Pharmaceutical prodrugs and methods of their preparation and use
AssigneeCephalon, Inc.
InventorsAnthony S. DRAGER, Paritosh WATTAMWAR
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Abstract
The disclosure provides compounds of Formula (I), wherein X, Y, and Z are defined herein. The disclosure also provides particles comprising one or more compounds described herein, compositions comprising one or more compounds or particles described herein and a pharmaceutically acceptable carrier, and methods of treating a subject in need thereof comprising administering one or more compounds, particles, or compositions described herein to the subject. X—Y—Z (I).
Claims43
A compound of Formula (I):
- X—Y—Z (I)
- wherein:
- X is a biologically active moiety derived from a water-soluble, biologically active compound;
- Y comprises a pH-sensitive linker;
- and
- Z is a hydrophobic moiety.
The compound of any one of the preceding claims, wherein the water-soluble, biologically active compound is an anti-inflammatory agent, anti-psychotic agent, anti-viral agent, chemotherapeutic agent, or dopamine modulating agent, or is indicated for the treatment of migraine or pain.
The compound of any one of the preceding claims, wherein the water-soluble biologically active compound is actinomycin, azacitidine, belinostat, bendamustine, bleomycin, bortezomib, cabazitaxel, cadarbazine, cladribine, clofarabine, cytarabine, cyproterone, daunorubicin, decitabine, docetaxel, doxorubicin, epirubicin, eribulin, etoposide, floxuridine, fludarabine, gemcitabine, idarubicin, irinotecan, ixabepilone, levodopa, melphalan, methotrexate, mitomycin, mitoxantrone, nelarabine, paclitaxel, pemetrexed, pentostatin, pixantrone, pralatreate, raltitrexed, streptozocin, temozolomide, temsirolimus, teniposide, topotecan, trabectedin, treosulfan, vincristine, vindesine, vinflunine, or a salt thereof.
The compound of any one of the preceding claims, wherein the water-soluble, biologically active compound is bendamustine, decitabine, doxorubicin, celecoxib or a salt thereof.
The compound of any one of the preceding claims, wherein the water-soluble, biologically active compound comprises a nucleoside such as abacavir, didanosine, emtricitabine, lamivudine, stavudine, telbivudine, entecavir, or.
The compound of any one of the preceding claims, wherein Y is cleaved from the water-soluble, biologically active moiety upon exposure to a target pH.
The compound of any one of the preceding claims, wherein Y comprises one pH sensitive linker.
The compound of any one of the preceding claims, wherein Y comprises a first pH sensitive linker and a second pH sensitive linker.
The compound of any one of the preceding claims, wherein Y comprises an optionally substituted tetrahydropyranyl ether, an optionally substituted tetrahydropyranyl ester, an optionally substituted azide, an optionally substituted histidine, an optionally substituted hydrazone, or an optionally substituted β-amino ester.
The compound of any one of the preceding claims, wherein Y comprises -(tetrahydropyran ether)-(azide), -(hydrazone)-, -(hydrazone)-(azide)-, -(β-amino ester)-, -(β-amino ester)-(azide)-, or -(tetrahydropyran ester)-.
The compound of any one of the preceding claims, wherein Y is -(tetrahydropyran ether)-(azide)-(His)-, -(hydrazone)-(azide)-(His)-, or -(β-amino ester)-(azide)-(His)-.
The compound of any one of the preceding claims, wherein Z is an optionally substituted C2-30alkyl, C2-30alkenyl, or C2-30alkynyl.
The compound of any one of the preceding claims, wherein Z is C2-18alkyl such as C12alkyl, C14alkyl, C16alkyl, or C18alkyl.
The compound of any one of the preceding claims, wherein the compound of formula I is cleaved to produce the water soluble biological compound after crossing the cell membrane of a cell.
Particles comprising one or more compounds of any one of the preceding claims.
Dependencies are inferred from the claim text.