Prodrugs of NH-acidic compounds

Patent metadata

Field	Value
Publication number	US-10040787-B2
Application number	US-201615227117-A
Country	US
Kind code	B2
Filing date	Aug 3, 2016
Priority date	Jun 25, 2009
Publication date	Aug 7, 2018
Grant date	Aug 7, 2018

Abstract

The invention provides a method of sustained delivery of a lactam, imide, amide, sulfonamide, carbamate or urea containing parent drug by administering to a patient an effective amount of a prodrug compound of the invention wherein upon administration to the patient, release of the parent drug from the prodrug is sustained release. Prodrug compounds suitable for use in the methods of the invention are labile conjugates of parent drugs that are derivatized through carbonyl linked prodrug moieties. The prodrug compounds of the invention can be used to treat any condition for which the lactam, imide, amide, sulfonamide, carbamate or urea containing parent drug is useful as a treatment.

First claim

What is claimed is:

1. A compound of formula XV and pharmaceutically acceptable salts and solvates thereof:

wherein
each R 50 , R 51 , R 52 , R 53 , R 54 and R 55 is independently selected from hydrogen, halogen, —OR 10 , —SR 10 , —NR 10 R 11 —, optionally substituted aliphatic, optionally substituted aryl or aryl or optionally substituted heterocyclyl;
alternatively, two or more R 50 , R 51 , R 52 , R 53 , and R 54 together with the atoms to which they are attached form an optionally substituted ring;
each R 10 and R 11 is independently absent, hydrogen, halogen, aliphatic, substituted aliphatic, aryl or substituted aryl; alternatively two R 10 and R 11 together with the atoms to which they are attached may form an additional optionally substituted, 3, 4, 5, 6 or 7 membered ring;
wherein the term “substituted” refers to the replacement of one or more hydrogen radicals in a given structure with the radical of a specified substituent selected from halo, alkyl, alkenyl, alkynyl, aryl, heterocyclyl, thiol, alkylthio, arylthio, alkylthioalkyl, arylthioalkyl, alkylsulfonyl, alkylsulfonylalkyl, arylsulfonylalkyl, alkoxy, aryloxy, aralkoxy, aminocarbonyl, alkylaminocarbonyl, arylaminocarbonyl, alkoxycarbonyl, aryloxycarbonyl, haloalkyl, amino, trifluoromethyl, cyano, nitro, alkylamino, arylamino, alkylaminoalkyl, arylaminoalkyl, aminoalkylamino, hydroxy, alkoxyalkyl, carboxyalkyl, alkoxycarbonylalkyl, aminocarbonylalkyl, acyl, aralkoxycarbonyl, carboxylic acid, sulfonic acid, sulfonyl, phosphonic acid, heteroaryl, and aliphatic;
R 1 is selected from:

2. A compound of claim 1 or a pharmaceutically acceptable salt or solvate thereof, selected from:

or a pharmaceutically acceptable salt thereof.

3. A compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein R 1 is selected from:

4. A compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein R 1 is selected from:

5. A compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein R 1 is selected from:

6. A compound of claim 2 , or a pharmaceutically acceptable salt thereof, wherein R 1 is selected from:

7. A compound of claim 2 , or a pharmaceutically acceptable salt thereof, wherein R 1 is selected from:

8. A compound of claim 2 , or a pharmaceutically acceptable salt thereof, wherein R 1 is selected from:

Assignees

• Alkermes Pharma Ireland Ltd

Inventors

• Blumberg Laura Cook
• Remenar Julius F
• Almarsson Orn
• Zeidan Tarek A

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• A61P25/22

  Anxiolytics · CPC title

• A61P25/00

  Drugs for disorders of the nervous system · CPC title

• A61K31/496

  Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin · CPC title