| 摘要 |
The present invention relates to compounds of formula (I):;
or a pharmaceutically acceptable salt, hydrate, solvate, or prodrug thereof, wherein U, J, V, X, R2a, R2b, R2c, R5 and t are as described herein. The present invention relates generally to inhibitors of histone deacetylase and to methods of making and using them. These compounds are useful for promoting cognitive function and enhancing learning and memory formation. In addition, these compounds are useful for treating, alleviating, and/or preventing various conditions, including for example, neurological disorders, memory and cognitive function disorders/impairments, extinction learning disorders, fungal diseases and infections, inflammatory diseases, hematological diseases, and neoplastic diseases in humans and animals. |
| 主权项 |
1. A compound of formula I:or a pharmaceutically acceptable salt, hydrate, solvate, or prodrug thereof, wherein:
J′ is selected from NH2, OH, and SH; each X is independently selected from hydrogen, deuterium, methyl, CF3, and halogen; R5 is selected from C2-C8 alkenyl; (CH2)u-5-6 membered, saturated, unsaturated, or partially unsaturated heterocyclic ring: (CH2)v—C4-C8 cycloalkyl ring; (C1-C8-alkyl)w-C4-C8cycloalkenyl ring; (CH2)s-aromatic ring; and (CH2)s-heteroaromatic ring; wherein said heterocyclic ring, cycloalkyl ring, cycloalkenyl ring, heteroaromatic ring, and aromatic ring are unsubstituted or substituted with one or more Ry, and said alkenyl is substituted with one or more RT; R2aR2bR2cV(CH2)tU— is b is selected from 0, 1, 2, and 3; a is selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10; each Rx is independently selected from (CH2)zNH2, (CH2)zNHR3, (CH2)zNR3R3, OR3, OCF3, OCH2F, OCHF2, (CH2)z-aromatic ring, (CH2)z-heterocyclic ring, hydroxyl, halogen, C1-C8 alkyl, (C1-C8 alkyl)CF3, (C1-C8 alkyl)OH, C(O)R3, (CH2)zC(O)NH2, (CH2)zC(O)NHR3, (CH2)zC(O)NR3R3, (CH2)zNHC(O)R4, and (CH2)zNR4C(O)R4; or taken together two Rx attached to the same carbon atom form ═O; or taken together two Rx form a C3-C8 cycloalkyl ring, C4-C8 cycloalkenyl ring, or 3 to 8 membered, saturated or partially unsaturated heterocyclic ring, wherein said cycloalkyl ring, cycloalkenyl ring, and heterocyclic ring are unsubstituted or substituted with one or more Rz; or taken together two Rx form an aromatic ring or heteroaromatic ring, wherein said aromatic ring and heteroaromatic ring are unsubstituted or substituted with one or more Rz; each Rz is independently selected from halogen, C1-C4 alkyl, OH, OR3, CF3, OCF3, OCH2F, OCHF2, NH2, NHR3, NR3R3, and C(O)CH3; each R3 is independently selected from C1-C8 alkyl and O(C1-C8 alkyl); each R4 is independently selected from C1-C8 alkyl and CF3; each Ry is independently selected from halogen, OR6, NH2, NHR6, NR6R6, OH, CF3, aromatic ring, C(O)R6, C1-C8 alkyl, C2-C8 alkenyl, and C2-C8 alkynyl, wherein each R6 is independently C1-C8 alkyl; each RT is independently selected from hydrogen, halogen, Si(R3)3, phenyl, and C1-C8 alkyl; u is selected from 0, 1, and 2; v″ is selected from 0, 1, and 2; w is selected from 0, 1, and 2; s is selected from 0, 1, and 2; and each z is independently selected from 0, 1, 2, and 3. |
