CA2671984A1 - New pyridazine derivatives with mch antagonistic activity and medicaments comprising these compounds - Google Patents
New pyridazine derivatives with mch antagonistic activity and medicaments comprising these compounds Download PDFInfo
- Publication number
- CA2671984A1 CA2671984A1 CA002671984A CA2671984A CA2671984A1 CA 2671984 A1 CA2671984 A1 CA 2671984A1 CA 002671984 A CA002671984 A CA 002671984A CA 2671984 A CA2671984 A CA 2671984A CA 2671984 A1 CA2671984 A1 CA 2671984A1
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- CA
- Canada
- Prior art keywords
- alkyl
- group
- amino
- groups
- denotes
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 142
- 230000003042 antagnostic effect Effects 0.000 title abstract description 10
- 150000004892 pyridazines Chemical class 0.000 title description 6
- 239000003814 drug Substances 0.000 title description 5
- 208000008589 Obesity Diseases 0.000 claims abstract description 38
- 235000020824 obesity Nutrition 0.000 claims abstract description 38
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 25
- 206010012601 diabetes mellitus Diseases 0.000 claims abstract description 18
- 206010061428 decreased appetite Diseases 0.000 claims abstract description 9
- 206010006550 Bulimia nervosa Diseases 0.000 claims abstract description 8
- 208000032841 Bulimia Diseases 0.000 claims abstract description 5
- 208000030814 Eating disease Diseases 0.000 claims abstract description 5
- 208000019454 Feeding and Eating disease Diseases 0.000 claims abstract description 5
- 235000014632 disordered eating Nutrition 0.000 claims abstract description 5
- 208000030159 metabolic disease Diseases 0.000 claims abstract description 5
- 206010020710 Hyperphagia Diseases 0.000 claims abstract description 4
- 208000022531 anorexia Diseases 0.000 claims abstract description 4
- -1 aminosulphonyl Chemical group 0.000 claims description 166
- 239000000203 mixture Substances 0.000 claims description 139
- 238000000034 method Methods 0.000 claims description 103
- 239000013543 active substance Substances 0.000 claims description 79
- 150000003839 salts Chemical class 0.000 claims description 78
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 67
- 125000004432 carbon atom Chemical group C* 0.000 claims description 60
- 125000001424 substituent group Chemical group 0.000 claims description 53
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 49
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 48
- 229910052739 hydrogen Inorganic materials 0.000 claims description 43
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 33
- 229910052794 bromium Inorganic materials 0.000 claims description 30
- 125000004122 cyclic group Chemical group 0.000 claims description 29
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 29
- 125000000623 heterocyclic group Chemical group 0.000 claims description 28
- 229910052801 chlorine Inorganic materials 0.000 claims description 27
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 26
- 229910052731 fluorine Inorganic materials 0.000 claims description 25
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 24
- 125000004076 pyridyl group Chemical group 0.000 claims description 22
- 239000005557 antagonist Substances 0.000 claims description 21
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 21
- 125000000217 alkyl group Chemical group 0.000 claims description 20
- 239000000126 substance Substances 0.000 claims description 20
- 230000037396 body weight Effects 0.000 claims description 19
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 18
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 17
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 16
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 16
- 229910052736 halogen Inorganic materials 0.000 claims description 15
- 150000002367 halogens Chemical class 0.000 claims description 15
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 14
- 201000010099 disease Diseases 0.000 claims description 13
- 125000005842 heteroatom Chemical group 0.000 claims description 13
- 229920006395 saturated elastomer Polymers 0.000 claims description 13
- 125000003118 aryl group Chemical group 0.000 claims description 12
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 12
- 229910052740 iodine Inorganic materials 0.000 claims description 12
- 241000124008 Mammalia Species 0.000 claims description 11
- 206010003246 arthritis Diseases 0.000 claims description 11
- 208000035475 disorder Diseases 0.000 claims description 11
- 125000000335 thiazolyl group Chemical group 0.000 claims description 11
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 10
- 208000011775 arteriosclerosis disease Diseases 0.000 claims description 10
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 10
- 239000011737 fluorine Substances 0.000 claims description 10
- 125000001544 thienyl group Chemical group 0.000 claims description 10
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 9
- 206010003210 Arteriosclerosis Diseases 0.000 claims description 9
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 8
- 206010020772 Hypertension Diseases 0.000 claims description 8
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 8
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 8
- 125000002541 furyl group Chemical group 0.000 claims description 8
- 125000002883 imidazolyl group Chemical group 0.000 claims description 8
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 8
- 208000019901 Anxiety disease Diseases 0.000 claims description 7
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 7
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 7
- 208000031226 Hyperlipidaemia Diseases 0.000 claims description 7
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 7
- 239000003085 diluting agent Substances 0.000 claims description 7
- 230000020595 eating behavior Effects 0.000 claims description 7
- 125000001153 fluoro group Chemical group F* 0.000 claims description 7
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 7
- 208000024891 symptom Diseases 0.000 claims description 7
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 6
- 208000002249 Diabetes Complications Diseases 0.000 claims description 6
- 125000002837 carbocyclic group Chemical group 0.000 claims description 6
- 239000000969 carrier Substances 0.000 claims description 6
- 230000000694 effects Effects 0.000 claims description 6
- 125000001841 imino group Chemical group [H]N=* 0.000 claims description 6
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 6
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 6
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 6
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 6
- VRJHQPZVIGNGMX-UHFFFAOYSA-N 4-piperidinone Chemical compound O=C1CCNCC1 VRJHQPZVIGNGMX-UHFFFAOYSA-N 0.000 claims description 5
- 206010012655 Diabetic complications Diseases 0.000 claims description 5
- 208000007271 Substance Withdrawal Syndrome Diseases 0.000 claims description 5
- HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 claims description 5
- 238000001727 in vivo Methods 0.000 claims description 5
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 5
- 125000001960 7 membered carbocyclic group Chemical group 0.000 claims description 4
- 125000003341 7 membered heterocyclic group Chemical group 0.000 claims description 4
- 208000020401 Depressive disease Diseases 0.000 claims description 4
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 4
- 206010046543 Urinary incontinence Diseases 0.000 claims description 4
- 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 claims description 4
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 claims description 4
- 239000008103 glucose Substances 0.000 claims description 4
- 230000001575 pathological effect Effects 0.000 claims description 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 4
- 125000004434 sulfur atom Chemical group 0.000 claims description 4
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 4
- 125000006698 (C1-C3) dialkylamino group Chemical group 0.000 claims description 3
- YHCUZRJTNSWYCY-UHFFFAOYSA-N 2,3,4,7-tetrahydro-1h-azepine Chemical compound C1CNCC=CC1 YHCUZRJTNSWYCY-UHFFFAOYSA-N 0.000 claims description 3
- SMOHMDMTVAYPAI-UHFFFAOYSA-N 2,3,6,7-tetrahydro-1h-azepine Chemical compound C1CC=CCCN1 SMOHMDMTVAYPAI-UHFFFAOYSA-N 0.000 claims description 3
- FTAHXMZRJCZXDL-UHFFFAOYSA-N 3-piperideine Chemical compound C1CC=CCN1 FTAHXMZRJCZXDL-UHFFFAOYSA-N 0.000 claims description 3
- JVQIKJMSUIMUDI-UHFFFAOYSA-N 3-pyrroline Chemical compound C1NCC=C1 JVQIKJMSUIMUDI-UHFFFAOYSA-N 0.000 claims description 3
- 241001421185 Anomis Species 0.000 claims description 3
- 206010006895 Cachexia Diseases 0.000 claims description 3
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 3
- 206010007882 Cellulitis Diseases 0.000 claims description 3
- 206010012289 Dementia Diseases 0.000 claims description 3
- 208000007342 Diabetic Nephropathies Diseases 0.000 claims description 3
- 208000032131 Diabetic Neuropathies Diseases 0.000 claims description 3
- 206010012689 Diabetic retinopathy Diseases 0.000 claims description 3
- 208000027534 Emotional disease Diseases 0.000 claims description 3
- 208000008967 Enuresis Diseases 0.000 claims description 3
- 206010019280 Heart failures Diseases 0.000 claims description 3
- 206010022489 Insulin Resistance Diseases 0.000 claims description 3
- 208000026139 Memory disease Diseases 0.000 claims description 3
- 208000021891 Micturition disease Diseases 0.000 claims description 3
- 201000008736 Systemic mastocytosis Diseases 0.000 claims description 3
- 238000009825 accumulation Methods 0.000 claims description 3
- 125000006598 aminocarbonylamino group Chemical group 0.000 claims description 3
- 125000006615 aromatic heterocyclic group Chemical group 0.000 claims description 3
- ZSIQJIWKELUFRJ-UHFFFAOYSA-N azepane Chemical compound C1CCCNCC1 ZSIQJIWKELUFRJ-UHFFFAOYSA-N 0.000 claims description 3
- 208000033679 diabetic kidney disease Diseases 0.000 claims description 3
- 206010015037 epilepsy Diseases 0.000 claims description 3
- 230000003054 hormonal effect Effects 0.000 claims description 3
- 230000003211 malignant effect Effects 0.000 claims description 3
- 208000008585 mastocytosis Diseases 0.000 claims description 3
- 206010029446 nocturia Diseases 0.000 claims description 3
- 229910052760 oxygen Inorganic materials 0.000 claims description 3
- 230000001850 reproductive effect Effects 0.000 claims description 3
- 208000012201 sexual and gender identity disease Diseases 0.000 claims description 3
- 208000015891 sexual disease Diseases 0.000 claims description 3
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 claims description 3
- 125000001425 triazolyl group Chemical group 0.000 claims description 3
- 125000006559 (C1-C3) alkylamino group Chemical group 0.000 claims description 2
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims description 2
- 125000004575 3-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 2
- 208000000103 Anorexia Nervosa Diseases 0.000 claims description 2
- 208000019022 Mood disease Diseases 0.000 claims description 2
- IYABWNGZIDDRAK-UHFFFAOYSA-N allene Chemical group C=C=C IYABWNGZIDDRAK-UHFFFAOYSA-N 0.000 claims description 2
- 230000036506 anxiety Effects 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 125000004483 piperidin-3-yl group Chemical group N1CC(CCC1)* 0.000 claims description 2
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 2
- 208000019116 sleep disease Diseases 0.000 claims description 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 13
- 125000006528 (C2-C6) alkyl group Chemical group 0.000 claims 9
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims 6
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 5
- 125000004430 oxygen atom Chemical group O* 0.000 claims 2
- 125000006594 (C1-C3) alkylsulfony group Chemical group 0.000 claims 1
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims 1
- 125000003830 C1- C4 alkylcarbonylamino group Chemical group 0.000 claims 1
- 125000003342 alkenyl group Chemical group 0.000 claims 1
- 125000000879 imine group Chemical group 0.000 claims 1
- 210000003932 urinary bladder Anatomy 0.000 claims 1
- 108010047068 Melanin-concentrating hormone receptor Proteins 0.000 abstract description 11
- 229910052721 tungsten Inorganic materials 0.000 abstract description 2
- 102000006953 melanin-concentrating hormone receptor activity proteins Human genes 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 265
- 238000001819 mass spectrum Methods 0.000 description 161
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 144
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 135
- 238000004128 high performance liquid chromatography Methods 0.000 description 91
- 239000011541 reaction mixture Substances 0.000 description 83
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 80
- 230000014759 maintenance of location Effects 0.000 description 77
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 64
- 102400001132 Melanin-concentrating hormone Human genes 0.000 description 59
- 101800002739 Melanin-concentrating hormone Proteins 0.000 description 59
- 239000000243 solution Substances 0.000 description 59
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 58
- ORRDHOMWDPJSNL-UHFFFAOYSA-N melanin concentrating hormone Chemical compound N1C(=O)C(C(C)C)NC(=O)C(CCCNC(N)=N)NC(=O)CNC(=O)C(C(C)C)NC(=O)C(CCSC)NC(=O)C(NC(=O)C(CCCNC(N)=N)NC(=O)C(NC(=O)C(NC(=O)C(N)CC(O)=O)C(C)O)CCSC)CSSCC(C(=O)NC(CC=2C3=CC=CC=C3NC=2)C(=O)NC(CCC(O)=O)C(=O)NC(C(C)C)C(O)=O)NC(=O)C2CCCN2C(=O)C(CCCNC(N)=N)NC(=O)C1CC1=CC=C(O)C=C1 ORRDHOMWDPJSNL-UHFFFAOYSA-N 0.000 description 58
- 235000019439 ethyl acetate Nutrition 0.000 description 56
- 235000002639 sodium chloride Nutrition 0.000 description 56
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 54
- 239000012074 organic phase Substances 0.000 description 47
- 229910052799 carbon Inorganic materials 0.000 description 46
- 239000000741 silica gel Substances 0.000 description 46
- 229910002027 silica gel Inorganic materials 0.000 description 46
- 239000002904 solvent Substances 0.000 description 46
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 45
- WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 41
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 32
- 229910052938 sodium sulfate Inorganic materials 0.000 description 32
- 235000011152 sodium sulphate Nutrition 0.000 description 32
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 30
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 29
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 28
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 28
- 239000001257 hydrogen Substances 0.000 description 27
- 229910052757 nitrogen Inorganic materials 0.000 description 27
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 27
- 239000002585 base Substances 0.000 description 26
- 238000006243 chemical reaction Methods 0.000 description 26
- 230000015572 biosynthetic process Effects 0.000 description 25
- 238000000746 purification Methods 0.000 description 25
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 24
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 24
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 24
- 239000000460 chlorine Substances 0.000 description 24
- 239000003480 eluent Substances 0.000 description 24
- 238000010898 silica gel chromatography Methods 0.000 description 24
- 238000003786 synthesis reaction Methods 0.000 description 24
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 23
- 229940093499 ethyl acetate Drugs 0.000 description 23
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical class [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 21
- 235000011114 ammonium hydroxide Nutrition 0.000 description 21
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 21
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 20
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 20
- 239000003054 catalyst Substances 0.000 description 20
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 20
- 239000002243 precursor Substances 0.000 description 19
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 18
- 238000003477 Sonogashira cross-coupling reaction Methods 0.000 description 17
- 239000002253 acid Substances 0.000 description 17
- 230000002265 prevention Effects 0.000 description 17
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 16
- 239000012071 phase Substances 0.000 description 16
- 210000004027 cell Anatomy 0.000 description 14
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 14
- 229910000027 potassium carbonate Inorganic materials 0.000 description 14
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 13
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 13
- FLAAJFFOTRKBSR-UHFFFAOYSA-N 3-ethynyl-6-phenylmethoxypyridazine Chemical compound N1=NC(C#C)=CC=C1OCC1=CC=CC=C1 FLAAJFFOTRKBSR-UHFFFAOYSA-N 0.000 description 12
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 12
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 12
- 238000012360 testing method Methods 0.000 description 12
- 102000004877 Insulin Human genes 0.000 description 11
- 108090001061 Insulin Proteins 0.000 description 11
- 239000007868 Raney catalyst Substances 0.000 description 11
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 11
- 229910000564 Raney nickel Inorganic materials 0.000 description 11
- 238000002360 preparation method Methods 0.000 description 11
- 239000007787 solid Substances 0.000 description 11
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 11
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 10
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 10
- 102000029828 Melanin-concentrating hormone receptor Human genes 0.000 description 10
- 150000001412 amines Chemical class 0.000 description 10
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 10
- 239000003112 inhibitor Substances 0.000 description 10
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- NILBCFFQQYIKAN-UHFFFAOYSA-N tert-butyl 3-(2-trimethylsilylethynyl)-7,8-dihydro-5h-1,6-naphthyridine-6-carboxylate Chemical compound C1=C(C#C[Si](C)(C)C)C=C2CN(C(=O)OC(C)(C)C)CCC2=N1 NILBCFFQQYIKAN-UHFFFAOYSA-N 0.000 description 1
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- 125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
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Classifications
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- C07D237/10—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP06125763.0 | 2006-12-11 | ||
| EP06125763 | 2006-12-11 | ||
| PCT/EP2007/063575 WO2008071646A1 (en) | 2006-12-11 | 2007-12-10 | New pyridazine derivatives with mch antagonistic activity and medicaments comprising these compounds |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2671984A1 true CA2671984A1 (en) | 2008-06-19 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002671984A Abandoned CA2671984A1 (en) | 2006-12-11 | 2007-12-10 | New pyridazine derivatives with mch antagonistic activity and medicaments comprising these compounds |
Country Status (8)
| Country | Link |
|---|---|
| US (1) | US20100197908A1 (enExample) |
| EP (1) | EP2102171A1 (enExample) |
| JP (1) | JP2010512366A (enExample) |
| AR (1) | AR064293A1 (enExample) |
| CA (1) | CA2671984A1 (enExample) |
| CL (1) | CL2007003580A1 (enExample) |
| TW (1) | TW200831485A (enExample) |
| WO (1) | WO2008071646A1 (enExample) |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2008319397B2 (en) * | 2007-11-01 | 2013-01-31 | Acucela, Inc. | Amine derivative compounds for treating ophthalmic diseases and disorders |
| US9133123B2 (en) | 2010-04-23 | 2015-09-15 | Cytokinetics, Inc. | Certain amino-pyridines and amino-triazines, compositions thereof, and methods for their use |
| AR081331A1 (es) | 2010-04-23 | 2012-08-08 | Cytokinetics Inc | Amino- pirimidinas composiciones de las mismas y metodos para el uso de los mismos |
| AR081626A1 (es) * | 2010-04-23 | 2012-10-10 | Cytokinetics Inc | Compuestos amino-piridazinicos, composiciones farmaceuticas que los contienen y uso de los mismos para tratar trastornos musculares cardiacos y esqueleticos |
| EP2650284A1 (en) * | 2012-04-10 | 2013-10-16 | Merz Pharma GmbH & Co. KGaA | Heterocyclic derivatives as metabotropic glutamate receptor modulators |
| CN104971286A (zh) * | 2015-05-25 | 2015-10-14 | 广东工业大学 | 一种治疗肩腰腿不适症的中药组合物 |
| BR112018077281A2 (pt) * | 2016-07-01 | 2019-04-02 | Boulos & Cooper Pharmaceuticals Pty Ltd | novos antibióticos |
| PE20190414A1 (es) | 2016-08-05 | 2019-03-19 | Boehringer Ingelheim Int | Derivados de oxadiazolopiridina para el uso como inhibidores de ghrelin o-aciltransferasa (goat) |
| MY206745A (en) | 2018-10-29 | 2025-01-04 | Boehringer Ingelheim Int | Pyridinyl sulfonamide derivatives, pharmaceutical compositions and uses thereof |
| JP7425793B2 (ja) | 2018-10-29 | 2024-01-31 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | ピリジニルスルホンアミド誘導体、医薬組成物およびそれらの使用 |
| US11465982B2 (en) | 2019-07-22 | 2022-10-11 | Boehringer Ingelheim International Gmbh | Pyridazines |
| US11485727B2 (en) * | 2019-07-22 | 2022-11-01 | Boehringer Ingelheim International Gmbh | N-methyl, n-(6-(methoxy)pyridazin-3-yl) amine derivatives as autotaxin (ATX) modulators |
| JP7240554B2 (ja) * | 2019-07-22 | 2023-03-15 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 炎症性気道疾患又は線維性疾患の治療のためのオートタキシン(atx)モジュレーターとしてのn-メチル,1-(6-(メトキシ)ピリダジン-3-イル)アミン誘導体 |
| JP7720846B2 (ja) * | 2020-07-08 | 2025-08-08 | 第一三共株式会社 | 1,3-ベンゾジオキソール誘導体の製造方法 |
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| AU7315700A (en) | 1999-09-20 | 2001-04-24 | Takeda Chemical Industries Ltd. | Melanin concentrating hormone antagonist |
| EP1285651B1 (en) | 2000-04-28 | 2010-09-01 | Takeda Pharmaceutical Company Limited | Melanin concentrating hormone antagonists |
| BR0306988A (pt) | 2002-01-18 | 2004-11-23 | Pharmacia Corp | Piridazinonas substituìdas como inibidores de p38 |
| DE60330126D1 (de) | 2002-02-14 | 2009-12-31 | Pharmacia Corp | Substituierte pyridinone als modulatoren für p38 map kinase |
| US6953787B2 (en) * | 2002-04-12 | 2005-10-11 | Arena Pharmaceuticals, Inc. | 5HT2C receptor modulators |
| DE10238865A1 (de) | 2002-08-24 | 2004-03-11 | Boehringer Ingelheim International Gmbh | Neue Carbonsäureamid-Verbindungen mit MCH-antagonistischer Wirkung, diese Verbindungen enthaltende Arzneimittel und Verfahren zu ihrer Herstellung |
| DE10250708A1 (de) | 2002-10-31 | 2004-05-19 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Neue Alkin-Verbindungen mit MCH-antagonistischer Wirkung und diese Verbindungen enthaltende Arzneimittel |
| DE10250743A1 (de) | 2002-10-31 | 2004-05-19 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Neue Amid-Verbindungen mit MCH-antagonistischer Wirkung und diese Verbindungen enthaltende Arzneimittel |
| US7183287B2 (en) | 2003-04-03 | 2007-02-27 | Pharmacia Corporation | Substituted pyrimidinones |
| WO2005007632A1 (en) | 2003-07-18 | 2005-01-27 | Pharmacia Corporation | Substituted pyridazinones as inhibitors of p38 |
| NL1026826C2 (nl) | 2003-08-13 | 2007-01-04 | Pharmacia Corp | Gesubstitueerde pyridinonen. |
| DE10360745A1 (de) | 2003-12-23 | 2005-07-28 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Neue Amid-Verbindungen mit MCH-antagonistischer Wirkung und diese Verbindungen enthaltende Arzneimittel |
| DE102004010893A1 (de) | 2004-03-06 | 2005-09-22 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Neue ß-Ketoamid-Verbindungen mit MCH-antagonistischer Wirkung und diese Verbindungen enthaltende Arzneimittel |
| DE102004017930A1 (de) * | 2004-04-14 | 2005-11-03 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Neue Alkin-Verbindungen mit MCH-antagonistischer Wirkung und diese Verbindungen enthaltende Arzneimittel |
| DE102004017933A1 (de) | 2004-04-14 | 2005-11-03 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Neue Alkin-Verbindungen mit MCH-antagonistischer Wirkung und diese Verbindungen enthaltende Arzneimittel |
| DE102004017934A1 (de) | 2004-04-14 | 2005-11-03 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Neue Alkin-Verbindungen mit MCH-antagonistischer Wirkung und diese Verbindungen enthaltende Arzneimittel |
| DE102004017935A1 (de) | 2004-04-14 | 2005-11-03 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Neue Alkin-Verbindungen mit MCH-antagonistischer Wirkung und diese Verbindungen enthaltende Arzneimittel |
| DE102004017932A1 (de) * | 2004-04-14 | 2005-11-03 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Neue Alkin-Verbindungen mit MCH-antagonistischer Wirkung und diese Verbindungen enthaltende Arzneimittel |
| CA2622944A1 (en) * | 2005-09-30 | 2007-04-12 | F. Hoffmann-La Roche Ag | Diazine azole derivatives, their manufacture and use as pharmaceutical agents |
| US20110039860A1 (en) * | 2008-05-07 | 2011-02-17 | Cangming Yang | Soluble epoxide hydrolase inhibitors, compositions containing such compounds and methods of treatment |
-
2007
- 2007-12-10 TW TW096147077A patent/TW200831485A/zh unknown
- 2007-12-10 CA CA002671984A patent/CA2671984A1/en not_active Abandoned
- 2007-12-10 CL CL2007003580A patent/CL2007003580A1/es unknown
- 2007-12-10 US US12/518,321 patent/US20100197908A1/en not_active Abandoned
- 2007-12-10 EP EP07848015A patent/EP2102171A1/en not_active Withdrawn
- 2007-12-10 JP JP2009540731A patent/JP2010512366A/ja active Pending
- 2007-12-10 WO PCT/EP2007/063575 patent/WO2008071646A1/en not_active Ceased
- 2007-12-11 AR ARP070105552A patent/AR064293A1/es unknown
Also Published As
| Publication number | Publication date |
|---|---|
| US20100197908A1 (en) | 2010-08-05 |
| AR064293A1 (es) | 2009-03-25 |
| TW200831485A (en) | 2008-08-01 |
| JP2010512366A (ja) | 2010-04-22 |
| WO2008071646A1 (en) | 2008-06-19 |
| CL2007003580A1 (es) | 2009-03-27 |
| EP2102171A1 (en) | 2009-09-23 |
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