US 7,531,550 B2
Pseudobase benzo[c]phenanthridines with improved efficacy, stability, and safety
Kenneth Shaw, Weston, Conn. (US); and Mingbao Zhang, Stamford, Conn. (US)
Assigned to Yale University, New Haven, Conn. (US)
Filed on Jul. 31, 2007, as Appl. No. 11/831,498.
Claims priority of provisional application 60/834375, filed on Jul. 31, 2006.
Prior Publication US 2008/0076781 A1, Mar. 27, 2008
Int. Cl. A61K 31/4741 (2006.01); C07D 491/113 (2006.01)
U.S. Cl. 514—280  [546/48; 546/61; 544/125; 544/336; 514/232.8; 514/253; 514/284] 27 Claims
 
1. A compound of the formula

OG Complex Work Unit Drawing
or a pharmaceutically acceptable salt thereof wherein:
R1 and R2 are each independently hydrogen, halogen, hydroxyl, C1-C3alkyl, C1-C6alkoxy, or C1-C6alkylester; or
R1 and R2 are joined by a —O—CH2—O— group;
R3 is hydrogen or methoxy;
R4 and R5 are independently methyl or hydrogen; or
R4 and R5 are joined to form a 5-membered heterocyclic ring containing no additional heteroatoms; and
R is
(i) a group of the formula -AB, where
A is —NR6—, —O—, —NR6(C═O)—, —S(O)m—, —CH2C(═O)—, —S(O)mNR6—, —NR6S(O)m—, —OS(O)m—NR6(S═O)NR7—, —O(C═O)—, or —NR6(C═O)NR7—, where m is 0, 1, or 2;
B is C2-C8alkenyl, C2-C8alkynyl, C2-C4alkanoyl, (carbocycle)C0-C2alkyl or (heterocycle)C0-C2alkyl, wherein the heterocycle has from 1 to 3 fused or pendant rings, each of which B is substituted with from 0 to 4 substituents independently chosen from halogen, hydroxyl, amino, cyano, C1-C4alkyl, C1-C4alkoxy, C1-C6alkylester, mono- and di-(C1-C4alkyl)amino, C1-C2haloalkyl, and C1-C2haloalkoxy;
(ii)

OG Complex Work Unit Drawing
(iii) a 5-membered heteroaryl group having at least one nitrogen ring member, and 0, 1, or 2 additional ring members independently chosen from N, O, and S, wherein the 5-membered heteroaryl group is attached via a nitrogen atom and is substituted with 0 to 3 substituents independently chosen from halogen, hydroxyl, amino, cyano, C1-C4alkyl, C1-C4alkoxy, mono- and di-(C1-C4alkyl)amino, C1-C2haloalkyl, and C1-C2haloalkoxy; or
(iv) a 5- or 6-membered heterocycloalkyl group linked via a nitrogen atom, wherein the heterocycloalkyl is substituted with from 0 to 4 substituents independently chosen from halogen, hydroxyl, amino, cyano, C1-C4alkyl, C1-C4alkoxy, C1-C6alkylester, mono- and di-(C1-C4alkyl)amino, C1-C2haloalkyl, C1-C2haloalkoxy, and 5- and 6-membered heterocycloalkyl; where
R6, R7, R8, R9, and R10 are each independently hydrogen, or
C1-C8alkyl, C2-C8alkenyl, C2-C8alkynyl, C2-C4alkanoyl, (C3-C10cycloalkyl)C0-C8alkyl, (heterocycloalkyl)C0-C8alkyl, or phenyl each of which is substituted with from 0 to 4 substituents independently chosen from halogen, hydroxyl, amino, cyano, C1-C4alkyl, C1-C4alkoxy, mono- and di-(C1-C4alkyl)amino, C1-C2haloalkyl, and C1-C2haloalkoxy.