Patent ID: 9585963
Date: 2017-03-07
CPC Classifications: A61K,A61P,C07D,C12Q,G01N

Claim:
1. A method to treat a patient comprising administering to a patient in need thereof a pharmaceutical composition comprising an opioid prodrug comprising a ketone-containing opioid covalently bound to a promoiety comprising a GI enzyme-cleavable moiety and a GI enzyme inhibitor that interacts with the GI enzyme that mediates enzymatically-controlled release of the opioid from the opioid prodrug following ingestion of the composition, wherein the opioid prodrug comprises: a) a compound of formula KC-(Ia): wherein: R R each R each R or R n is an integer from 2 to 4; R R each R each W is independently —NR each R p is an integer from one to 100; and R b) a compound of formula KC-(Ib): wherein: R R each R each R or R n is an integer from 2 to 4; R R each R each W is independently —NR each R p is an integer from one to 100; and R c) a compound of formula KC-(II): wherein: R R each R each R or R n is 2 or 3; R R d) a compound of formula KC-(IIIa): wherein: X represents a residue of a ketone-containing opioid, wherein the hydrogen atom of the corresponding enolic group of the ketone is replaced by a covalent bond to —C(O)—NR R each R each R or R n is an integer from 2 to 4; R R each R each W is independently —NR each R p is an integer from one to 100; and R e) a compound of formula KC-(IIIb): wherein: X represents a residue of a ketone-containing opioid, wherein the hydrogen atom of the corresponding enolic group of the ketone is replaced by a covalent bond to —C(O)—NR R each R each R or R n is an integer from 2 to 4; R R each R each W is independently —NR each R p is an integer from one to 100; and R f) a compound of formula KC-(IV): wherein: X represents a residue of a ketone-containing opioid, wherein the hydrogen atom of the corresponding enolic group of the ketone is replaced by a covalent bond to —C(O)—NR R each R each R or R n is 2 or 3; R R g) a compound of formula KC-(Va): wherein: X represents a residue of a ketone-containing opioid, wherein the hydrogen atom of the corresponding enolic group of the ketone is replaced by a covalent bond to —C(O)—NR R each R each R or R n is an integer from 2 to 4; R R h) a compound of formula KC-(Vb): wherein: X represents a residue of a ketone-containing opioid, wherein the hydrogen atom of the corresponding enolic group of the ketone is replaced by a covalent bond to —C(O)—NR R each R each R or R n is an integer from 2 to 4; R R i) a compound of formula KC-(VI): wherein: X represents a residue of a ketone-containing opioid, wherein the hydrogen atom of the corresponding enolic group of the ketone is replaced by a covalent bond to —C(O)—Y—(C(R Y is —NR n is an integer from 1 to 4; each R R each R R p is an integer from 1 to 10; each W is independently —NR each R j) a compound of formula KC-(VII): or salts, solvates or hydrates thereof wherein: X represents a residue of a ketone-containing opioid, wherein the hydrogen atom of the corresponding enolic group of the ketone is replaced by a covalent bond —(CR R Y is aryl, heteroaryl or arylaryl optionally substituted with one or more —F, —Cl, —Br, —I, —R R Z is N(R R each W is independently —NR each R each R R n is an integer from 0 to 5; R each U is independently —NR each R each R R o is an integer from 1 to 100; provided that Z is oriented para or ortho to X—(CR k) a compound of formula KC-(VIII): X represents a residue of a ketone-containing opioid, wherein the hydrogen atom of the corresponding enolic group of the ketone is replaced by a covalent bond to —(CR R R R R each U is independently —NR each R R o is an integer from 1 to 100; or 1) a compound of formula KC-(IX): or a salt, hydrate or solvate thereof wherein: X represents a residue of a ketone-containing opioid, wherein the hydrogen atom of the corresponding enolic group of the ketone is replaced by a covalent bond to —(C(R R Ar is aryl, heteroaryl or arylaryl optionally substituted with one or more —F, —Cl, —Br, —I, —R R Z is O, S or NH; Y is —NR n is an integer from 1 to 10; each R R each R the atoms to which they are bonded form a cycloheteroalkyl or substituted cycloheteroalkyl ring; R p is an integer from 1 to 5; each W is independently —NR each R A′ represents an anion; or a salt, hydrate or solvate thereof.