Boronic ester and acid compositions
AssigneeMillennium Pharmaceuticals, Inc.
InventorsJulian Adams, Yu-Ting Ma, Ross Stein, Matthew Baevsky, Louis Grenier, Louis Plamondon
Life of this patent
Estimating the term…
Abstract
Disclosed herein is a method for reducing the rate of degradation of proteins in an animal comprising contacting cells of the animal with certain boronic ester and acid compounds. Also disclosed herein are novel boronic ester and acid compounds, their synthesis and uses.
Claims22
A composition, which upon combination with a physiologically acceptable saline carrier forms a solution suitable for intravenous, intramuscular or subcutaneous administration to a patient, said solution comprising a compound of the formula (1a)
- or a pharmaceutically acceptable salt thereof;
- wherein
- P is R7—C(O)— or R7—SO2—, where R7 is pyrazinyl;
- X2 is —C(O)-NH—;
- R is hydrogen or alkyl;
- R2 and R3 are independently hydrogen, alky, cycloalkyl, aryl, or —CH2—R3;
- R5, in each instance, is one of aryl, aralkyl, alkaryl, cycloalkyl, or —W—R6, where W is a chalcogen and R6 is alkyl;
- where the ring portion of any of said aryl, aralkyl, or alkaryl in R2, R3 and R5 can be optionally substituted by one or two substituents independently selected from the group consisting of C1-6 alkyl, C3-8 cycloalkyl, C1-6alkyl(C3-8)cycloalkyl, C2-8 alkenyl;
- C2-8 alkynyl, cyano, amino, C1-6 alkylamino, di(C1-6)alkylamino, benzylamino, dibenzylamino, nitro, carboxy, carbo(C1-6)-alkoxy, trifluoromethyl, halogen, C1-6 alkoxy, C6-10 aryl, C6-10 aryl(C1-6)alkyl, C6-10 aryl(C1-6)alkoxy, hydroxy, C1-6 alkylthio, C1-6 alkylsulfinyl, C1-6 alkylsulfonyl, C6-10 arylthio, C6-10 arylsulfinyl, C6-10 arylsulfonyl, C6-10 aryl, C1-6 alkyl(C6-10)aryl, and halo(C6-10)aryl;
- Z1 and Z2 are both hydroxy;
- and
- A is zero.
A composition, which upon combination with a physiologically acceptable aqueous carrier forms a solution suitable for intravenous, intramuscular, or sub-cutaneous administration to a patient, said solution comprising N-(2-pyrazine)carbonyl-L-phenylalanine-L-leucine boronic acid.
A composition, which upon combination with a physiologically acceptable saline carrier forms a solution suitable for intravenous, intramuscular, or subcutaneous administration to a patient, said solution comprising a compound having the formula (1a):
- or a pharmaceutically acceptable salt thereof;
- wherein
- P is R7—C(O)— or R7—SO2—, where R7 is quinolinyl, pyrazinyl, pyridyl, quinoxalinyl, furyl, pyrrolyl, or N-morpholinyl;
- X2 is —C(O)—NH—;
- R is hydrogen or alkyl;
- R2 and R3 are independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, heterocycle, and —CH2—R5,
- where R5, in each instance, is one of aryl, aralkyl, alkaryl, cycloalkyl, or —W—R6, where W is a chalcogen and R6 is alkyl;
- where the ring portion of any of said aryl, aralkyl or alkaryl in R2, R3 and R5 can be optionally substituted by one or two substituents independently selected from the group consisting of C1-6 alkyl C3-8 cycloalkyl, C1-6alkyl(C3-8)cycloalkyl, C2-8 alkenyl, C2-8 alkynyl, cyano, amino, C1-6 alkylamino, di(C1-6)alkylamino, benzylamino, dibenzylamino, nitro, carboxy, carbo(C1-6)alkoxy, trifluoromethyl, halogen, C1-6 alkoxy, C6-10 aryl, C6-10 aryl(C1-6)alkyl, C6-10 aryl(C1-6)alkoxy, hydroxy, C1-6 alkylthio, C1-6 alkylsulfinyl, C1-6 alkylsulfonyl, C6-10 arylthio, C6-10 arylsulfinyl, C6-10 arylsulfonyl, C6-10 aryl, C1-6 alkyl(C6-10)aryl, and halo(C6-10)aryl;
- Z1 and Z2 are both hydroxy;
- and
- A is zero.
A composition, which upon combination with a physiologically acceptable saline carrier forms a solution suitable for intravenous, intramuscular, or subcutaneous administration to a patient, said solution comprising a compound having the formula (1a):
- or a pharmaceutically acceptable salt thereof;
- wherein
- P is H or an amino-group-protecting moiety;
- X2 is —C(O)—NH—;
- R is hydrogen or alkyl;
- R2 is naphthylmethyl, pyridylmethyl, or quinolylmethyl;
- R3 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, heterocycle, and —CH2—R5,
- where R5 is one of aryl, aralkyl, alkaryl, cycloalkyl or —W—R6,
- where W is a chalcogen and R6 is alkyl;
- where the ring portion of any of said aryl, aralkyl, or alkaryl in R2, R3 and R5 can be optionally substituted by one or two substituents independently selected from the group consisting of C1-6 alkyl, C3-8 cycloalkyl, C1-6alkyl(C3-8)cycloalkyl, C2-8 alkenyl, C2-8 alkynyl, cyano, amino, C1-6 alkylamino, di(C1-6)alkylamino, benzylamino, dibenzylamino, nitro, carboxy, carbo(C1-6)alkoxy, trifluoromethyl, halogen, C1-6 alkoxy, C6-10 aryl, C6-10 aryl(C1-6)alkyl, C6-10 aryl(C1-6)alkoxy, hydroxy, C1-6 alkylthio, C1-6 alkylsulfinyl, C1-6 alkylsulfonyl, C6-10 arylthio, C6-10 arylsulfinyl, C6-10 arylsulfonyl, C6-10 aryl,C1-6 alkyl(C6-10)aryl, and halo(C6-10)aryl;
- Z1 and Z2 are both hydroxy;
- and
- A is zero.
Dependencies are inferred from the claim text.