Benzodiazepine derivatives, compositions, and methods for treating cognitive impairment

A compound of formula II:

• or a pharmaceutically acceptable salt, hydrate, isomer, or combination thereof, wherein:
• m is 0-3;
• each R1 is independently selected from:
• halogen, —H, —(C1-C6)alkyl, —OH, —O((C1-C6)alkyl), —NO2, —CN, —CF3, and —OCF3, wherein each of said —(C1-C6)alkyl or —O((C1-C6)alkyl is independently substituted with 0-5 R′;
• R2 is selected from:
• —(C1-C6)alkyl, —OH, —O((C1-C6)alkyl), —C(O)O((C1-C6)alkyl),
• (C6-C10)-aryl-(C1-C12)aliphatic-,
• (C6-C10)-aryl-O—(C1-C12)aliphatic-,
• (C6-C10)-aryl-N(R″)—(C1-C12)aliphatic-,
• (5- to 10-membered heteroaryl)-(C1-C12)aliphatic-,
• (5- to 10-membered heteroaryl)-O—(C1-C12)aliphatic-,
• (5- to 10-membered heteroaryl)-N(R″)—(C1-C12)aliphatic-,
• (3- to 10-membered heterocyclyl)-(C1-C12)aliphatic-,
• (3- to 10-membered heterocyclyl)-O—(C1-C12)aliphatic-, and
• (3- to 10-membered heterocyclyl)-N(R″)—(C1-C12)aliphatic-,
• wherein R2, with the exception of —OH, is independently substituted with 0-5 R′;
• R3 is selected from:
• —(C1-C6)alkyl, —C≡CH, —CN, halogen, —SO2((C6-C10)-aryl), —SO2((C1-C6)alkyl), —C(O)N((C1-C6)alkyl)2, —C(O)NH2, —C(O)O((C1-C6)alkyl), —C(O)((C1-C6)alkyl), —(C6-C10)aryl, and 5- to 10-membered heteroaryl, wherein R3 with the exception of halogen and —CN is independently substituted with 0-5 R′;
• R4 and R5 are each independently selected from —H, halogen and -(C1-C6)alkyl;
• and
• R6 is selected from —H and -(C1-C6)alkyl;
• wherein each occurrence of R′ is independently selected from halogen, —R″, —OR″, oxo, —CH2OR″, —CH2NR″2, —C(O)N(R″)2, —C(O)OR″, —NO2, —NCS, —CN, —CF3, —OCF3 and —N(R″)2;
• and
• wherein each occurrence of R″ is independently selected from H, —(C1-C6)-alkyl, (C3-C6)-cycloalkyl, 3- to 6-membered heterocyclyl, 5- to 10-membered heteroaryl-, (C6-C10)-aryl-, (5- to 10-membered heteroaryl)-(C1-C6)-alkyl-, (C6-C10)-aryl-(C1-C6)-alkyl-, (5- to 10-membered heteroaryl)-O—(C1-C6)-alkyl-, and (C6-C10)-aryl-O—(C1-C6)-alkyl-.

A compound selected from:

• Compound
• Structure
• 1
• 2
• 3
• 4
• 5
• 6
• 9
• 10
• 11
• 12
• 44
• 45
• 46
• 47
• 48
• 49
• 50
• 51
• 52
• 53
• 54
• 101
• 102
• 107
• 108
• 109
• 110
• 111
• 112
• 113
• 114
• 115
• 116
• 117
• 121
• 125
• 126
• 127
• 132
• 133
• 134
• 135
• 136
• 139
• 140
• 143
• 144
• 145
• 146
• 149
• 150
• 151
• 152
• 153
• 154
• 155
• 160
• 161
• 167
• 168
• 170
• or a pharmaceutically acceptable salt, hydrate, isomer, or combination thereof.