Patent EA-002358-B1 (EA)
Title: Substituted n-[(aminoiminomethyl or aminomethyl)phenyl]propyl amides
Inventor: KLEIN SCOTT I
IPC: A61K31/24
Filed: 1998-06-26
Abstract: 1. A compound of the formula   ----- is a single or double bond; Ra is hydrogen, hydroxy or amino: R1 and R2 are hydrogen or taken together are =NR9; R3 is hydrogen, -CO2R6, -C(O)R6, -CONR6R6, -CH2OR7 or -CH2SR7; R4 is hydrogen, C1-C15 alkyl, Q-C1-C15 alkyl or thioheterocyclyl, wherein heterocyclyl is a mono- or polycyclyc system with 3-10 atoms in the ring, where one or more atoms in the ring are different then carbon, optionally nitrogen atoms, oxygen or sulfur, or a group of formula   R5 is C1-C15 alkyl, C2-C15 alkenyl, C2-C15 alkynyl, C3-C10 mono- or polycyclyc cycloalkyl, C3-C10 mono- or polycyclyc cycloalkenyl, mono- or polycyclyc heterocyclyl with 3-10 ring atoms with one or more atoms in the ring different then carbon, optionally nitrogen atoms, oxygen or sulfur; mono- or polycyclyc heterocyclenyl with 3-10 ring atoms with one or more atoms in the ring different then carbon, optionally nitrogen atoms, oxygen or sulfur, and which comprises at least one carbon-carbon or carbon-nitrogen double bond; fused C6-C14 mono- or polycyclyc aryl-C3-C10 mono- or polycyclyc cycloalkyl; with 5-14 ring atoms fused mono- or polycyclyc heteroaryl-C3-C10 mono- or polycyclyc cycloalkyl with one or more atoms in heteroaryl ring different then carbon, optionally nitrogen atoms, oxygen or sulfur; fused C6-C14 mono- or polycyclyc aryl-C3-C10 mono- or polycyclyc cycloalkenyl; with 5-14 ring atoms fused mono- or polycyclyc heteroaryl-C3-C10 mono- or polycyclyc cycloalkenyl with one or more atoms in heteroaryl ring different then carbon, optionally nitrogen atoms, oxygen or sulfur; fused C6-C14 mono- or polycyclyc aryl-heterocyclyl, wherein heterocyclyl is mono- or polycyclyc system with 3-10 ring atoms with one or more atoms in the ring different then carbon, optionally nitrogen atoms, oxygen or sulfur; with 5-14 ring atoms fused mono- or polycyclyc heteroaryl-heterocyclyl with one or more atoms in heteroaryl ring different then carbon, optionally nitrogen atoms, oxygen or sulfur, and wherein heterocyclyl is mono- or polycyclyc system with 3-10 ring atoms with one or more atoms in the ring different then carbon, optionally nitrogen atoms, oxygen or sulfur; fused C6-C14 mono- or polycyclyc aryl-heterocyclenyl, wherein heterocyclenyl is mono- or polycyclyc system with 3-10 ring atoms with one or more atoms in the ring different then carbon, optionally nitrogen atoms, oxygen or sulfur; and which comprises at least one carbon-carbon or carbon-nitrogen double bond; fused having 5-14 ring atoms mono- or polycyclyc heteroaryl-heterocyclenyl with one or more atoms in heteroaryl ring different then carbon, optionally nitrogen atoms, oxygen or sulfur, and wherein heterocyclenyl is mono- or polycyclyc system with 3-10 ring atoms with one or more atoms in the ring different then carbon, optionally nitrogen atoms, oxygen or sulfur; and which comprises at least one carbon-carbon or carbon-nitrogen double bond; C6-C14 mono- or polycyclyc aryl, fused C3-C10 mono- or polycyclyc cycloalkenyl-C6-C14 mono- or polycyclyc aryl; fused C3-C10 mono- or polycyclyc cycloalkyl-C6-C14 mono- or polycyclyc aryl; fused heterocyclyl-C6-C14 mono- or polycyclyc aryl, wherein heterocyclyl is mono- or polycyclyc system with 3-10 ring atoms with one or more atoms in the ring different then carbon, optionally nitrogen atoms, oxygen or sulfur; fused heterocyclenyl-C6-C14 mono- or polycyclyc aryl, wherein heterocyclenyl is mono- or polycyclyc system with 3-10 ring atoms with one or more atoms in the ring different then carbon, optionally nitrogen atoms, oxygen or sulfur, and which comprises at least one carbon-carbon or carbon-nitrogen double bond; having 5-14 ring atoms mono- or polycyclyc heteroaryl with one or more atoms in heteroaryl ring different then carbon, optionally nitrogen atoms, oxygen or sulfur; fused C3-C10 mono- or polycyclyc cycloalkyl-mono- or polycyclyc having 5-14 ring atoms heteroaryl with one or more atoms in heteroaryl ring different then carbon, optionally nitrogen atoms, oxygen or sulfur; fused C3-C10 mono- or polycyclyc cycloalkenyl-mono- or polycyclyc having 5-14 ring atoms heteroaryl with one or more atoms in heteroaryl ring different then carbon, optionally nitrogen atoms, oxygen or sulfur; fused heterocyclenyl-mono- or polycyclyc having 5-14 ring atoms heteroaryl, wherein heterocyclenyl is mono- or polycyclyc system with 3-10 ring atoms with one or more atoms in the ring different then carbon, optionally nitrogen atoms, oxygen or sulfur, and which comprises at least one carbon-carbon or carbon-nitrogen double bond; fused heterocyclyl-mono- or polycyclyc heteroaryl having 5-14 ring atoms with one or more atoms in heteroaryl ring different then carbon, optionally nitrogen atoms, oxygen or sulfur, and wherein heterocyclyl is mono- or polycyclyc system with 3-10 ring atoms with one or more atoms in the ring different then carbon, optionally nitrogen atoms, oxygen or sulfur; C6-C14 mono- or polycyclyc aryl-C1-C15 alkyl; with 5-14 ring atoms mono- or polycyclyc heteroaryl-C1-C15 alkyl with one or more atoms in heteroaryl ring different then carbon, optionally nitrogen atoms, oxygen or sulfur; C6-C14 mono- or polycyclyc aryl-C2-C15 alkenyl; with 5-14 ring atoms mono- or polycyclyc hetero-aryl-C2-C15 alkenyl with one or more atoms in heteroaryl ring different then carbon, optionally nitrogen atoms, oxygen or sulfur; C6-C14 mono- or polycyclyc aryl-C2-C15 alkynyl; or with 5-14 ring atoms mono- or polycyclyc heteroaryl-C2-C15 alkynyl with one or more atoms in heteroaryl ring different then carbon, optionally nitrogen atoms, oxygen or sulfur; R6 is hydrogen or C1-C6 alkyl; R7 is hydrogen, C1-C6 alkyl, C6-C14 mono- or polycyclyc Ar (lower C1-C6 alkyl), C1-C6 acyl, aroyl with C6-C14 mono- or polycyclyc aryl group or heteroaroyl with mono- or polycyclyc heteroaryl group with 5-14 ring atoms and with one or more atoms in heteroaryl ring different then carbon, optionally nitrogen atoms, oxygen or sulfur; R8 is hydrogen or C1-C6 alkyl; R9 is hydrogen, R10O2C-, R10O-, HO-, cyano, R10CO-, HCO-, C1-C6 alkyl, nitro, or Y<1a>Y<2a>N-; R10 is C1-C15 alkyl, C6-C14 mono- or polycyclyc aryl-C1-C15 alkyl; or with 5-14 ring atoms mono- or polycyclyc heteroaryl-C1-C15 alkyl with one or more atoms in heteroaryl ring different then carbon, optionally nitrogen atoms, oxygen or sulfur; Y<la> and Y<2a> are independently hydrogen or C1-C15 alkyl; A and B are hydrogen or taken together are a bond; Q is R7O- or R7S- or Y<1>Y<2>N-; Y<1> and Y<2> are independently hydrogen, C1-C15 alkyl, C6-C14 mono- or polycyclyc aryl and C6-C14 mono- or polycyclyc aryl-C1-C15 alkyl, or one of Y<1> and Y<2> is C1-C15 acyl or aroyl with C6-C14 mono- or polycyclyc aryl group, and the other of Y<1> and Y<2> is hydrogen, C1-C15 alkyl, C6-C14 mono- or polycyclyc aryl, and C6-C14 mono- or polycyclyc aryl-C1-C15 alkyl; Ar is C6-C14 mono- or polycyclyc aryl or with 5-14 ring atoms mono- or polycyclyc heteroaryl with one or more atoms in heteroaryl ring different then carbon, optionally nitrogen atoms, oxygen or sulfur; and n is 0, 1 or 2; or a pharmaceutically acceptable salt thereof, a solvate thereof, or prodrug thereof. 2. The compound according to Claim 1 wherein - - - - - is a single bond, or a pharmaceutically acceptable salt thereof, a solvate thereof, or prodrug thereof. 3. The compound according to Claim 1 wherein - - - - - is a double bond, or a pharmaceutically acceptable salt thereof, a solvate thereof, or prodrug thereof. 4. The compound according to Claim 1 wherein Ra is hydrogen, or a pharmaceutically acceptable salt thereof, a solvate thereof, or prodrug thereof. 5. The compound according to Claim 1 wherein Ra is hydroxy or amino; more preferred is hydroxy, or a pharmaceutically acceptable salt thereof, a solvate thereof, or prodrug thereof. 6. The compound according to Claim 1 wherein R1 and R2 taken together are =NR9, or a pharmaceutically acceptable salt thereof, a solvate thereof, or prodrug thereof. 7. The compound according to Claim 1 wherein R1 and R2 taken together are =NH, or a pharmaceutically acceptable salt thereof, a solvate thereof, or prodrug thereof. 8. The compound according to Claim 1 wherein R3 is hydrogen, or a pharmaceutically acceptable salt thereof, a solvate thereof, or prodrug thereof. 9. The compound according to Claim 1 wherein R3 is -CO2R6, -C(O)R6, -CH2OR7 or -CH2SR7, or a pharmaceutically acceptable salt thereof, a solvate thereof, or prodrug thereof. 10. The compound according to Claim 1 wherein R3 is -CO2R6, -CH2OR7 or -CH2SR7, or a pharmaceutically acceptable salt thereof, a solvate thereof, or prodrug thereof. 11. The compound according to Claim 1 wherein R3 is -CO2R6 or -CH2OR7, or a pharmaceutically acceptable salt thereof, a solvate thereof, or prodrug thereof. 12. The compound according to Claim 1 wherein R3 is -CO2R6 and R6 is C1-C6 alkyl, or a pharmaceutically acceptable salt thereof, a solvate thereof, or prodrug thereof. 13. The compound according to Claim 1 wherein R3 is -CH2OR7 or -CH2SR7 and R7 is hydrogen or C1-C6 alkyl, or a pharmaceutically acceptable salt thereof, a solvate thereof, or prodrug thereof. 14. The compound according to Claim 1 wherein R4 is hydrogen, C1-C15 alkyl or Q-C1-C15 alkyl, or a group of formula   or a pharmaceutically acceptable salt thereof, a solvate thereof, or prodrug thereof. 15. The compound according to Claim 1 wherein R4 is C1-C6 alkyl or a group of formula   where A and B are hydrogen and n is 1, or a pharmaceutically acceptable salt thereof, a solvate thereof, or prodrug thereof. 16. The compound according to Claim 1 wherein R4 is Q-C1-C6 alkyl, or a pharmaceutically acceptable salt thereof, a solvate thereof, or prodrug thereof. 17. The compound according to Claim 1 wherein R4 is R7O(C1-C6 alkyl)-, or a pharmaceutically acceptable salt thereof, a solvate thereof, or prodrug thereof. 18. The compound according to Claim 1 wherein R4 is thioheterocyclyl, wherein heterocyclyl is mono- or polycyclyc system wi