CA3186217A1 - Tetrahydropyrazolo-pyrazinyl-dihydroimidazolone or tetrahydropyrazolo-pyridinyl-dihydroimidazolone compounds and methods of using same - Google Patents
Tetrahydropyrazolo-pyrazinyl-dihydroimidazolone or tetrahydropyrazolo-pyridinyl-dihydroimidazolone compounds and methods of using sameInfo
- Publication number
- CA3186217A1 CA3186217A1 CA3186217A CA3186217A CA3186217A1 CA 3186217 A1 CA3186217 A1 CA 3186217A1 CA 3186217 A CA3186217 A CA 3186217A CA 3186217 A CA3186217 A CA 3186217A CA 3186217 A1 CA3186217 A1 CA 3186217A1
- Authority
- CA
- Canada
- Prior art keywords
- alkyl
- compound
- butyl
- alkoxy
- halogen
- 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.)
- Pending
Links
- 238000000034 method Methods 0.000 title claims abstract description 63
- DLXWQDKMPJRDRU-UHFFFAOYSA-N 3-(2,3,3a,4-tetrahydropyrazolo[3,4-b]pyrazin-1-yl)-1H-imidazol-2-one Chemical compound O=C(NC=C1)N1N1NCC2NC=CN=C12 DLXWQDKMPJRDRU-UHFFFAOYSA-N 0.000 title 1
- BEJNFSHENVLWBC-UHFFFAOYSA-N 3-(2,3,3a,4-tetrahydropyrazolo[4,3-b]pyridin-1-yl)-1H-imidazol-2-one Chemical class O=C(NC=C1)N1N1NCC2NC=CC=C12 BEJNFSHENVLWBC-UHFFFAOYSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 339
- 102000007446 Glucagon-Like Peptide-1 Receptor Human genes 0.000 claims abstract description 108
- 108010086246 Glucagon-Like Peptide-1 Receptor Proteins 0.000 claims abstract description 108
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 88
- 150000003839 salts Chemical class 0.000 claims abstract description 80
- 239000000651 prodrug Substances 0.000 claims abstract description 79
- 229940002612 prodrug Drugs 0.000 claims abstract description 79
- 239000012453 solvate Substances 0.000 claims abstract description 61
- 201000010099 disease Diseases 0.000 claims abstract description 45
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 33
- -1 oxadiazolonyl Chemical group 0.000 claims description 259
- 125000001424 substituent group Chemical group 0.000 claims description 212
- 229910052736 halogen Inorganic materials 0.000 claims description 204
- 150000002367 halogens Chemical class 0.000 claims description 204
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 174
- 125000003545 alkoxy group Chemical group 0.000 claims description 153
- 125000001188 haloalkyl group Chemical group 0.000 claims description 147
- 125000005842 heteroatom Chemical group 0.000 claims description 127
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 124
- 125000001072 heteroaryl group Chemical group 0.000 claims description 121
- 125000000623 heterocyclic group Chemical group 0.000 claims description 75
- 125000000217 alkyl group Chemical group 0.000 claims description 66
- 208000035475 disorder Diseases 0.000 claims description 43
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 38
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 38
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 36
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 34
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 34
- 125000003003 spiro group Chemical group 0.000 claims description 29
- 229910052799 carbon Inorganic materials 0.000 claims description 24
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 23
- 208000008338 non-alcoholic fatty liver disease Diseases 0.000 claims description 23
- 239000003814 drug Substances 0.000 claims description 22
- 125000004432 carbon atom Chemical group C* 0.000 claims description 19
- 125000004737 (C1-C6) haloalkoxy group Chemical group 0.000 claims description 18
- 206010012601 diabetes mellitus Diseases 0.000 claims description 17
- 230000001404 mediated effect Effects 0.000 claims description 17
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 16
- 206010053219 non-alcoholic steatohepatitis Diseases 0.000 claims description 15
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 14
- 208000019423 liver disease Diseases 0.000 claims description 12
- 239000003085 diluting agent Substances 0.000 claims description 11
- 208000008589 Obesity Diseases 0.000 claims description 9
- 125000004857 imidazopyridinyl group Chemical group N1C(=NC2=C1C=CC=N2)* 0.000 claims description 9
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 9
- 238000004519 manufacturing process Methods 0.000 claims description 9
- 235000020824 obesity Nutrition 0.000 claims description 9
- 229910052739 hydrogen Inorganic materials 0.000 claims description 7
- 229910052760 oxygen Inorganic materials 0.000 claims description 6
- 125000004076 pyridyl group Chemical group 0.000 claims description 6
- 229910052717 sulfur Inorganic materials 0.000 claims description 6
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 6
- 206010012289 Dementia Diseases 0.000 claims description 5
- 208000007342 Diabetic Nephropathies Diseases 0.000 claims description 5
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 5
- 208000033679 diabetic kidney disease Diseases 0.000 claims description 5
- 125000004767 (C1-C4) haloalkoxy group Chemical group 0.000 claims description 4
- 201000001320 Atherosclerosis Diseases 0.000 claims description 4
- 206010007559 Cardiac failure congestive Diseases 0.000 claims description 4
- 206010019280 Heart failures Diseases 0.000 claims description 4
- 208000035150 Hypercholesterolemia Diseases 0.000 claims description 4
- 208000031226 Hyperlipidaemia Diseases 0.000 claims description 4
- 206010020772 Hypertension Diseases 0.000 claims description 4
- 206010033307 Overweight Diseases 0.000 claims description 4
- 208000018737 Parkinson disease Diseases 0.000 claims description 4
- 208000006011 Stroke Diseases 0.000 claims description 4
- 206010003119 arrhythmia Diseases 0.000 claims description 4
- 208000029078 coronary artery disease Diseases 0.000 claims description 4
- 125000001715 oxadiazolyl group Chemical group 0.000 claims description 4
- 125000002971 oxazolyl group Chemical group 0.000 claims description 4
- 125000001113 thiadiazolyl group Chemical group 0.000 claims description 4
- 125000000335 thiazolyl group Chemical group 0.000 claims description 4
- 208000002249 Diabetes Complications Diseases 0.000 claims description 3
- 206010012655 Diabetic complications Diseases 0.000 claims description 3
- 125000001786 isothiazolyl group Chemical group 0.000 claims description 3
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 3
- 208000002705 Glucose Intolerance Diseases 0.000 claims description 2
- 201000008247 brain infarction Diseases 0.000 claims description 2
- 206010008118 cerebral infarction Diseases 0.000 claims description 2
- 201000009104 prediabetes syndrome Diseases 0.000 claims description 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 19
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims 1
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 10
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 222
- 239000000543 intermediate Substances 0.000 description 206
- 239000000203 mixture Substances 0.000 description 185
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 167
- 229910052731 fluorine Inorganic materials 0.000 description 160
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 156
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 154
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 154
- 239000000460 chlorine Substances 0.000 description 145
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 145
- 229910052801 chlorine Inorganic materials 0.000 description 144
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 137
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 132
- 239000000243 solution Substances 0.000 description 119
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 100
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 100
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 81
- 125000003707 hexyloxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 71
- 239000011541 reaction mixture Substances 0.000 description 70
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 67
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 65
- 239000012044 organic layer Substances 0.000 description 60
- 239000004698 Polyethylene Substances 0.000 description 52
- 229910052938 sodium sulfate Inorganic materials 0.000 description 52
- 235000011152 sodium sulphate Nutrition 0.000 description 52
- 239000012267 brine Substances 0.000 description 51
- 229910052794 bromium Inorganic materials 0.000 description 51
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 51
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 48
- 238000006243 chemical reaction Methods 0.000 description 46
- 125000002619 bicyclic group Chemical group 0.000 description 42
- 238000003786 synthesis reaction Methods 0.000 description 42
- 239000000126 substance Substances 0.000 description 40
- 230000015572 biosynthetic process Effects 0.000 description 38
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 36
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 33
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 32
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 28
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 28
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 26
- 239000012043 crude product Substances 0.000 description 25
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 24
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 24
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 24
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 24
- 239000002904 solvent Substances 0.000 description 24
- 125000004247 indolizin-1-yl group Chemical group [H]C1=C([H])C(*)=C2C([H])=C([H])C([H])=C([H])N12 0.000 description 23
- 239000000741 silica gel Substances 0.000 description 23
- 229910002027 silica gel Inorganic materials 0.000 description 23
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 21
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 21
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
- 239000003795 chemical substances by application Substances 0.000 description 21
- 239000000706 filtrate Substances 0.000 description 21
- 238000011282 treatment Methods 0.000 description 19
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 18
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 17
- 229910052757 nitrogen Inorganic materials 0.000 description 17
- CTQPPUPWHLGKOB-UHFFFAOYSA-N 4h-oxadiazol-5-one Chemical compound O=C1CN=NO1 CTQPPUPWHLGKOB-UHFFFAOYSA-N 0.000 description 16
- 239000012071 phase Substances 0.000 description 16
- 230000002829 reductive effect Effects 0.000 description 16
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 15
- 150000001721 carbon Chemical group 0.000 description 15
- 229910002091 carbon monoxide Inorganic materials 0.000 description 14
- 229910000027 potassium carbonate Inorganic materials 0.000 description 14
- 229920006395 saturated elastomer Polymers 0.000 description 14
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 14
- 238000003818 flash chromatography Methods 0.000 description 13
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 13
- 239000007787 solid Substances 0.000 description 13
- 230000001225 therapeutic effect Effects 0.000 description 13
- 239000012074 organic phase Substances 0.000 description 12
- 235000015320 potassium carbonate Nutrition 0.000 description 12
- 101150041968 CDC13 gene Proteins 0.000 description 11
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 11
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 11
- 238000005481 NMR spectroscopy Methods 0.000 description 11
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 11
- 230000003213 activating effect Effects 0.000 description 11
- 150000002148 esters Chemical class 0.000 description 11
- 125000004538 indolizin-3-yl group Chemical group C=1C=C(N2C=CC=CC12)* 0.000 description 11
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 11
- 238000010898 silica gel chromatography Methods 0.000 description 11
- 230000004936 stimulating effect Effects 0.000 description 11
- WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 11
- 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 description 10
- 238000004440 column chromatography Methods 0.000 description 10
- 239000003937 drug carrier Substances 0.000 description 10
- PXHVJJICTQNCMI-UHFFFAOYSA-N nickel Substances [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 10
- 238000002360 preparation method Methods 0.000 description 10
- KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 9
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 9
- 125000004429 atom Chemical group 0.000 description 9
- 229910052796 boron Inorganic materials 0.000 description 9
- 229910002092 carbon dioxide Inorganic materials 0.000 description 9
- 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 9
- 238000009472 formulation Methods 0.000 description 9
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- DTHNMHAUYICORS-KTKZVXAJSA-N Glucagon-like peptide 1 Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1N=CNC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 DTHNMHAUYICORS-KTKZVXAJSA-N 0.000 description 8
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 8
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 8
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 8
- 125000003118 aryl group Chemical group 0.000 description 8
- 239000013078 crystal Substances 0.000 description 8
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 8
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- 238000005160 1H NMR spectroscopy Methods 0.000 description 7
- PCJFEVUKVKQSSL-UHFFFAOYSA-N 2h-1,2,4-oxadiazol-5-one Chemical compound O=C1N=CNO1 PCJFEVUKVKQSSL-UHFFFAOYSA-N 0.000 description 7
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 7
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- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 5
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- 125000002950 monocyclic group Chemical group 0.000 description 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- 238000002560 therapeutic procedure Methods 0.000 description 5
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 4
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/437—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
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- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/444—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
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- A—HUMAN NECESSITIES
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/4985—Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
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- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
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- C07D—HETEROCYCLIC COMPOUNDS
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| JOP20190060A1 (ar) | 2016-09-26 | 2019-03-26 | Chugai Pharmaceutical Co Ltd | مشتق بيرازولو بيريدين له تأثير مساعد لمستقبل glp-1 |
| EP4211139A4 (en) * | 2020-09-10 | 2024-12-18 | Gasherbrum Bio, Inc. | HETEROCYCLIC GLP-1 AGONISTS |
| US12479854B2 (en) | 2021-07-29 | 2025-11-25 | Enanta Pharmaceuticals, Inc. | Spiropyrrolidine derived antiviral agents |
| WO2023016546A1 (en) * | 2021-08-12 | 2023-02-16 | Gasherbrum Bio, Inc. | Heterocyclic glp-1 agonists |
| US20230150998A1 (en) | 2021-09-27 | 2023-05-18 | Terns Pharmaceuticals, Inc. | Compounds as glp-1r agonists |
| US12024507B2 (en) | 2021-10-25 | 2024-07-02 | Terns Pharmaceuticals, Inc. | Compounds as GLP-1R agonists |
| KR20240150488A (ko) | 2022-02-23 | 2024-10-15 | 테른스 파마슈티칼스, 인크. | Glp-1r 작용제로서의 화합물 |
| CN116003403B (zh) * | 2022-11-20 | 2024-07-23 | 药康众拓(北京)医药科技有限公司 | 一种氘代吲唑类化合物、药物组合物及其应用 |
| CN120457107A (zh) * | 2022-12-15 | 2025-08-08 | 维泰瑞隆有限公司 | Sarm1调节剂、其制备和用途 |
| CN121002015A (zh) * | 2023-01-17 | 2025-11-21 | 重庆复尚源创医药技术有限公司 | Glp-1r激动剂及其用途 |
| KR20250168210A (ko) | 2023-02-16 | 2025-12-02 | 가셔브룸 바이오, 인크. | 헤테로시클릭 glp-1 효능제 |
| KR20250166323A (ko) | 2023-04-07 | 2025-11-27 | 테른스 파마슈티칼스, 인크. | 간 장애 또는 심장대사 질환의 치료에 사용하기 위한 thr베타 효현제 및 glp-1r 효현제를 포함하는 조합 |
| TW202502322A (zh) * | 2023-06-29 | 2025-01-16 | 大陸商韋恩生物科技有限公司 | 一種glp-1受體激動劑及其製備方法和用途 |
| TW202506108A (zh) * | 2023-06-30 | 2025-02-16 | 大陸商正大天晴藥業集團股份有限公司 | 含多稠環結構的化合物 |
| WO2025011664A1 (zh) * | 2023-07-12 | 2025-01-16 | 歌礼制药(中国)有限公司 | Glp-1r激动剂的制剂及其制备方法 |
| TW202508571A (zh) * | 2023-07-28 | 2025-03-01 | 大陸商上海翰森生物醫藥科技有限公司 | 一種苯并含氮雜環類衍生物調節劑、其製備方法和應用 |
| WO2025026436A1 (zh) * | 2023-08-02 | 2025-02-06 | 韦恩生物科技有限公司 | 一种含氮并环化合物及其制备方法和用途 |
| WO2025045208A1 (en) * | 2023-08-31 | 2025-03-06 | Gasherbrum Bio, Inc. | Heteroaryl-heterocycloalkyl-based glp-1 agonists |
| CN120981457A (zh) | 2023-09-14 | 2025-11-18 | 歌礼制药(中国)有限公司 | Glp-1r激动剂及其治疗方法 |
| WO2025097835A1 (zh) * | 2023-11-10 | 2025-05-15 | 重庆医药工业研究院有限责任公司 | 一种glp-1r激动剂化合物及其应用 |
| WO2025103443A1 (zh) * | 2023-11-16 | 2025-05-22 | 海思科医药集团股份有限公司 | 一种咪唑-2-酮衍生物及其在医药上的应用 |
| WO2025108361A1 (zh) * | 2023-11-21 | 2025-05-30 | 江苏恒瑞医药股份有限公司 | 杂环类化合物、其制备方法及其在医药上的应用 |
| US12291530B1 (en) | 2023-11-24 | 2025-05-06 | Ascletis Pharma (China) Co., Limited | GLP-1R agonist and therapeutic method thereof |
| WO2025119206A1 (en) * | 2023-12-05 | 2025-06-12 | Fortvita Biologics Inc. | Glp-1 receptor targeting compounds and uses thereof |
| WO2025124357A1 (zh) * | 2023-12-14 | 2025-06-19 | 广东众生睿创生物科技有限公司 | 一种杂环glp-1受体激动剂及其应用 |
| TW202527937A (zh) * | 2023-12-22 | 2025-07-16 | 大陸商石藥集團百克（山東）生物製藥股份有限公司 | 多環化合物及其用途 |
| CN117447493A (zh) * | 2023-12-25 | 2024-01-26 | 药康众拓(北京)医药科技有限公司 | 氘代吲哚嗪类化合物、药物组合物及其应用 |
| WO2025148997A1 (zh) * | 2024-01-10 | 2025-07-17 | 海思科医药集团股份有限公司 | 一种四氢吡啶并吡唑衍生物及其在医药上的应用 |
| WO2025158275A1 (en) | 2024-01-24 | 2025-07-31 | Pfizer Inc. | Combination therapy using glucose-dependent insulinotropic polypeptide receptor antagonist compounds and glp-1 receptor agonist compounds |
| WO2025162065A1 (zh) * | 2024-01-30 | 2025-08-07 | 海创药业股份有限公司 | 一种具有glp-1受体激动剂作用的小分子化合物及其用途 |
| WO2025175249A1 (en) | 2024-02-14 | 2025-08-21 | Olema Pharmaceuticals, Inc. | Estrogen receptor modulators and uses thereof |
| WO2025176130A1 (zh) * | 2024-02-19 | 2025-08-28 | 上海壹迪生物技术有限公司 | 一种含吡唑并环类化合物、其药物组合物及其用途 |
| WO2025189141A1 (en) | 2024-03-08 | 2025-09-12 | Annapurna Bio, Inc. | Methods for treating obesity and increasing weight loss |
| US20250304572A1 (en) * | 2024-03-29 | 2025-10-02 | Biomea Fusion, Inc. | Heterocyclic glp-1r agonists |
| WO2025209515A1 (zh) * | 2024-04-03 | 2025-10-09 | 广州市联瑞制药有限公司 | 一种glp-1受体激动剂及其制备方法和应用 |
| WO2025237355A1 (zh) * | 2024-05-17 | 2025-11-20 | 成都地奥九泓制药厂 | 一种glp-1受体激动剂化合物、其制备方法及其应用 |
| WO2025247390A1 (zh) * | 2024-05-31 | 2025-12-04 | 福佑泰生物制药公司 | 可用作glp-1r激动剂的杂双环化合物 |
| WO2025259825A1 (en) | 2024-06-12 | 2025-12-18 | Eli Lilly And Company | Glp-1 npa therapies for maintaining body weight loss or reduced hba1c levels following a prior glp-1 ra treatment |
| CN119100966B (zh) * | 2024-09-02 | 2025-09-09 | 上海毕得医药科技股份有限公司 | 一种溴代吡咯甲酸甲酯的合成方法 |
| CN120309500B (zh) * | 2025-06-19 | 2025-08-15 | 南昌大学 | 奥格列龙原料中间体及合成方法与奥格列龙原料合成方法 |
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| US4522811A (en) | 1982-07-08 | 1985-06-11 | Syntex (U.S.A.) Inc. | Serial injection of muramyldipeptides and liposomes enhances the anti-infective activity of muramyldipeptides |
| EP2963013A4 (en) * | 2013-02-27 | 2016-09-14 | Shionogi & Co | INDOLE AND AZAINDOLE DERIVATIVES HAVING AMPK ACTIVATION ACTIVITY EACH |
| JOP20190060A1 (ar) * | 2016-09-26 | 2019-03-26 | Chugai Pharmaceutical Co Ltd | مشتق بيرازولو بيريدين له تأثير مساعد لمستقبل glp-1 |
| JP7461104B2 (ja) * | 2017-11-29 | 2024-04-03 | 中外製薬株式会社 | Ｇｌｐ－１受容体アゴニスト作用を持つピラゾロピリジン誘導体を含有する医薬組成物 |
| JP2021514982A (ja) | 2018-02-28 | 2021-06-17 | ノバルティス アーゲー | インドール−２−カルボニル化合物及びｂ型肝炎治療のためのそれらの使用 |
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