KR20050006126A - 당뇨병 및 기타 질환 치료용 헤테로시클릭 아미드 유도체 - Google Patents

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Publication number

KR20050006126A

KR20050006126A KR10-2004-7014099A KR20047014099A KR20050006126A KR 20050006126 A KR20050006126 A KR 20050006126A KR 20047014099 A KR20047014099 A KR 20047014099A KR 20050006126 A KR20050006126 A KR 20050006126A

Authority

KR

South Korea

Prior art keywords

compound

carbon atoms

oxo

substituted

trimethyl

Prior art date

2002-03-08

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.)

Withdrawn

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• -1 Heterocyclic amide Chemical class 0.000 title claims description 227
• 206010012601 diabetes mellitus Diseases 0.000 title claims description 24
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title abstract description 31
• 201000010099 disease Diseases 0.000 title abstract description 30
• 150000001875 compounds Chemical class 0.000 claims abstract description 248
• 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 92
• 150000003839 salts Chemical class 0.000 claims abstract description 48
• 229910052796 boron Inorganic materials 0.000 claims abstract description 37
• 208000001072 type 2 diabetes mellitus Diseases 0.000 claims abstract description 34
• 206010028980 Neoplasm Diseases 0.000 claims abstract description 31
• 230000023852 carbohydrate metabolic process Effects 0.000 claims abstract description 27
• 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 26
• 235000021256 carbohydrate metabolism Nutrition 0.000 claims abstract description 25
• 208000026310 Breast neoplasm Diseases 0.000 claims abstract description 20
• 150000001408 amides Chemical group 0.000 claims abstract description 19
• 150000002632 lipids Chemical class 0.000 claims abstract description 17
• ZOBPZXTWZATXDG-UHFFFAOYSA-N 1,3-thiazolidine-2,4-dione Chemical compound O=C1CSC(=O)N1 ZOBPZXTWZATXDG-UHFFFAOYSA-N 0.000 claims abstract description 15
• 201000011510 cancer Diseases 0.000 claims abstract description 15
• 201000001320 Atherosclerosis Diseases 0.000 claims abstract description 14
• 206010006187 Breast cancer Diseases 0.000 claims abstract description 14
• WJRBRSLFGCUECM-UHFFFAOYSA-N hydantoin Chemical compound O=C1CNC(=O)N1 WJRBRSLFGCUECM-UHFFFAOYSA-N 0.000 claims abstract description 14
• 230000037356 lipid metabolism Effects 0.000 claims abstract description 14
• KIWUVOGUEXMXSV-UHFFFAOYSA-N rhodanine Chemical compound O=C1CSC(=S)N1 KIWUVOGUEXMXSV-UHFFFAOYSA-N 0.000 claims abstract description 6
• 125000004432 carbon atom Chemical group C* 0.000 claims description 116
• HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 claims description 92
• 238000000034 method Methods 0.000 claims description 80
• 125000000217 alkyl group Chemical group 0.000 claims description 62
• 239000001257 hydrogen Substances 0.000 claims description 59
• 125000001424 substituent group Chemical group 0.000 claims description 50
• 125000001072 heteroaryl group Chemical group 0.000 claims description 49
• 229910052736 halogen Inorganic materials 0.000 claims description 46
• 150000002367 halogens Chemical class 0.000 claims description 46
• 150000001450 anions Chemical class 0.000 claims description 45
• 125000003118 aryl group Chemical group 0.000 claims description 45
• 210000004027 cell Anatomy 0.000 claims description 37
• 241000699670 Mus sp. Species 0.000 claims description 33
• 125000003545 alkoxy group Chemical group 0.000 claims description 33
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 31
• 210000002966 serum Anatomy 0.000 claims description 31
• 241001465754 Metazoa Species 0.000 claims description 30
• 210000001789 adipocyte Anatomy 0.000 claims description 30
• 230000004069 differentiation Effects 0.000 claims description 30
• 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 28
• 239000008103 glucose Substances 0.000 claims description 28
• 125000004438 haloalkoxy group Chemical group 0.000 claims description 28
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 27
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 26
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 23
• 230000004060 metabolic process Effects 0.000 claims description 23
• 238000006243 chemical reaction Methods 0.000 claims description 21
• 229910052760 oxygen Inorganic materials 0.000 claims description 21
• 239000002243 precursor Substances 0.000 claims description 21
• 125000003107 substituted aryl group Chemical group 0.000 claims description 20
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 19
• 229910052757 nitrogen Inorganic materials 0.000 claims description 19
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 18
• 125000001188 haloalkyl group Chemical group 0.000 claims description 18
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 17
• 241000124008 Mammalia Species 0.000 claims description 17
• 125000004423 acyloxy group Chemical group 0.000 claims description 16
• 239000008194 pharmaceutical composition Substances 0.000 claims description 16
• 229910052717 sulfur Inorganic materials 0.000 claims description 16
• 238000005859 coupling reaction Methods 0.000 claims description 15
• UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 claims description 15
• 210000004369 blood Anatomy 0.000 claims description 14
• 239000008280 blood Substances 0.000 claims description 14
• 230000001603 reducing effect Effects 0.000 claims description 14
• 208000035150 Hypercholesterolemia Diseases 0.000 claims description 13
• 125000005842 heteroatom Chemical group 0.000 claims description 12
• 238000010168 coupling process Methods 0.000 claims description 11
• 230000008878 coupling Effects 0.000 claims description 10
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 10
• 235000012054 meals Nutrition 0.000 claims description 9
• 239000000126 substance Substances 0.000 claims description 9
• 241000699666 Mus <mouse, genus> Species 0.000 claims description 8
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 8
• 238000002360 preparation method Methods 0.000 claims description 8
• 150000001768 cations Chemical class 0.000 claims description 7
• 230000001965 increasing effect Effects 0.000 claims description 7
• 229910052751 metal Inorganic materials 0.000 claims description 7
• 239000002184 metal Substances 0.000 claims description 6
• UGWULZWUXSCWPX-UHFFFAOYSA-N 2-sulfanylideneimidazolidin-4-one Chemical group O=C1CNC(=S)N1 UGWULZWUXSCWPX-UHFFFAOYSA-N 0.000 claims description 5
• 229910052744 lithium Inorganic materials 0.000 claims description 5
• 208000032928 Dyslipidaemia Diseases 0.000 claims description 4
• 208000017170 Lipid metabolism disease Diseases 0.000 claims description 4
• CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 4
• 229910052782 aluminium Inorganic materials 0.000 claims description 4
• XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 claims description 4
• 239000003937 drug carrier Substances 0.000 claims description 4
• 230000008569 process Effects 0.000 claims description 4
• TUMQVWIXFYQMPE-UHFFFAOYSA-N 5-[[3-(1,4,4,6-tetramethyl-2-oxo-3h-quinolin-7-yl)-4-(trifluoromethoxy)phenyl]methylidene]-1,3-thiazolidine-2,4-dione Chemical compound C1=C2N(C)C(=O)CC(C)(C)C2=CC(C)=C1C(C(=CC=1)OC(F)(F)F)=CC=1C=C1SC(=O)NC1=O TUMQVWIXFYQMPE-UHFFFAOYSA-N 0.000 claims description 3
• HWJYWTWTNWGEPW-UHFFFAOYSA-N 5-[[3-(1-ethyl-4,4,6-trimethyl-2-oxo-3h-quinolin-7-yl)-4-(trifluoromethoxy)phenyl]methylidene]-1,3-thiazolidine-2,4-dione Chemical compound C1=C2N(CC)C(=O)CC(C)(C)C2=CC(C)=C1C(C(=CC=1)OC(F)(F)F)=CC=1C=C1SC(=O)NC1=O HWJYWTWTNWGEPW-UHFFFAOYSA-N 0.000 claims description 3
• WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 claims description 3
• 230000001276 controlling effect Effects 0.000 claims description 3
• 235000009200 high fat diet Nutrition 0.000 claims description 3
• 239000011777 magnesium Substances 0.000 claims description 3
• 229910052749 magnesium Inorganic materials 0.000 claims description 3
• 229910052700 potassium Inorganic materials 0.000 claims description 3
• 125000003373 pyrazinyl group Chemical group 0.000 claims description 3
• 239000011734 sodium Substances 0.000 claims description 3
• IGHXENSMRWDRKA-UHFFFAOYSA-N 5-[[2,5-difluoro-4-methoxy-3-(1,4,4,6-tetramethyl-2-oxo-3h-quinolin-7-yl)phenyl]methylidene]-1,3-thiazolidine-2,4-dione Chemical compound FC1=C(C=2C(=CC=3C(C)(C)CC(=O)N(C)C=3C=2)C)C(OC)=C(F)C=C1C=C1SC(=O)NC1=O IGHXENSMRWDRKA-UHFFFAOYSA-N 0.000 claims description 2
• CXFIOEDVSRZEQP-UHFFFAOYSA-N 5-[[3-(1-ethyl-4,4,6-trimethyl-2-oxo-3h-quinolin-7-yl)-2-fluoro-4-methoxyphenyl]methylidene]-1,3-thiazolidine-2,4-dione Chemical compound C1=C2N(CC)C(=O)CC(C)(C)C2=CC(C)=C1C(C(=CC=1)OC)=C(F)C=1C=C1SC(=O)NC1=O CXFIOEDVSRZEQP-UHFFFAOYSA-N 0.000 claims description 2
• BTDIBTFOEQGYNN-UHFFFAOYSA-N 5-[[3-(1-ethyl-4,4,6-trimethyl-2-oxo-3h-quinolin-7-yl)-5-fluoro-4-methoxyphenyl]methylidene]-1,3-thiazolidine-2,4-dione Chemical compound C1=C2N(CC)C(=O)CC(C)(C)C2=CC(C)=C1C(C(=C(F)C=1)OC)=CC=1C=C1SC(=O)NC1=O BTDIBTFOEQGYNN-UHFFFAOYSA-N 0.000 claims description 2
• OVGKEHDDXLFCLP-UHFFFAOYSA-N 5-[[4-(dimethylamino)-3-(1,4,4,6-tetramethyl-2-oxo-3h-quinolin-7-yl)phenyl]methylidene]-1,3-thiazolidine-2,4-dione Chemical compound C1=C(C=2C(=CC=3C(C)(C)CC(=O)N(C)C=3C=2)C)C(N(C)C)=CC=C1C=C1SC(=O)NC1=O OVGKEHDDXLFCLP-UHFFFAOYSA-N 0.000 claims description 2
• GTWRJNHQYADCSI-UHFFFAOYSA-N 5-[[4-(dimethylamino)-3-(1,4,7-trimethyl-2,3-dioxoquinoxalin-6-yl)phenyl]methylidene]-1,3-thiazolidine-2,4-dione Chemical compound C1=C(C=2C(=CC=3N(C)C(=O)C(=O)N(C)C=3C=2)C)C(N(C)C)=CC=C1C=C1SC(=O)NC1=O GTWRJNHQYADCSI-UHFFFAOYSA-N 0.000 claims description 2
• NDSWOANBUNAJAY-UHFFFAOYSA-N 5-[[4-(dimethylamino)-3-(4,4,6-trimethyl-2-oxo-1-propan-2-yl-3h-quinolin-7-yl)phenyl]methylidene]-1,3-thiazolidine-2,4-dione Chemical compound C1=C2N(C(C)C)C(=O)CC(C)(C)C2=CC(C)=C1C(C(=CC=1)N(C)C)=CC=1C=C1SC(=O)NC1=O NDSWOANBUNAJAY-UHFFFAOYSA-N 0.000 claims description 2
• YJRYNJSRYJEBRJ-UHFFFAOYSA-N 5-[[4-(trifluoromethoxy)-3-(4,4,6-trimethyl-2-oxo-1,3-dihydroquinolin-7-yl)phenyl]methylidene]-1,3-thiazolidine-2,4-dione Chemical compound CC1=CC(C(CC(=O)N2)(C)C)=C2C=C1C(C(=CC=1)OC(F)(F)F)=CC=1C=C1SC(=O)NC1=O YJRYNJSRYJEBRJ-UHFFFAOYSA-N 0.000 claims description 2
• KBJIHTLGARZNBW-UHFFFAOYSA-N 5-[[4-(trifluoromethoxy)-3-(4,4,6-trimethyl-2-oxo-1-propyl-3h-quinolin-7-yl)phenyl]methylidene]-1,3-thiazolidine-2,4-dione Chemical compound C1=C2N(CCC)C(=O)CC(C)(C)C2=CC(C)=C1C(C(=CC=1)OC(F)(F)F)=CC=1C=C1SC(=O)NC1=O KBJIHTLGARZNBW-UHFFFAOYSA-N 0.000 claims description 2
• JMABEOVVSGPWJR-UHFFFAOYSA-N 5-[[4-chloro-3-(1,4,4,6-tetramethyl-2-oxo-3h-quinolin-7-yl)phenyl]methylidene]-1,3-thiazolidine-2,4-dione Chemical compound C1=C2N(C)C(=O)CC(C)(C)C2=CC(C)=C1C(C(=CC=1)Cl)=CC=1C=C1SC(=O)NC1=O JMABEOVVSGPWJR-UHFFFAOYSA-N 0.000 claims description 2
• JNBZPXIGSUERNY-UHFFFAOYSA-N 5-[[4-chloro-3-(1-ethyl-4,4,6-trimethyl-2-oxo-3h-quinolin-7-yl)phenyl]methylidene]-1,3-thiazolidine-2,4-dione Chemical compound C1=C2N(CC)C(=O)CC(C)(C)C2=CC(C)=C1C(C(=CC=1)Cl)=CC=1C=C1SC(=O)NC1=O JNBZPXIGSUERNY-UHFFFAOYSA-N 0.000 claims description 2
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims description 2
• PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 claims description 2
• DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 2
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims description 2
• MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 claims description 2
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 2
• 239000011575 calcium Substances 0.000 claims description 2
• 229910052791 calcium Inorganic materials 0.000 claims description 2
• VDANGULDQQJODZ-UHFFFAOYSA-N chloroprocaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1Cl VDANGULDQQJODZ-UHFFFAOYSA-N 0.000 claims description 2
• 229960002023 chloroprocaine Drugs 0.000 claims description 2
• OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 claims description 2
• 229960001231 choline Drugs 0.000 claims description 2
• ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 claims description 2
• 229940043237 diethanolamine Drugs 0.000 claims description 2
• 229940012017 ethylenediamine Drugs 0.000 claims description 2
• 229960003194 meglumine Drugs 0.000 claims description 2
• 239000011591 potassium Substances 0.000 claims description 2
• MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 claims description 2
• 229960004919 procaine Drugs 0.000 claims description 2
• 229910052708 sodium Inorganic materials 0.000 claims description 2
• YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 claims description 2
• 229910052725 zinc Inorganic materials 0.000 claims description 2
• 239000011701 zinc Substances 0.000 claims description 2
• 150000002431 hydrogen Chemical class 0.000 claims 13
• 230000001105 regulatory effect Effects 0.000 claims 2
• 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 1
• AJWYRAPTULXKLY-UHFFFAOYSA-N 5-[[3-(1-ethyl-4,4,6-trimethyl-2-oxo-3h-quinolin-7-yl)-2,5-difluoro-4-methoxyphenyl]methylidene]-1,3-thiazolidine-2,4-dione Chemical compound C1=C2N(CC)C(=O)CC(C)(C)C2=CC(C)=C1C(C(=C(F)C=1)OC)=C(F)C=1C=C1SC(=O)NC1=O AJWYRAPTULXKLY-UHFFFAOYSA-N 0.000 claims 1
• RXSDNKZJROLXLW-UHFFFAOYSA-N 5-[[4-(trifluoromethoxy)-3-(4,4,6-trimethyl-2-oxo-1-propan-2-yl-3h-quinolin-7-yl)phenyl]methylidene]-1,3-thiazolidine-2,4-dione Chemical compound C1=C2N(C(C)C)C(=O)CC(C)(C)C2=CC(C)=C1C(C(=CC=1)OC(F)(F)F)=CC=1C=C1SC(=O)NC1=O RXSDNKZJROLXLW-UHFFFAOYSA-N 0.000 claims 1
• QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 claims 1
• HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims 1
• 150000004703 alkoxides Chemical class 0.000 claims 1
• 150000001555 benzenes Chemical group 0.000 claims 1
• 125000005456 glyceride group Chemical group 0.000 claims 1
• 230000006372 lipid accumulation Effects 0.000 claims 1
• 239000008177 pharmaceutical agent Substances 0.000 claims 1
• 230000002062 proliferating effect Effects 0.000 abstract description 5
• SEPPVOUBHWNCAW-FNORWQNLSA-N (E)-4-oxonon-2-enal Chemical group CCCCCC(=O)\C=C\C=O SEPPVOUBHWNCAW-FNORWQNLSA-N 0.000 abstract 1
• LLBZPESJRQGYMB-UHFFFAOYSA-N 4-one Natural products O1C(C(=O)CC)CC(C)C11C2(C)CCC(C3(C)C(C(C)(CO)C(OC4C(C(O)C(O)C(COC5C(C(O)C(O)CO5)OC5C(C(OC6C(C(O)C(O)C(CO)O6)O)C(O)C(CO)O5)OC5C(C(O)C(O)C(C)O5)O)O4)O)CC3)CC3)=C3C2(C)CC1 LLBZPESJRQGYMB-UHFFFAOYSA-N 0.000 abstract 1
• PDQAZBWRQCGBEV-UHFFFAOYSA-N Ethylenethiourea Chemical compound S=C1NCCN1 PDQAZBWRQCGBEV-UHFFFAOYSA-N 0.000 abstract 1
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 199
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 102
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 97
• 239000000243 solution Substances 0.000 description 94
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 86
• 150000003254 radicals Chemical class 0.000 description 73
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• 239000000203 mixture Substances 0.000 description 68
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 65
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 64
• 238000005481 NMR spectroscopy Methods 0.000 description 62
• 239000012267 brine Substances 0.000 description 55
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 55
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 51
• 239000011541 reaction mixture Substances 0.000 description 39
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 37
• 239000000741 silica gel Substances 0.000 description 34
• 229910002027 silica gel Inorganic materials 0.000 description 34
• 229910052786 argon Inorganic materials 0.000 description 32
• QBWKPGNFQQJGFY-QLFBSQMISA-N 3-[(1r)-1-[(2r,6s)-2,6-dimethylmorpholin-4-yl]ethyl]-n-[6-methyl-3-(1h-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl]-1,2-thiazol-5-amine Chemical compound N1([C@H](C)C2=NSC(NC=3C4=NC=C(N4C=C(C)N=3)C3=CNN=C3)=C2)C[C@H](C)O[C@H](C)C1 QBWKPGNFQQJGFY-QLFBSQMISA-N 0.000 description 31
• 235000012000 cholesterol Nutrition 0.000 description 31
• 229940125846 compound 25 Drugs 0.000 description 31
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 30
• 239000003925 fat Substances 0.000 description 30
• 125000005432 dialkylcarboxamide group Chemical group 0.000 description 29
• 235000019197 fats Nutrition 0.000 description 29
• 125000005431 alkyl carboxamide group Chemical group 0.000 description 26
• 238000005160 1H NMR spectroscopy Methods 0.000 description 24
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 24
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 24
• 125000004435 hydrogen atom Chemical class [H]* 0.000 description 24
• 239000000543 intermediate Substances 0.000 description 23
• 125000000547 substituted alkyl group Chemical group 0.000 description 23
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 22
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 20
• 230000000694 effects Effects 0.000 description 20
• 238000012360 testing method Methods 0.000 description 20
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 18
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 18
• LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical group OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 17
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