Back to results
US 6,486,185 B1Granted
3-heteroarylidene-2-indolinone protein kinase inhibitors
AssigneeSugen, Inc.
InventorsGerald McMahon, Peng Cho Tang, Li Sun
Life of this patent
Estimating the term…
Abstract
The present invention relates to novel 3-heteroarylidene-2-indolinone compounds and physiologically acceptable salts thereof which modulate the activity of protein kinases and therefore are expected to be useful in the prevention and treatment of protein kinase related cellular disorders such as cancer.
Claims52
A 3-heteroarylidene-2-indolinone having the chemical structure:
- or a physiologically acceptable salt or prodrug thereof wherein,
- A, B, D and E are selected from the group consisting of carbon and nitrogen, it being understood that the nitrogen-containing 9-member bicyclic ring formed is one known in the chemical arts;
- it being further understood that when A, B, D, or E is nitrogen, R3, R4, R5 or R6, respectively, does not exist;
- R1 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, hydroxy, alkoxy, carboxyl, C-amido and sulfonyl;
- R2 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, heteroaryl, and heteroalicyclic;
- R3, R4, R5 and R6 are independently selected from the group consisting of hydrogen, alkyl, trihaloalkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, heteroalicyclic, hydroxy, alkoxy, aryloxy, —SH, —S-alkyl, —S-cycloalkyl, —S-aryl, —S-heteroaryl, sulfinyl, sulfonyl, sulfonamido, carbonyl, carboxyl, cyano, nitro, halo, —OC(O)NR10R11, N-carbamyl, —OC(S)NR10R11, N-thiocarbamyl, C-amido, N-amido, amino and —NR10R11;
- R10 and R11 are independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, carbonyl, sulfonyl and, combined, a five- or six-member heteroalicyclic ring containing at least one nitrogen;
- R3 and R4, R4 and R5, or R4 and R5 may combine to form a six-member aryl or heteroaryl ring;
- Q is a heteroaryl group having the following structure:
- J is selected from the group consisting of oxygen, nitrogen and sulfur;
- K, L and M are independently selected from the group consisting of carbon, nitrogen, oxygen and sulfur such that the five-member heteroaryl ring formed is one known in the chemical arts, it being understood that when K, L and M are nitrogen, sulfur or oxygen, R8 or -(alk1)nZ cannot be covalently bonded to that atom;
- when J is nitrogen, R7 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, hydroxy, alkoxy, aryloxy, carbonyl, carboxyl, C-amido, guanyl and sulfonyl and when J is oxygen or sulfur, R7 does not exist and there is no bond;
- R8 is selected from the group consisting of hydrogen, alkyl, trihaloalkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, heteroalicyclic, hydroxy, alkoxy, aryloxy, —SH, —S-alkyl, —S-cycloalkyl, —S-aryl, —S-heteroaryl, sulfinyl, sulfonyl, sulfonamido, carbonyl, carboxyl, cyano, nitro, halo, —OC(O)NR10R11, N-carbamyl, —OC(S)NR10R11 N-thiocarbamyl, C-amido, N-amido, amino, —NR10R11, trihalomethyl, a five member cycloalkyl, aryl, heteroaryl or heteroalicyclic ring fused to two adjacent atoms of the Q ring;
- and a six-member cycloalkyl, aryl, heteroaryl, or heteroalicyclic ring fused to two adjacent atoms of the Q ring;
- R10 and R11 are independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, carbonyl, sulfonyl and, combined, a five- or six-member heteroalicyclic ring containing at least one nitrogen;
- alk1 is selected from the group consisting of optionally substituted methylene (—CRR′—), optionally substituted ethylene (—C(R)═C(R′)—) and acetylene (—C≡C—);
- R and R′ are independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, alkoxy, —S-alkyl, —S-cycloalkyl, aryloxy and halo;
- n is 0 to 10, inclusive with the proviso that when n is 0, R7 is not alkyl substituted with aryl;
- and
- Z is a polar group selected from the group consisting of hydroxy, alkoxy, carboxy, nitro, cyano, carbamyl, amino, quaternary ammonium, amido, ureido, sulfonamido, sulfinyl, sulfonyl, phosphono, phosphonyl, morpholino, piperazinyl and tetrazolo.
17 more elements
A 3-heteroarylidene-2-indolinone having the chemical structure:
- or a physiologically acceptable salt or prodrug thereof wherein,
- A, B, D and E are selected from the group consisting of carbon and nitrogen, it being understood that the nitrogen-containing 9-member bicyclic ring formed is one known in the chemical arts;
- it being further understood that when A, B, D, or E is nitrogen, R3, R4, R5 or R6, respectively, does not exist;
- R1 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, hydroxy, alkoxy, carboxyl, C-amido and sulfonyl;
- R2 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, heteroaryl, and heteroalicyclic;
- R3, R4, R5 and R6 are independently selected from the group consisting of hydrogen, alkyl, trihaloalkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, heteroalicyclic, hydroxy, alkoxy, aryloxy, —SH, —S-alkyl, —S-cycloalkyl, —S-aryl, —S-heteroaryl, sulfinyl, sulfonyl, sulfonamido, carbonyl, carboxyl, cyano, nitro, halo, —OC(O)NR10R11, N-carbamyl, —OC(S)NR10R11, N-thiocarbamyl, C-amido, N-amido, amino and —NR10R11;
- wherein
- R10 and R11 are independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, carbonyl, sulfonyl and, combined, a five- or six-member heteroalicyclic ring containing at least one nitrogen;
- R3 and R4, R4 and R5, or R4 and R5 may combine to form a six-member aryl or heteroaryl ring;
- Q is a heteroaryl group having the following structure:
- J is selected from the group consisting of oxygen, nitrogen and sulfur;
- K, L and M are independently selected from the group consisting of carbon, nitrogen, oxygen and sulfur such that the five-member heteroaryl ring formed is one known in the chemical arts, it being understood that when K, L and M are nitrogen, sulfur or oxygen, R8 or -(alk1)nZ cannot be covalently bonded to that atom;
- when J is nitrogen, R7 is selected from the group consisting of hydrogen, lower unsubstituted alkyl, cycloalkyl, aryl, hydroxy, alkoxy, aryloxy, carbonyl, carboxyl, C-amido, guanyl and sulfonyl and when J is oxygen or sulfur, R7 does not exist and there is no bond;
- R8 is selected from the group consisting of hydrogen, alkyl, trihaloalkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, heteroalicyclic, hydroxy, alkoxy, aryloxy, —SH,
- —S-alkyl, —S-cycloalkyl, —S-aryl, —S-heteroaryl, sulfinyl, sulfonyl, sulfonamido, carbonyl, carboxyl, cyano, nitro, halo, —OC(O)NR10R11, N-carbamyl, —OC(S)NR10R11, N-thiocarbamyl, C-amido, N-amido, amino, —NR10R11, trihalomethyl, a five-member cycloalkyl, aryl, heteroaryl or heteroalicyclic ring fused to two adjacent atoms of the Q ring;
- and a six-member cycloalkyl, aryl, heteroaryl, or heteroalicyclic ring fused to two adjacent atoms of the Q ring;
- R10 and R11 are independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, carbonyl, sulfonyl and, combined, a five- or six-member heteroalicyclic ring containing at least one nitrogen;
- alk1 is selected from the group consisting of optionally substituted methylene (—CRR′—), optionally substituted ethylene (—C(R)═C(R′)—) and acetylene (—C≡C—);
- R and R′ are independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, alkoxy, —S-alkyl, —S-cycloalkyl, aryloxy and halo;
- n is 0 to 10, inclusive;
- and
- Z is a polar group selected from the group consisting of hydroxy, alkoxy, carboxy, nitro, cyano, carbamyl, amino, quaternary ammonium, amido, ureido, sulfonamido, sulfinyl, sulfonyl, phosphono, phosphonyl, morpholino, piperazinyl and tetrazolo.
19 more elements
A 3-heteroarylidene-2-indolinone having the chemical structure:
- or a physiologically acceptable salt or prodrug thereof wherein,
- A, B, D and E are selected from the group consisting of carbon and nitrogen, it being understood that the nitrogen-containing 9-member bicyclic ring formed is one known in the chemical arts;
- it being further understood that when A, B, D, or E is nitrogen, R3, R4, R5 or R6, respectively, does not exist;
- R1 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, hydroxy, alkoxy, carboxyl, C-amido and sulfonyl;
- R2 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, heteroaryl, and heteroalicyclic;
- R3, R4, R5 and R6 are independently selected from the group consisting of hydrogen, alkyl, trihaloalkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, heteroalicyclic, hydroxy, alkoxy, aryloxy, —SH, —S-alkyl, —S-cycloalkyl, —S-aryl, —S-heteroaryl, sulfinyl, sulfonyl, sulfonamido, carbonyl, carboxyl, cyano, nitro, halo, —OC(O)NR10R11, N-carbamyl, —OC(S)NR10R11, N-thiocarbamyl, C-amido, N-amido, amino and —NR10R11;
- R10 and R11 are independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, carbonyl, sulfonyl and, combined, a five- or six-member heteroalicyclic ring containing at least one nitrogen;
- R3 and R4, R4 and R5, or R5 and R6 may combine to form a six-member aryl or heteroaryl ring;
- Q is a heteroaryl group having the following structure:
- J is selected from the group consisting of oxygen, nitrogen and sulfur;
- K, L and M are independently selected from the group consisting of carbon, nitrogen, oxygen and sulfur such that the five-member heteroaryl ring formed is one known in the chemical arts, it being understood that when K, L and M are nitrogen, sulfur or oxygen, R8 or -(alk1)nZ cannot be covalently bonded to that atom;
- when J is nitrogen,
- R7 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, hydroxy, alkoxy, aryloxy, carbonyl, carboxyl, C-amido, guanyl and sulfonyl and when J is oxygen or sulfur, R7 does not exist and there is no bond, wherein alkyl is a saturated straight chain or branched chain aliphatic hydrocarbon, and wherein alkyl is unsubstituted or substituted with one or more members selected from the group consisting of cycloalkyl, heteroaryl, heteroalicyclic, hydroxy, alkoxy, aryloxy, thiohydroxy, thioalkoxy, thioaryloxy, cyano, halo, carbonyl, thiocarbonyl, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, C-amido, N-amido, carboxy, nitro, silyl, amino and NR10R11, wherein R10 and R11 are independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, carbonyl, sulfonyl, trihalomethanesulfonyl and, combined, a five-member or six-member heteroalicyclic ring;
- R8 is selected from the group consisting of hydrogen, alkyl, trihaloalkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, heteroalicyclic, hydroxy, alkoxy, aryloxy, —SH, —S-alkyl, —S-cycloalkyl, —S-aryl, —S-heteroaryl, sulfinyl, sulfonyl, sulfonamido, carbonyl, carboxyl, cyano, nitro, halo, —OC(O)NR10R11, N-carbamyl, —OC(S)NR10R11, N-thiocarbamyl, C-amido, N-amido, amino, —NR10R11, trihalomethyl, a five-member cycloalkyl, aryl, heteroaryl or heteroalicyclic ring fused to two adjacent atoms of the Q ring;
- and a six-member cycloalkyl, aryl, heteroaryl, or heteroalicyclic ring fused to two adjacent atoms of the Q ring;
- R10 and R11 are independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, carbonyl, sulfonyl and, combined, a five- or six-member heteroalicyclic ring containing at least one nitrogen;
- alk1 is selected from the group consisting of optionally substituted methylene (—CRR′—), optionally substituted ethylene (—C(R)═C(R′)—) and acetylene (—C≡C—);
- R and R′ are independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, alkoxy, —S-alkyl, —S-cycloalkyl, aryloxy and halo;
- n is 0 to 10, inclusive;
- and
- Z is a polar group selected from the group consisting of hydroxy, alkoxy, carboxy, nitro, cyano, carbamyl, amino, quaternary ammonium, amido, ureido, sulfonamido, sulfinyl, sulfonyl, phosphono, phosphonyl, morpholino, piperazinyl and tetrazolo.
18 more elements
A 3-heteroarylidene-2-indolinone selected from the group consisting of:
- 3-[3-(2-carboxyethyl-4-methylpyrrol-2-methylidenyl]-2-indolinone,
- 3-(2-acetyl-3,4-dimethylpyrrol-5-methylidenyl)-2-indolinone,
- 3-[4-(2-methoxycarbonylethyl-3-methylpyrrol-2-methylidenyl]-2-indolinone,
- 3-(2,4-dimethyl-3-ethoxycarbonylpyrrol-5-methylidenyl)-2-indolinone,
- 3-[2-ethoxycarbonyl-3-(2-ethoxycarbonylethyl)-4-ethoxycarbonylmethyl)pyrrol-5-methylidenyl)-2-indolinone,
- 3-(2-carboxy-4-ethyl-3-methylpyrrol-5-methylidenyl)-2-indolinone,
- 3-(2-chloro-4-methoxycarbonyl-3-methoxycarbonylmethylpyrrol-5-methylidenyl)-2-indolinone,
- 3-(4-acetyl-2-ethoxycarbonyl-3-methylpyrrol-5-methylidenyl)-2-indolinone,
- 3-(4-ethoxycarbonyl-3-methylpyrrol-2-methylidenyl)-2-indolinone,
- 3-[4-(2-methoxycarbonylethyl)-3-methylpyrrol-2-methylidenyl]-5,6-dimethoxy-2-indolinone,
- 3-(2,4-dimethyl-3-ethoxycarbonylpyrrol-5-methylidenyl)-5-(4-methoxycarbonylbenzamido)-2-indolinone,
- 3-(2,4-dimethyl-3-ethoxycarbonylpyrrol-5-methylidenyl)-5-bromo-2-indolinone,
- 3-[4-(2-carboxyethyl)-3,5-dimethylpyrrol-2-methylidenyl]-2-indolinone, and
- 3-[4-(2-carboxyethyl)-3-methylpyrrol-2-methylidenyl]-2-indolinone.
11 more elements
A combinatorial library of at least 13 indolinone compounds that can be formed by reacting an oxindole with an acyl compound, wherein said oxindole has a structure set forth in formula 2
- wherein
- A, B, D and E are selected from the group consisting of carbon and nitrogen, it being understood that the nitrogen-containing 9-member bicyclic ring formed is one known in the chemical arts;
- it being further understood that when A, B, D, or E is nitrogen, R3, R4, R5 or R6, respectively, does not exist;
- R1 is selected from the group consisting of hydrogcn, alkyl, cycloalkyl, aryl, hydroxy, alkoxy, carboxyl, C-amido and sulfonyl;
- R3, R4, R5 and R6 are independently selected from the group consisting of hydrogen, alkyl, trihaloalkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, heteroalicyclic, hydroxy, alkoxy, aryloxy, —SH, —S-alkyl, —S-cycloalkyl, —S-aryl, —S-heteroaryl, sulfinyl, sulfonyl, sulfonamido, carbonyl, carboxyl, cyano, nitro, halo, —OC(O)NR10R11, N-carbamyl, —OC(S)NR10R11, N-thiocarbamyl, C-amido, N-amido, amino and —NR10R11, wherein
- R10 and R11 are independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, carbonyl, sulfonyl and, combined, a five- or six-member heteroalicyclic ring containing at least one nitrogen;
- R3 and R4, R4 and R5, or R5 and R6 may combine to form a six-member aryl or heteroaryl ring;
- and wherein said acyl compound has the structure set forth in formula 3
- wherein
- J is selected from the group consisting of oxygen, nitrogen and sulfur;
- K, L and M are independently selected from the group consisting of carbon, nitrogen, oxygen and sulfur such that the five-member heteroaryl ring formed is one known in the chemical arts, it being understood that when K, L and M are nitrogen, sulfur or oxygen, R8 or -(alk1)nZ cannot be covalently bonded to that atom;
- when J is nitrogen, R7 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, hydroxy, alkoxy, aryloxy, carbonyl, carboxyl, C-amido, guanyl and sulfonyl and when J is oxygen or sulfur, R7 does not exist and there is no bond;
- R8 is selected from the group consisting of hydrogen, alkyl, trihaloalkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, heteroalicyclic, hydroxy, alkoxy, aryloxy, —SH, —S-alkyl, —S-cycloalkyl, —S-aryl, —S-heteroaryl, sulfinyl, sulfonyl, sulfonamido, carbonyl, carboxyl, cyano, nitro, halo, —OC(O)NR10R11, N-carbamyl, —OC(S)NR10R11, N-thiocarbamyl, C-amido, N-amido, amino, —NR10R11, trihalomethyl, a five-member cycloalkyl, aryl, heteroaryl or heteroalicyclic ring fused to two adjacent atoms of the five-membered ring;
- and a six-member cycloalkyl, aryl, heteroaryl, or heteroalicyclic ring fused to two adjacent atoms of the five-membered ring;
- R10 and R11 are independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, carbonyl, sulfonyl and, combined, a five- or six-member heteroalicyclic ring containing at least one nitrogen;
- alk1 is selected from the group consisting of optionally substituted methylene (—CRR′—), optionally substituted ethylene (—C(R)═C(R′)—) and acetylene (—C≡C—);
- R2 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, heteroaryl, and heteroalicyclic;
- R and R′ are independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, alkoxy, —S-alkyl, —S-cycloalkyl, aryloxy and halo;
- n is 0 to 10, inclusive, with the proviso that when n is 0, R7 is not alkyl substituted with aryl and
- Z is a polar group selected from the group consisting of hydroxy, alkoxy, carboxy, nitro, cyano, carbamyl, amino, quaternary ammonium, amido, ureido, sulfonamido, sulfinyl, sulfonyl, phosphono, phosphonyl, morpholino, piperazinyl and tetrazolo.
17 more elements
A combinatorial library of at least 13 indolinone compounds that can be formed by reacting an oxindole with an acyl compound, wherein said oxindole has a structure set forth in formula 2
- wherein
- A, B, D and E are selected from the group consisting of carbon and nitrogen, it being understood that the nitrogen-containing 9-member bicyclic ring formed is one known in the chemical arts;
- it being further understood that when A, B, D, or E is nitrogen, R3, R4, R5 or R6, respectively, does not exist;
- R1 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, hydroxy, alkoxy, carboxyl, C-amido and sulfonyl;
- R3, R4, R5 and R6 are independently selected from the group consisting of hydrogen, alkyl, trihaloalkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, heteroalicyclic, hydroxy, alkoxy, aryloxy, —SH, —S-alkyl, —S-cycloalkyl, —S-aryl, —S-heteroaryl, sulfinyl, sulfonyl, sulfonamido, carbonyl, carboxyl, cyano, nitro, halo, —OC(O)NR10R11, N-carbamyl, —OC(S)NR10R11, N-thiocarbamyl, C-amido, N-amido, amino and —NR10R11, wherein
- R10 and R11 are independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, carbonyl, sulfonyl and, combined, a five- or six-member heteroalicyclic ring containing at least one nitrogen;
- R3 and R4, R4 and R5, or R5 and R6 may combine to form a six-member aryl or heteroaryl ring;
- and wherein said acyl compound has the structure set forth in formula 3
- wherein
- J is selected from the group consisting of oxygen, nitrogen and sulfur;
- K, L and M are independently selected from the group consisting of carbon, nitrogen, oxygen and sulfur such that the five-member heteroaryl ring formed is one known in the chemical arts, it being understood that when K, L and M are nitrogen, sulfur or oxygen, R8 or -(alk1)nZ cannot be covalently bonded to that atom;
- when J is nitrogen, R7 is selected from the group consisting of hydrogen, lower unsubstituted alkyl, cycloalkyl, aryl, hydroxy, alkoxy, aryloxy, carbonyl, carboxyl, C-amido, guanyl and sulfonyl and when J is oxygen or sulfur, R7 does not exist and there is no bond;
- R8 is selected from the group consisting of hydrogen, alkyl, trihaloalkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, heteroalicyclic, hydroxy, alkoxy, aryloxy, —SH, —S-alkyl, —S-cycloalkyl, —S-aryl, —S-heteroaryl, sulfinyl, sulfonyl, sulfonamido, carbonyl, carboxyl, cyano, nitro, halo, —OC(O)NR10R11, N-carbamyl, —OC(S)NR10R11, N-thiocarbamyl, C-amido, N-amido, amino, —NR10R11, trihalomethyl, a five-member cycloalkyl, aryl, heteroaryl or heteroalicyclic ring fused to two adjacent atoms of the five-membered ring;
- and a six-member cycloalkyl, aryl, heteroaryl, or heteroalicyclic ring fused to two adjacent atoms of the five-membered ring;
- R10 and R11 are independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, carbonyl, sulfonyl and, combined, a five- or six-member heteroalicyclic ring containing at least one nitrogen;
- alk1 is selected from the group consisting of optionally substituted methylene (—CRR′—), optionally substituted ethylene (—C(R)═C(R′)—) and acetylene (—C≡C—);
- R2 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, heteroaryl, and heteroalicyclic;
- R and R′ are independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, alkoxy, —S-alkyl, —S-cycloalkyl, aryloxy and halo;
- n is 0 to 10, inclusive and
- Z is a polar group selected from the group consisting of hydroxy, alkoxy, carboxy, nitro, cyano, carbamyl, amino, quaternary ammonium, amido, ureido, sulfonamido, sulfinyl, sulfonyl, phosphono, phosphonyl, morpholino, piperazinyl and tetrazolo.
17 more elements
A combinatorial library of at least 13 indolinone compounds that can be formed by reacting an oxindole with an acyl compound, wherein said oxindole has a structure set forth in formula 2
- wherein
- A, B, D and E are selected from the group consisting of carbon and nitrogen, it being understood that the nitrogen-containing 9-member bicyclic ring formed is one known in the chemical arts;
- it being further understood that when A, B, D, or E is nitrogen, R3, R4, R5 or R6, respectively, does not exist;
- R1 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, hydroxy, alkoxy, carboxyl, C-amido and sulfonyl;
- R3, R4, R5 and R6 are independently selected from the group consisting of hydrogen, alkyl, trihaloalkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, heteroalicyclic, hydroxy, alkoxy, aryloxy, —SH, —S-alkyl, —S-cycloalkyl, —S-aryl, —S-heteroaryl, sulfinyl, sulfonyl, sulfonamido, carbonyl, carboxyl, cyano, nitro, halo, —OC(O)NR10R11, N-carbamyl, —OC(S)NR10R11, N-thiocarbamyl, C-amido, N-amido, amino and —NR10R11, wherein
- R10 and R11 are independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, carbonyl, sulfonyl and, combined, a five- or six-member heteroalicyclic ring containing at least one nitrogen;
- R3 and R4, R4 and R5, or R5 and R6 may combine to form a six-member aryl or heteroaryl ring;
- and wherein said acyl compound has the structure set forth in formula 3
- wherein
- J is selected from the group consisting of oxygen, nitrogen and sulfur;
- K, L and M are independently selected from the group consisting of carbon, nitrogen, oxygen and sulfur such that the five-member heteroaryl ring formed is one known in the chemical arts, it being understood that when K, L and M are nitrogen, sulfur or oxygen, R8 or -(alk1)nZ cannot be covalently bonded to that atom;
- when J is nitrogen,
- R7 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, hydroxy, alkoxy, aryloxy, carbonyl, carboxyl, C-amido, guanyl and sulfonyl and when J is oxygen or sulfur, R7 does not exist and there is no bond, wherein alkyl is a saturated straight chain or branched chain aliphatic hydrocarbon, and wherein alkyl is unsubstituted or substituted with one or more members selected from the group consisting of cycloalkyl, heteroaryl, heteroalicyclic, hydroxy, alkoxy, aryloxy, thiohydroxy, thioalkoxy, thioaryloxy, cyano, halo, carbonyl, thiocarbonyl, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, C-amido, N-amido, carboxy, nitro, silyl, amino and NR10R11, wherein R10 and R11 are independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, carbonyl, sulfonyl, trihalomethanesulfonyl and, combined, a five-member or six-member heteroalicyclic ring;
- R8 is selected from the group consisting of hydrogen, alkyl, trihaloalkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, heteroalicyclic, hydroxy, alkoxy, aryloxy, —SH, —S-alkyl, —S-cycloalkyl, —S-aryl, —S-heteroaryl, sulfinyl, sulfonyl, sulfonamido, carbonyl, carboxyl, cyano, nitro, halo, —OC(O)NR10R11, N-carbamyl, —OC(S)NR10R11, N-thiocarbamyl, C-amido, N-amido, amino, —NR10R11, trihalomethyl, a five-member cycloalkyl, aryl, heteroaryl or heteroalicyclic ring fused to two adjacent atoms of the five-membered ring;
- and a six-member cycloalkyl, aryl, heteroaryl, or heteroalicyclic ring fused to two adjacent atoms of the five-membered ring;
- R10 and R11 are independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, carbonyl, sulfonyl and, combined, a five- or six-member heteroalicyclic ring containing at least one nitrogen;
- alk1 is selected from the group consisting of optionally substituted methylene (—CRR′—), optionally substituted ethylene (—C(R)═C(R′)—) and acetylene (—C≡C—);
- R2 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, heteroaryl, and heteroalicyclic;
- R and R′ are independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, alkoxy, —S-alkyl, —S-cycloalkyl, aryloxy and halo;
- n is 0 to 10, inclusive and
- Z is a polar group selected from the group consisting of hydroxy, alkoxy, carboxy, nitro, cyano, carbamyl, amino, quaternary ammonium, amido, ureido, sulfonamido, sulfinyl, sulfonyl, phosphono, phosphonyl, morpholino, piperazinyl and tetrazolo.
18 more elements
Dependencies are inferred from the claim text.