KR100335704B1 - 모르폴린및티오모르폴린타키키닌수용체길항제 - Google Patents

Info

Publication number

KR100335704B1

KR100335704B1 KR1019960703198A KR19960703198A KR100335704B1 KR 100335704 B1 KR100335704 B1 KR 100335704B1 KR 1019960703198 A KR1019960703198 A KR 1019960703198A KR 19960703198 A KR19960703198 A KR 19960703198A KR 100335704 B1 KR100335704 B1 KR 100335704B1

Authority

KR

South Korea

Prior art keywords

morpholine

phenyl

methyl

ethoxy

trifluoromethyl

Prior art date

1993-12-17

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.)

Expired - Lifetime

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• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 title claims description 173
• 239000002462 tachykinin receptor antagonist Substances 0.000 title abstract description 9
• BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 title description 2
• -1 angina Chemical compound 0.000 claims abstract description 602
• 125000000217 alkyl group Chemical group 0.000 claims abstract description 90
• 239000001257 hydrogen Substances 0.000 claims abstract description 35
• 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 35
• 150000003839 salts Chemical class 0.000 claims abstract description 34
• 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 22
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims abstract description 16
• 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims abstract description 13
• 206010047700 Vomiting Diseases 0.000 claims abstract description 13
• 230000008673 vomiting Effects 0.000 claims abstract description 11
• 125000002541 furyl group Chemical group 0.000 claims abstract description 9
• SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 claims description 522
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 468
• 150000001875 compounds Chemical class 0.000 claims description 229
• 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 150
• 239000000203 mixture Substances 0.000 claims description 140
• 125000003545 alkoxy group Chemical group 0.000 claims description 99
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 89
• 125000001424 substituent group Chemical group 0.000 claims description 85
• 125000005843 halogen group Chemical group 0.000 claims description 75
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 56
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 54
• 238000000034 method Methods 0.000 claims description 52
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 43
• 238000003786 synthesis reaction Methods 0.000 claims description 41
• 125000000066 S-methyl group Chemical group [H]C([H])([H])S* 0.000 claims description 37
• 230000015572 biosynthetic process Effects 0.000 claims description 37
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 36
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 34
• 102100024304 Protachykinin-1 Human genes 0.000 claims description 34
• 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 claims description 31
• QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 26
• QDZOEBFLNHCSSF-PFFBOGFISA-N (2S)-2-[[(2R)-2-[[(2S)-1-[(2S)-6-amino-2-[[(2S)-1-[(2R)-2-amino-5-carbamimidamidopentanoyl]pyrrolidine-2-carbonyl]amino]hexanoyl]pyrrolidine-2-carbonyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-N-[(2R)-1-[[(2S)-1-[[(2R)-1-[[(2S)-1-[[(2S)-1-amino-4-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]pentanediamide Chemical compound C([C@@H](C(=O)N[C@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(N)=O)NC(=O)[C@@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](N)CCCNC(N)=N)C1=CC=CC=C1 QDZOEBFLNHCSSF-PFFBOGFISA-N 0.000 claims description 24
• 101800003906 Substance P Proteins 0.000 claims description 23
• 229910052757 nitrogen Inorganic materials 0.000 claims description 23
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 18
• 125000003342 alkenyl group Chemical group 0.000 claims description 18
• 239000003054 catalyst Substances 0.000 claims description 17
• 125000004076 pyridyl group Chemical group 0.000 claims description 15
• 125000002883 imidazolyl group Chemical group 0.000 claims description 14
• 125000003386 piperidinyl group Chemical group 0.000 claims description 14
• 125000000168 pyrrolyl group Chemical group 0.000 claims description 14
• LZTSCEYDCZBRCJ-UHFFFAOYSA-N 1,2-dihydro-1,2,4-triazol-3-one Chemical compound OC=1N=CNN=1 LZTSCEYDCZBRCJ-UHFFFAOYSA-N 0.000 claims description 13
• 125000001153 fluoro group Chemical group F* 0.000 claims description 13
• 239000003153 chemical reaction reagent Substances 0.000 claims description 12
• 125000002971 oxazolyl group Chemical group 0.000 claims description 12
• 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 12
• 125000000335 thiazolyl group Chemical group 0.000 claims description 12
• 125000001309 chloro group Chemical group Cl* 0.000 claims description 11
• 125000004100 3-methylphenylethoxy group Chemical group [H]C1=C([H])C(=C([H])C(=C1[H])C([H])([H])[H])C([H])([H])C([H])([H])O* 0.000 claims description 10
• FHQRDEDZJIFJAL-UHFFFAOYSA-N 4-phenylmorpholine Chemical compound C1COCCN1C1=CC=CC=C1 FHQRDEDZJIFJAL-UHFFFAOYSA-N 0.000 claims description 10
• 125000000068 chlorophenyl group Chemical group 0.000 claims description 10
• 125000001207 fluorophenyl group Chemical group 0.000 claims description 10
• 125000001246 bromo group Chemical group Br* 0.000 claims description 9
• 108010040718 Neurokinin-1 Receptors Proteins 0.000 claims description 8
• 102000002002 Neurokinin-1 Receptors Human genes 0.000 claims description 8
• 125000002346 iodo group Chemical group I* 0.000 claims description 8
• 125000001544 thienyl group Chemical group 0.000 claims description 8
• 230000000694 effects Effects 0.000 claims description 7
• 125000001425 triazolyl group Chemical group 0.000 claims description 7
• QEASJVYPHMYPJM-UHFFFAOYSA-N 1,2-dihydrotriazol-5-one Chemical compound OC1=CNN=N1 QEASJVYPHMYPJM-UHFFFAOYSA-N 0.000 claims description 6
• WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 claims description 6
• 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 6
• 239000003795 chemical substances by application Substances 0.000 claims description 6
• 239000003937 drug carrier Substances 0.000 claims description 6
• 125000001786 isothiazolyl group Chemical group 0.000 claims description 6
• 125000000842 isoxazolyl group Chemical group 0.000 claims description 6
• 229910052744 lithium Inorganic materials 0.000 claims description 6
• 125000001715 oxadiazolyl group Chemical group 0.000 claims description 6
• 239000008194 pharmaceutical composition Substances 0.000 claims description 6
• 125000003226 pyrazolyl group Chemical group 0.000 claims description 6
• MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 claims description 6
• 125000003831 tetrazolyl group Chemical group 0.000 claims description 6
• 125000001113 thiadiazolyl group Chemical group 0.000 claims description 6
• 125000000464 thioxo group Chemical group S=* 0.000 claims description 6
• 125000003373 pyrazinyl group Chemical group 0.000 claims description 5
• 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 4
• 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 4
• 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 4
• 150000008064 anhydrides Chemical class 0.000 claims description 4
• 125000002393 azetidinyl group Chemical group 0.000 claims description 4
• 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 4
• 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 4
• 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 4
• SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 claims description 4
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
• 125000002837 carbocyclic group Chemical group 0.000 claims description 4
• 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 4
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 4
• 125000004634 hexahydroazepinyl group Chemical group N1(CCCCCC1)* 0.000 claims description 4
• 150000004678 hydrides Chemical class 0.000 claims description 4
• 125000001041 indolyl group Chemical group 0.000 claims description 4
• 125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 claims description 4
• 239000012280 lithium aluminium hydride Substances 0.000 claims description 4
• 125000004193 piperazinyl group Chemical group 0.000 claims description 4
• 125000000714 pyrimidinyl group Chemical group 0.000 claims description 4
• 125000005493 quinolyl group Chemical group 0.000 claims description 4
• 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 4
• 125000005958 tetrahydrothienyl group Chemical group 0.000 claims description 4
• XSALUACENXIXKO-MDASCCDHSA-N (2r,3s)-2-[(1r)-1-(3-chloro-5-methylphenyl)ethoxy]-3-phenylmorpholine Chemical compound C1([C@@H]2NCCO[C@@H]2O[C@H](C)C=2C=C(Cl)C=C(C)C=2)=CC=CC=C1 XSALUACENXIXKO-MDASCCDHSA-N 0.000 claims description 3
• FSZSXNHVHXRIPX-GQWLDOHISA-N (2r,3s)-2-[(1r)-1-(3-chloro-5-propan-2-yloxyphenyl)ethoxy]-3-phenylmorpholine Chemical compound CC(C)OC1=CC(Cl)=CC([C@@H](C)O[C@@H]2[C@@H](NCCO2)C=2C=CC=CC=2)=C1 FSZSXNHVHXRIPX-GQWLDOHISA-N 0.000 claims description 3
• UUZYDUWBYXQIJM-MDASCCDHSA-N (2r,3s)-2-[(1r)-1-(3-fluoro-5-methylphenyl)ethoxy]-3-phenylmorpholine Chemical compound C1([C@@H]2NCCO[C@@H]2O[C@H](C)C=2C=C(F)C=C(C)C=2)=CC=CC=C1 UUZYDUWBYXQIJM-MDASCCDHSA-N 0.000 claims description 3
• FCXDRRVJPDYPGR-GQWLDOHISA-N (2r,3s)-2-[(1r)-1-(3-fluoro-5-propan-2-yloxyphenyl)ethoxy]-3-phenylmorpholine Chemical compound CC(C)OC1=CC(F)=CC([C@@H](C)O[C@@H]2[C@@H](NCCO2)C=2C=CC=CC=2)=C1 FCXDRRVJPDYPGR-GQWLDOHISA-N 0.000 claims description 3
• TYBDKZULYJZJHG-JEBQAFNWSA-N (2r,3s)-2-[(1r)-1-(3-fluorophenyl)ethoxy]-3-phenylmorpholine Chemical compound C1([C@@H]2NCCO[C@@H]2O[C@H](C)C=2C=C(F)C=CC=2)=CC=CC=C1 TYBDKZULYJZJHG-JEBQAFNWSA-N 0.000 claims description 3
• GZYHKFCJYSGQLI-GQWLDOHISA-N (2r,3s)-2-[(1r)-1-(3-tert-butyl-5-chlorophenyl)ethoxy]-3-phenylmorpholine Chemical compound C1([C@@H]2NCCO[C@@H]2O[C@H](C)C=2C=C(C=C(Cl)C=2)C(C)(C)C)=CC=CC=C1 GZYHKFCJYSGQLI-GQWLDOHISA-N 0.000 claims description 3
• ROWAVFJDBQLRRX-JEBQAFNWSA-N (2r,3s)-2-[(1r)-1-(4-fluorophenyl)ethoxy]-3-phenylmorpholine Chemical compound C1([C@@H]2NCCO[C@@H]2O[C@H](C)C=2C=CC(F)=CC=2)=CC=CC=C1 ROWAVFJDBQLRRX-JEBQAFNWSA-N 0.000 claims description 3
• UTDANMPTVJPQFZ-OCBCSQNSSA-N (2r,3s)-2-[(1r)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy]-3-phenylmorpholine Chemical compound C1([C@@H]2NCCO[C@@H]2O[C@H](C)C=2C=C(C=C(C=2)C(F)(F)F)C(F)(F)F)=CC=CC=C1 UTDANMPTVJPQFZ-OCBCSQNSSA-N 0.000 claims description 3
• VATKTLKLUWNHOT-OCBCSQNSSA-N (2r,3s)-2-[(1r)-1-[3-fluoro-5-(trifluoromethyl)phenyl]ethoxy]-3-phenylmorpholine Chemical compound C1([C@@H]2NCCO[C@@H]2O[C@H](C)C=2C=C(C=C(F)C=2)C(F)(F)F)=CC=CC=C1 VATKTLKLUWNHOT-OCBCSQNSSA-N 0.000 claims description 3
• DGRPRBMQPYZAEY-GQWLDOHISA-N (2r,3s)-2-[(1r)-1-[3-tert-butyl-5-(trifluoromethyl)phenyl]ethoxy]-3-phenylmorpholine Chemical compound C1([C@@H]2NCCO[C@@H]2O[C@H](C)C=2C=C(C=C(C=2)C(C)(C)C)C(F)(F)F)=CC=CC=C1 DGRPRBMQPYZAEY-GQWLDOHISA-N 0.000 claims description 3
• UHFOWTRPYYCNIS-CNOZUTPLSA-N (2r,3s)-2-[(1r)-1-[4-chloro-3,5-bis(trifluoromethyl)phenyl]ethoxy]-3-phenylmorpholine Chemical compound C1([C@@H]2NCCO[C@@H]2O[C@H](C)C=2C=C(C(Cl)=C(C=2)C(F)(F)F)C(F)(F)F)=CC=CC=C1 UHFOWTRPYYCNIS-CNOZUTPLSA-N 0.000 claims description 3
• MYAVTJWBVDSCNS-TYCQWZJGSA-N (2r,3s)-3-phenyl-2-[(1r)-1-(3-propan-2-yloxyphenyl)ethoxy]morpholine Chemical compound CC(C)OC1=CC=CC([C@@H](C)O[C@@H]2[C@@H](NCCO2)C=2C=CC=CC=2)=C1 MYAVTJWBVDSCNS-TYCQWZJGSA-N 0.000 claims description 3
• AOHUTFLEHKBVQC-FHLIZLRMSA-N (2r,3s)-3-phenyl-2-[(1r)-1-phenylethoxy]morpholine Chemical compound C1([C@@H]2NCCO[C@@H]2O[C@H](C)C=2C=CC=CC=2)=CC=CC=C1 AOHUTFLEHKBVQC-FHLIZLRMSA-N 0.000 claims description 3
• 125000005940 1,4-dioxanyl group Chemical group 0.000 claims description 3
• GIEVLRPLUQUMSH-SSKADXOYSA-N CC(C)OC1=CC(C(F)(F)F)=CC([C@@H](C)O[C@H]2OCCNC2C2=CC=CC=C2)=C1 Chemical compound CC(C)OC1=CC(C(F)(F)F)=CC([C@@H](C)O[C@H]2OCCNC2C2=CC=CC=C2)=C1 GIEVLRPLUQUMSH-SSKADXOYSA-N 0.000 claims description 3
• HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 3
• 239000003960 organic solvent Substances 0.000 claims description 3
• 229910052725 zinc Inorganic materials 0.000 claims description 3
• 239000011701 zinc Substances 0.000 claims description 3
• MCFDDLSGKLCKMZ-MDASCCDHSA-N (2r,3s)-2-[(1r)-1-(3-bromo-5-methylphenyl)ethoxy]-3-phenylmorpholine Chemical compound C1([C@@H]2NCCO[C@@H]2O[C@H](C)C=2C=C(Br)C=C(C)C=2)=CC=CC=C1 MCFDDLSGKLCKMZ-MDASCCDHSA-N 0.000 claims description 2
• PRRZOZPOIBFIIO-CNOZUTPLSA-N (2r,3s)-2-[(1r)-1-[2,5-bis(trifluoromethyl)phenyl]ethoxy]-3-(4-fluorophenyl)morpholine Chemical compound C1([C@@H]2NCCO[C@@H]2O[C@H](C)C=2C(=CC=C(C=2)C(F)(F)F)C(F)(F)F)=CC=C(F)C=C1 PRRZOZPOIBFIIO-CNOZUTPLSA-N 0.000 claims description 2
• XNKRXVKJFYNGEO-OCBCSQNSSA-N (2r,3s)-2-[(1r)-1-[3-chloro-5-(trifluoromethyl)phenyl]ethoxy]-3-phenylmorpholine Chemical compound C1([C@@H]2NCCO[C@@H]2O[C@H](C)C=2C=C(C=C(Cl)C=2)C(F)(F)F)=CC=CC=C1 XNKRXVKJFYNGEO-OCBCSQNSSA-N 0.000 claims description 2
• UTDANMPTVJPQFZ-UYHISHBKSA-N (2r,3s)-2-[(1s)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy]-3-phenylmorpholine Chemical compound C1([C@@H]2NCCO[C@@H]2O[C@@H](C)C=2C=C(C=C(C=2)C(F)(F)F)C(F)(F)F)=CC=CC=C1 UTDANMPTVJPQFZ-UYHISHBKSA-N 0.000 claims description 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 description 2
• WPYMKLBDIGXBTP-UHFFFAOYSA-N Benzoic acid Natural products OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 2
• RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 claims description 2
• 239000003638 chemical reducing agent Substances 0.000 claims description 2
• 239000010936 titanium Substances 0.000 claims description 2
• 229910052719 titanium Inorganic materials 0.000 claims description 2
• XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 claims description 2
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 28
• 239000005711 Benzoic acid Substances 0.000 claims 1
• 150000004703 alkoxides Chemical class 0.000 claims 1
• 230000003042 antagnostic effect Effects 0.000 claims 1
• 235000010233 benzoic acid Nutrition 0.000 claims 1
• 150000001558 benzoic acid derivatives Chemical class 0.000 claims 1
• CHIHQLCVLOXUJW-UHFFFAOYSA-N benzoic anhydride Chemical class C=1C=CC=CC=1C(=O)OC(=O)C1=CC=CC=C1 CHIHQLCVLOXUJW-UHFFFAOYSA-N 0.000 claims 1
• 230000000903 blocking effect Effects 0.000 claims 1
• PESYEWKSBIWTAK-UHFFFAOYSA-N cyclopenta-1,3-diene;titanium(2+) Chemical compound [Ti+2].C=1C=C[CH-]C=1.C=1C=C[CH-]C=1 PESYEWKSBIWTAK-UHFFFAOYSA-N 0.000 claims 1
• ORVACBDINATSAR-UHFFFAOYSA-N dimethylaluminum Chemical compound C[Al]C ORVACBDINATSAR-UHFFFAOYSA-N 0.000 claims 1
• BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 claims 1
• 238000011282 treatment Methods 0.000 abstract description 43
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 37
• 201000010099 disease Diseases 0.000 abstract description 28
• 230000036407 pain Effects 0.000 abstract description 20
• 208000019695 Migraine disease Diseases 0.000 abstract description 14
• 206010027599 migraine Diseases 0.000 abstract description 13
• 208000006673 asthma Diseases 0.000 abstract description 12
• 208000027866 inflammatory disease Diseases 0.000 abstract description 7
• 206010002383 Angina Pectoris Diseases 0.000 abstract description 4
• 206010065390 Inflammatory pain Diseases 0.000 abstract description 4
• 229940127291 Calcium channel antagonist Drugs 0.000 abstract description 3
• 206010020772 Hypertension Diseases 0.000 abstract description 3
• 239000000480 calcium channel blocker Substances 0.000 abstract description 3
• 208000028867 ischemia Diseases 0.000 abstract description 2
• 239000002327 cardiovascular agent Substances 0.000 abstract 1
• 229940125692 cardiovascular agent Drugs 0.000 abstract 1
• 239000002895 emetic Substances 0.000 abstract 1
• 125000004435 hydrogen atom Chemical class [H]* 0.000 abstract 1
• IMCGHZIGRANKHV-AJNGGQMLSA-N tert-butyl (3s,5s)-2-oxo-5-[(2s,4s)-5-oxo-4-propan-2-yloxolan-2-yl]-3-propan-2-ylpyrrolidine-1-carboxylate Chemical compound O1C(=O)[C@H](C(C)C)C[C@H]1[C@H]1N(C(=O)OC(C)(C)C)C(=O)[C@H](C(C)C)C1 IMCGHZIGRANKHV-AJNGGQMLSA-N 0.000 abstract 1
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 192
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 177
• 239000000243 solution Substances 0.000 description 171
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 138
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 135
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 130
• 206010057190 Respiratory tract infections Diseases 0.000 description 123
• 235000019439 ethyl acetate Nutrition 0.000 description 69
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 68
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 64
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 54
• 239000010410 layer Substances 0.000 description 53
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 53
• 238000003818 flash chromatography Methods 0.000 description 48
• 239000012044 organic layer Substances 0.000 description 48
• 238000006243 chemical reaction Methods 0.000 description 39
• 239000003921 oil Substances 0.000 description 39
• 235000019198 oils Nutrition 0.000 description 39
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 38
• 239000007787 solid Substances 0.000 description 38
• 239000000741 silica gel Substances 0.000 description 37
• 229910002027 silica gel Inorganic materials 0.000 description 37
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