JP2500279C

JP2500279C -

Info

Publication number: JP2500279C
Authority: JP; Japan
Prior art keywords: azabicyclo; diphenylmethyl; octane; cis; trans
Prior art date: 1999-07-05
Legal status : Expired - Lifetime

Application number

Other languages

English (en)

Japanese (ja)

Original Assignee

メルクシャープエンドドームリミテッド

Publication date

1999-07-05

Links

150000001875 compounds Chemical class 0.000 claims description 86
YMWUJEATGCHHMB-UHFFFAOYSA-N methylene dichloride Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 70
239000000203 mixture Substances 0.000 claims description 50
125000005982 diphenylmethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 32
229910052799 carbon Inorganic materials 0.000 claims description 29
-1 3,5-dimethylbenzyloxy Chemical group 0.000 claims description 27
239000011780 sodium chloride Substances 0.000 claims description 26
150000003839 salts Chemical class 0.000 claims description 21
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 21
229910052739 hydrogen Inorganic materials 0.000 claims description 17
238000006243 chemical reaction Methods 0.000 claims description 14
125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 12
125000000217 alkyl group Chemical group 0.000 claims description 9
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 8
125000004122 cyclic group Chemical group 0.000 claims description 8
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 6
238000004519 manufacturing process Methods 0.000 claims description 6
125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims description 5
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 5
125000001424 substituent group Chemical group 0.000 claims description 4
239000002462 tachykinin receptor antagonist Substances 0.000 claims description 3
TVMXDCGIABBOFY-UHFFFAOYSA-N Octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 claims description 2
125000001475 halogen functional group Chemical group 0.000 claims 2
VDWODSPSMJMZQI-UHFFFAOYSA-N 2-methyl-1-azabicyclo[2.2.2]octane Chemical compound C1CN2C(C)CC1CC2 VDWODSPSMJMZQI-UHFFFAOYSA-N 0.000 claims 1
239000000969 carrier Substances 0.000 claims 1
IMNFDUFMRHMDMM-UHFFFAOYSA-N n-heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 claims 1
RTZKZFJDLAIYFH-UHFFFAOYSA-N diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 50
XEKOWRVHYACXOJ-UHFFFAOYSA-N acetic acid ethyl ester Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 48
OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 47
YXFVVABEGXRONW-UHFFFAOYSA-N toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 34
VYPSYNLAJGMNEJ-UHFFFAOYSA-N silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 33
239000000243 solution Substances 0.000 description 32
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 28
VEXZGXHMUGYJMC-UHFFFAOYSA-N HCl Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 26
MUBZPKHOEPUJKR-UHFFFAOYSA-N oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 24
238000004587 chromatography analysis Methods 0.000 description 21
HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
239000002904 solvent Substances 0.000 description 18
WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 17
239000007787 solid Substances 0.000 description 16
238000005160 1H NMR spectroscopy Methods 0.000 description 15
VLKZOEOYAKHREP-UHFFFAOYSA-N hexane Substances CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 15
125000005843 halogen group Chemical group 0.000 description 14
239000000047 product Substances 0.000 description 14
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 13
239000000377 silicon dioxide Substances 0.000 description 13
238000003756 stirring Methods 0.000 description 13
ADNPLDHMAVUMIW-CUZNLEPHSA-N (2S)-2-[[(2S)-1-[(2S)-6-amino-2-[[(2S)-1-[(2S)-2-amino-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]amino]hexanoyl]pyrrolidine-2-carbonyl]amino]-N-[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-1-[[(2S)-1-amino-4-methylsulfanyl-1-oxobutan-2-y Chemical compound C([C@@H](C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(N)=O)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](N)CCCN=C(N)N)C1=CC=CC=C1 ADNPLDHMAVUMIW-CUZNLEPHSA-N 0.000 description 12
102100002996 TAC1 Human genes 0.000 description 12
101700065588 TAC1 Proteins 0.000 description 12
XTHFKEDIFFGKHM-UHFFFAOYSA-N dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 12
239000003480 eluent Substances 0.000 description 12
239000012458 free base Substances 0.000 description 12
125000000473 carbonimidoyl group Chemical group [H]\N=C(/*)* 0.000 description 11
LFQSCWFLJHTTHZ-UHFFFAOYSA-N ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 11
125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 11
CSNNHWWHGAXBCP-UHFFFAOYSA-L mgso4 Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 10
UIIMBOGNXHQVGW-UHFFFAOYSA-M NaHCO3 Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 9
201000010099 disease Diseases 0.000 description 9
KFZMGEQAYNKOFK-UHFFFAOYSA-N iso-propanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 9
239000012299 nitrogen atmosphere Substances 0.000 description 9
238000010992 reflux Methods 0.000 description 9
PNEYBMLMFCGWSK-UHFFFAOYSA-N AI2O3 Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 8
230000035693 Fab Effects 0.000 description 8
102000003141 Tachykinins Human genes 0.000 description 8
108060008037 Tachykinins Proteins 0.000 description 8
239000012298 atmosphere Substances 0.000 description 8
239000002585 base Substances 0.000 description 8
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
KWYUFKZDYYNOTN-UHFFFAOYSA-M potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 8
238000000746 purification Methods 0.000 description 8
239000011734 sodium Substances 0.000 description 8
206010003246 Arthritis Diseases 0.000 description 7
239000008079 hexane Substances 0.000 description 7
229910000041 hydrogen chloride Inorganic materials 0.000 description 7
239000003921 oil Substances 0.000 description 7
235000019198 oils Nutrition 0.000 description 7
235000006408 oxalic acid Nutrition 0.000 description 7
IAZDPXIOMUYVGZ-WFGJKAKNSA-N DMSO-d6 Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 6
208000002193 Pain Diseases 0.000 description 6
IUBQJLUDMLPAGT-UHFFFAOYSA-N Potassium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([K])[Si](C)(C)C IUBQJLUDMLPAGT-UHFFFAOYSA-N 0.000 description 6
239000002253 acid Substances 0.000 description 6
125000001309 chloro group Chemical group Cl* 0.000 description 6
HPQVWDOOUQVBTO-UHFFFAOYSA-N lithium aluminium hydride Substances [Li+].[Al-] HPQVWDOOUQVBTO-UHFFFAOYSA-N 0.000 description 6
OCZDCIYGECBNKL-UHFFFAOYSA-N lithium;alumanuide Chemical compound [Li+].[AlH4-] OCZDCIYGECBNKL-UHFFFAOYSA-N 0.000 description 6
239000012044 organic layer Substances 0.000 description 6
230000036407 pain Effects 0.000 description 6
239000002244 precipitate Substances 0.000 description 6
QXDHXCVJGBTQMK-UHFFFAOYSA-N 1-(bromomethyl)-3,5-dimethylbenzene Chemical compound CC1=CC(C)=CC(CBr)=C1 QXDHXCVJGBTQMK-UHFFFAOYSA-N 0.000 description 5
NMRPBPVERJPACX-UHFFFAOYSA-N 3-Octanol Chemical compound CCCCCC(O)CC NMRPBPVERJPACX-UHFFFAOYSA-N 0.000 description 5
150000001408 amides Chemical class 0.000 description 5
230000000694 effects Effects 0.000 description 5
239000000284 extract Substances 0.000 description 5
239000000706 filtrate Substances 0.000 description 5
239000001257 hydrogen Substances 0.000 description 5
239000010410 layer Substances 0.000 description 5
229910052943 magnesium sulfate Inorganic materials 0.000 description 5
235000019341 magnesium sulphate Nutrition 0.000 description 5
238000000034 method Methods 0.000 description 5
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 5
229910052757 nitrogen Inorganic materials 0.000 description 5
239000006187 pill Substances 0.000 description 5
238000001953 recrystallisation Methods 0.000 description 5
239000003826 tablet Substances 0.000 description 5
GKIOTMSOXQMART-UHFFFAOYSA-N 2-benzhydryl-1-azabicyclo[2.2.2]octan-3-ol Chemical compound OC1C(CC2)CCN2C1C(C=1C=CC=CC=1)C1=CC=CC=C1 GKIOTMSOXQMART-UHFFFAOYSA-N 0.000 description 4
206010001897 Alzheimer's disease Diseases 0.000 description 4
VZGDMQKNWNREIO-UHFFFAOYSA-N Carbon tetrachloride Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 4
RIOQSEWOXXDEQQ-UHFFFAOYSA-N Triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 4
CSCPPACGZOOCGX-UHFFFAOYSA-N acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
125000003545 alkoxy group Chemical group 0.000 description 4
230000003042 antagnostic Effects 0.000 description 4
239000005557 antagonist Substances 0.000 description 4
239000012267 brine Substances 0.000 description 4
239000003054 catalyst Substances 0.000 description 4
239000002552 dosage form Substances 0.000 description 4
239000003814 drug Substances 0.000 description 4
238000001704 evaporation Methods 0.000 description 4
230000002496 gastric Effects 0.000 description 4
238000004128 high performance liquid chromatography Methods 0.000 description 4
150000003840 hydrochlorides Chemical class 0.000 description 4
239000000543 intermediate Substances 0.000 description 4
150000002576 ketones Chemical class 0.000 description 4
230000003000 nontoxic Effects 0.000 description 4
231100000252 nontoxic Toxicity 0.000 description 4
201000008482 osteoarthritis Diseases 0.000 description 4
235000017557 sodium bicarbonate Nutrition 0.000 description 4
229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
239000000126 substance Substances 0.000 description 4
XEZNGIUYQVAUSS-UHFFFAOYSA-N 18-Crown-6 Chemical compound C1COCCOCCOCCOCCOCCO1 XEZNGIUYQVAUSS-UHFFFAOYSA-N 0.000 description 3
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 3
AGEZXYOZHKGVCM-UHFFFAOYSA-N Benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 3
206010027599 Migraine Diseases 0.000 description 3
208000008085 Migraine Disorders Diseases 0.000 description 3
SBYHFKPVCBCYGV-UHFFFAOYSA-N Quinuclidine Chemical compound C1CC2CCN1CC2 SBYHFKPVCBCYGV-UHFFFAOYSA-N 0.000 description 3
239000004480 active ingredient Substances 0.000 description 3
238000007792 addition Methods 0.000 description 3
235000019270 ammonium chloride Nutrition 0.000 description 3
230000003197 catalytic Effects 0.000 description 3
235000008504 concentrate Nutrition 0.000 description 3
239000012141 concentrate Substances 0.000 description 3
238000004090 dissolution Methods 0.000 description 3
238000010828 elution Methods 0.000 description 3
150000002148 esters Chemical class 0.000 description 3
UFHFLCQGNIYNRP-UHFFFAOYSA-N hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
239000007788 liquid Substances 0.000 description 3
QDHHCQZDFGDHMP-UHFFFAOYSA-N monochloramine Chemical compound ClN QDHHCQZDFGDHMP-UHFFFAOYSA-N 0.000 description 3
239000012452 mother liquor Substances 0.000 description 3
ZHVULPDNOFUIML-UHFFFAOYSA-N octane;hydrochloride Chemical compound Cl.CCCCCCCC ZHVULPDNOFUIML-UHFFFAOYSA-N 0.000 description 3
ZLMJMSJWJFRBEC-UHFFFAOYSA-N potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 3
WZZYMDMRFBBOOZ-NQCAZLHCSA-L potassium;(2S)-5-oxopyrrolidine-2-carboxylate;(2R)-5-oxopyrrolidine-2-carboxylate Chemical compound [K+].[O-]C(=O)[C@H]1CCC(=O)N1.[O-]C(=O)[C@@H]1CCC(=O)N1 WZZYMDMRFBBOOZ-NQCAZLHCSA-L 0.000 description 3
239000000651 prodrug Substances 0.000 description 3
229940002612 prodrugs Drugs 0.000 description 3
125000006239 protecting group Chemical group 0.000 description 3
239000011541 reaction mixture Substances 0.000 description 3
FAPWRFPIFSIZLT-UHFFFAOYSA-M sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
BZKBCQXYZZXSCO-UHFFFAOYSA-N sodium hydride Chemical compound [H-].[Na+] BZKBCQXYZZXSCO-UHFFFAOYSA-N 0.000 description 3
239000007858 starting material Substances 0.000 description 3
239000012258 stirred mixture Substances 0.000 description 3
239000000725 suspension Substances 0.000 description 3
230000001702 transmitter Effects 0.000 description 3
VZCYOOQTPOCHFL-OWOJBTEDSA-N (E)-but-2-enedioate;hydron Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
HMDQPBSDHHTRNI-UHFFFAOYSA-N 1-(chloromethyl)-3-ethenylbenzene Chemical compound ClCC1=CC=CC(C=C)=C1 HMDQPBSDHHTRNI-UHFFFAOYSA-N 0.000 description 2
ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 2
206010002026 Amyotrophic lateral sclerosis Diseases 0.000 description 2
OZAIFHULBGXAKX-VAWYXSNFSA-N Azobisisobutyronitrile Chemical compound N#CC(C)(C)\N=N\C(C)(C)C#N OZAIFHULBGXAKX-VAWYXSNFSA-N 0.000 description 2
208000006561 Cluster Headache Diseases 0.000 description 2
208000004275 Demyelinating Disease Diseases 0.000 description 2
201000010374 Down syndrome Diseases 0.000 description 2
210000001035 Gastrointestinal Tract Anatomy 0.000 description 2
206010021972 Inflammatory bowel disease Diseases 0.000 description 2
YNESATAKKCNGOF-UHFFFAOYSA-N Lithium bis(trimethylsilyl)amide Chemical group [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 2
PCLIMKBDDGJMGD-UHFFFAOYSA-N N-Bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 2
229910004664 ORa Inorganic materials 0.000 description 2
NROKBHXJSPEDAR-UHFFFAOYSA-M Potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 description 2
206010039073 Rheumatoid arthritis Diseases 0.000 description 2
RXZBMPWDPOLZGW-XMRMVWPWSA-N Roxithromycin Chemical group O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=N/OCOCCOC)/[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 RXZBMPWDPOLZGW-XMRMVWPWSA-N 0.000 description 2
GEHJYWRUCIMESM-UHFFFAOYSA-L Sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
QIQXTHQIDYTFRH-UHFFFAOYSA-N Stearic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 2
206010044688 Trisomy 21 Diseases 0.000 description 2
ZCHPKWUIAASXPV-UHFFFAOYSA-N acetic acid;methanol Chemical compound OC.CC(O)=O ZCHPKWUIAASXPV-UHFFFAOYSA-N 0.000 description 2
WEVYAHXRMPXWCK-UHFFFAOYSA-N acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 2
150000007513 acids Chemical class 0.000 description 2
229910052783 alkali metal Inorganic materials 0.000 description 2
229910000102 alkali metal hydride Inorganic materials 0.000 description 2
150000008046 alkali metal hydrides Chemical class 0.000 description 2
XAGFODPZIPBFFR-UHFFFAOYSA-N aluminum Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 2
239000007864 aqueous solution Substances 0.000 description 2
239000012300 argon atmosphere Substances 0.000 description 2
235000020127 ayran Nutrition 0.000 description 2
230000005540 biological transmission Effects 0.000 description 2
125000001246 bromo group Chemical group Br* 0.000 description 2
239000002775 capsule Substances 0.000 description 2
230000000875 corresponding Effects 0.000 description 2
239000012043 crude product Substances 0.000 description 2
238000002425 crystallisation Methods 0.000 description 2
230000005712 crystallization Effects 0.000 description 2
IAZDPXIOMUYVGZ-UHFFFAOYSA-N dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
150000002009 diols Chemical class 0.000 description 2
239000003937 drug carrier Substances 0.000 description 2
239000000839 emulsion Substances 0.000 description 2
125000001153 fluoro group Chemical group F* 0.000 description 2
230000005484 gravity Effects 0.000 description 2
KLGZELKXQMTEMM-UHFFFAOYSA-N hydride Chemical compound [H-] KLGZELKXQMTEMM-UHFFFAOYSA-N 0.000 description 2
238000005984 hydrogenation reaction Methods 0.000 description 2
200000000018 inflammatory disease Diseases 0.000 description 2
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
MBKUHNGECMPIHH-UHFFFAOYSA-N methyl 3-ethenylbenzoate Chemical compound COC(=O)C1=CC=CC(C=C)=C1 MBKUHNGECMPIHH-UHFFFAOYSA-N 0.000 description 2
210000000653 nervous system Anatomy 0.000 description 2
239000003960 organic solvent Substances 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
OAICVXFJPJFONN-UHFFFAOYSA-N phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 2
229910052698 phosphorus Inorganic materials 0.000 description 2
239000011574 phosphorus Substances 0.000 description 2
OCFVSFVLVRNXFJ-UHFFFAOYSA-N potassium hydride Inorganic materials [H-].[K+] OCFVSFVLVRNXFJ-UHFFFAOYSA-N 0.000 description 2
238000002360 preparation method Methods 0.000 description 2
230000002265 prevention Effects 0.000 description 2
102000004196 processed proteins & peptides Human genes 0.000 description 2
108090000765 processed proteins & peptides Proteins 0.000 description 2
BDERNNFJNOPAEC-UHFFFAOYSA-N propanol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
239000003638 reducing agent Substances 0.000 description 2
230000001953 sensory Effects 0.000 description 2
KEAYESYHFKHZAL-UHFFFAOYSA-N sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
229910052708 sodium Inorganic materials 0.000 description 2
238000003786 synthesis reaction Methods 0.000 description 2
210000001519 tissues Anatomy 0.000 description 2
ZMANZCXQSJIPKH-UHFFFAOYSA-N triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 2
238000007738 vacuum evaporation Methods 0.000 description 2
230000024883 vasodilation Effects 0.000 description 2
OJFWESQAJYZOKE-UHFFFAOYSA-N (2-bromo-1,1,1,3,3,3-hexafluoropropan-2-yl)benzene Chemical compound FC(F)(F)C(Br)(C(F)(F)F)C1=CC=CC=C1 OJFWESQAJYZOKE-UHFFFAOYSA-N 0.000 description 1
LNAZSHAWQACDHT-XIYTZBAFSA-N (2R,3R,4S,5R,6S)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2S,3R,4S,5R,6R)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2R,3R,4S,5R,6R)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
FPDDOFWJHHYHOU-UHFFFAOYSA-N (3-ethenylphenyl)methanol Chemical compound OCC1=CC=CC(C=C)=C1 FPDDOFWJHHYHOU-UHFFFAOYSA-N 0.000 description 1
JEIWMMMVZOQQHT-UHFFFAOYSA-N 1,2,2-trimethylcyclopentane-1,3-dicarbonyl chloride Chemical compound CC1(C)C(C(Cl)=O)CCC1(C)C(Cl)=O JEIWMMMVZOQQHT-UHFFFAOYSA-N 0.000 description 1
ZFLRKAMKGYNFPH-UHFFFAOYSA-N 1,3-dichloro-5-(chloromethyl)benzene Chemical compound ClCC1=CC(Cl)=CC(Cl)=C1 ZFLRKAMKGYNFPH-UHFFFAOYSA-N 0.000 description 1
TXVVVEUSVBLDED-UHFFFAOYSA-N 1-(bromomethyl)-2-(trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=CC=C1CBr TXVVVEUSVBLDED-UHFFFAOYSA-N 0.000 description 1
LZIYAIRGDHSVED-UHFFFAOYSA-N 1-(bromomethyl)-3-chlorobenzene Chemical compound ClC1=CC=CC(CBr)=C1 LZIYAIRGDHSVED-UHFFFAOYSA-N 0.000 description 1
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238000004809 thin layer chromatography Methods 0.000 description 1
ZSLUVFAKFWKJRC-UHFFFAOYSA-N thorium Chemical compound [Th] ZSLUVFAKFWKJRC-UHFFFAOYSA-N 0.000 description 1
JOXIMZWYDAKGHI-UHFFFAOYSA-M toluene-4-sulfonate Chemical compound CC1=CC=C(S([O-])(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-M 0.000 description 1
QIWRFOJWQSSRJZ-UHFFFAOYSA-N tributyl(ethenyl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C=C QIWRFOJWQSSRJZ-UHFFFAOYSA-N 0.000 description 1
UZEVVLMPUHZSOZ-UHFFFAOYSA-N triethylboranuide Chemical compound CC[BH-](CC)CC UZEVVLMPUHZSOZ-UHFFFAOYSA-N 0.000 description 1
USXXUTHCANUHBW-UHFFFAOYSA-N trimethylsilylazanide Chemical compound C[Si](C)(C)[NH-] USXXUTHCANUHBW-UHFFFAOYSA-N 0.000 description 1
201000006704 ulcerative colitis Diseases 0.000 description 1
239000003039 volatile agent Substances 0.000 description 1
238000010626 work up procedure Methods 0.000 description 1