof, wherein, R 1 is (CH 2) m1 X 1 , wherein X 1 is selected from the group consisting of: [chemical expression included] wherein each of R 1A and R 1B is, independently, H, optionally substituted C 1-6 alkyl, optionally substituted C 3-8 cycloalkyl, optionally substituted C 6-10 aryl, optionally substituted C 1-4 alkaryl, C 2-9 heterocyclyl, or optionally substituted C 1-4 alkheterocyclyl; each of R 1C and R 1D is, independently, H, OH, CO 2 R 1E , or NR 1F R 1G , wherein each of R 1E , R 1F , and R 1G is, independently, H, optionally substituted C 1-6 alkyl, optionally substituted C 3-8 cycloalkyl, optionally substituted C 6-10 aryl, optionally substituted C 1-4 alkaryl, C 2-9 heterocyclyl, or optionally substituted C 1-4 alkheterocyclyl, or R 1G and R 1D together with the carbon they are bonded to are C═O; Z 1 is NR 1H , NC(O)R 1H , NC(O)OR 1H , NC(O)NHR 1H , NC(S)R 1H , NC(S)NHR 1H , NS(O) 2 R 1H , O, S, S(O), or S(O) 2 , wherein R 1H is H, optionally substituted C 1-6 alkyl, optionally substituted C 3-8 cycloalkyl, optionally substituted C 6-10 aryl, optionally substituted C 1-4 alkaryl, C 2-9 heterocyclyl, or optionally substituted C 1-4 alkheterocyclyl; m1 is an integer of 2 to 6; n1 is an integer of 1 to 4; p1 is an integer of 0 to 2; and q1 is an integer of 0 to 5; R 2 is H, Hal, optionally substituted C 1-6 alkyl, optionally substituted C 6-10 aryl, optionally substituted C 1-4 alkaryl, optionally substituted C 2-9 bridged heterocyclyl, optionally substituted C 1-4 bridged alkheterocyclyl, optionally substituted C 2-9 heterocyclyl, or optionally substituted C 1-4 alkheterocyclyl; R 3 is [chemical expression included] wherein each of R 3J2 , R 3J3 , R 3J4 , R 3J5 , and R 3J6 is, independently, C 1-6 alkyl; OH; C 1-6 alkoxy; SH; C 1-6 thioalkoxy; Halo; NO 2 ; CN; CF 3 ; OCF 3 ; NR 3Ja R 3Jb , where each Of R 3Ja and R 3Jb is, independently, H or C 1-6 alkyl; C(O)R 3Jc , where R 3Jc is H or C 1-6 alkyl; CO 2 R 3Jd , where R 3Jd is H or C 1-6 alkyl; tetrazolyl; C(O)NR 3Je R 3Jf , where each of R 3Je and R 3Jf is, independently, H or C 1-6 alkyl; OC(O)R 3Jg , where R 3Jg is C 1-6 alkyl; NHC(O)R 3Jh , where R 3Jh is H or C 1-6 alkyl; SO 3 H; S(O) 2 NR 3Ji R 3Jj , where each of R 3Ji and R 3Jj is, independently, H or C 1-6 alkyl; S(O)R 3Jk , where R 3Jk is C 1-6 alkyl; and S(O) 2 R 3Jl , where R 3Jl is C 1-6 alkyl; each of R 4 and R 7 is, independently, H, F, C 1-6 alkyl, or C 1-6 alkoxy; R 5 is H, R 5A C(NH)NH(CH 2) r5 or R 5A NHC(S)NH(CH 2) r5 , wherein r5 is an integer from 0 to 2, R 5A is optionally substituted C 1-6 alkyl, optionally substituted C 6-10 aryl, optionally substituted C 1-4 alkaryl, optionally substituted C 2-9 heterocyclyl, optionally substituted C 1-4 alkheterocyclyl, optionally substituted C 1-6 thioalkoxy, optionally substituted C 1-4 thioalkaryl, optionally substituted aryloyl, or optionally substituted C 1-4 thioalkheterocyclyl; and R 6 is H or R 6A C(NH)NH(CH 2) r6 or R 6A NHC(S)NH(CH 2) r6 , wherein r6 is an integer from 0 to 2, R 6A is optionally substituted C 1-6 alkyl, optionally substituted C 6-10 aryl, optionally substituted C 1-4 alkaryl, optionally substituted C 2-9 heterocyclyl, optionally substituted C 1-4 alkheterocyclyl, optionally substituted C 1-6 thioalkoxy, optionally substituted C 1-4 thioalkaryl, optionally substituted aryloyl, or optionally substituted C 1-4 thioalkheterocyclyl; wherein one, but not both, of R 5 and R 6 is H.
- Claim: 7. A compound selected from the group consisting of: 2-ethyl-1-(1H-indol-5-yl)-isothiourea; N-(1H-indol-5-yl)-thiophene-2-carboxamidine; N-[1-(2-dimethylamino-ethyl)-1H-indol-6-yl]-thiophene-2-carboxamidine; N-{1-[2-(1-methyl-pyrrolidin-2-yl)-ethyl]-1H-indol-6-yl }-thiophene-2-carboxamidine; 1-[1-(2-dimethylamino-ethyl)-1H-indol-6-yl]-2-ethyl-isothiourea; N-[1-(2-pyrrolidin-1-yl-ethyl)-1H-indol-6-yl]-thiophene-2-carboxamidine; N-(1-phenethyl-1H-indol-6-yl)-thiophene-2-carboxamidine; N-[3-(2-dimethylamino-ethyl)-1H-indol-5-yl]-thiophene-2-carboxamidine; N-(1-{2-[2-(4-bromo-phenyl)-ethylamino]-ethyl}-1H-indol-6-yl)-thiophene-2-carboxamidine; (+)-N-{1-[2-(1-methyl-pyrrolidin-2-yl)-ethyl]-1H-indol-6-yl}-thiophene-2-carboxamidine; (−)-N-{1-[2-(1-methyl-pyrrolidin-2-yl)-ethyl]-1H-indol-6-yl}-thiophene-2-carboxamidine; N-[1-(1-methyl-azepan-4-yl)-1H-indol-6-yl]-thiophene-2-carboxamidine; and N-[1-(2-piperidin-1-yl-ethyl)-1H-indol-6-yl]-thiophene-2-carboxamidine.
- Claim: 8. A compound having the formula: [chemical expression included] or a pharmaceutically acceptable salt or prodrug thereof, wherein, R 1 or R 3 is [chemical expression included] wherein Z is NR X , R X is H or C 1-6 alkyl, o is an integer from 0-3, p is an integer from 1 to 2, q is an integer from 0 to 2, r is an integer from 0 to 1, s is an integer from 1 to 3, u is an integer from 0 to 1, and t is an integer from 5 to 7, and wherein said R 1 or R 3 substituent includes 0 to 6 carbon-carbon double bonds or 0 or 1 carbon-nitrogen double bonds; R 2 is H, Hal, optionally substituted C 1-6 alkyl, optionally substituted C 6-10 aryl, optionally substituted C 1-4 alkaryl, optionally substituted C 2-9 bridged heterocyclyl, optionally substituted C 1-4 bridged alkheterocyclyl, optionally substituted C 2-9 heterocyclyl, or optionally substituted C 1-4 alkheterocyclyl; each of R 4 and R 7 is, independently, H, F, C 1-6 alkyl, or C 1-6 alkoxy; R 5 is H, R 5A C(NH)NH(CH 2) r5 or R 5A NHC(S)NH(CH 2) r5 , wherein r5 is an integer from 0 to 2, R 5A is optionally substituted C 1-6 alkyl, optionally substituted C 6-10 aryl, optionally substituted C 1-4 alkaryl, optionally substituted C 2-9 heterocyclyl, optionally substituted C 1-4 alkheterocyclyl, optionally substituted C 1-6 thioalkoxy, optionally substituted C 1-4 thioalkaryl, optionally substituted aryloyl, or optionally substituted C 1-4 thioalkheterocyclyl; R 6 is H or R 6A C(NH)NH(CH 2) r6 or R 6A NHC(S)NH(CH 2) r6 , wherein r6 is an integer from 0 to 2, R 6A is optionally substituted C 1-6 alkyl, optionally substituted C 6-10 aryl, optionally substituted C 1-4 alkaryl, optionally substituted C 2-9 heterocyclyl, optionally substituted C 1-4 alkheterocyclyl, optionally substituted C 1-6 thioalkoxy, optionally substituted C 1-4 thioalkaryl, optionally substituted aryloyl, or optionally substituted C 1-4 thioalkheterocyclyl; wherein one, but not both, of R 5 and R 6 is H; and when R 1 or R 3 is not [chemical expression included] R 1 is selected from H, optionally substituted C 1-6 alkyl, optionally substituted C 1-4 alkaryl, or optionally substituted C 1-4 alkheterocyclyl; and R 3 is selected from H, Hal, optionally substituted C 1-6 alkyl, optionally substituted C 6-10 aryl, optionally substituted C 1-4 alkaryl, optionally substituted C 2-9 bridged heterocyclyl, optionally substituted C 1-4 bridged alkheterocyclyl, optionally substituted C 2-9 heterocyclyl, or optionally substituted C 1-4 alkheterocyclyl.
- Claim: 9. The compound of claim 8 , wherein said compound selectively inhibits nNOS over both eNOS and iNOS.
- Claim: 10. A compound having the formula: [chemical expression included] or a pharmaceutically acceptable salt or prodrug thereof, wherein, X is O or S; R 1 is H, optionally substituted C 1-6 alkyl, optionally substituted C 1-4 alkaryl, or optionally substituted C 1 -4 alkheterocyclyl; each of R 2 and R 3 is, independently, H, Hal, optionally substituted C 1-6 alkyl, optionally substituted C 6-10 aryl, optionally substituted C 1-4 alkaryl, optionally substituted C 2-9 bridged heterocyclyl, optionally substituted C 1-4 bridged alkheterocyclyl, optionally substituted C 2-9 heterocyclyl, or optionally substituted C 1-4 alkheterocyclyl; and each of R 4 and R 7 is, independently, H, F, C 1-6 alkyl, or C 1-6 alkoxy.
- Claim: 11. A compound having the formula: [chemical expression included] or a pharmaceutically acceptable salt or prodrug thereof, wherein, X is O or S; R 1 is H, optionally substituted C 1-6 alkyl, optionally substituted C 1-4 alkaryl, or optionally substituted C 1-4 alkheterocyclyl; each of R 2 and R 3 is, independently, H, Hal, optionally substituted C 1-6 alkyl, optionally substituted C 6-10 aryl, optionally substituted C 1-4 alkaryl, optionally substituted C 2-9 bridged heterocyclyl, optionally substituted C C 1-4 bridged alkheterocyclyl, optionally substituted C 2-9 heterocyclyl, or optionally substituted C 1-4 alkheterocyclyl; and each of R 4 and R 7 is, independently, H, F, C 1-6 alkyl, or C 1-6 alkoxy.
- Claim: 12. A compound selected from the group consisting of: [chemical expression included] [chemical expression included] [chemical expression included] [chemical expression included] [chemical expression included] [chemical expression included]
- Claim: 13. The compound of claim 11 , selected from the group consisting of: [chemical expression included] [chemical expression included] [chemical expression included]
- Claim: 14. The compound of claim 10 , wherein X is S.
- Claim: 15. The compound of claim 11 , wherein X is S.
- Claim: 16. The compound of claim 14 , having the formula: [chemical expression included] or a pharmaceutically acceptable salt thereof.
- Claim: 17. The compound of claim 1 , wherein R 3 is, independently, H, Hal, optionally substituted C 1-6 alkyl, optionally substituted C 6-10 aryl, optionally substituted C 1-4 alkaryl, optionally substituted C 2-9 heterocyclyl, or optionally substituted C 1-4 alkheterocyclyl; R 5 is H or R 5A C(NH)NH(CH 2) r5 , wherein r5 is an integer from 0 to 2, R 5A is optionally substituted C 1-6 alkyl, optionally substituted C 6-10 aryl, optionally substituted C 1-4 alkaryl, optionally substituted C 2-9 heterocyclyl, optionally substituted C 1-4 alkheterocyclyl, optionally substituted C 1-6 thioalkoxy, optionally substituted C 1-4 thioalkaryl, or optionally substituted C 1-4 thioalkheterocyclyl; and R 6 is H or R 6A C(NH)NH(CH 2) r6 , wherein r6 is an integer from 0 to 2, R 6A is optionally substituted C 1-6 alkyl, optionally substituted C 6-10 aryl, optionally substituted C 1-4 alkaryl, optionally substituted C 2-9 heterocyclyl, optionally substituted C 1-4 alkheterocyclyl, optionally substituted C 1-6 thioalkoxy, optionally substituted 1-4 thioalkaryl, or optionally substituted C 1-4 thioalkheterocyclyl.
- Claim: 18. The compound of claim 2 , wherein each of R 2 and R 3 is, independently, H, Hal, optionally substituted C 1-6 alkyl, optionally substituted C 6-10 aryl, optionally substituted C 1-4 alkaryl, optionally substituted C 2-9 heterocyclyl, or optionally substituted C 1-4 alkheterocyclyl; R 5 is H or R 5A C(NH)NH(CH 2) r5 , wherein r5 is an integer from 0 to 2, R 5A is optionally substituted C 1-6 alkyl, optionally substituted C 6-10 aryl, optionally substituted C 1-4 alkaryl, optionally substituted C 2-9 heterocyclyl, optionally substituted C 1-4 alkheterocyclyl, optionally substituted C 1-6 thioalkoxy, optionally substituted C 1-4 thioalkaryl, or optionally substituted C 1-4 thioalkheterocyclyl; and R 6 is H or R 6A C(NH)NH(CH 2) r6 , wherein r6 is an integer from 0 to 2, R 6A is optionally substituted C 1-6 alkyl, optionally substituted C 6-10 aryl, optionally substituted C 1-4 alkaryl, optionally substituted C 2-9 heterocyclyl, optionally substituted C 1-4 alkheterocyclyl, optionally substituted C 1-6 thioalkoxy, optionally substituted C 1-4 thioalkaryl, or optionally substituted C 1-4 thioalkheterocyclyl.
- Claim: 19. The compound of claim 3 , wherein R 3 is, independently, H, Hal, optionally substituted C 1-6 alkyl, optionally substituted C 6-10 aryl, optionally substituted C 1-4 alkaryl, optionally substituted C 2-9 heterocyclyl, or optionally substituted C 1-4 alkheterocyclyl; R 5 is H or R 5A C(NH)NH(CH 2) r5 , wherein r5 is an integer from 0 to 2, R 5A is optionally substituted C 1-6 alkyl, optionally substituted C 6-10 aryl, optionally substituted C 1-4 alkaryl, optionally substituted C 2-9 heterocyclyl, optionally substituted C 1-4 alkheterocyclyl, optionally substituted C 1-6 thioalkoxy, optionally substituted C 1-4 thioalkaryl, or optionally substituted C 1-4 thioalkheterocyclyl; and R 6 is H or R 6A C(NH)NH(CH 2) r6 , wherein r6 is an integer from 0 to 2, R 6A is optionally substituted C 1-6 alkyl, optionally substituted C 6-10 aryl, optionally substituted C 1-4 alkaryl, optionally substituted C 2-9 heterocyclyl, optionally substituted C 1-4 alkheterocyclyl, optionally substituted C 1-6 thioalkoxy, optionally substituted C 1-4 thioalkaryl, or optionally substituted C 1-4 thioalkheterocyclyl.
- Claim: 20. The compound of claim 4 , wherein R 2 is, independently, H, Hal, optionally substituted C 1-6 alkyl, optionally substituted C 6-10 aryl, optionally substituted C 1-4 alkaryl, optionally substituted C 2-9 heterocyclyl, or optionally substituted C 1-4 alkheterocyclyl; R 5 is H or R 5A C(NH)NH(CH 2) r5 , wherein r5 is an integer from 0 to 2, R 5A is optionally substituted C 1-6 alkyl, optionally substituted C 6-10 aryl, optionally substituted C 1-4 alkaryl, optionally substituted C 2-9 heterocyclyl, optionally substituted C 1-4 alkheterocyclyl, optionally substituted C 1-6 thioalkoxy, optionally substituted C 1-4 thioalkaryl, or optionally substituted C 1-4 thioalkheterocyclyl; and R 6 is H or R 6A C(NH)NH(CH 2) r6 , wherein r6 is an integer from 0 to 2, R 6A is optionally substituted C 1-6 alkyl, optionally substituted C 6-10 aryl, optionally substituted C 1-4 alkaryl, optionally substituted C 2-9 heterocyclyl, optionally substituted C 1-4 alkheterocyclyl, optionally substituted C 1-6 thioalkoxy, optionally substituted C 1-4 thioalkaryl, or optionally substituted C 1-4 thioalkheterocyclyl.
- Claim: 21. The compound of claim 5 , wherein R 3 is, independently, H, Hal, optionally substituted C 1-6 alkyl, optionally substituted C 6-10 aryl, optionally substituted C 1-4 alkaryl, optionally substituted C 2-9 heterocyclyl, or optionally substituted C 1-4 alkheterocyclyl; R 5 is H or R 5A C(NH)NH(CH 2) r5 , wherein r5 is an integer from 0 to 2, R 5A is optionally substituted C 1-6 alkyl, optionally substituted C 6-10 aryl, optionally substituted C 1-4 alkaryl, optionally substituted C 2-9 heterocyclyl, optionally substituted C 1-4 alkheterocyclyl, optionally substituted C 1-6 thioalkoxy, optionally substituted C 1-4 thioalkaryl, or optionally substituted C 1-4 thioalkheterocyclyl; and R 6 is H or R 6A C(NH)NH(CH 2) r6 , wherein r6 is an integer from 0 to 2, R 6A is optionally substituted C 1-6 alkyl, optionally substituted C 6-10 aryl, optionally substituted C 1-4 alkaryl, optionally substituted C 2-9 heterocyclyl, optionally substituted C 1-4 alkheterocyclyl, optionally substituted C 1-6 thioalkoxy, optionally substituted C 1-4 thioalkaryl, or optionally substituted C 1-4 thioalkheterocyclyl.
- Claim: 22. The compound of claim 6 , wherein R 2 is, independently, H, Hal, optionally substituted C 1-6 alkyl, optionally substituted C 6-10 aryl, optionally substituted C 1-4 alkaryl, optionally substituted C 2-9 heterocyclyl, or optionally substituted C 1-4 alkheterocyclyl; R 5 is H or R 5A C(NH)NH(CH 2) r5 , wherein r5 is an integer from 0 to 2, R 5A is optionally substituted C 1-6 alkyl, optionally substituted C 6-10 aryl, optionally substituted C 1-4 alkaryl, optionally substituted C 2-9 heterocyclyl, optionally substituted C 1-4 alkheterocyclyl, optionally substituted C 1-6 thioalkoxy, optionally substituted C 1-4 thioalkaryl, or optionally substituted C 1-4 thioalkheterocyclyl; and R 6 is H or R 6A C(NH)NH(CH 2) r6 , wherein r6 is an integer from 0 to 2, R 6A is optionally substituted C 1-6 alkyl, optionally substituted C 6-10 aryl, optionally substituted C 1-4 alkaryl, optionally substituted C 2-9 heterocyclyl, optionally substituted C 1-4 alkheterocyclyl, optionally substituted C 1-6 thioalkoxy, optionally substituted C 1-4 thioalkaryl, or optionally substituted C 1-4 thioalkheterocyclyl.
- Claim: 23. The compound of claim 10 , wherein each of R 2 and R 3 is, independently, H, Hal, optionally substituted C 1-6 alkyl, optionally substituted C 6-10 aryl, optionally substituted C 1-4 alkaryl, optionally substituted C 2-9 heterocyclyl, or optionally substituted C 1-4 alkheterocyclyl.
- Claim: 24. The compound of claim 11 , wherein each of R 2 and R 3 is, independently, H, Hal, optionally substituted C 1-6 alkyl, optionally substituted C 6-10 aryl, optionally substituted C 1-4 alkaryl, optionally substituted C 2-9 heterocyclyl, or optionally substituted C 1-4 alkheterocyclyl.
- Current U.S. Class: 540/524
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- Primary Examiner: Powers, Fiona T
- Attorney, Agent or Firm: Clark & Elbing LLP
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