1. A fixing control apparatus which controls a fixing apparatus which includes multiple heating elements to fix an unfixed toner image formed based on image data to a recording material, the fixing control apparatus comprising:
a processor configured to:
determine a presenceabsence of an image for each of multiple areas into which the image data are divided;
obtain an accumulated value of a pixel count value for each of the areas;
determine that the image is present in the area when the accumulated value is at least a predetermined value;
select a heating element located at a position corresponding to an area in which the image is present from the multiple heating elements; and
cause the heating element selected to be heated.
2. The fixing control apparatus as claimed in claim 1, further comprising:
a memory which stores therein heating element information including information related to a width of the heating element and an arrangement of the heating element, wherein the processor is configured to select the heating element based on the heating element information.
3. The fixing control apparatus as claimed in claim 1, further comprising:
a register corresponding to the area in which the accumulated value is stored, wherein the processor is configured to determine a position of the area in the image data based on an address of the register and to select a heating element located at a position corresponding to the area based on a width of the heating elements and an arrangement of the heating elements that are included in heating element information.
4. A non-transitory computer readable medium having a fixing control computer program recorded thereon, the fixing control computer program configured to perform a method when executed by a fixing control apparatus which controls a fixing apparatus which includes multiple heating elements to fix an unfixed toner image formed based on image data to a recording material, the method comprising:
determining a presenceabsence of an image for each of multiple areas into which the image data are divided;
obtaining an accumulated value of a pixel count value for each of the areas;
determining that the image is present in the area when the accumulated value is at least a predetermined value;
selecting a heating element located at a position corresponding to an area in which the image is present from the multiple heating elements; and
causing the heating element selected to be heated.
5. An image forming apparatus, comprising:
a fixing control apparatus which controls a fixing apparatus which includes multiple heating elements to fix an unfixed toner image formed based on image data to a recording material,
the fixing control apparatus including a processor that is configured to:
determine a presenceabsence of an image for each of multiple areas into which the image data are divided;
obtain an accumulated value of a pixel count value for each of the areas;
determine that the image is present in the area when the accumulated value is at least a predetermined value;
select a heating element located at a position corresponding to an area in which the image is present from the multiple heating elements; and
cause the heating element selected to be heated.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
1. A compound of formula Ia
and pharmaceutically acceptable salts thereof;
wherein R1 is selected from the group consisting of phenyl, heterocyclic ring and heteroaryl ring containing 1 to 3 ring heteroatoms selected from nitrogen, oxygen, and sulfur, wherein said phenyl, heterocyclic, and heteroaryl ring are each optionally substituted with from one to four substituents independently selected from the group consisting of -J, \u2014NO2, \u2014CN, \u2014N3, \u2014CHO, \u2014CF3, \u2014OCF3, \u2014R7, \u2014OR7, \u2014S(O)mR7, \u2014NR7R7, \u2014NR7S(O)mR7, \u2014OR9OR7, \u2014OR9NR7R7, \u2014N(R7)R9OR7, \u2014N(R7)R9NR7R7, \u2014NR7C(O)R7, \u2014C(O)R7, \u2014C(O)OR7, \u2014C(O)NR7R7, \u2014OC(O)R7, \u2014OC(O)OR7, \u2014OC(O)NR7R7, NR7C(O)R7, \u2014NR7C(O)OR7, \u2014NR7C(O)NR7R7, \u2014R8OR7, \u2014R8NR7R7, \u2014R8S(O)mR7, \u2014R8C(O)R7, \u2014R8C(O)OR7, \u2014R8C(O)NR7R7, \u2014R8OC(O)R7, \u2014R8OC(O)OR7, \u2014R8OC(O)NR7R7, \u2014R8NR7C(O)R7, \u2014R8NR7C(O)OR7, \u2014R8NR7C(O)NR7R7, and YR10;
R2 and R3 are independently selected from the group consisting of \u2014H, -J, \u2014C(O)OR7, \u2014C(O)NR7R7, \u2014NR6C(O)R7, \u2014CN, heterocyclic ring and heteroaryl ring having 5 to 7 ring atoms and containing 1 to 3 ring heteroatoms selected from nitrogen, oxygen, and sulfur, and C6-C14 aryl ring, wherein \u2014R7, heterocyclic, heteroaryl and aryl rings are optionally substituted with from one to four substituents independently selected from the group consisting of -J, \u2014NO2, \u2014CN, \u2014N3, \u2014CHO, \u2014CF3, \u2014OCF3, \u2014R7, \u2014OR7, \u2014S(O)mR7, \u2014NR7R7, \u2014NR7S(O)mR7, \u2014OR9OR7, \u2014OR9NR7R7, \u2014N(R7)R9OR7, \u2014\u2014N(R7)R9NR7R7, \u2014NR7C(O)R7, \u2014C(O)R7, \u2014C(O)OR7, \u2014C(O)NR7R7, \u2014OC(O)R7, \u2014OC(O)OR7, \u2014OC(O)NR7R7, NR7C(O)R7, \u2014NR7C(O)OR7, \u2014NR7C(O)NR7R7, \u2014R8OR7, \u2014R8NR7R7, \u2014R8S(O)mR7, \u2014R8C(O)R7, \u2014R8C(O)OR7, \u2014R8C(O)NR7R7, \u2014R8OC(O)R7, \u2014R8OC(O)OR7, \u2014R8OC(O)NR7R7, \u2014R8NR7C(O)R7, \u2014R8NR7C(O)OR7, \u2014R8NR7C(O)NR7R7, and \u2014YR10;
R4 is selected from the group consisting of \u2014H, C1-C8 alkyl, C2-C6 alkenyl, and C2-C6 alkynyl;
R5, at each occurrence, is from one to four substituents independently selected from the group consisting of \u2014H, -J, \u2014NO2, \u2014CN, \u2014N3, \u2014CHO, \u2014CF3, \u2014OCF3, \u2014R7, \u2014OR7, \u2014S(O)mR7, \u2014NR7R7, \u2014NR7S(O)mR7, \u2014OR9OR7, \u2014OR9NR7R7, \u2014N(R7)R9OR7, \u2014N(R7)R9NR7R7, \u2014NR7C(O)R7, \u2014C(O)R7, \u2014C(O)OR7, \u2014C(O)NR7R7, \u2014OC(O)R7, \u2014OC(O)OR7, \u2014OC(O)NR7R7, NR7C(O)R7, \u2014NR7C(O)OR7, \u2014NR7C(O)NR7R7, \u2014R8OR7, \u2014R8NR7R7, \u2014R8S(O)mR7, \u2014R8C(O)R7, \u2014R8C(O)OR7, \u2014R8C(O)NR7R7, \u2014R8OC(O)R7, \u2014R8OC(O)OR7, \u2014R8OC(O)NR7R7, \u2014R8NR7C(O)R7, \u2014R8NR7C(O)OR7, \u2014R8NR7C(O)NR7R7, and YR10; \u2014R6, at each occurrence, is selected from the group consisting of \u2014H, \u2014C(O)OR7, \u2014C(O)NR7R7, C3-C10 carbocyclic ring, heterocyclic ring and heteroaryl ring having 5 to 7 ring atoms and containing 1 to 3 ring heteroatoms selected from nitrogen, oxygen, and sulfur, and C6-C14 aryl ring, wherein said R7, carbocyclic ring, heterocyclic ring, heteroaryl ring, and aryl ring are each optionally substituted with from one to four substituents independently selected from the group consisting of -J, \u2014NO2, \u2014CN, \u2014N3, \u2014CHO, \u2014CF3, \u2014OCF3, \u2014R7, \u2014OR7, \u2014S(O)mR7, \u2014NR7R7, \u2014NR7S(O)mR7, \u2014OR9OR7, \u2014OR9NR7R7, \u2014N(R7)R9OR7, \u2014N(R7)R9NR7R7, \u2014NR7C(O)R7, \u2014C(O)R7, \u2014C(O)OR7, \u2014C(O)NR7R7, \u2014OC(O)R7, \u2014OC(O)OR7, \u2014OC(O)NR7R7, NR7C(O)R7, \u2014NR7C(O)OR7, \u2014NR7C(O)NR7R7, \u2014R8OR7, \u2014R8NR7R7, \u2014R8S(O)mR7, \u2014R8C(O)R7, \u2014R8C(O)OR7, \u2014R8C(O)NR7R7, \u2014R8OC(O)R7, \u2014R8OC(O)OR7, \u2014R8OC(O)NR7R7, \u2014R8NR7C(O)R7, \u2014R8NR7C(O)OR7, \u2014R8NR7C(O)NR7R7, and \u2014R10;
R7, at each occurrence, is selected from the group consisting of \u2014H, C1-C8 alkyl, C2-C6 alkenyl, and C2-C6 alkynyl;
R8 is a divalent group selected from the group consisting of C1-C6 alkyl, C2-C6 alkenyl, and C2-C6 alkynyl;
R9 is a divalent C2-C6 alkyl group;
R10, at each occurrence, is selected from the group consisting of a C3-C10 carbocyclic ring; a heterocyclic ring and a heteroaryl ring containing 1 to 3 ring heteroatoms selected from nitrogen, oxygen, and sulfur; and C6-C14 aryl ring; wherein the carbocyclic ring, heterocyclic ring, heteroaryl ring, and aryl ring are optionally substituted with from one to four substituents independently selected from the group consisting of \u2014H, -J, \u2014NO2, \u2014CN, \u2014N3, \u2014CHO, \u2014CF3, \u2014OCF3, \u2014R7, \u2014OR7, \u2014S(O)mR7, \u2014NR7R7, \u2014NR7S(O)mR7, \u2014OR9OR7, \u2014OR9NR7R7, \u2014N(R7)R9OR7, \u2014N(R7)R9NR7R7, \u2014NR7C(O)R7, \u2014C(O)R7, \u2014C(O)OR7, \u2014C(O)NR7R7, \u2014OC(O)R7\u2014, \u2014OC(O)OR7, \u2014OC(O)NR7R7, \u2014NR7C(O)R7, \u2014NR7C(O)OR7, \u2014NR7C(O)N R7R7, \u2014R8OR7, R8NR7R7, \u2014R8S(O)mR7, \u2014R8C(O)R7, \u2014R8C(O)OR7, \u2014R8C(O)NR7R7, \u2014R8C(O)R7, \u2014R8C(O)OR7, \u2014R8C(O)NR7R7, \u2014R8OC(O)R7, \u2014R8OC(O)OR7, \u2014R8OC(O)NR7R7, \u2014R8NR7C(O)R7, \u2014R8NR7C(O)OR7, and \u2014R8NR7C(O)NR7R7;
J is selected from fluoro, chloro, bromo, and iodo;
m is an integer from 0 to 2;
W is \u2014C(O)\u2014 or \u2014C(O)NR7\u2014;
X is N, C\u2014CN or C\u2014C(O)NH2;
X\u2032 is \u2014S\u2014, \u2014N(R6)\u2014, or \u2550C(R3)\u2014;
Z is \u2014S\u2014 or \u2550C(R3)\u2014, with the proviso wherein only one of X\u2032 and Z is \u2550C(R3)\u2014;
Y is selected from a bond, \u2014NH\u2014, \u2014O\u2014, \u2014NR7\u2014, and R8; and
represents a single bond or a double bond.
2. The compound according to claim 1 wherein X is N; X\u2032 is \u2014N(R6)\u2014; and Z is \u2550C(R3)\u2014.
3. The compound according to claim 2 where R6 is selected from the group consisting of methylsulfonyl, phenylsulfonyl, tosyl, pyridin-4-yl, 4-(piperazin-1-ylmethyl)phenyl, 2-aminopyrimidin-5-yl, N-methylpicolinamide, 4-(dimethylamino)methylphenyl, 3-dimethylaminopropyl, and (2-(pyrrolidin-1-yl)ethyl).
4. The compound according to claim 1 wherein X is N; X\u2032 is \u2014S\u2014; and Z is \u2550C(R3)\u2014.
5. The compound according to claim 1 wherein X is N; X\u2032 is \u2550C(R3)\u2014; and Z is \u2014S\u2014.
6. The compound according to any of claims 1-5 wherein R1 is selected from the group consisting of 3-trifluoromethylphenyl, 4-fluoro-3-trifluoromethylphenyl, 4-methyl-3-trifluoromethylphenyl, 4-chloro-3-trifluoromethylphenyl, 4-methoxy-3-trifluoromethylphenyl, 3,4-dimethylphenyl 4-methylphenyl, 3-methylphenyl, 2-methylphenyl, 4-bromophenyl, 3-bromophenyl, 2-bromophenyl, 4-fluorophenyl, 3-fluorophenyl, 2-fluorophenyl, 4-chlorophenyl, 3-chlorophenyl, 2-chlorophenyl and 3,4-dichlorophenyl.
7. The compound according to any of claims 1-5 wherein R2 is selected from the group consisting of 4-methylphenyl, 3-methylphenyl, 2-methylphenyl, 4-aminophenyl, 4-acetamidophenyl, 4-chlorophenyl, 3-chlorophenyl, 2-chlorophenyl, 4-hydroxypiperidin-4-yl, N-methyl-5-picolinamido, N,N-dimethyl-4-carbamoylphenyl, N,N-dimethyl-3-carbamoylphenyl, 4-acetylphenyl, and 3-acetylphenyl.
8. A method for making a compound of formula Ia according to claim 1 and pharmaceutically acceptable salts thereof, comprising
(a) reacting, in the presence of a palladium catalyst, a heterocyclic compound of formula II
with a boronic acid of formula III,
to obtain a compound of formula If,
wherein R11 is \u2014H or \u2014W\u2014R1;
and, step (b) when R11 is H reacting the compound If obtained with an electrophile containing the \u2014W\u2014R1 radical.
9. The method according to claim 8 wherein the electrophile containing the \u2014W\u2014R1 radical is selected from the group of acid chlorides, isocyanates, anhydrides, 1-hydroxybenzotriazole esters, and mixed carboxylic phosphoric acid anhydrides.
10. The method according to claim 8 wherein the heterocyclic compound of formula II is prepared by a process comprising the steps of
(a) reacting a compound of formula VI wherein X\u2032 is \u2014S\u2014 or \u2014N(R6)\u2014,
with a formamidine compound of formula VII
to obtain a compound of formula VIII
and, (b) reacting compound VIII with a chlorinating agent.
11. A pharmaceutical composition comprising a compound according to any of claims 1-7 and a pharmaceutically acceptable carrier.
12. A pharmaceutical composition comprising a compound according to any of claims 1-7 in combination with other kinase-inhibiting pharmaceutical compositions or chemotherapeutic agents, and a pharmaceutically acceptable carrier.
13. A method of inhibiting kinase activity in a mammal comprising administering to a mammal a kinase-inhibiting amount of a compound according to any of claims 1-7.
14. The method of claim 13, wherein the mammal is a human.
15. A method of treating a kinase-dependent condition comprising administering to a subject a kinase-inhibiting amount of a pharmaceutical composition according to any of claims 1-7.
16. A method of treating a B-Raf kinase-dependent condition comprising inflammation or cancer, by administering to a patient a compound of any of claims 1-7.
17. The method of claim 16, wherein the cancer is cancer is selected from the group consisting of breast, kidney, bladder, mouth, larynx, esophagus, stomach, colon, ovary, lung, pancreas, skin, liver, prostate and brain cancer.
18. A method of treating cancer, by administering to a patient a compound of any of claims 1-7.
19. The method of claim 18, wherein the cancer is cancer is selected from the group consisting of breast, kidney, bladder, mouth, larynx, esophagus, stomach, colon, ovary, lung, pancreas, skin, liver, prostate and brain cancer.