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US 6,548,668 B2Granted
Boronic ester and acid compounds, synthesis and uses
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.
Claims19
A compound having the formula:
- or a pharmaceutically acceptable salt thereof, wherein:
- P is R7—C(O)— or R7—SO2—, and R7 is heteroaryl or a saturated or partially unsaturated heterocycle;
- A is 1;
- B1 is CH;
- X1 is —C(O)—NH—;
- X2 is —C(O)—NH—;
- R is hydrogen or alkyl;
- R1 is hydrogen, C1-8alkyl, C3-10cycloalkyl, C6-10aryl, or —CH2—R5, where the ring portion of said aryl can be optionally substituted;
- R2 is hydrogen, C1-8alkyl, C3-10cycloalkyl, C6-10aryl, or —CH2—R5, where the ring portion of said aryl can be optionally substituted;
- R3 is C4alkyl;
- R5 is one of C6-10aryl, C6-10ar(C1-6)alkyl, C1-6alk(C6-10)aryl, C3-10 cycloalkyl, C1-8alkoxy or —W—R6, where W is a chalcogen and R6 is alkyl, where the ring portion of any of said aryl, aralkyl, or alkaryl can be optionally substituted;
- and
- Z1 and Z2 are independently one of hydroxy, alkoxy, or aryloxy, or together Z1 and Z2 form a moiety derived from a dihydroxy compound having at least two hydroxy groups separated by at least two connecting atoms in a chain or ring, said chain or ring comprising carbon atoms and, optionally, a heteroatom or heteroatoms which can be N, S, or O.
10 more elements
A compound having the formula:
- or a pharmaceutically acceptable salt thereof, wherein:
- P is R7—C(O)— or R7—SO2—, and R7 is heteroaryl or a saturated or partially unsaturated heterocycle;
- A is 1;
- B1 is CH;
- X1 is —C(O)—NH—;
- X2 is —C(O)—NH—;
- R is hydrogen or alkyl;
- R1 and R2 are each independently —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 R1, R2 and R5 can be optionally substituted by one or two substitutes 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;
- R3 is C4alkyl;
- Z1 and Z2 are independently one of hydroxy, alkoxy, or aryloxy, or together Z1 and Z2 form a moiety derived from a dihydroxy compound having at least two hydroxy groups separated by at least two connecting atoms in a chain or ring, said chain or ring comprising carbon atoms and, optionally, a heteroatom or heteroatoms which can be N, S, or O.
9 more elements
A compound having the formula:
- or a pharmaceutically acceptable salt thereof, wherein:
- P is R7—C(O)— and R7 is pyrazinyl;
- A is 1;
- B1 is CH;
- X1 is —C(O)—NH—;
- X2 is —C(O)—NH—;
- R is hydrogen or alkyl;
- R1 and R2 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 R1, R2 and R5 can be optionally substituted by one or two substitutes 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;
- R3 is C4alkyl;
- Z1 and Z2 are independently one of hydroxy, alkoxy, or aryloxy, or together Z1 and Z2 form a moiety derived from a dihydroxy compound having at least two hydroxy groups separated by at least two connecting atoms in a chain or ring, said chain or ring comprising carbon atoms and, optionally, a heteroatom or heteroatoms which can be N, S, or O.
9 more elements
A compound having the formula:
- or a pharmaceutically acceptable salt thereof, wherein:
- P is R7—C(O)— or R7—SO2—, and R7 is heteroaryl or a saturated or partially unsaturated heterocycle;
- A is 1;
- B1 is CH;
- X1 is —C(O)—NH—;
- X2 is —C(O)—NH—;
- R is hydrogen;
- R1—CH2—R5, where R5 is C6-10aryl;
- R2 is benzyl;
- R3 is C4alkyl;
- and
- Z1 and Z2 are independently one of hydroxy, alkoxy, or aryloxy, or together Z1 and Z2 form a moiety derived from a dihydroxy compound having at least two hydroxy groups separated by at least two connecting atoms in a chain or ring, said chain or ring comprising carbon atoms and, optionally, a heteroatom or heteroatoms which can be N, S, or O.
9 more elements
A compound having the formula:
- or a pharmaceutically acceptable salt thereof, wherein:
- P is 2-pyrazinecarbonyl;
- A is 1;
- B1 is CH;
- X1 is —C(O)—NH—;
- X2 is —C(O)—NH—;
- R is hydrogen;
- R1 is —CH2—R5, where R5 is phenyl;
- R2 is benzyl;
- R3 is isobutyl;
- and
- Z1 and Z2 are both hydroxy.
9 more elements
Dependencies are inferred from the claim text.