BRPI0115193B1 - derivados de indolilmaleimida, processo para preparação dos mesmos, bem como composição farmacêutica que os compreende - Google Patents
derivados de indolilmaleimida, processo para preparação dos mesmos, bem como composição farmacêutica que os compreende Download PDFInfo
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- BRPI0115193B1 BRPI0115193B1 BRPI0115193A BR0115193A BRPI0115193B1 BR PI0115193 B1 BRPI0115193 B1 BR PI0115193B1 BR PI0115193 A BRPI0115193 A BR PI0115193A BR 0115193 A BR0115193 A BR 0115193A BR PI0115193 B1 BRPI0115193 B1 BR PI0115193B1
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- 239000008194 pharmaceutical composition Substances 0.000 title claims description 9
- 238000004519 manufacturing process Methods 0.000 title claims description 5
- WIQRSJOCVVPMPS-UHFFFAOYSA-N 3-(1h-indol-2-yl)pyrrole-2,5-dione Chemical class O=C1NC(=O)C(C=2NC3=CC=CC=C3C=2)=C1 WIQRSJOCVVPMPS-UHFFFAOYSA-N 0.000 title abstract description 5
- 230000001404 mediated effect Effects 0.000 claims abstract description 9
- 230000001154 acute effect Effects 0.000 claims abstract description 7
- 230000001684 chronic effect Effects 0.000 claims abstract description 7
- 208000027866 inflammatory disease Diseases 0.000 claims abstract description 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 6
- 230000002265 prevention Effects 0.000 claims abstract description 6
- 208000023275 Autoimmune disease Diseases 0.000 claims abstract description 5
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 4
- 201000011510 cancer Diseases 0.000 claims abstract description 4
- 150000001875 compounds Chemical class 0.000 claims description 150
- 125000000217 alkyl group Chemical group 0.000 claims description 34
- 150000003839 salts Chemical class 0.000 claims description 23
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 20
- 125000001424 substituent group Chemical group 0.000 claims description 15
- 229910052736 halogen Inorganic materials 0.000 claims description 11
- 150000002367 halogens Chemical class 0.000 claims description 11
- 230000002757 inflammatory effect Effects 0.000 claims description 11
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 10
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 9
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 7
- 210000001744 T-lymphocyte Anatomy 0.000 claims description 6
- 229910052801 chlorine Inorganic materials 0.000 claims description 6
- 229910052731 fluorine Inorganic materials 0.000 claims description 6
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 6
- 208000035475 disorder Diseases 0.000 claims description 5
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 4
- 159000000021 acetate salts Chemical class 0.000 claims description 4
- 239000003085 diluting agent Substances 0.000 claims description 4
- 201000010099 disease Diseases 0.000 claims description 4
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 4
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 3
- 201000004624 Dermatitis Diseases 0.000 claims description 3
- 125000003545 alkoxy group Chemical group 0.000 claims description 3
- 206010012601 diabetes mellitus Diseases 0.000 claims description 3
- 125000004193 piperazinyl group Chemical group 0.000 claims description 3
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 claims description 2
- 201000001320 Atherosclerosis Diseases 0.000 claims description 2
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 2
- 206010009900 Colitis ulcerative Diseases 0.000 claims description 2
- 208000035473 Communicable disease Diseases 0.000 claims description 2
- 208000011231 Crohn disease Diseases 0.000 claims description 2
- 206010012438 Dermatitis atopic Diseases 0.000 claims description 2
- 206010012442 Dermatitis contact Diseases 0.000 claims description 2
- 208000030836 Hashimoto thyroiditis Diseases 0.000 claims description 2
- 206010019280 Heart failures Diseases 0.000 claims description 2
- 208000032456 Hemorrhagic Shock Diseases 0.000 claims description 2
- 206010020772 Hypertension Diseases 0.000 claims description 2
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 2
- 206010022680 Intestinal ischaemia Diseases 0.000 claims description 2
- 206010067125 Liver injury Diseases 0.000 claims description 2
- 208000004852 Lung Injury Diseases 0.000 claims description 2
- 201000004681 Psoriasis Diseases 0.000 claims description 2
- 208000001647 Renal Insufficiency Diseases 0.000 claims description 2
- 208000013616 Respiratory Distress Syndrome Diseases 0.000 claims description 2
- 206010039793 Seborrhoeic dermatitis Diseases 0.000 claims description 2
- 206010040070 Septic Shock Diseases 0.000 claims description 2
- 206010049771 Shock haemorrhagic Diseases 0.000 claims description 2
- 208000021386 Sjogren Syndrome Diseases 0.000 claims description 2
- 208000006011 Stroke Diseases 0.000 claims description 2
- 206010069363 Traumatic lung injury Diseases 0.000 claims description 2
- 206010044541 Traumatic shock Diseases 0.000 claims description 2
- 201000006704 Ulcerative Colitis Diseases 0.000 claims description 2
- 206010046851 Uveitis Diseases 0.000 claims description 2
- 206010053648 Vascular occlusion Diseases 0.000 claims description 2
- 208000011341 adult acute respiratory distress syndrome Diseases 0.000 claims description 2
- 201000000028 adult respiratory distress syndrome Diseases 0.000 claims description 2
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- 201000008937 atopic dermatitis Diseases 0.000 claims description 2
- 208000010668 atopic eczema Diseases 0.000 claims description 2
- 208000015114 central nervous system disease Diseases 0.000 claims description 2
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 2
- 230000001434 glomerular Effects 0.000 claims description 2
- 231100000753 hepatic injury Toxicity 0.000 claims description 2
- 229910052740 iodine Inorganic materials 0.000 claims description 2
- 208000001875 irritant dermatitis Diseases 0.000 claims description 2
- 208000028867 ischemia Diseases 0.000 claims description 2
- 206010023332 keratitis Diseases 0.000 claims description 2
- 201000010666 keratoconjunctivitis Diseases 0.000 claims description 2
- 201000006370 kidney failure Diseases 0.000 claims description 2
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- 208000037803 restenosis Diseases 0.000 claims description 2
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- 230000036303 septic shock Effects 0.000 claims description 2
- 201000000596 systemic lupus erythematosus Diseases 0.000 claims description 2
- 238000011200 topical administration Methods 0.000 claims description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
- 208000021331 vascular occlusion disease Diseases 0.000 claims description 2
- JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 claims 1
- 206010063837 Reperfusion injury Diseases 0.000 claims 1
- 125000004414 alkyl thio group Chemical group 0.000 claims 1
- MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 claims 1
- 239000000825 pharmaceutical preparation Substances 0.000 claims 1
- 229940127557 pharmaceutical product Drugs 0.000 claims 1
- -1 naphtho Chemical group 0.000 abstract description 28
- 125000000714 pyrimidinyl group Chemical group 0.000 abstract description 2
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 abstract 1
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 abstract 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 abstract 1
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 171
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 62
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 62
- 235000019439 ethyl acetate Nutrition 0.000 description 59
- 239000000243 solution Substances 0.000 description 55
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 54
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 38
- 238000000034 method Methods 0.000 description 37
- 239000000203 mixture Substances 0.000 description 36
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 32
- 239000011541 reaction mixture Substances 0.000 description 26
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 24
- 239000007858 starting material Substances 0.000 description 23
- 238000012360 testing method Methods 0.000 description 23
- 230000002829 reductive effect Effects 0.000 description 22
- 229920006395 saturated elastomer Polymers 0.000 description 21
- 239000007787 solid Substances 0.000 description 21
- 238000005160 1H NMR spectroscopy Methods 0.000 description 20
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 19
- 239000000741 silica gel Substances 0.000 description 19
- 229910002027 silica gel Inorganic materials 0.000 description 19
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 19
- 235000017557 sodium bicarbonate Nutrition 0.000 description 19
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 18
- 239000010410 layer Substances 0.000 description 17
- 239000012044 organic layer Substances 0.000 description 17
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 16
- 238000006243 chemical reaction Methods 0.000 description 16
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 16
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 15
- 239000011734 sodium Substances 0.000 description 14
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 13
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 13
- 102000003923 Protein Kinase C Human genes 0.000 description 13
- 108090000315 Protein Kinase C Proteins 0.000 description 13
- 125000000623 heterocyclic group Chemical group 0.000 description 13
- 239000002904 solvent Substances 0.000 description 13
- 229910052799 carbon Inorganic materials 0.000 description 12
- 210000004027 cell Anatomy 0.000 description 12
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 10
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 10
- 238000003556 assay Methods 0.000 description 10
- 239000012074 organic phase Substances 0.000 description 10
- 239000000047 product Substances 0.000 description 10
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 238000010898 silica gel chromatography Methods 0.000 description 9
- 229910052786 argon Inorganic materials 0.000 description 8
- 150000001721 carbon Chemical group 0.000 description 8
- 229910052757 nitrogen Inorganic materials 0.000 description 8
- 239000000725 suspension Substances 0.000 description 8
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 7
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 7
- 239000002253 acid Substances 0.000 description 7
- 230000005764 inhibitory process Effects 0.000 description 7
- 125000004433 nitrogen atom Chemical group N* 0.000 description 7
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- 229910001868 water Inorganic materials 0.000 description 7
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 6
- 125000002947 alkylene group Chemical group 0.000 description 6
- 239000012267 brine Substances 0.000 description 6
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 6
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- 229910052739 hydrogen Inorganic materials 0.000 description 6
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- VFIJGAWYVXDYLK-UHFFFAOYSA-N methyl 2-(1h-indol-3-yl)-2-oxoacetate Chemical compound C1=CC=C2C(C(=O)C(=O)OC)=CNC2=C1 VFIJGAWYVXDYLK-UHFFFAOYSA-N 0.000 description 6
- 229910052760 oxygen Inorganic materials 0.000 description 6
- 239000002953 phosphate buffered saline Substances 0.000 description 6
- 239000000843 powder Substances 0.000 description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 5
- 230000001028 anti-proliverative effect Effects 0.000 description 5
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- 238000001914 filtration Methods 0.000 description 5
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- PHEDXBVPIONUQT-RGYGYFBISA-N phorbol 13-acetate 12-myristate Chemical compound C([C@]1(O)C(=O)C(C)=C[C@H]1[C@@]1(O)[C@H](C)[C@H]2OC(=O)CCCCCCCCCCCCC)C(CO)=C[C@H]1[C@H]1[C@]2(OC(C)=O)C1(C)C PHEDXBVPIONUQT-RGYGYFBISA-N 0.000 description 5
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- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 5
- VGLZGJAGMYELEB-UHFFFAOYSA-N 2-(2-chloroquinolin-4-yl)acetamide Chemical compound C1=CC=C2C(CC(=O)N)=CC(Cl)=NC2=C1 VGLZGJAGMYELEB-UHFFFAOYSA-N 0.000 description 4
- KLOWIXPCHFPKSU-UHFFFAOYSA-N 2-[3-(4-methylpiperazin-1-yl)-5,6,7,8-tetrahydronaphthalen-1-yl]acetamide Chemical compound C1CN(C)CCN1C1=CC(CC(N)=O)=C(CCCC2)C2=C1 KLOWIXPCHFPKSU-UHFFFAOYSA-N 0.000 description 4
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 4
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 4
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 108060001084 Luciferase Proteins 0.000 description 4
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- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 4
- 102000001253 Protein Kinase Human genes 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
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- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 4
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 4
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- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 4
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- 125000004195 4-methylpiperazin-1-yl group Chemical group [H]C([H])([H])N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
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- 125000000814 indol-3-yl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([H])=C([*])C2=C1[H] 0.000 description 3
- PGHMRUGBZOYCAA-UHFFFAOYSA-N ionomycin Natural products O1C(CC(O)C(C)C(O)C(C)C=CCC(C)CC(C)C(O)=CC(=O)C(C)CC(C)CC(CCC(O)=O)C)CCC1(C)C1OC(C)(C(C)O)CC1 PGHMRUGBZOYCAA-UHFFFAOYSA-N 0.000 description 3
- PGHMRUGBZOYCAA-ADZNBVRBSA-N ionomycin Chemical compound O1[C@H](C[C@H](O)[C@H](C)[C@H](O)[C@H](C)/C=C/C[C@@H](C)C[C@@H](C)C(/O)=C/C(=O)[C@@H](C)C[C@@H](C)C[C@@H](CCC(O)=O)C)CC[C@@]1(C)[C@@H]1O[C@](C)([C@@H](C)O)CC1 PGHMRUGBZOYCAA-ADZNBVRBSA-N 0.000 description 3
- IZDROVVXIHRYMH-UHFFFAOYSA-N methanesulfonic anhydride Chemical compound CS(=O)(=O)OS(C)(=O)=O IZDROVVXIHRYMH-UHFFFAOYSA-N 0.000 description 3
- MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 3
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- 230000004083 survival effect Effects 0.000 description 3
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- NHBKXEKEPDILRR-UHFFFAOYSA-N 2,3-bis(butanoylsulfanyl)propyl butanoate Chemical compound CCCC(=O)OCC(SC(=O)CCC)CSC(=O)CCC NHBKXEKEPDILRR-UHFFFAOYSA-N 0.000 description 2
- TUQSVSYUEBNNKQ-UHFFFAOYSA-N 2,4-dichloroquinazoline Chemical compound C1=CC=CC2=NC(Cl)=NC(Cl)=C21 TUQSVSYUEBNNKQ-UHFFFAOYSA-N 0.000 description 2
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
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- C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
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| US24640000P | 2000-11-07 | 2000-11-07 | |
| US28370501P | 2001-04-13 | 2001-04-13 | |
| PCT/EP2001/012785 WO2002038561A1 (en) | 2000-11-07 | 2001-11-05 | Indolylmaleimide derivatives as protein kinase c inhibitors |
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| BR0115193A BR0115193A (pt) | 2004-02-03 |
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| BRPI0115193A BRPI0115193B1 (pt) | 2000-11-07 | 2001-11-05 | derivados de indolilmaleimida, processo para preparação dos mesmos, bem como composição farmacêutica que os compreende |
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| MX2015005737A (es) | 2012-11-07 | 2015-09-16 | Novartis Ag | Derivados de indol sustituido. |
| TW201422625A (zh) | 2012-11-26 | 2014-06-16 | Novartis Ag | 二氫－吡啶并－□衍生物之固體形式 |
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