KR102408272B1 - 베타-3 아드레날린성 수용체와 관련된 장애의 치료 또는 예방에 유용한 베타-3 아드레날린성 수용체의 조정제 - Google Patents
베타-3 아드레날린성 수용체와 관련된 장애의 치료 또는 예방에 유용한 베타-3 아드레날린성 수용체의 조정제 Download PDFInfo
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- KR102408272B1 KR102408272B1 KR1020227004041A KR20227004041A KR102408272B1 KR 102408272 B1 KR102408272 B1 KR 102408272B1 KR 1020227004041 A KR1020227004041 A KR 1020227004041A KR 20227004041 A KR20227004041 A KR 20227004041A KR 102408272 B1 KR102408272 B1 KR 102408272B1
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- methyl
- oxa
- azaspiro
- phenyl
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- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 101
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- 230000002526 effect on cardiovascular system Effects 0.000 claims abstract description 16
- 208000010125 myocardial infarction Diseases 0.000 claims abstract description 14
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- 231100000234 hepatic damage Toxicity 0.000 claims abstract description 8
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- 230000008818 liver damage Effects 0.000 claims abstract description 8
- 230000008816 organ damage Effects 0.000 claims abstract description 8
- 230000033764 rhythmic process Effects 0.000 claims abstract description 8
- -1 C 1 -C 6 alkoxy Chemical group 0.000 claims description 1571
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 232
- 238000002360 preparation method Methods 0.000 claims description 169
- 239000000203 mixture Substances 0.000 claims description 119
- 125000001424 substituent group Chemical group 0.000 claims description 86
- 150000003839 salts Chemical class 0.000 claims description 70
- 239000012453 solvate Substances 0.000 claims description 47
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 46
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 46
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 46
- 229910052736 halogen Inorganic materials 0.000 claims description 43
- 150000002367 halogens Chemical class 0.000 claims description 43
- 150000004677 hydrates Chemical class 0.000 claims description 43
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 43
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 42
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 42
- 125000004043 oxo group Chemical group O=* 0.000 claims description 37
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 35
- 229910052799 carbon Inorganic materials 0.000 claims description 34
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 32
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 31
- PMZDQRJGMBOQBF-UHFFFAOYSA-N quinolin-4-ol Chemical compound C1=CC=C2C(O)=CC=NC2=C1 PMZDQRJGMBOQBF-UHFFFAOYSA-N 0.000 claims description 31
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 29
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 29
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 27
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 26
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 26
- 229910052757 nitrogen Inorganic materials 0.000 claims description 26
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 24
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 24
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 24
- 125000003118 aryl group Chemical group 0.000 claims description 23
- 125000001153 fluoro group Chemical group F* 0.000 claims description 23
- 229940127557 pharmaceutical product Drugs 0.000 claims description 23
- 125000004076 pyridyl group Chemical group 0.000 claims description 23
- SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 claims description 23
- 125000000623 heterocyclic group Chemical group 0.000 claims description 21
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 19
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 18
- 238000009472 formulation Methods 0.000 claims description 18
- 125000001072 heteroaryl group Chemical group 0.000 claims description 18
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 18
- 229910052739 hydrogen Inorganic materials 0.000 claims description 17
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 17
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims description 17
- 125000004776 1-fluoroethyl group Chemical group [H]C([H])([H])C([H])(F)* 0.000 claims description 15
- 125000006798 (C1-C6) haloalkylamino group Chemical group 0.000 claims description 14
- 125000004939 6-pyridyl group Chemical group N1=CC=CC=C1* 0.000 claims description 14
- 235000010290 biphenyl Nutrition 0.000 claims description 13
- 239000004305 biphenyl Substances 0.000 claims description 12
- 239000002552 dosage form Substances 0.000 claims description 12
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 11
- 229910052731 fluorine Inorganic materials 0.000 claims description 11
- 125000002249 indol-2-yl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([*])=C([H])C2=C1[H] 0.000 claims description 11
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 11
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 11
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 11
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 11
- 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 claims description 10
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 10
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 10
- XASOHFCUIQARJT-UHFFFAOYSA-N 8-methoxy-6-[7-(2-morpholin-4-ylethoxy)imidazo[1,2-a]pyridin-3-yl]-2-(2,2,2-trifluoroethyl)-3,4-dihydroisoquinolin-1-one Chemical compound C(N1C(=O)C2=C(OC)C=C(C=3N4C(=NC=3)C=C(C=C4)OCCN3CCOCC3)C=C2CC1)C(F)(F)F XASOHFCUIQARJT-UHFFFAOYSA-N 0.000 claims description 10
- 125000004244 benzofuran-2-yl group Chemical group [H]C1=C(*)OC2=C([H])C([H])=C([H])C([H])=C12 0.000 claims description 10
- 125000004533 benzofuran-5-yl group Chemical group O1C=CC2=C1C=CC(=C2)* 0.000 claims description 10
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 10
- 125000000319 biphenyl-4-yl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 10
- 125000000814 indol-3-yl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([H])=C([*])C2=C1[H] 0.000 claims description 10
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 10
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 10
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 10
- 125000001624 naphthyl group Chemical group 0.000 claims description 10
- 125000004548 quinolin-3-yl group Chemical group N1=CC(=CC2=CC=CC=C12)* 0.000 claims description 10
- 125000000335 thiazolyl group Chemical group 0.000 claims description 10
- 125000000979 2-amino-2-oxoethyl group Chemical group [H]C([*])([H])C(=O)N([H])[H] 0.000 claims description 9
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 9
- XWQVQSXLXAXOPJ-QNGMFEMESA-N 4-[[[6-[5-chloro-2-[[4-[[(2r)-1-methoxypropan-2-yl]amino]cyclohexyl]amino]pyridin-4-yl]pyridin-2-yl]amino]methyl]oxane-4-carbonitrile Chemical compound C1CC(N[C@H](C)COC)CCC1NC1=CC(C=2N=C(NCC3(CCOCC3)C#N)C=CC=2)=C(Cl)C=N1 XWQVQSXLXAXOPJ-QNGMFEMESA-N 0.000 claims description 9
- 125000004608 5,6,7,8-tetrahydroquinolinyl group Chemical group N1=C(C=CC=2CCCCC12)* 0.000 claims description 9
- 125000003016 chromanyl group Chemical group O1C(CCC2=CC=CC=C12)* 0.000 claims description 9
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 9
- 239000003937 drug carrier Substances 0.000 claims description 9
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 claims description 9
- 125000004531 indol-5-yl group Chemical group [H]N1C([H])=C([H])C2=C([H])C(*)=C([H])C([H])=C12 0.000 claims description 9
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 claims description 9
- 125000004550 quinolin-6-yl group Chemical group N1=CC=CC2=CC(=CC=C12)* 0.000 claims description 9
- 125000006002 1,1-difluoroethyl group Chemical group 0.000 claims description 8
- 125000005899 2,3-dihydro-1H-pyrrolo[2,3-b]pyridinyl group Chemical group 0.000 claims description 8
- 125000004567 azetidin-3-yl group Chemical group N1CC(C1)* 0.000 claims description 8
- 125000002883 imidazolyl group Chemical group 0.000 claims description 8
- 125000006299 oxetan-3-yl group Chemical group [H]C1([H])OC([H])([H])C1([H])* 0.000 claims description 8
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 8
- 229920002554 vinyl polymer Polymers 0.000 claims description 8
- PVXLIOIISUUKOQ-YADHBBJMSA-N 1-ethyl-3-[[(3R)-3-[[(2S)-2-hydroxy-3-(3-methylsulfonylphenoxy)propyl]amino]-1-oxa-8-azaspiro[4.5]decan-8-yl]sulfonyl]quinolin-4-one Chemical compound CCn1cc(c(=O)c2ccccc12)S(=O)(=O)N1CCC2(C[C@H](CO2)NC[C@H](O)COc2cccc(c2)S(C)(=O)=O)CC1 PVXLIOIISUUKOQ-YADHBBJMSA-N 0.000 claims description 7
- BKRHXZUEUCCODF-RTWAWAEBSA-N 1-ethyl-8-fluoro-3-[[(3R)-3-[[(2S)-2-hydroxy-3-(3-methylsulfonylphenoxy)propyl]amino]-1-oxa-8-azaspiro[4.5]decan-8-yl]sulfonyl]quinolin-4-one Chemical compound CCn1cc(c(=O)c2cccc(F)c12)S(=O)(=O)N1CCC2(C[C@H](CO2)NC[C@H](O)COc2cccc(c2)S(C)(=O)=O)CC1 BKRHXZUEUCCODF-RTWAWAEBSA-N 0.000 claims description 7
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 claims description 7
- 230000000747 cardiac effect Effects 0.000 claims description 7
- 125000005347 halocycloalkyl group Chemical group 0.000 claims description 7
- 125000000981 3-amino-3-oxopropyl group Chemical group [H]C([*])([H])C([H])([H])C(=O)N([H])[H] 0.000 claims description 6
- QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 claims description 6
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 6
- 125000006268 biphenyl-3-yl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C1=C([H])C(*)=C([H])C([H])=C1[H] 0.000 claims description 6
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 6
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 5
- 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 5
- 125000000336 imidazol-5-yl group Chemical group [H]N1C([H])=NC([H])=C1[*] 0.000 claims description 5
- SHAYHNRTJQKVNJ-LQKDOSGMSA-N (2S)-1-[3-(1-fluoroethylsulfonyl)phenoxy]-3-[[(3R)-8-quinolin-6-ylsulfonyl-1-oxa-8-azaspiro[4.5]decan-3-yl]amino]propan-2-ol Chemical compound CC(F)S(=O)(=O)c1cccc(OC[C@@H](O)CN[C@H]2COC3(C2)CCN(CC3)S(=O)(=O)c2ccc3ncccc3c2)c1 SHAYHNRTJQKVNJ-LQKDOSGMSA-N 0.000 claims description 4
- SFDPMSWBGNUFHL-FTJBHMTQSA-N (2S)-1-[3-[1-(hydroxymethyl)cyclopropyl]sulfonylphenoxy]-3-[[(3R)-8-naphthalen-2-ylsulfonyl-1-oxa-8-azaspiro[4.5]decan-3-yl]amino]propan-2-ol Chemical compound OCC1(CC1)S(=O)(=O)c1cccc(OC[C@@H](O)CN[C@H]2COC3(C2)CCN(CC3)S(=O)(=O)c2ccc3ccccc3c2)c1 SFDPMSWBGNUFHL-FTJBHMTQSA-N 0.000 claims description 4
- ZUYFAHYJNMCDJP-RPWUZVMVSA-N (2S)-1-[3-[1-(hydroxymethyl)cyclopropyl]sulfonylphenoxy]-3-[[(3R)-8-quinolin-3-ylsulfonyl-1-oxa-8-azaspiro[4.5]decan-3-yl]amino]propan-2-ol Chemical compound OCC1(CC1)S(=O)(=O)c1cccc(OC[C@@H](O)CN[C@H]2COC3(C2)CCN(CC3)S(=O)(=O)c2cnc3ccccc3c2)c1 ZUYFAHYJNMCDJP-RPWUZVMVSA-N 0.000 claims description 4
- AIZVEJXGKOPKCT-LQJZCPKCSA-N (2S)-1-[3-[1-(hydroxymethyl)cyclopropyl]sulfonylphenoxy]-3-[[(3S)-8-[3-[4-[(2-methylbutan-2-ylamino)methyl]phenyl]phenyl]sulfonyl-1-oxa-8-azaspiro[4.5]decan-3-yl]amino]propan-2-ol Chemical compound CCC(C)(C)NCC1=CC=C(C=C1)C1=CC(=CC=C1)S(=O)(=O)N1CCC2(C[C@@H](CO2)NC[C@H](O)COC2=CC(=CC=C2)S(=O)(=O)C2(CO)CC2)CC1 AIZVEJXGKOPKCT-LQJZCPKCSA-N 0.000 claims description 4
- OTTAXHQDRZQBSM-NSOVKSMOSA-N (2S)-1-[[(3S)-8-[3-[4-(2-aminoethyl)phenyl]phenyl]sulfonyl-1-oxa-8-azaspiro[4.5]decan-3-yl]amino]-3-[3-(1,1-difluoro-2-hydroxyethyl)sulfonylphenoxy]propan-2-ol Chemical compound NCCC1=CC=C(C=C1)C1=CC(=CC=C1)S(=O)(=O)N1CCC2(C[C@@H](CO2)NC[C@H](O)COC2=CC(=CC=C2)S(=O)(=O)C(F)(F)CO)CC1 OTTAXHQDRZQBSM-NSOVKSMOSA-N 0.000 claims description 4
- MBIXCUIOHLJBGG-KYJUHHDHSA-N (2S)-1-[[(3S)-8-[3-[4-(2-aminoethyl)phenyl]phenyl]sulfonyl-1-oxa-8-azaspiro[4.5]decan-3-yl]amino]-3-[3-[1-(hydroxymethyl)cyclopropyl]sulfonylphenoxy]propan-2-ol Chemical compound NCCC1=CC=C(C=C1)C1=CC(=CC=C1)S(=O)(=O)N1CCC2(C[C@@H](CO2)NC[C@H](O)COC2=CC(=CC=C2)S(=O)(=O)C2(CO)CC2)CC1 MBIXCUIOHLJBGG-KYJUHHDHSA-N 0.000 claims description 4
- RZYWIPZOLSCULT-SVBPBHIXSA-N (2S)-1-[[(3S)-8-[3-[4-(aminomethyl)phenyl]-4-methoxyphenyl]sulfonyl-1-oxa-8-azaspiro[4.5]decan-3-yl]amino]-3-(3-cyclopropylsulfonylphenoxy)propan-2-ol Chemical compound COC1=CC=C(C=C1C1=CC=C(CN)C=C1)S(=O)(=O)N1CCC2(C[C@@H](CO2)NC[C@H](O)COC2=CC(=CC=C2)S(=O)(=O)C2CC2)CC1 RZYWIPZOLSCULT-SVBPBHIXSA-N 0.000 claims description 4
- CZGOTIBAUNXPDM-LQJZCPKCSA-N (2S)-1-[[(3S)-8-[3-[4-(butylaminomethyl)phenyl]phenyl]sulfonyl-1-oxa-8-azaspiro[4.5]decan-3-yl]amino]-3-[3-[1-(hydroxymethyl)cyclopropyl]sulfonylphenoxy]propan-2-ol Chemical compound CCCCNCC1=CC=C(C=C1)C1=CC(=CC=C1)S(=O)(=O)N1CCC2(C[C@@H](CO2)NC[C@H](O)COC2=CC(=CC=C2)S(=O)(=O)C2(CO)CC2)CC1 CZGOTIBAUNXPDM-LQJZCPKCSA-N 0.000 claims description 4
- ZOUMUQSUBBTKJK-VMPREFPWSA-N (2S)-1-[[(3S)-8-[5-[4-(aminomethyl)-3-fluorophenyl]-2-ethoxyphenyl]sulfonyl-1-oxa-8-azaspiro[4.5]decan-3-yl]amino]-3-[3-[1-(hydroxymethyl)cyclopropyl]sulfonylphenoxy]propan-2-ol Chemical compound CCOc1ccc(cc1S(=O)(=O)N1CCC2(C[C@@H](CO2)NC[C@H](O)COc2cccc(c2)S(=O)(=O)C2(CO)CC2)CC1)-c1ccc(CN)c(F)c1 ZOUMUQSUBBTKJK-VMPREFPWSA-N 0.000 claims description 4
- YRGFWSXWUWTZSV-KYJUHHDHSA-N (2S)-1-[[(3S)-8-[5-[4-(aminomethyl)phenyl]-2-ethoxyphenyl]sulfonyl-1-oxa-8-azaspiro[4.5]decan-3-yl]amino]-3-(3-propan-2-ylsulfonylphenoxy)propan-2-ol Chemical compound CCOc1ccc(cc1S(=O)(=O)N1CCC2(C[C@@H](CO2)NC[C@H](O)COc2cccc(c2)S(=O)(=O)C(C)C)CC1)-c1ccc(CN)cc1 YRGFWSXWUWTZSV-KYJUHHDHSA-N 0.000 claims description 4
- MWQGFMMWRHXINT-VMPREFPWSA-N (2S)-1-[[(3S)-8-[5-[4-(aminomethyl)phenyl]-2-ethoxyphenyl]sulfonyl-1-oxa-8-azaspiro[4.5]decan-3-yl]amino]-3-[3-(methoxymethylsulfonyl)phenoxy]propan-2-ol Chemical compound CCOc1ccc(cc1S(=O)(=O)N1CCC2(C[C@@H](CO2)NC[C@H](O)COc2cccc(c2)S(=O)(=O)COC)CC1)-c1ccc(CN)cc1 MWQGFMMWRHXINT-VMPREFPWSA-N 0.000 claims description 4
- VUHKCOWMKWKROS-KYJUHHDHSA-N (2S)-1-[[(3S)-8-[5-[4-(aminomethyl)phenyl]-2-ethoxyphenyl]sulfonyl-1-oxa-8-azaspiro[4.5]decan-3-yl]amino]-3-[3-[1-(hydroxymethyl)cyclopropyl]sulfonylphenoxy]propan-2-ol Chemical compound CCOC1=C(C=C(C=C1)C1=CC=C(CN)C=C1)S(=O)(=O)N1CCC2(C[C@@H](CO2)NC[C@H](O)COC2=CC(=CC=C2)S(=O)(=O)C2(CO)CC2)CC1 VUHKCOWMKWKROS-KYJUHHDHSA-N 0.000 claims description 4
- 125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 claims description 4
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 4
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 4
- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 claims description 4
- 125000004498 isoxazol-4-yl group Chemical group O1N=CC(=C1)* 0.000 claims description 4
- 125000001064 morpholinomethyl group Chemical group [H]C([H])(*)N1C([H])([H])C([H])([H])OC([H])([H])C1([H])[H] 0.000 claims description 4
- 230000008569 process Effects 0.000 claims description 4
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 4
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Classifications
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- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/10—Spiro-condensed systems
- C07D491/107—Spiro-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
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- 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
- A61K31/438—The ring being spiro-condensed with carbocyclic or heterocyclic ring systems
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- 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
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- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
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- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/4525—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with oxygen as a ring hetero atom
Landscapes
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- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
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| US11014927B2 (en) | 2017-03-20 | 2021-05-25 | Forma Therapeutics, Inc. | Pyrrolopyrrole compositions as pyruvate kinase (PKR) activators |
| TWI822713B (zh) * | 2017-12-06 | 2023-11-21 | 美商艾尼納製藥公司 | 適用於治療或預防與其相關之病症之β－３腎上腺素受體的調節劑 |
| US12053458B2 (en) | 2018-09-19 | 2024-08-06 | Novo Nordisk Health Care Ag | Treating sickle cell disease with a pyruvate kinase R activating compound |
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| US12128035B2 (en) | 2021-03-19 | 2024-10-29 | Novo Nordisk Health Care Ag | Activating pyruvate kinase R |
| WO2023017388A1 (en) * | 2021-08-09 | 2023-02-16 | Arena Pharmaceuticals, Inc. | Modulators of the beta-3 adrenergic receptor useful for the treatment or prevention of heart failure |
| WO2023026185A1 (en) * | 2021-08-26 | 2023-03-02 | Arena Pharmaceuticals, Inc. | Modulators of the beta-3 adrenergic receptor for the treatment or prevention of renal cystic disease and cardiorenal syndrome |
| US20240409548A1 (en) * | 2021-10-06 | 2024-12-12 | Arena Pharmaceuticals, Inc. | Modulators of the beta-3 adrenergic receptor useful for the treatment or prevention of disorders related thereto |
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