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US 6,395,724 B1Granted
Multibinding inhibitors of cyclooxygenase-2
AssigneeAdvanced Medicine, Inc.
InventorsJ. Kevin Judice, Deborah L. Higgins, John H. Griffin
Life of this patent
Estimating the term…
Abstract
Disclosed are multibinding compounds which inhibit cyclooxygenase-2 (COX-2), an enzyme which catalyzes the first committed step in the biosynthesis of prostaglandins. The multibinding compounds of this invention containing from 2 to 10 ligands covalently attached to one or more linkers. Each ligand is a moiety capable of binding to COX-2. The multibinding compounds of this invention are useful in the treatment inflammation, pain, fever and the like.
Claims10
A compound of formula I:
- (L)p(X)q I
- wherein each L is a ligand independently selected from formula IA, IB or IC:
- wherein
- ring A, together with the atoms to which it is attached, forms a cyclobut-2-en-1-one, thiazole, isothiazole, thiadiazole, oxazole, isoxazole, 5(H)-furanone, benzene, pyridine, imidazopyridine, imidazothiazole or thiazolotriazole ring;
- ring B, together with the atoms to which it is attached, forms a pyrazole ring;
- ring C, together with the atoms to which it is attached, forms an imidazole ring;
- R1 is selected from the group consisting of —SO2CH3, —SO2NH2, —SO2NHC(O)CF3, —SO2(NH)NH2 and —SO(NH)NHC(O)CF3;
- each R2 is independently selected from the group consisting of alkyl, substituted alkyl, alkoxy, substituted alkoxy, alkoxycarbonyl, amino, substituted amino, azido, carboxyl, cyano, cycloalkyl, substituted cycloalkyl, halo, hydroxyl, nitro, thioalkoxy and substituted thioalkoxy;
- R3 is a covalent bond linking the ligand to a linker;
- and
- α is an integer from 0 to 3;
- and
- each X is independently a linker of the formula:
- —Xa—Z—(Ya—Z)m—Yb—Z—Xa—
- wherein
- m is an integer of from 0 to 20;
- Xa at each separate occurrence is selected from the group consisting of —O—, —S—, —NR—, —C(O)—, —C(O)O—, —C(O)NR—, —C(S)—, —C(S)O—, —C(S)NR— and a covalent bond where R is as defined below;
- Z is at each separate occurrence is selected from the group consisting of alkylene, substituted alkylene, cycloalkylene, substituted cycloalkylene, alkenylene, substituted alkenylene, alkynylene, substituted alkynylene, cycloalkenylene, substituted cycloalkenylene, arylene, heteroarylene, heterocyclene, and a covalent bond;
- Ya and Yb at each separate occurrence are selected from the group consisting of —C(O)NR′—, —NR′C(O)—, —NR′C(O)NR′—, —C(═NR′)—NR′—, —NR′—C(═NR′)—, —NR′—C(O)—O—, —P(O)(OR′)—O—, —S(O)nCR′R″—, —S(O)n—NR′—, —S—S— and a covalent bond;
- where n is 0, 1 or 2;
- R, R′ and R″ at each separate occurrence are selected from the group consisting of hydrogen, alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, alkenyl, substituted alkenyl, cycloalkenyl, substituted cycloalkenyl, alkynyl, substituted alkynyl, aryl, heteroaryl and heterocyclic;
- p is an integer of from 2 to 10;
- q is an integer of from 1 to 20, provided that q is less than p;
- and pharmaceutically-acceptable salts thereof.
21 more elements
A compound of formula II:
- L′—X′—L′ II
- wherein each L′ is a ligand independently selected from the group consisting of:
- (a) a ligand of formula IIA:
- wherein
- R4 is selected from the group consisting of —SO2CH3, —SO2NH2, —SO2NHC(O)CF3, —SO(NH)NH2 and —SO(NH)NHC(O)CF3;
- each R5 is independently selected from the group consisting of alkyl, substituted alkyl, alkoxy, substituted alkoxy, alkoxycarbonyl, amino, substituted amino, azido, carboxyl, cyano, cycloalkyl, substituted cycloalkyl, halo, hydroxyl, nitro, thioalkoxy and substituted thioalkoxy;
- R6 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, aryl, cyano, fluoro and heteroaryl;
- R7 is a covalent bond linking the ligand to a linker;
- and
- b is an integer from 0 to 3;
- (b) a ligand of formula IIB:
- wherein
- R8 is selected from the group consisting of —SO2CH3, —SO2NH2, —SO2NHC(O)CF3, —SO(NH)NH2 and —SO(NH)NHC(O)CF3;
- each R9 is independently selected from the group consisting of alkyl, substituted alkyl, alkoxy, substituted alkoxy, alkoxycarbonyl, amino, substituted amino, azido, carboxyl, cyano, cycloalkyl, substituted cycloalkyl, halo, hydroxyl, nitro, thioalkoxy and substituted thioalkoxy;
- R10 is a covalent bond linking the ligand to a linker;
- R11 is selected from the group consisting of hydrogen, alkyl, substituted alkyl and fluoro;
- and
- c is an integer from 0 to 3;
- and
- (c) a ligand of formula IIC:
- wherein
- R12 is selected from the group consisting of —SO2CH3, —SO2NH2, —SO2NHC(O)CF3, —SO(NH)NH2 and —SO(NH)NHC(O)CF3;
- each R13 is independently selected from the group consisting of alkyl, substituted alkyl, alkoxy, substituted alkoxy, alkoxycarbonyl, amino, substituted amino, azido, carboxyl, cyano, cycloalkyl, substituted cycloalkyl, halo, hydroxyl, nitro, thioalkoxy and substituted thioalkoxy;
- R14 and R16 are independently selected from the group consisting of hydrogen, alkyl, substituted alkyl and fluoro;
- R15 is a covalent bond linking the ligand to a linker;
- and
- d is an integer from 0 to 3;
- and
- X′ is a linker of the formula:
- —Xa—Z—(Ya—Z)m—Yb—Z—Xa—
- wherein
- m is an integer of from 0 to 20;
- Xa at each separate occurrence is selected from the group consisting of —O—, —S—, —NR—, —C(O)—, —C(O)O—, —C(O)NR—, —C(S)—, —C(S)O—, —C(S)NR— and a covalent bond where R is as defined below;
- Z is at each separate occurrence is selected from the group consisting of alkylene, substituted alkylene, cycloalkylene, substituted cylcoalkylene, alkenylene, substituted alkenylene, alkynylene, substituted alkynylene, cycloalkenylene, substituted cycloalkenylene, arylene, heteroarylene, heterocyclene, and a covalent bond;
- Ya and Yb at each separate occurrence are selected from the group consisting of —C(O)NR′—, —NR′C(O)—, —NR′C(O)NR′—, —C(═NR′)—NR′—, —NR′—C(═NR′)—, —NR′—C(O)—O—, —P(O)(OR′)—O—, —S(O)nCR′R″—, —S(O)n—NR′—, —S—S— and a covalent bond;
- where n is 0, 1 or 2;
- R, R′ and R″ at each separate occurrence are selected from the group consisting of hydrogen, alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, alkenyl, substituted alkenyl, cycloalkenyl, substituted cycloalkenyl, alkynyl, substituted alkynyl, aryl, heteroaryl and heterocyclic;
- and pharmaceutically-acceptable salts thereof.
35 more elements
A compound of formula III:
- wherein
- each R17 is independently selected from the group consisting of —SO2CH3, —SO2NH2, —SO2NHC(O)CF3, —SO(NH)NH2 and —SO(NH)NHC(O)CF3;
- each R18 is independently selected from the group consisting of alkyl, substituted alkyl, alkoxy, substituted alkoxy, alkoxycarbonyl, amino, substituted amino, azido, carboxyl, cyano, cycloalkyl, substituted cycloalkyl, halo, hydroxyl, nitro, thioalkoxy and substituted thioalkoxy;
- each R19 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, aryl, cyano, fluoro and heteroaryl;
- e is an integer from 0 to 3;
- and
- X″ is a linker of the formula:
- —Xa—Z—(Ya—Z)m—Yb—Z—Xa—
- wherein
- m is an integer of from 0 to 20;
- Xa at each separate occurrence is selected from the group consisting of —O—, —S—, —NR—, —C(O)—, —C(O)O—, —C(O)NR—, —C(S)—, —C(S)O—, —C(S)NR— and a covalent bond where R is as defined below;
- Z is at each separate occurrence is selected from the group consisting of alkylene, substituted alkylene, cycloalkylene, substituted cylcoalkylene, alkenylene, substituted alkenylene, alkynylene, substituted alkynylene, cycloalkenylene, substituted cycloalkenylene, arylene, heteroarylene, heterocyclene, and a covalent bond;
- Ya and Yb at each separate occurrence are selected from the group consisting of —C(O)NR′—, —NR′C(O)—, —NR′C(O)NR′—, —C(═NR′)—NR′—, —NR′—C(═NR′)—, —NR′—C(O)—O—, —P(O)(OR′)—O—, —S(O)nCR′R″—, —S(O)n—NR′—, —S—S— and a covalent bond;
- where n is 0, 1 or 2;
- R, R′ and R″ at each separate occurrence are selected from the group consisting of hydrogen, alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, alkenyl, substituted alkenyl, cycloalkenyl, substituted cycloalkenyl, alkynyl, substituted alkynyl, aryl, heteroaryl and heterocyclic;
- and pharmaceutically-acceptable salts thereof.
13 more elements
A compound of formula IV:
- wherein
- each R20 is independently selected from the group consisting of —SO2CH3, —SO2NH2, —SO2NHC(O)CF3, —SO(NH)NH2 and —SO(NH)NHC(O)CF3;
- each R21 is independently selected from the group consisting of alkyl, substituted alkyl, alkoxy, substituted alkoxy, alkoxycarbonyl, amino, substituted amino, azido, carboxyl, cyano, cycloalkyl, substituted cycloalkyl, halo, hydroxyl, nitro, thioalkoxy and substituted thioalkoxy;
- f is an integer from 0 to 3;
- and
- X″ is a linker of the formula:
- —Xa—Z—(Ya—Z)m—Yb—Z—Xa—
- wherein
- m is an integer of from 0 to 20;
- Xa at each separate occurrence is selected from the group consisting of —O—, —S—, —NR—, —C(O)—, —C(O)O—, —C(O)NR—, —C(S)—, —C(S)O—, —C(S)NR— and a covalent bond where R is as defined below;
- Z is at each separate occurrence is selected from the group consisting of alkylene, substituted alkylene, cycloalkylene, substituted cylcoalkylene, alkenylene, substituted alkenylene, alkynylene, substituted alkynylene, cycloalkenylene, substituted cycloalkenylene, arylene, heteroarylene, heterocyclene, and a covalent bond;
- Ya and Yb at each separate occurrence are selected from the group consisting of —C(O)NR′—, —NR′C(O)—, —NR′C(O)NR′—, —C(═NR′)—NR′—, —NR′—C(═NR′)—, —NR′—C(O)—O—, —P(O)(OR′)—O—, —S(O)nCR′R″—, —S(O)n—NR′—, —S—S— and a covalent bond;
- where n is 0, 1 or 2;
- R, R′ and R″ at each separate occurrence are selected from the group consisting of hydrogen, alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, alkenyl, substituted alkenyl, cycloalkenyl, substituted cycloalkenyl, alkynyl, substituted alkynyl, aryl, heteroaryl and heterocyclic;
- and pharmaceutically-acceptable salts thereof.
12 more elements
A compound of formula V:
- wherein
- each R22 is independently selected from the group consisting of —SO2CH3, —SO2NH2, —SO2NHC(O)CF3, —SO(NH)NH2 and —SO(NH)NHC(O)CF3;
- each R23 is independently selected from the group consisting of alkyl, substituted alkyl, alkoxy, substituted alkoxy, alkoxycarbonyl, amino, substituted amino, azido, carboxyl, cyano, cycloalkyl, substituted cycloalkyl, halo, hydroxyl, nitro, thioalkoxy and substituted thioalkoxy;
- each R24 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, aryl, cyano, fluoro and heteroaryl;
- g is an integer from 0 to 3;
- and
- X″ is a linker of the formula:
- —Xa—Z—(Ya—Z)m—Yb—Z—Xa—
- wherein
- m is an integer of from 0 to 20;
- Xa at each separate occurrence is selected from the group consisting of —O—, —S—, —NR—, —C(O)—, —C(O)O—, —C(O)NR—, —C(S)—, —C(S)O—, —C(S)NR— and a covalent bond where R is as defined below;
- Z is at each separate occurrence is selected from the group consisting of alkylene, substituted alkylene, cycloalkylene, substituted cylcoalkylene, alkenylene, substituted alkenylene, alkynylene, substituted alkynylene, cycloalkenylene, substituted cycloalkenylene, arylene, heteroarylene, heterocyclene, and a covalent bond;
- Ya and Yb at each separate occurrence are selected from the group consisting of —C(O)NR′—, —NR′C(O)—, —NR′C(O)NR′—, —C(═NR′)—NR′—, —NR′—C(═NR′)—, —NR′—C(O)—O—, —P(O)(OR′)—O—, —S(O)nCR′R″—, —S(O)n—NR′—, —S—S— and a covalent bond;
- where n is 0, 1 or 2;
- R, R′ and R″ at each separate occurrence are selected from the group consisting of hydrogen, alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, alkenyl, substituted alkenyl, cycloalkenyl, substituted cycloalkenyl, alkynyl, substituted alkynyl, aryl, heteroaryl and heterocyclic;
- and pharmaceutically-acceptable salts thereof.
13 more elements
A pharmaceutical composition comprising a pharmaceutically acceptable carrier and an effective amount of a compound of formula I:
- (L)p(X)q I
- wherein each L is a ligand independently selected from formula IA, IB or IC:
- wherein
- ring A, together with the atoms to which it is attached, forms a cyclobut-2-en-1-one, thiazole, isothiazole, thiadiazole, oxazole, isoxazole, S(H)-furanone, benzene, pyridine, imidazopyridine, imidazothiazole or thiazolotriazole ring;
- ring B, together with the atoms to which it is attached, forms a pyrazole ring;
- ring C, together with the atoms to which it is attached, forms an imidazole ring;
- R1 is selected from the group consisting of —SO2CH3, —SO2NH2, —SO2NHC(O)CF3, —SO(NH)NH2 and —SO(NH)NHC(O)CF3;
- each R2 is independently selected from the group consisting of alkyl, substituted alkyl, alkoxy, substituted alkoxy, alkoxycarbonyl, amino, substituted amino, azido, carboxyl, cyano, cycloalkyl, substituted cycloalkyl, halo, hydroxyl, nitro, thioalkoxy and substituted thioalkoxy;
- R3 is a covalent bond linking the ligand to a linker;
- and
- α is an integer from 0 to 3;
- each X is independently a linker of the formula:
- —Xa—Z—(Ya—Z)m—Yb—Z—Xa—
- wherein
- m is an integer of from 0 to 20;
- Xa at each separate occurrence is selected from the group consisting of —O—, —S—, —NR—, —C(O)—, —C(O)O—, —C(O)NR—, —C(S)—, —C(S)O—, —C(S)NR— and a covalent bond where R is as defined below;
- Z is at each separate occurrence is selected from the group consisting of alkylene, substituted alkylene, cycloalkylene, substituted cylcoalkylene, alkenylene, substituted alkenylene, alkynylene, substituted alkynylene, cycloalkenylene, substituted cycloalkenylene, arylene, heteroarylene, heterocyclene, and a covalent bond;
- Ya and Yb at each separate occurrence are selected from the group consisting of —C(O)NR′—, —NR′C(O)—, —NR′C(O)NR′—, —C(═NR′)—NR′—, —NR′—C(═NR′)—, —NR′—C(O)—O—, —P(O)(OR′)—O—, —S(O)nCR′R″—, —S(O)n—NR′—, —S—S— and a covalent bond;
- where n is 0, 1 or 2;
- R, R′ and R″ at each separate occurrence are selected from the group consisting of hydrogen, alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, alkenyl, substituted alkenyl, cycloalkenyl, substituted cycloalkenyl, alkynyl, substituted alkynyl, aryl, heteroaryl and heterocyclic;
- p is an integer of from 2 to 10;
- q is an integer of from 1 to 20, provided that q is less than p;
- and pharmaceutically-acceptable salts thereof.
20 more elements
A pharmaceutical composition comprising a pharmaceutically acceptable carrier and an effective amount of a compound of formula II:
- L′—X′—L′ II
- wherein each L′ is a ligand independently selected from the group consisting of:
- (a) a ligand of formula IIA:
- wherein
- R4 is selected from the group consisting of —SO2CH3, —SO2NH2, —SO2NHC(O)CF3, —SO(NH)NH2 and —SO(NH)NHC(O)CF3;
- each R5 is independently selected from the group consisting of alkyl, substituted alkyl, alkoxy, substituted alkoxy, alkoxycarbonyl, amino, substituted amino, azido, carboxyl, cyano, cycloalkyl, substituted cycloalkyl, halo, hydroxyl, nitro, thioalkoxy and substituted thioalkoxy;
- R6 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, aryl, cyano, fluoro and heteroaryl;
- R7 is a covalent bond linking the ligand to a linker;
- and
- b is an integer from 0 to 3;
- (b) a ligand of formula IIB:
- wherein
- R8 is selected from the group consisting of —SO2CH3, —SO2NH2, —SO2NHC(O)CF3, —SO(NH)NH2 and —SO(NH)NHC(O)CF3;
- each R9 is independently selected from the group consisting of alkyl, substituted alkyl, alkoxy, substituted alkoxy, alkoxycarbonyl, amino, substituted amino, azido, carboxyl, cyano, cycloalkyl, substituted cycloalkyl, halo, hydroxyl, nitro, thioalkoxy and substituted thioalkoxy;
- R10 is a covalent bond linking the ligand to a linker;
- R11 is selected from the group consisting of hydrogen, alkyl, substituted alkyl and fluoro;
- and
- c is an integer from 0 to 3;
- and
- (c) a ligand of formula IIC:
- wherein
- R12 is selected from the group consisting of —SO2CH3, —SO2NH2, —SO2NHC(O)CF3, —SO(NH)NH2 and —SO(NH)NHC(O)CF3;
- each R13 is independently selected from the group consisting of alkyl, substituted alkyl, alkoxy, substituted alkoxy, alkoxycarbonyl, amino, substituted amino, azido, carboxyl, cyano, cycloalkyl, substituted cycloalkyl, halo, hydroxyl, nitro, thioalkoxy and substituted thioalkoxy;
- R14 and R16 are independently selected from the group consisting of hydrogen, alkyl, substituted alkyl and fluoro;
- R15 is a covalent bond linking the ligand to a linker;
- and
- d is an integer from 0 to 3;
- and
- X′ is a linker of the formula:
- —Xa—Z—(Ya—Z)m—Yb—Z—Xa—
- wherein
- m is an integer of from 0 to 20;
- Xa at each separate occurrence is selected from the group consisting of —O—, —S—, —NR—, —C(O)—, —C(O)O—, —C(O)NR—, —C(S)—, —C(S)O—, —C(S)NR— and a covalent bond where R is as defined below;
- Z is at each separate occurrence is selected from the group consisting of alkylene, substituted alkylene, cycloalkylene, substituted cylcoalkylene, alkenylene, substituted alkenylene, alkynylene, substituted alkynylene, cycloalkenylene, substituted cycloalkenylene, arylene, heteroarylene, heterocyclene, and a covalent bond;
- Ya and Yb at each separate occurrence are selected from the group consisting of —C(O)NR′—, —NR′C(O)—, —NR′C(O)NR′—, —C(═NR′)—NR′—, —NR′—C(═NR′)—, —NR′—C(O)—O—, —P(O)(OR′)—O—, —S(O)nCR′R″—, —S(O)n—NR′—, —S—S— and a covalent bond;
- where n is 0, 1 or 2;
- R, R′ and R″ at each separate occurrence are selected from the group consisting of hydrogen, alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, alkenyl, substituted alkenyl, cycloalkenyl, substituted cycloalkenyl, alkynyl, substituted alkynyl, aryl, heteroaryl and heterocyclic;
- and pharmaceutically-acceptable salts thereof.
35 more elements
A pharmaceutical composition comprising a pharmaceutically acceptable carrier and an effective amount of a compound of formula III:
- wherein
- each R17 is independently selected from the group consisting of —SO2CH3, —SO2NH2, —SO2NHC(O)CF3, —SO(NH)NH2 and —SO(NH)NHC(O)CF3;
- each R18 is independently selected from the group consisting of alkyl, substituted alkyl, alkoxy, substituted alkoxy, alkoxycarbonyl, amino, substituted amino, azido, carboxyl, cyano, cycloalkyl, substituted cycloalkyl, halo, hydroxyl, nitro, thioalkoxy and substituted thioalkoxy;
- each R19 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, aryl, cyano, fluoro and heteroaryl;
- e is an integer from 0 to 3;
- and
- X″ is a linker of the formula:
- —Xa—Z—(Ya—Z)m—Yb—Z—Xa—
- wherein
- m is an integer of from 0 to 20;
- Xa at each separate occurrence is selected from the group consisting of —O—, —S—, —NR—, —C(O)—, —C(O)O—, —C(O)NR—, —C(S)—, —C(S)O—, —C(S)NR— and a covalent bond where R is as defined below;
- Z is at each separate occurrence is selected from the group consisting of alkylene, substituted alkylene, cycloalkylene, substituted cylcoalkylene, alkenylene, substituted alkenylene, alkynylene, substituted alkynylene, cycloalkenylene, substituted cycloalkenylene, arylene, heteroarylene, heterocyclene, and a covalent bond;
- Ya and Yb at each separate occurrence are selected from the group consisting of —C(O)NR′—, —NR′C(O)—, —NR′C(O)NR′—, —C(═NR′)—NR′—, —NR′—C(═NR′)—, —NR′—C(O)—O—, —P(O)(OR′)—O—, —S(O)nCR′R″—, —S(O)n—NR′—, —S—S— and a covalent bond;
- where n is 0, 1 or 2;
- R, R′ and R″ at each separate occurrence are selected from the group consisting of hydrogen, alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, alkenyl, substituted alkenyl, cycloalkenyl, substituted cycloalkenyl, alkynyl, substituted alkynyl, aryl, heteroaryl and heterocyclic;
- and pharmaceutically-acceptable salts thereof.
13 more elements
A pharmaceutical composition comprising a pharmaceutically acceptable carrier and an effective amount of a compound of formula IV:
- wherein
- each R20 is independently selected from the group consisting of —SO2CH3, —SO2NH2, —SO2NHC(O)CF3, —SO(NH)NH2 and —SO(NH)NHC(O)CF3;
- each R21 is independently selected from the group consisting of alkyl, substituted alkyl, alkoxy, substituted alkoxy, alkoxycarbonyl, amino, substituted amino, azido, carboxyl, cyano, cycloalkyl, substituted cycloalkyl, halo, hydroxyl, nitro, thioalkoxy and substituted thioalkoxy;
- f is an integer from 0 to 3;
- and
- X″ is a linker of the formula:
- —Xa—Z—(Ya—Z)m—Yb—Z—Xa—
- wherein
- m is an integer of from 0 to 20;
- Xa at each separate occurrence is selected from the group consisting of —O—, —S—, —NR—, —C(O)—, —C(O)O—, —C(O)NR—, —C(S)—, —C(S)O—, —C(S)NR— and a covalent bond where R is as defined below;
- Z is at each separate occurrence is selected from the group consisting of alkylene, substituted alkylene, cycloalkylene, substituted cylcoalkylene, alkenylene, substituted alkenylene, alkynylene, substituted alkynylene, cycloalkenylene, substituted cycloalkenylene, arylene, heteroarylene, heterocyclene, and a covalent bond;
- Ya and Yb at each separate occurrence are selected from the group consisting of —C(O)NR′—, —NR′C(O)—, —NR′C(O)NR′—, —C(═NR′)—NR′—, —NR′—C(═NR′)—, —NR′—C(O)—O—, —P(O)(OR′)—O—, —S(O)nCR′R″—, —S(O)n—NR′—, —S—S— and a covalent bond;
- where n is 0, 1 or 2;
- R, R′ and R″ at each separate occurrence are selected from the group consisting of hydrogen, alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, alkenyl, substituted alkenyl, cycloalkenyl, substituted cycloalkenyl, alkynyl, substituted alkynyl, aryl, heteroaryl and heterocyclic;
- and pharmaceutically-acceptable salts thereof.
12 more elements
A pharmaceutical composition comprising a pharmaceutically acceptable carrier and an effective amount of a compound of formula V:
- wherein
- each R22 is independently selected from the group consisting of —SO2CH3, —SO2NH2, —SO2NHC(O)CF3, —SO(NH)NH2 and —SO(NH)NHC(O)CF3;
- each R23 is independently selected from the group consisting of alkyl, substituted alkyl, alkoxy, substituted alkoxy, alkoxycarbonyl, amino, substituted amino, azido, carboxyl, cyano, cycloalkyl, substituted cycloalkyl, halo, hydroxyl, nitro, thioalkoxy and substituted thioalkoxy;
- each R24 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, aryl, cyano, fluoro and heteroaryl;
- g is an integer from 0 to 3;
- and
- X″ is a linker of the formula:
- —Xa—Z—(Ya—Z)m—Yb—Z—Xa—
- wherein
- m is an integer of from 0 to 20;
- Xa at each separate occurrence is selected from the group consisting of —O—, —S—, —NR—, —C(O)—, —C(O)O—, —C(O)NR—, —C(S)—, —C(S)O—, —C(S)NR— and a covalent bond where R is as defined below;
- Z is at each separate occurrence is selected from the group consisting of alkylene, substituted alkylene, cycloalkylene, substituted cylcoalkylene, alkenylene, substituted alkenylene, alkynylene, substituted alkynylene, cycloalkenylene, substituted cycloalkenylene, arylene, heteroarylene, heterocyclene, and a covalent bond;
- Ya and Yb at each separate occurrence are selected from the group consisting of —C(O)NR′—, —NR′C(O)—, —NR′C(O)NR′—, —C(═NR′)—NR′—, —NR′—C(═NR′)—, —NR′—C(O)—O—, —P(O)(OR′)—O—, —S(O)nCR′R″—, —S(O)n—NR′—, —S—S— and a covalent bond;
- where n is 0, 1 or 2;
- R, R′ and R″ at each separate occurrence are selected from the group consisting of hydrogen, alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, alkenyl, substituted alkenyl, cycloalkenyl, substituted cycloalkenyl, alkynyl, substituted alkynyl, aryl, heteroaryl and heterocyclic;
- and pharmaceutically-acceptable salts thereof.
13 more elements
Dependencies are inferred from the claim text.