JPS6222986B2 - - Google Patents

Info

Publication number: JPS6222986B2
Authority: JP; Japan
Prior art keywords: hydantoin; formula; carboxyhexyl; compound; alkyl
Prior art date: 1976-06-03
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

Application number

JP52065252A

Other languages

English (en)

Japanese (ja)

Other versions

JPS52151168A (en

Inventor

Goodon Karudoeru Arubaato

Uitsutoteikaa Nooman

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Wellcome Foundation Ltd

Original Assignee

Wellcome Foundation Ltd

Priority date (The priority date 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 date listed.)

1976-06-03

Filing date

1977-06-02

Publication date

1987-05-20

1977-06-02 Application filed by Wellcome Foundation Ltd filed Critical Wellcome Foundation Ltd

1977-12-15 Publication of JPS52151168A publication Critical patent/JPS52151168A/ja

1987-05-20 Publication of JPS6222986B2 publication Critical patent/JPS6222986B2/ja

Status Granted legal-status Critical Current

Links

150000001875 compounds Chemical class 0.000 claims description 94
125000000217 alkyl group Chemical group 0.000 claims description 35
239000001257 hydrogen Substances 0.000 claims description 28
229910052739 hydrogen Inorganic materials 0.000 claims description 28
150000003839 salts Chemical class 0.000 claims description 17
150000002148 esters Chemical class 0.000 claims description 16
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 15
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 12
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 10
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 9
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 9
ICXMXDCVHKIDJF-UHFFFAOYSA-N 7-[3-(3-hydroxyoctyl)-2,5-dioxoimidazolidin-4-yl]heptanoic acid Chemical compound CCCCCC(O)CCN1C(CCCCCCC(O)=O)C(=O)NC1=O ICXMXDCVHKIDJF-UHFFFAOYSA-N 0.000 claims description 6
125000004432 carbon atom Chemical group C* 0.000 claims description 6
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 5
125000003710 aryl alkyl group Chemical group 0.000 claims description 3
CWNBYFYKHCQJOK-UHFFFAOYSA-N 7-[3-(3-cyclobutyl-3-hydroxypropyl)-2,5-dioxoimidazolidin-4-yl]heptanoic acid Chemical compound C1CCC1C(O)CCN1C(CCCCCCC(O)=O)C(=O)NC1=O CWNBYFYKHCQJOK-UHFFFAOYSA-N 0.000 claims description 2
ZIDQIOZJEJFMOH-UHFFFAOYSA-N 7-[3-(3-cyclohexyl-3-hydroxypropyl)-2,5-dioxoimidazolidin-4-yl]heptanoic acid Chemical compound C1CCCCC1C(O)CCN1C(CCCCCCC(O)=O)C(=O)NC1=O ZIDQIOZJEJFMOH-UHFFFAOYSA-N 0.000 claims description 2
OBWREGPIKZZJLZ-UHFFFAOYSA-N 7-[3-(3-hydroxy-4,4-dimethyloctyl)-2,5-dioxoimidazolidin-4-yl]heptanoic acid Chemical compound CCCCC(C)(C)C(O)CCN1C(CCCCCCC(O)=O)C(=O)NC1=O OBWREGPIKZZJLZ-UHFFFAOYSA-N 0.000 claims description 2
MMKYCYXOGGDSNF-UHFFFAOYSA-N 7-[3-(3-hydroxy-4,4-dimethylpentyl)-2,5-dioxoimidazolidin-4-yl]heptanoic acid Chemical compound CC(C)(C)C(O)CCN1C(CCCCCCC(O)=O)C(=O)NC1=O MMKYCYXOGGDSNF-UHFFFAOYSA-N 0.000 claims description 2
KZAUFLQTAMVHIV-UHFFFAOYSA-N 7-[3-(3-hydroxynonyl)-2,5-dioxoimidazolidin-4-yl]heptanoic acid Chemical compound CCCCCCC(O)CCN1C(CCCCCCC(O)=O)C(=O)NC1=O KZAUFLQTAMVHIV-UHFFFAOYSA-N 0.000 claims description 2
QQMADWFRXYPOPL-UHFFFAOYSA-N 1-(3-oxooctyl)imidazolidine-2,4-dione Chemical compound O=C(CCN1C(=O)NC(=O)C1)CCCCC QQMADWFRXYPOPL-UHFFFAOYSA-N 0.000 claims 1
AMAYXRDWNRWCBM-UHFFFAOYSA-N 7-[3-(3-cyclopentyl-3-hydroxypropyl)-2,5-dioxoimidazolidin-4-yl]heptanoic acid Chemical compound C1CCCC1C(O)CCN1C(CCCCCCC(O)=O)C(=O)NC1=O AMAYXRDWNRWCBM-UHFFFAOYSA-N 0.000 claims 1
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims 1
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 125
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 77
239000000243 solution Substances 0.000 description 77
-1 Lithium metals Chemical class 0.000 description 70
239000003921 oil Substances 0.000 description 56
239000000203 mixture Substances 0.000 description 51
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 49
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 45
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 44
238000002844 melting Methods 0.000 description 43
230000008018 melting Effects 0.000 description 43
229940091173 hydantoin Drugs 0.000 description 39
235000019441 ethanol Nutrition 0.000 description 35
238000000034 method Methods 0.000 description 34
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 33
WJRBRSLFGCUECM-UHFFFAOYSA-N hydantoin Chemical compound O=C1CNC(=O)N1 WJRBRSLFGCUECM-UHFFFAOYSA-N 0.000 description 33
238000006243 chemical reaction Methods 0.000 description 27
CQMYCPZZIPXILQ-UHFFFAOYSA-N diethyl nonanedioate Chemical compound CCOC(=O)CCCCCCCC(=O)OCC CQMYCPZZIPXILQ-UHFFFAOYSA-N 0.000 description 23
239000002253 acid Substances 0.000 description 22
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 20
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 19
239000012230 colorless oil Substances 0.000 description 19
150000001469 hydantoins Chemical class 0.000 description 19
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 18
238000009835 boiling Methods 0.000 description 18
239000000284 extract Substances 0.000 description 18
238000003756 stirring Methods 0.000 description 18
239000002904 solvent Substances 0.000 description 16
GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical compound C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 description 15
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
229940125797 compound 12 Drugs 0.000 description 15
238000004519 manufacturing process Methods 0.000 description 15
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 15
VGUWZCUCNQXGBU-UHFFFAOYSA-N 3-[(4-methylpiperazin-1-yl)methyl]-5-nitro-1h-indole Chemical compound C1CN(C)CCN1CC1=CNC2=CC=C([N+]([O-])=O)C=C12 VGUWZCUCNQXGBU-UHFFFAOYSA-N 0.000 description 14
230000000694 effects Effects 0.000 description 14
239000000047 product Substances 0.000 description 14
238000002347 injection Methods 0.000 description 11
239000007924 injection Substances 0.000 description 11
241000124008 Mammalia Species 0.000 description 10
239000013078 crystal Substances 0.000 description 10
238000002360 preparation method Methods 0.000 description 10
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
239000002585 base Substances 0.000 description 9
239000003814 drug Substances 0.000 description 9
238000009472 formulation Methods 0.000 description 9
239000005457 ice water Substances 0.000 description 9
239000000843 powder Substances 0.000 description 9
239000007787 solid Substances 0.000 description 9
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
239000000543 intermediate Substances 0.000 description 8
GKKCIDNWFBPDBW-UHFFFAOYSA-M potassium cyanate Chemical compound [K]OC#N GKKCIDNWFBPDBW-UHFFFAOYSA-M 0.000 description 8
229910052708 sodium Inorganic materials 0.000 description 8
239000011734 sodium Substances 0.000 description 8
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 7
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 description 7
239000003153 chemical reaction reagent Substances 0.000 description 7
239000012442 inert solvent Substances 0.000 description 7
238000000746 purification Methods 0.000 description 7
239000000377 silicon dioxide Substances 0.000 description 7
229910000033 sodium borohydride Inorganic materials 0.000 description 7
239000012279 sodium borohydride Substances 0.000 description 7
239000000126 substance Substances 0.000 description 7
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
241000700159 Rattus Species 0.000 description 6
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
229910052799 carbon Inorganic materials 0.000 description 6
239000003638 chemical reducing agent Substances 0.000 description 6
239000012259 ether extract Substances 0.000 description 6
238000004128 high performance liquid chromatography Methods 0.000 description 6
229930195733 hydrocarbon Natural products 0.000 description 6
230000007062 hydrolysis Effects 0.000 description 6
238000006460 hydrolysis reaction Methods 0.000 description 6
239000007788 liquid Substances 0.000 description 6
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
239000008213 purified water Substances 0.000 description 6
238000010992 reflux Methods 0.000 description 6
239000003826 tablet Substances 0.000 description 6
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 6
150000001298 alcohols Chemical class 0.000 description 5
229910052783 alkali metal Inorganic materials 0.000 description 5
150000001721 carbon Chemical group 0.000 description 5
238000004440 column chromatography Methods 0.000 description 5
238000001816 cooling Methods 0.000 description 5
229940079593 drug Drugs 0.000 description 5
239000008187 granular material Substances 0.000 description 5
150000002430 hydrocarbons Chemical class 0.000 description 5
231100000252 nontoxic Toxicity 0.000 description 5
230000003000 nontoxic effect Effects 0.000 description 5
239000011541 reaction mixture Substances 0.000 description 5
239000000741 silica gel Substances 0.000 description 5
229910002027 silica gel Inorganic materials 0.000 description 5
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 4
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
150000007513 acids Chemical class 0.000 description 4
150000001408 amides Chemical class 0.000 description 4
230000003042 antagnostic effect Effects 0.000 description 4
239000007864 aqueous solution Substances 0.000 description 4
210000004369 blood Anatomy 0.000 description 4
239000008280 blood Substances 0.000 description 4
239000002775 capsule Substances 0.000 description 4
150000001732 carboxylic acid derivatives Chemical class 0.000 description 4
238000004587 chromatography analysis Methods 0.000 description 4
229940125782 compound 2 Drugs 0.000 description 4
VZNFKFKDZBVGNF-UHFFFAOYSA-N diethyl 2-(3-hydroxyoctylamino)nonanedioate Chemical compound CCCCCC(O)CCNC(C(=O)OCC)CCCCCCC(=O)OCC VZNFKFKDZBVGNF-UHFFFAOYSA-N 0.000 description 4
IWPQQEFLLHFOCF-UHFFFAOYSA-N ethyl 2-[(7-ethoxy-7-oxoheptyl)amino]decanoate Chemical compound CCCCCCCCC(C(=O)OCC)NCCCCCCC(=O)OCC IWPQQEFLLHFOCF-UHFFFAOYSA-N 0.000 description 4
125000004494 ethyl ester group Chemical group 0.000 description 4
238000010438 heat treatment Methods 0.000 description 4
150000002431 hydrogen Chemical class 0.000 description 4
150000002576 ketones Chemical class 0.000 description 4
229910052757 nitrogen Inorganic materials 0.000 description 4
230000009467 reduction Effects 0.000 description 4
238000007363 ring formation reaction Methods 0.000 description 4
208000010110 spontaneous platelet aggregation Diseases 0.000 description 4
239000000725 suspension Substances 0.000 description 4
208000024891 symptom Diseases 0.000 description 4
150000003536 tetrazoles Chemical class 0.000 description 4
SZUVGFMDDVSKSI-WIFOCOSTSA-N (1s,2s,3s,5r)-1-(carboxymethyl)-3,5-bis[(4-phenoxyphenyl)methyl-propylcarbamoyl]cyclopentane-1,2-dicarboxylic acid Chemical compound O=C([C@@H]1[C@@H]([C@](CC(O)=O)([C@H](C(=O)N(CCC)CC=2C=CC(OC=3C=CC=CC=3)=CC=2)C1)C(O)=O)C(O)=O)N(CCC)CC(C=C1)=CC=C1OC1=CC=CC=C1 SZUVGFMDDVSKSI-WIFOCOSTSA-N 0.000 description 3
RAIXQSNYRUTLRE-UHFFFAOYSA-N 1-octylimidazolidine-2,4-dione Chemical compound CCCCCCCCN1CC(=O)NC1=O RAIXQSNYRUTLRE-UHFFFAOYSA-N 0.000 description 3
QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 3
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
206010006482 Bronchospasm Diseases 0.000 description 3
208000031226 Hyperlipidaemia Diseases 0.000 description 3
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 3
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
229920002472 Starch Polymers 0.000 description 3
208000007536 Thrombosis Diseases 0.000 description 3
239000004015 abortifacient agent Substances 0.000 description 3
231100000641 abortifacient agent Toxicity 0.000 description 3
230000002378 acidificating effect Effects 0.000 description 3
238000004220 aggregation Methods 0.000 description 3
230000002776 aggregation Effects 0.000 description 3
125000002947 alkylene group Chemical group 0.000 description 3
150000001412 amines Chemical class 0.000 description 3
230000002744 anti-aggregatory effect Effects 0.000 description 3
230000004071 biological effect Effects 0.000 description 3
230000015572 biosynthetic process Effects 0.000 description 3
230000036772 blood pressure Effects 0.000 description 3
230000007885 bronchoconstriction Effects 0.000 description 3
150000001768 cations Chemical class 0.000 description 3
229940126543 compound 14 Drugs 0.000 description 3
238000002425 crystallisation Methods 0.000 description 3
230000008025 crystallization Effects 0.000 description 3
LMVIQDQFGKIILS-UHFFFAOYSA-N diethyl 2-(octylamino)nonanedioate Chemical compound CCCCCCCCNC(C(=O)OCC)CCCCCCC(=O)OCC LMVIQDQFGKIILS-UHFFFAOYSA-N 0.000 description 3
239000003085 diluting agent Substances 0.000 description 3
239000002552 dosage form Substances 0.000 description 3
150000002170 ethers Chemical class 0.000 description 3
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
238000001704 evaporation Methods 0.000 description 3
238000001914 filtration Methods 0.000 description 3
239000004615 ingredient Substances 0.000 description 3
229910052500 inorganic mineral Inorganic materials 0.000 description 3
238000001990 intravenous administration Methods 0.000 description 3
239000012948 isocyanate Substances 0.000 description 3
239000008101 lactose Substances 0.000 description 3
235000019359 magnesium stearate Nutrition 0.000 description 3
229910052943 magnesium sulfate Inorganic materials 0.000 description 3
235000019341 magnesium sulphate Nutrition 0.000 description 3
239000012528 membrane Substances 0.000 description 3
235000010755 mineral Nutrition 0.000 description 3
239000011707 mineral Substances 0.000 description 3
238000000465 moulding Methods 0.000 description 3
150000002825 nitriles Chemical class 0.000 description 3
230000000144 pharmacologic effect Effects 0.000 description 3
125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 description 3
210000004623 platelet-rich plasma Anatomy 0.000 description 3
239000011148 porous material Substances 0.000 description 3
150000003180 prostaglandins Chemical class 0.000 description 3
239000002994 raw material Substances 0.000 description 3
229920006395 saturated elastomer Polymers 0.000 description 3
239000008107 starch Substances 0.000 description 3
235000019698 starch Nutrition 0.000 description 3
239000007858 starting material Substances 0.000 description 3
210000002784 stomach Anatomy 0.000 description 3
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
238000004809 thin layer chromatography Methods 0.000 description 3
231100000816 toxic dose Toxicity 0.000 description 3
QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 description 2
UZFMOKQJFYMBGY-UHFFFAOYSA-N 4-hydroxy-TEMPO Chemical compound CC1(C)CC(O)CC(C)(C)N1[O] UZFMOKQJFYMBGY-UHFFFAOYSA-N 0.000 description 2
QMKZSSRYCAZEFT-UHFFFAOYSA-N 5-octylimidazolidine-2,4-dione Chemical compound CCCCCCCCC1NC(=O)NC1=O QMKZSSRYCAZEFT-UHFFFAOYSA-N 0.000 description 2
NYJNESBEEDOJQB-UHFFFAOYSA-N 7-(5-octyl-2,4-dioxoimidazolidin-1-yl)heptanoic acid Chemical compound CCCCCCCCC1N(CCCCCCC(O)=O)C(=O)NC1=O NYJNESBEEDOJQB-UHFFFAOYSA-N 0.000 description 2
QAHBEAJDPRONLZ-NTCAYCPXSA-N 7-[(5e)-2,4-dioxo-5-(3-oxooctylidene)imidazolidin-1-yl]heptanoic acid Chemical compound CCCCCC(=O)C\C=C1\N(CCCCCCC(O)=O)C(=O)NC1=O QAHBEAJDPRONLZ-NTCAYCPXSA-N 0.000 description 2
WODBPAHYQHBSAP-NTCAYCPXSA-N 7-[(5e)-5-(3-hydroxyoctylidene)-2,4-dioxoimidazolidin-1-yl]heptanoic acid Chemical compound CCCCCC(O)C\C=C1\N(CCCCCCC(O)=O)C(=O)NC1=O WODBPAHYQHBSAP-NTCAYCPXSA-N 0.000 description 2
WMFMAAVGKGMXMB-UHFFFAOYSA-N 7-[2,5-dioxo-3-(3-oxooctyl)imidazolidin-4-yl]heptanoic acid Chemical compound CCCCCC(=O)CCN1C(CCCCCCC(O)=O)C(=O)NC1=O WMFMAAVGKGMXMB-UHFFFAOYSA-N 0.000 description 2
LONCVEMSOKBZHZ-UHFFFAOYSA-N 7-[3-[3-(oxan-2-yloxy)octyl]-2,5-dioxoimidazolidin-4-yl]heptanoic acid Chemical compound C1CCCOC1OC(CCCCC)CCN1C(CCCCCCC(O)=O)C(=O)NC1=O LONCVEMSOKBZHZ-UHFFFAOYSA-N 0.000 description 2
244000215068 Acacia senegal Species 0.000 description 2
DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 2
HGINCPLSRVDWNT-UHFFFAOYSA-N Acrolein Chemical compound C=CC=O HGINCPLSRVDWNT-UHFFFAOYSA-N 0.000 description 2
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
206010003210 Arteriosclerosis Diseases 0.000 description 2
BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 2
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 2
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 2
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
IYXGSMUGOJNHAZ-UHFFFAOYSA-N Ethyl malonate Chemical compound CCOC(=O)CC(=O)OCC IYXGSMUGOJNHAZ-UHFFFAOYSA-N 0.000 description 2
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
229920000084 Gum arabic Polymers 0.000 description 2
206010020772 Hypertension Diseases 0.000 description 2
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
229930195725 Mannitol Natural products 0.000 description 2
241001465754 Metazoa Species 0.000 description 2
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
BDJRBEYXGGNYIS-UHFFFAOYSA-N Nonanedioid acid Natural products OC(=O)CCCCCCCC(O)=O BDJRBEYXGGNYIS-UHFFFAOYSA-N 0.000 description 2
206010030113 Oedema Diseases 0.000 description 2
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical class [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
229930006000 Sucrose Natural products 0.000 description 2
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
208000025865 Ulcer Diseases 0.000 description 2
XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
235000010489 acacia gum Nutrition 0.000 description 2
239000000205 acacia gum Substances 0.000 description 2
229960001138 acetylsalicylic acid Drugs 0.000 description 2
125000002252 acyl group Chemical group 0.000 description 2
OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 description 2
239000003513 alkali Substances 0.000 description 2
150000001340 alkali metals Chemical class 0.000 description 2
150000004703 alkoxides Chemical class 0.000 description 2
125000004453 alkoxycarbonyl group Chemical group 0.000 description 2
125000005907 alkyl ester group Chemical group 0.000 description 2
229910052782 aluminium Inorganic materials 0.000 description 2
XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 2
150000001409 amidines Chemical class 0.000 description 2
150000001411 amidrazones Chemical class 0.000 description 2
239000003708 ampul Substances 0.000 description 2
150000008064 anhydrides Chemical class 0.000 description 2
208000011775 arteriosclerosis disease Diseases 0.000 description 2
229960002255 azelaic acid Drugs 0.000 description 2
210000004204 blood vessel Anatomy 0.000 description 2
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
229910052794 bromium Inorganic materials 0.000 description 2
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
150000004649 carbonic acid derivatives Chemical class 0.000 description 2
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 2
229940127573 compound 38 Drugs 0.000 description 2
239000004020 conductor Substances 0.000 description 2
239000012043 crude product Substances 0.000 description 2
XLJMAIOERFSOGZ-UHFFFAOYSA-N cyanic acid Chemical compound OC#N XLJMAIOERFSOGZ-UHFFFAOYSA-N 0.000 description 2
MMXLZXKREFMNSR-UHFFFAOYSA-N diethyl 2-(3-hydroxydecylamino)nonanedioate Chemical compound CCCCCCCC(O)CCNC(C(=O)OCC)CCCCCCC(=O)OCC MMXLZXKREFMNSR-UHFFFAOYSA-N 0.000 description 2
SHUROOIEQQXLJG-UHFFFAOYSA-N diethyl 2-(3-hydroxynonylamino)nonanedioate Chemical compound CCCCCCC(O)CCNC(C(=O)OCC)CCCCCCC(=O)OCC SHUROOIEQQXLJG-UHFFFAOYSA-N 0.000 description 2
KACRUFCHLHVJSN-UHFFFAOYSA-N diethyl 2-(3-hydroxyoctylamino)pentanedioate Chemical compound CCCCCC(O)CCNC(C(=O)OCC)CCC(=O)OCC KACRUFCHLHVJSN-UHFFFAOYSA-N 0.000 description 2
WACZTVHLJVHECR-UHFFFAOYSA-N diethyl 2-(3-hydroxyoctylamino)undecanedioate Chemical compound CCCCCC(O)CCNC(C(=O)OCC)CCCCCCCCC(=O)OCC WACZTVHLJVHECR-UHFFFAOYSA-N 0.000 description 2
UKAAGXWXCCQNJM-UHFFFAOYSA-N diethyl 2-(3-hydroxypentylamino)nonanedioate Chemical compound CCOC(=O)CCCCCCC(C(=O)OCC)NCCC(O)CC UKAAGXWXCCQNJM-UHFFFAOYSA-N 0.000 description 2
INMGGXFKNXANLH-UHFFFAOYSA-N diethyl 2-(3-oxooctylamino)nonanedioate Chemical compound CCCCCC(=O)CCNC(C(=O)OCC)CCCCCCC(=O)OCC INMGGXFKNXANLH-UHFFFAOYSA-N 0.000 description 2
PSGLWSHCTRBZAK-UHFFFAOYSA-N diethyl 2-(3-oxooctylamino)pentanedioate Chemical compound CCCCCC(=O)CCNC(C(=O)OCC)CCC(=O)OCC PSGLWSHCTRBZAK-UHFFFAOYSA-N 0.000 description 2
MHWLISSHXNDKJX-UHFFFAOYSA-N diethyl 2-(3-oxooctylamino)undecanedioate Chemical compound CCCCCC(=O)CCNC(C(=O)OCC)CCCCCCCCC(=O)OCC MHWLISSHXNDKJX-UHFFFAOYSA-N 0.000 description 2
BZDRVDDVAKMJRN-UHFFFAOYSA-N diethyl 2-(4-phenoxybutylamino)nonanedioate Chemical compound CCOC(=O)CCCCCCC(C(=O)OCC)NCCCCOC1=CC=CC=C1 BZDRVDDVAKMJRN-UHFFFAOYSA-N 0.000 description 2
VDGBEYFARQFPKH-UHFFFAOYSA-N diethyl 2-(4-propoxybutylamino)nonanedioate Chemical compound CCCOCCCCNC(C(=O)OCC)CCCCCCC(=O)OCC VDGBEYFARQFPKH-UHFFFAOYSA-N 0.000 description 2
DAESGDAJPKUPQH-UHFFFAOYSA-N diethyl 2-[(3-cyclobutyl-3-hydroxypropyl)amino]nonanedioate Chemical compound CCOC(=O)CCCCCCC(C(=O)OCC)NCCC(O)C1CCC1 DAESGDAJPKUPQH-UHFFFAOYSA-N 0.000 description 2
DAUGXNLNZLVGBV-UHFFFAOYSA-N diethyl 2-[(3-cycloheptyl-3-oxopropyl)amino]nonanedioate Chemical compound CCOC(=O)CCCCCCC(C(=O)OCC)NCCC(=O)C1CCCCCC1 DAUGXNLNZLVGBV-UHFFFAOYSA-N 0.000 description 2
DWBUWRWBSIVVAH-UHFFFAOYSA-N diethyl 2-[(3-cyclohexyl-3-hydroxypropyl)amino]nonanedioate Chemical compound CCOC(=O)CCCCCCC(C(=O)OCC)NCCC(O)C1CCCCC1 DWBUWRWBSIVVAH-UHFFFAOYSA-N 0.000 description 2
CXZWPQUTSPAXLM-UHFFFAOYSA-N diethyl 2-[(3-cyclohexyl-3-oxopropyl)amino]nonanedioate Chemical compound CCOC(=O)CCCCCCC(C(=O)OCC)NCCC(=O)C1CCCCC1 CXZWPQUTSPAXLM-UHFFFAOYSA-N 0.000 description 2
JHSJPCBRJZOPAK-UHFFFAOYSA-N diethyl 2-[(3-cyclopentyl-3-hydroxypropyl)amino]nonanedioate Chemical compound CCOC(=O)CCCCCCC(C(=O)OCC)NCCC(O)C1CCCC1 JHSJPCBRJZOPAK-UHFFFAOYSA-N 0.000 description 2
UUKNCRPLWDCTNH-UHFFFAOYSA-N diethyl 2-[(3-hydroxy-3-phenylpropyl)amino]nonanedioate Chemical compound CCOC(=O)CCCCCCC(C(=O)OCC)NCCC(O)C1=CC=CC=C1 UUKNCRPLWDCTNH-UHFFFAOYSA-N 0.000 description 2
MXMROBOXEXVICR-UHFFFAOYSA-N diethyl 2-[(3-hydroxy-4,4-dimethyloctyl)amino]nonanedioate Chemical compound CCCCC(C)(C)C(O)CCNC(C(=O)OCC)CCCCCCC(=O)OCC MXMROBOXEXVICR-UHFFFAOYSA-N 0.000 description 2
AXDQKWRQUDMBNN-UHFFFAOYSA-N diethyl 2-[(3-hydroxy-4,4-dimethylpentyl)amino]nonanedioate Chemical compound CCOC(=O)CCCCCCC(C(=O)OCC)NCCC(O)C(C)(C)C AXDQKWRQUDMBNN-UHFFFAOYSA-N 0.000 description 2
CYKDZWOAIPWZKB-UHFFFAOYSA-N diethyl 2-[(3-hydroxy-4-methyloctyl)amino]nonanedioate Chemical compound CCCCC(C)C(O)CCNC(C(=O)OCC)CCCCCCC(=O)OCC CYKDZWOAIPWZKB-UHFFFAOYSA-N 0.000 description 2
CBWGKWQWSKWIGB-UHFFFAOYSA-N diethyl 2-[(3-hydroxy-4-methylpentyl)amino]nonanedioate Chemical compound CCOC(=O)CCCCCCC(C(=O)OCC)NCCC(O)C(C)C CBWGKWQWSKWIGB-UHFFFAOYSA-N 0.000 description 2
UMSXXLYLOHBOIF-UHFFFAOYSA-N diethyl 2-[(3-hydroxy-4-phenylbutyl)amino]nonanedioate Chemical compound CCOC(=O)CCCCCCC(C(=O)OCC)NCCC(O)CC1=CC=CC=C1 UMSXXLYLOHBOIF-UHFFFAOYSA-N 0.000 description 2
IYFKNXBRKPPMAO-UHFFFAOYSA-N diethyl 2-[(3-oxo-3-phenylpropyl)amino]nonanedioate Chemical compound CCOC(=O)CCCCCCC(C(=O)OCC)NCCC(=O)C1=CC=CC=C1 IYFKNXBRKPPMAO-UHFFFAOYSA-N 0.000 description 2
MBCQWNFCPMRZSC-UHFFFAOYSA-N diethyl 2-[(3-oxo-4-phenylbutyl)amino]nonanedioate Chemical compound CCOC(=O)CCCCCCC(C(=O)OCC)NCCC(=O)CC1=CC=CC=C1 MBCQWNFCPMRZSC-UHFFFAOYSA-N 0.000 description 2
DIPFELRTXLNTRF-UHFFFAOYSA-N diethyl 2-[[3-hydroxy-4,4-dimethyl-5-[3-(trifluoromethyl)phenyl]pentyl]amino]nonanedioate Chemical compound CCOC(=O)CCCCCCC(C(=O)OCC)NCCC(O)C(C)(C)CC1=CC=CC(C(F)(F)F)=C1 DIPFELRTXLNTRF-UHFFFAOYSA-N 0.000 description 2
FIWJCAKIXBTJRD-UHFFFAOYSA-N diethyl 2-[[4,4-dimethyl-3-oxo-5-[3-(trifluoromethyl)phenyl]pentyl]amino]nonanedioate Chemical compound CCOC(=O)CCCCCCC(C(=O)OCC)NCCC(=O)C(C)(C)CC1=CC=CC(C(F)(F)F)=C1 FIWJCAKIXBTJRD-UHFFFAOYSA-N 0.000 description 2
YHIMFWJZBVHIPZ-UHFFFAOYSA-N diethyl 2-aminononanedioate Chemical compound CCOC(=O)CCCCCCC(N)C(=O)OCC YHIMFWJZBVHIPZ-UHFFFAOYSA-N 0.000 description 2
XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
238000001035 drying Methods 0.000 description 2
229920001971 elastomer Polymers 0.000 description 2
239000003480 eluent Substances 0.000 description 2
238000005516 engineering process Methods 0.000 description 2
HHFAWKCIHAUFRX-UHFFFAOYSA-N ethoxide Chemical compound CC[O-] HHFAWKCIHAUFRX-UHFFFAOYSA-N 0.000 description 2
BORQDYPKHBTMJQ-UHFFFAOYSA-N ethyl 2-[(3-cyclohexyl-3-hydroxypropyl)amino]-3-[3-(3-ethoxy-3-oxopropyl)phenyl]propanoate Chemical compound CCOC(=O)CCC1=CC=CC(CC(NCCC(O)C2CCCCC2)C(=O)OCC)=C1 BORQDYPKHBTMJQ-UHFFFAOYSA-N 0.000 description 2
OMLJXYCIWIGHEN-UHFFFAOYSA-N ethyl 2-[(3-cyclohexyl-3-oxopropyl)amino]-3-[3-(3-ethoxy-3-oxopropyl)phenyl]propanoate Chemical compound CCOC(=O)CCC1=CC=CC(CC(NCCC(=O)C2CCCCC2)C(=O)OCC)=C1 OMLJXYCIWIGHEN-UHFFFAOYSA-N 0.000 description 2
GJUMJJPMVOILQT-UHFFFAOYSA-N ethyl 2-[(3-cyclopentyl-3-hydroxypropyl)amino]-3-[3-(3-ethoxy-3-oxopropyl)phenyl]propanoate Chemical compound C1(CCCC1)C(CCNC(C(=O)OCC)CC1=CC(=CC=C1)CCC(=O)OCC)O GJUMJJPMVOILQT-UHFFFAOYSA-N 0.000 description 2
UGBXTARIWNGXAI-UHFFFAOYSA-N ethyl 3-[3-(2-ethoxy-2-oxoethoxy)phenyl]-2-(3-hydroxyoctylamino)propanoate Chemical compound CCCCCC(O)CCNC(C(=O)OCC)CC1=CC=CC(OCC(=O)OCC)=C1 UGBXTARIWNGXAI-UHFFFAOYSA-N 0.000 description 2
RCSUEZGZEYPPOB-UHFFFAOYSA-N ethyl 7-(5-octyl-2,4-dioxoimidazolidin-1-yl)heptanoate Chemical compound CCCCCCCCC1N(CCCCCCC(=O)OCC)C(=O)NC1=O RCSUEZGZEYPPOB-UHFFFAOYSA-N 0.000 description 2
OOBFNDGMAGSNKA-UHFFFAOYSA-N ethyl 7-bromoheptanoate Chemical compound CCOC(=O)CCCCCCBr OOBFNDGMAGSNKA-UHFFFAOYSA-N 0.000 description 2
RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 2
230000008020 evaporation Effects 0.000 description 2
238000000605 extraction Methods 0.000 description 2
210000003191 femoral vein Anatomy 0.000 description 2
239000000706 filtrate Substances 0.000 description 2
239000007789 gas Substances 0.000 description 2
210000004211 gastric acid Anatomy 0.000 description 2
230000002496 gastric effect Effects 0.000 description 2
239000011521 glass Substances 0.000 description 2
229910052736 halogen Inorganic materials 0.000 description 2
125000005843 halogen group Chemical group 0.000 description 2
PSFDQSOCUJVVGF-UHFFFAOYSA-N harman Chemical compound C12=CC=CC=C2NC2=C1C=CN=C2C PSFDQSOCUJVVGF-UHFFFAOYSA-N 0.000 description 2
229960001340 histamine Drugs 0.000 description 2
229910000042 hydrogen bromide Inorganic materials 0.000 description 2
125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
238000001802 infusion Methods 0.000 description 2
230000005764 inhibitory process Effects 0.000 description 2
238000010253 intravenous injection Methods 0.000 description 2
239000010410 layer Substances 0.000 description 2
230000003902 lesion Effects 0.000 description 2
239000007937 lozenge Substances 0.000 description 2
239000011777 magnesium Substances 0.000 description 2
229910052749 magnesium Inorganic materials 0.000 description 2
239000000594 mannitol Substances 0.000 description 2
235000010355 mannitol Nutrition 0.000 description 2
HAMGRBXTJNITHG-UHFFFAOYSA-N methyl isocyanate Chemical compound CN=C=O HAMGRBXTJNITHG-UHFFFAOYSA-N 0.000 description 2
238000002156 mixing Methods 0.000 description 2
WPBWJEYRHXACLR-UHFFFAOYSA-N nonanedioic acid Chemical compound OC(=O)CCCCCCCC(O)=O.OC(=O)CCCCCCCC(O)=O WPBWJEYRHXACLR-UHFFFAOYSA-N 0.000 description 2
238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 2
PIDFDZJZLOTZTM-KHVQSSSXSA-N ombitasvir Chemical compound COC(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@H]1C(=O)NC1=CC=C([C@H]2N([C@@H](CC2)C=2C=CC(NC(=O)[C@H]3N(CCC3)C(=O)[C@@H](NC(=O)OC)C(C)C)=CC=2)C=2C=CC(=CC=2)C(C)(C)C)C=C1 PIDFDZJZLOTZTM-KHVQSSSXSA-N 0.000 description 2
229940094443 oxytocics prostaglandins Drugs 0.000 description 2
239000003208 petroleum Substances 0.000 description 2
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
229940069328 povidone Drugs 0.000 description 2
230000002265 prevention Effects 0.000 description 2
125000006239 protecting group Chemical group 0.000 description 2
238000000926 separation method Methods 0.000 description 2
NDVLTYZPCACLMA-UHFFFAOYSA-N silver oxide Chemical compound [O-2].[Ag+].[Ag+] NDVLTYZPCACLMA-UHFFFAOYSA-N 0.000 description 2
210000002460 smooth muscle Anatomy 0.000 description 2
229910000029 sodium carbonate Inorganic materials 0.000 description 2
230000002269 spontaneous effect Effects 0.000 description 2
239000005720 sucrose Substances 0.000 description 2
239000000829 suppository Substances 0.000 description 2
239000002511 suppository base Substances 0.000 description 2
238000012360 testing method Methods 0.000 description 2
210000003437 trachea Anatomy 0.000 description 2
231100000397 ulcer Toxicity 0.000 description 2
238000005406 washing Methods 0.000 description 2
229910052727 yttrium Inorganic materials 0.000 description 2
TXUICONDJPYNPY-UHFFFAOYSA-N (1,10,13-trimethyl-3-oxo-4,5,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-17-yl) heptanoate Chemical compound C1CC2CC(=O)C=C(C)C2(C)C2C1C1CCC(OC(=O)CCCCCC)C1(C)CC2 TXUICONDJPYNPY-UHFFFAOYSA-N 0.000 description 1
GHPYJLCQYMAXGG-WCCKRBBISA-N (2R)-2-amino-3-(2-boronoethylsulfanyl)propanoic acid hydrochloride Chemical compound Cl.N[C@@H](CSCCB(O)O)C(O)=O GHPYJLCQYMAXGG-WCCKRBBISA-N 0.000 description 1
GLAQTZKKWLZVLC-BHQIHCQQSA-N (z)-7-[3-(3-cyclohexyl-3-hydroxypropyl)-2,5-dioxoimidazolidin-4-yl]hept-5-enoic acid Chemical compound C1CCCCC1C(O)CCN1C(C\C=C/CCCC(O)=O)C(=O)NC1=O GLAQTZKKWLZVLC-BHQIHCQQSA-N 0.000 description 1
KEQGZUUPPQEDPF-UHFFFAOYSA-N 1,3-dichloro-5,5-dimethylimidazolidine-2,4-dione Chemical class CC1(C)N(Cl)C(=O)N(Cl)C1=O KEQGZUUPPQEDPF-UHFFFAOYSA-N 0.000 description 1
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
QTUSPJIBXWEBKY-UHFFFAOYSA-N 1-(3-cyclohexyl-3-hydroxypropyl)imidazolidine-2,4-dione Chemical compound C1(CCCCC1)C(CCN1C(=O)NC(=O)C1)O QTUSPJIBXWEBKY-UHFFFAOYSA-N 0.000 description 1
DERLEQYHZCMIPL-UHFFFAOYSA-N 1-(triphenyl-$l^{5}-phosphanylidene)heptan-2-one Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=CC(=O)CCCCC)C1=CC=CC=C1 DERLEQYHZCMIPL-UHFFFAOYSA-N 0.000 description 1
KLTVSWGXIAYTHO-UHFFFAOYSA-N 1-Octen-3-one Chemical compound CCCCCC(=O)C=C KLTVSWGXIAYTHO-UHFFFAOYSA-N 0.000 description 1
MPPPKRYCTPRNTB-UHFFFAOYSA-N 1-bromobutane Chemical compound CCCCBr MPPPKRYCTPRNTB-UHFFFAOYSA-N 0.000 description 1
JNNARQTXEYTKFV-UHFFFAOYSA-N 1-bromooctan-3-ol Chemical compound CCCCCC(O)CCBr JNNARQTXEYTKFV-UHFFFAOYSA-N 0.000 description 1
PVJCTKLYKFHSND-UHFFFAOYSA-N 1-o,1-o-diethyl 7-o-methyl 1-acetamidohept-3-ene-1,1,7-tricarboxylate Chemical compound CCOC(=O)C(C(=O)OCC)(NC(C)=O)CC=CCCCC(=O)OC PVJCTKLYKFHSND-UHFFFAOYSA-N 0.000 description 1
KJUGUADJHNHALS-UHFFFAOYSA-N 1H-tetrazole Substances C=1N=NNN=1 KJUGUADJHNHALS-UHFFFAOYSA-N 0.000 description 1
LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
FWIYWOOFNQCTMU-UHFFFAOYSA-N 2-[3-[[3-(3-hydroxy-4,4-dimethylpentyl)-2,5-dioxoimidazolidin-4-yl]methyl]phenoxy]acetic acid Chemical compound O=C1NC(=O)N(CCC(O)C(C)(C)C)C1CC1=CC=CC(OCC(O)=O)=C1 FWIYWOOFNQCTMU-UHFFFAOYSA-N 0.000 description 1
QXRNMICTQAMAIE-UHFFFAOYSA-N 2-[3-[[3-(3-hydroxyoctyl)-2,5-dioxoimidazolidin-4-yl]methyl]phenoxy]acetic acid Chemical compound O=C1NC(=O)N(CCC(O)CCCCC)C1CC1=CC=CC(OCC(O)=O)=C1 QXRNMICTQAMAIE-UHFFFAOYSA-N 0.000 description 1
HWRGAWGWIMJPNU-UHFFFAOYSA-N 2-[4-[3-(3-cyclopentyl-3-hydroxypropyl)-2,5-dioxoimidazolidin-4-yl]butoxy]acetic acid Chemical compound C1CCCC1C(O)CCN1C(CCCCOCC(O)=O)C(=O)NC1=O HWRGAWGWIMJPNU-UHFFFAOYSA-N 0.000 description 1
MUXHGTXYHNMFNI-UHFFFAOYSA-N 2-[4-[3-(3-hydroxyoctyl)-2,5-dioxoimidazolidin-4-yl]butoxy]acetic acid Chemical compound CCCCCC(O)CCN1C(CCCCOCC(O)=O)C(=O)NC1=O MUXHGTXYHNMFNI-UHFFFAOYSA-N 0.000 description 1
GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 description 1
JINGUCXQUOKWKH-UHFFFAOYSA-N 2-aminodecanoic acid Chemical compound CCCCCCCCC(N)C(O)=O JINGUCXQUOKWKH-UHFFFAOYSA-N 0.000 description 1
FYWDUQCSMYWUHV-UHFFFAOYSA-N 3-chloro-5-hydroxypentan-2-one Chemical compound CC(=O)C(Cl)CCO FYWDUQCSMYWUHV-UHFFFAOYSA-N 0.000 description 1
FFPIQLSDMFNLKF-UHFFFAOYSA-N 4-[3-(3-hydroxyoctyl)-2,5-dioxoimidazolidin-4-yl]butanoic acid Chemical compound CCCCCC(O)CCN1C(CCCC(O)=O)C(=O)NC1=O FFPIQLSDMFNLKF-UHFFFAOYSA-N 0.000 description 1
QICUPOFVENZWSC-UHFFFAOYSA-N 5-bromopentylbenzene Chemical compound BrCCCCCC1=CC=CC=C1 QICUPOFVENZWSC-UHFFFAOYSA-N 0.000 description 1
MLHISULWZKQQDJ-UHFFFAOYSA-N 7-(1-methyl-3-octyl-2,5-dioxoimidazolidin-4-yl)heptanoic acid Chemical compound CCCCCCCCN1C(CCCCCCC(O)=O)C(=O)N(C)C1=O MLHISULWZKQQDJ-UHFFFAOYSA-N 0.000 description 1
BWARNZVFSYJMAY-UHFFFAOYSA-N 7-(3-butyl-5-octyl-2,4-dioxoimidazolidin-1-yl)heptanoic acid Chemical compound CCCCCCCCC1N(CCCCCCC(O)=O)C(=O)N(CCCC)C1=O BWARNZVFSYJMAY-UHFFFAOYSA-N 0.000 description 1
RLZBUKYONWICLO-UHFFFAOYSA-N 7-(3-octyl-2,5-dioxoimidazolidin-4-yl)heptanoic acid Chemical compound CCCCCCCCN1C(CCCCCCC(O)=O)C(=O)NC1=O RLZBUKYONWICLO-UHFFFAOYSA-N 0.000 description 1
ZXTIZPQCGHYQHG-UHFFFAOYSA-N 7-(5-formyl-2,4-dioxoimidazolidin-1-yl)heptanoic acid Chemical compound OC(=O)CCCCCCN1C(C=O)C(=O)NC1=O ZXTIZPQCGHYQHG-UHFFFAOYSA-N 0.000 description 1
XURWZFUZCWPAMI-UHFFFAOYSA-N 7-[1-methyl-2,5-dioxo-3-(3-oxooctyl)imidazolidin-4-yl]heptanoic acid Chemical compound CCCCCC(=O)CCN1C(CCCCCCC(O)=O)C(=O)N(C)C1=O XURWZFUZCWPAMI-UHFFFAOYSA-N 0.000 description 1
FSXJVTKZQYLNMU-UHFFFAOYSA-N 7-[2,4-dioxo-5-(3-oxooctyl)imidazolidin-1-yl]heptanoic acid Chemical compound CCCCCC(=O)CCC1N(CCCCCCC(O)=O)C(=O)NC1=O FSXJVTKZQYLNMU-UHFFFAOYSA-N 0.000 description 1
RZGKVXHDYQLVGY-UHFFFAOYSA-N 7-[2,5-dioxo-3-(4-phenoxybutyl)imidazolidin-4-yl]heptanoic acid Chemical compound O=C1NC(=O)C(CCCCCCC(=O)O)N1CCCCOC1=CC=CC=C1 RZGKVXHDYQLVGY-UHFFFAOYSA-N 0.000 description 1
ZTXVXLSPVLRDKM-UHFFFAOYSA-N 7-[2,5-dioxo-3-(4-propoxybutyl)imidazolidin-4-yl]heptanoic acid Chemical compound CCCOCCCCN1C(CCCCCCC(O)=O)C(=O)NC1=O ZTXVXLSPVLRDKM-UHFFFAOYSA-N 0.000 description 1
UUUCDDNHASTTBA-UHFFFAOYSA-N 7-[3-(3-hydroxy-3-phenylpropyl)-2,5-dioxoimidazolidin-4-yl]heptanoic acid Chemical compound C=1C=CC=CC=1C(O)CCN1C(CCCCCCC(O)=O)C(=O)NC1=O UUUCDDNHASTTBA-UHFFFAOYSA-N 0.000 description 1
IQHNNANEVWYPFY-UHFFFAOYSA-N 7-[3-(3-hydroxy-4-methyloctyl)-2,5-dioxoimidazolidin-4-yl]heptanoic acid Chemical compound CCCCC(C)C(O)CCN1C(CCCCCCC(O)=O)C(=O)NC1=O IQHNNANEVWYPFY-UHFFFAOYSA-N 0.000 description 1
FUGYRZAQEDGGKF-UHFFFAOYSA-N 7-[3-(3-hydroxy-4-phenylbutyl)-2,5-dioxoimidazolidin-4-yl]heptanoic acid Chemical compound C=1C=CC=CC=1CC(O)CCN1C(CCCCCCC(O)=O)C(=O)NC1=O FUGYRZAQEDGGKF-UHFFFAOYSA-N 0.000 description 1
IGVWEFVIOGSBRO-UHFFFAOYSA-N 7-[3-(3-hydroxyoctyl)-1-methyl-2,5-dioxoimidazolidin-4-yl]heptanoic acid Chemical compound CCCCCC(O)CCN1C(CCCCCCC(O)=O)C(=O)N(C)C1=O IGVWEFVIOGSBRO-UHFFFAOYSA-N 0.000 description 1
ZDAOQBLYUGKRHD-UHFFFAOYSA-N 7-[3-(3-hydroxyoctyl)-2,5-dioxoimidazolidin-4-yl]hept-5-enoic acid Chemical compound CCCCCC(O)CCN1C(CC=CCCCC(O)=O)C(=O)NC1=O ZDAOQBLYUGKRHD-UHFFFAOYSA-N 0.000 description 1
PEKVZILFMHNTFG-UHFFFAOYSA-N 7-[3-(3-hydroxyoctyl)-2,5-dioxoimidazolidin-4-yl]hept-5-ynoic acid Chemical compound CCCCCC(O)CCN1C(CC#CCCCC(O)=O)C(=O)NC1=O PEKVZILFMHNTFG-UHFFFAOYSA-N 0.000 description 1
NKYCZKRRSBNICR-UHFFFAOYSA-N 7-[3-(3-hydroxypropyl)-2,5-dioxoimidazolidin-4-yl]heptanoic acid Chemical compound OCCCN1C(CCCCCCC(O)=O)C(=O)NC1=O NKYCZKRRSBNICR-UHFFFAOYSA-N 0.000 description 1
QEVXDFBUIDMEFL-UHFFFAOYSA-N 7-[3-(4-ethyl-3-hydroxyhexyl)-2,5-dioxoimidazolidin-4-yl]heptanoic acid Chemical compound CCC(CC)C(O)CCN1C(CCCCCCC(O)=O)C(=O)NC1=O QEVXDFBUIDMEFL-UHFFFAOYSA-N 0.000 description 1
JDGTWHYHZXTDOQ-UHFFFAOYSA-N 7-[3-[3-(3-methylphenoxy)propyl]-2,5-dioxoimidazolidin-4-yl]heptanoic acid Chemical compound CC1=CC=CC(OCCCN2C(NC(=O)C2CCCCCCC(O)=O)=O)=C1 JDGTWHYHZXTDOQ-UHFFFAOYSA-N 0.000 description 1
QBJVCXDPRHDBHT-UHFFFAOYSA-N 7-[5-(3-hydroxyoctyl)-2,4-dioxoimidazolidin-1-yl]heptanoic acid Chemical compound CCCCCC(O)CCC1N(CCCCCCC(O)=O)C(=O)NC1=O QBJVCXDPRHDBHT-UHFFFAOYSA-N 0.000 description 1
FTQRPFYOHWHUHZ-UHFFFAOYSA-N 7-[5-(dibutoxymethyl)-2,4-dioxoimidazolidin-1-yl]heptanoic acid Chemical compound CCCCOC(OCCCC)C1N(CCCCCCC(O)=O)C(=O)NC1=O FTQRPFYOHWHUHZ-UHFFFAOYSA-N 0.000 description 1
CSEOUSBVQNMCCC-UHFFFAOYSA-N 7-[5-(hydroxymethylidene)-2,4-dioxoimidazolidin-1-yl]heptanoic acid Chemical compound OC=C1N(CCCCCCC(O)=O)C(=O)NC1=O CSEOUSBVQNMCCC-UHFFFAOYSA-N 0.000 description 1
MZMVBOJMGMYKAG-UHFFFAOYSA-N 9-[3-(3-hydroxyoctyl)-2,5-dioxoimidazolidin-4-yl]nonanoic acid Chemical compound CCCCCC(O)CCN1C(CCCCCCCCC(O)=O)C(=O)NC1=O MZMVBOJMGMYKAG-UHFFFAOYSA-N 0.000 description 1
208000003200 Adenoma Diseases 0.000 description 1
206010001233 Adenoma benign Diseases 0.000 description 1
206010002091 Anaesthesia Diseases 0.000 description 1
206010003178 Arterial thrombosis Diseases 0.000 description 1
241000416162 Astragalus gummifer Species 0.000 description 1
208000012639 Balance disease Diseases 0.000 description 1
IXBXLOSIWJXKPY-UHFFFAOYSA-N C(C)(=O)NC(C(=O)OCC)C(=O)OCC.NC(C(=O)OCC)CC1=CC(=CC=C1)OCC(=O)OCC Chemical compound C(C)(=O)NC(C(=O)OCC)C(=O)OCC.NC(C(=O)OCC)CC1=CC(=CC=C1)OCC(=O)OCC IXBXLOSIWJXKPY-UHFFFAOYSA-N 0.000 description 1
AOWFPJMOYFAOSW-UHFFFAOYSA-N C(C)OC(CNC=O)=O.C(C)OC(C(N)C(OCCCC)OCCCC)=O Chemical compound C(C)OC(CNC=O)=O.C(C)OC(C(N)C(OCCCC)OCCCC)=O AOWFPJMOYFAOSW-UHFFFAOYSA-N 0.000 description 1
239000002126 C01EB10 - Adenosine Substances 0.000 description 1
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
241000282472 Canis lupus familiaris Species 0.000 description 1
239000004215 Carbon black (E152) Substances 0.000 description 1
241000700198 Cavia Species 0.000 description 1
241000700199 Cavia porcellus Species 0.000 description 1
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
101000783577 Dendroaspis angusticeps Thrombostatin Proteins 0.000 description 1
101000783578 Dendroaspis jamesoni kaimosae Dendroaspin Proteins 0.000 description 1
208000010138 Diastema Diseases 0.000 description 1
BUDQDWGNQVEFAC-UHFFFAOYSA-N Dihydropyran Chemical compound C1COC=CC1 BUDQDWGNQVEFAC-UHFFFAOYSA-N 0.000 description 1
244000166102 Eucalyptus leucoxylon Species 0.000 description 1
235000004694 Eucalyptus leucoxylon Nutrition 0.000 description 1
206010061459 Gastrointestinal ulcer Diseases 0.000 description 1
108010010803 Gelatin Proteins 0.000 description 1
206010019280 Heart failures Diseases 0.000 description 1
206010019663 Hepatic failure Diseases 0.000 description 1
241001024304 Mino Species 0.000 description 1
241000699670 Mus sp. Species 0.000 description 1
IOVCWXUNBOPUCH-UHFFFAOYSA-N Nitrous acid Chemical group ON=O IOVCWXUNBOPUCH-UHFFFAOYSA-N 0.000 description 1
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
241000283973 Oryctolagus cuniculus Species 0.000 description 1
229930182555 Penicillin Natural products 0.000 description 1
JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
108010079943 Pentagastrin Proteins 0.000 description 1
CXOFVDLJLONNDW-UHFFFAOYSA-N Phenytoin Chemical compound N1C(=O)NC(=O)C1(C=1C=CC=CC=1)C1=CC=CC=C1 CXOFVDLJLONNDW-UHFFFAOYSA-N 0.000 description 1
YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 1
206010050661 Platelet aggregation inhibition Diseases 0.000 description 1
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
208000001647 Renal Insufficiency Diseases 0.000 description 1
KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 description 1
201000004239 Secondary hypertension Diseases 0.000 description 1
241000212342 Sium Species 0.000 description 1
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
208000007107 Stomach Ulcer Diseases 0.000 description 1
229910021626 Tin(II) chloride Inorganic materials 0.000 description 1
229920001615 Tragacanth Polymers 0.000 description 1
206010000210 abortion Diseases 0.000 description 1
231100000176 abortion Toxicity 0.000 description 1
125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 1
239000000654 additive Substances 0.000 description 1
230000000996 additive effect Effects 0.000 description 1
229960005305 adenosine Drugs 0.000 description 1
150000001299 aldehydes Chemical class 0.000 description 1
229910000102 alkali metal hydride Inorganic materials 0.000 description 1
150000008046 alkali metal hydrides Chemical class 0.000 description 1
150000008044 alkali metal hydroxides Chemical class 0.000 description 1
239000012670 alkaline solution Substances 0.000 description 1
125000003545 alkoxy group Chemical group 0.000 description 1
150000001350 alkyl halides Chemical class 0.000 description 1
125000004414 alkyl thio group Chemical group 0.000 description 1
239000002168 alkylating agent Substances 0.000 description 1
229940100198 alkylating agent Drugs 0.000 description 1
230000029936 alkylation Effects 0.000 description 1
238000005804 alkylation reaction Methods 0.000 description 1
230000000172 allergic effect Effects 0.000 description 1
150000003862 amino acid derivatives Chemical class 0.000 description 1
235000019270 ammonium chloride Nutrition 0.000 description 1
150000003863 ammonium salts Chemical class 0.000 description 1
230000037005 anaesthesia Effects 0.000 description 1
238000004458 analytical method Methods 0.000 description 1
230000003509 anti-fertility effect Effects 0.000 description 1
230000003276 anti-hypertensive effect Effects 0.000 description 1
230000002785 anti-thrombosis Effects 0.000 description 1
239000003146 anticoagulant agent Substances 0.000 description 1
239000002220 antihypertensive agent Substances 0.000 description 1
229940127088 antihypertensive drug Drugs 0.000 description 1
229940127218 antiplatelet drug Drugs 0.000 description 1
239000000010 aprotic solvent Substances 0.000 description 1
239000013011 aqueous formulation Substances 0.000 description 1
239000008346 aqueous phase Substances 0.000 description 1
125000003435 aroyl group Chemical group 0.000 description 1
230000004872 arterial blood pressure Effects 0.000 description 1
208000006673 asthma Diseases 0.000 description 1
125000004429 atom Chemical group 0.000 description 1
208000010668 atopic eczema Diseases 0.000 description 1
229940077388 benzenesulfonate Drugs 0.000 description 1
SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
150000001602 bicycloalkyls Chemical group 0.000 description 1
239000011230 binding agent Substances 0.000 description 1
SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 1
230000023555 blood coagulation Effects 0.000 description 1
230000037237 body shape Effects 0.000 description 1
230000037396 body weight Effects 0.000 description 1
125000001246 bromo group Chemical group Br* 0.000 description 1
206010006451 bronchitis Diseases 0.000 description 1
230000003182 bronchodilatating effect Effects 0.000 description 1
239000011575 calcium Substances 0.000 description 1
229910052791 calcium Inorganic materials 0.000 description 1
239000004202 carbamide Substances 0.000 description 1
KXDHJXZQYSOELW-UHFFFAOYSA-N carbonic acid monoamide Natural products NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 description 1
230000000747 cardiac effect Effects 0.000 description 1
239000000969 carrier Substances 0.000 description 1
239000003054 catalyst Substances 0.000 description 1
238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
210000004027 cell Anatomy 0.000 description 1
SFZULDYEOVSIKM-UHFFFAOYSA-N chembl321317 Chemical compound C1=CC(C(=N)NO)=CC=C1C1=CC=C(C=2C=CC(=CC=2)C(=N)NO)O1 SFZULDYEOVSIKM-UHFFFAOYSA-N 0.000 description 1
230000002925 chemical effect Effects 0.000 description 1
239000003795 chemical substances by application Substances 0.000 description 1
OJYGBLRPYBAHRT-IPQSZEQASA-N chloralose Chemical compound O1[C@H](C(Cl)(Cl)Cl)O[C@@H]2[C@@H](O)[C@@H]([C@H](O)CO)O[C@@H]21 OJYGBLRPYBAHRT-IPQSZEQASA-N 0.000 description 1
229950009941 chloralose Drugs 0.000 description 1
239000000460 chlorine Substances 0.000 description 1
229910052801 chlorine Inorganic materials 0.000 description 1
229940110456 cocoa butter Drugs 0.000 description 1
235000019868 cocoa butter Nutrition 0.000 description 1
210000001072 colon Anatomy 0.000 description 1
239000007891 compressed tablet Substances 0.000 description 1
239000003433 contraceptive agent Substances 0.000 description 1
230000002254 contraceptive effect Effects 0.000 description 1
230000008602 contraction Effects 0.000 description 1
230000001186 cumulative effect Effects 0.000 description 1
150000001913 cyanates Chemical class 0.000 description 1
125000000753 cycloalkyl group Chemical group 0.000 description 1
230000003247 decreasing effect Effects 0.000 description 1
230000018044 dehydration Effects 0.000 description 1
238000006297 dehydration reaction Methods 0.000 description 1
238000011161 development Methods 0.000 description 1
210000000475 diastema Anatomy 0.000 description 1
SOCTUWSJJQCPFX-UHFFFAOYSA-N dichromate(2-) Chemical compound [O-][Cr](=O)(=O)O[Cr]([O-])(=O)=O SOCTUWSJJQCPFX-UHFFFAOYSA-N 0.000 description 1
235000014113 dietary fatty acids Nutrition 0.000 description 1
PTRUOQRNXJQHSN-UHFFFAOYSA-N diethyl 2-(3-hydroxypropylamino)nonanedioate Chemical compound CCOC(=O)CCCCCCC(C(=O)OCC)NCCCO PTRUOQRNXJQHSN-UHFFFAOYSA-N 0.000 description 1
RWSZQFNODZWSEK-UHFFFAOYSA-N diethyl 2-(5-phenylpentylamino)nonanedioate;hydrobromide Chemical class Br.CCOC(=O)CCCCCCC(C(=O)OCC)NCCCCCC1=CC=CC=C1 RWSZQFNODZWSEK-UHFFFAOYSA-N 0.000 description 1
DPWOXFIWWXDQSZ-UHFFFAOYSA-N diethyl 2-[(3-cyclohexyl-3-oxopropyl)amino]non-4-enedioate Chemical compound CCOC(=O)CCCC=CCC(C(=O)OCC)NCCC(=O)C1CCCCC1 DPWOXFIWWXDQSZ-UHFFFAOYSA-N 0.000 description 1
DNWSJOKSXOICJJ-UHFFFAOYSA-N diethyl 2-[(3-hydroxy-4,4-dimethyl-5-phenylpentyl)amino]nonanedioate Chemical compound OC(CCNC(C(=O)OCC)CCCCCCC(=O)OCC)C(CC1=CC=CC=C1)(C)C DNWSJOKSXOICJJ-UHFFFAOYSA-N 0.000 description 1
SSHPOMIITFBZAZ-UHFFFAOYSA-N diethyl 2-[3-(oxan-2-yloxy)octylamino]nonanedioate Chemical compound CCOC(=O)CCCCCCC(C(=O)OCC)NCCC(CCCCC)OC1CCCCO1 SSHPOMIITFBZAZ-UHFFFAOYSA-N 0.000 description 1
AZJLJUNJOVEAQF-UHFFFAOYSA-N diethyl 2-acetamido-2-[3-(2-ethoxy-2-oxoethoxy)phenyl]propanedioate Chemical compound CCOC(=O)COC1=CC=CC(C(NC(C)=O)(C(=O)OCC)C(=O)OCC)=C1 AZJLJUNJOVEAQF-UHFFFAOYSA-N 0.000 description 1
ISOLMABRZPQKOV-UHFFFAOYSA-N diethyl 2-acetamidopropanedioate Chemical compound CCOC(=O)C(NC(C)=O)C(=O)OCC ISOLMABRZPQKOV-UHFFFAOYSA-N 0.000 description 1
LUYCGQMDJWJRKJ-UHFFFAOYSA-N diethyl 2-acetamidopropanedioate diethyl 2-aminononanedioate Chemical compound C(C)(=O)NC(C(=O)OCC)C(=O)OCC.NC(C(=O)OCC)CCCCCCC(=O)OCC LUYCGQMDJWJRKJ-UHFFFAOYSA-N 0.000 description 1
NWVWLOFHLYLTOD-UHFFFAOYSA-N diethyl 2-aminonon-4-enedioate Chemical compound CCOC(=O)CCCC=CCC(N)C(=O)OCC NWVWLOFHLYLTOD-UHFFFAOYSA-N 0.000 description 1
125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
XEYBRNLFEZDVAW-ARSRFYASSA-N dinoprostone Chemical compound CCCCC[C@H](O)\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1C\C=C/CCCC(O)=O XEYBRNLFEZDVAW-ARSRFYASSA-N 0.000 description 1
ROORDVPLFPIABK-UHFFFAOYSA-N diphenyl carbonate Chemical compound C=1C=CC=CC=1OC(=O)OC1=CC=CC=C1 ROORDVPLFPIABK-UHFFFAOYSA-N 0.000 description 1
XQRLCLUYWUNEEH-UHFFFAOYSA-L diphosphonate(2-) Chemical compound [O-]P(=O)OP([O-])=O XQRLCLUYWUNEEH-UHFFFAOYSA-L 0.000 description 1
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
208000035475 disorder Diseases 0.000 description 1
239000002270 dispersing agent Substances 0.000 description 1
239000002934 diuretic Substances 0.000 description 1
229940030606 diuretics Drugs 0.000 description 1
239000003937 drug carrier Substances 0.000 description 1
230000002526 effect on cardiovascular system Effects 0.000 description 1
ZKQFHRVKCYFVCN-UHFFFAOYSA-N ethoxyethane;hexane Chemical compound CCOCC.CCCCCC ZKQFHRVKCYFVCN-UHFFFAOYSA-N 0.000 description 1
AYDDHWOOPHEEMP-UHFFFAOYSA-N ethyl 2-(4-bromobutoxy)acetate Chemical compound CCOC(=O)COCCCCBr AYDDHWOOPHEEMP-UHFFFAOYSA-N 0.000 description 1
DJMXJCLTBXTETD-UHFFFAOYSA-N ethyl 2-[(3-cyclopentyl-3-oxopropyl)amino]-6-(2-ethoxy-2-oxoethoxy)hexanoate Chemical compound CCOC(=O)COCCCCC(C(=O)OCC)NCCC(=O)C1CCCC1 DJMXJCLTBXTETD-UHFFFAOYSA-N 0.000 description 1
HFIGMKDWQUAIMO-UHFFFAOYSA-N ethyl 2-[3-(chloromethyl)phenoxy]acetate Chemical compound CCOC(=O)COC1=CC=CC(CCl)=C1 HFIGMKDWQUAIMO-UHFFFAOYSA-N 0.000 description 1
KKBJRHWETQXPML-UHFFFAOYSA-N ethyl 2-amino-3-[3-(2-ethoxy-2-oxoethoxy)phenyl]propanoate Chemical compound CCOC(=O)COC1=CC=CC(CC(N)C(=O)OCC)=C1 KKBJRHWETQXPML-UHFFFAOYSA-N 0.000 description 1
BCQJKZGNIAMNPI-UHFFFAOYSA-N ethyl 2-amino-6-(2-ethoxy-2-oxoethoxy)hexanoate Chemical compound CCOC(=O)COCCCCC(N)C(=O)OCC BCQJKZGNIAMNPI-UHFFFAOYSA-N 0.000 description 1
NTNZTEQNFHNYBC-UHFFFAOYSA-N ethyl 2-aminoacetate Chemical compound CCOC(=O)CN NTNZTEQNFHNYBC-UHFFFAOYSA-N 0.000 description 1
XSTSHOZESJIYPK-UHFFFAOYSA-N ethyl 2-aminodecanoate Chemical compound CCCCCCCCC(N)C(=O)OCC XSTSHOZESJIYPK-UHFFFAOYSA-N 0.000 description 1
CQNHRAGQPQGULZ-UHFFFAOYSA-N ethyl 3-[3-(2-ethoxy-2-oxoethoxy)phenyl]-2-[(3-hydroxy-4,4-dimethylpentyl)amino]propanoate Chemical compound CCOC(=O)COC1=CC=CC(CC(NCCC(O)C(C)(C)C)C(=O)OCC)=C1 CQNHRAGQPQGULZ-UHFFFAOYSA-N 0.000 description 1
UHMRYUZCEQOICZ-UHFFFAOYSA-N ethyl 6-(2-ethoxy-2-oxoethoxy)-2-(3-oxooctylamino)hexanoate Chemical compound CCCCCC(=O)CCNC(C(=O)OCC)CCCCOCC(=O)OCC UHMRYUZCEQOICZ-UHFFFAOYSA-N 0.000 description 1
XZYUUAIDBSQELC-UHFFFAOYSA-N ethyl 7-(1-butyl-3-octyl-2,5-dioxoimidazolidin-4-yl)heptanoate Chemical compound CCCCCCCCN1C(CCCCCCC(=O)OCC)C(=O)N(CCCC)C1=O XZYUUAIDBSQELC-UHFFFAOYSA-N 0.000 description 1
CINVJQRLJFYIQW-UHFFFAOYSA-N ethyl 7-(3-butyl-5-octyl-2,4-dioxoimidazolidin-1-yl)heptanoate Chemical compound CCCCCCCCC1N(CCCCCCC(=O)OCC)C(=O)N(CCCC)C1=O CINVJQRLJFYIQW-UHFFFAOYSA-N 0.000 description 1
VHPHLYYCMCIEMQ-UHFFFAOYSA-N ethyl 7-(3-octyl-2,5-dioxoimidazolidin-4-yl)heptanoate Chemical compound CCCCCCCCN1C(CCCCCCC(=O)OCC)C(=O)NC1=O VHPHLYYCMCIEMQ-UHFFFAOYSA-N 0.000 description 1
VPNHTVSHQQOKHB-UHFFFAOYSA-N ethyl 7-[(1,1-dibutoxy-3-ethoxy-3-oxopropan-2-yl)amino]heptanoate;hydrobromide Chemical compound Br.CCCCOC(OCCCC)C(C(=O)OCC)NCCCCCCC(=O)OCC VPNHTVSHQQOKHB-UHFFFAOYSA-N 0.000 description 1
JWKLFXRLBZAPRK-UHFFFAOYSA-N ethyl 7-[1-methyl-2,5-dioxo-3-(3-oxooctyl)imidazolidin-4-yl]heptanoate Chemical compound CCCCCC(=O)CCN1C(CCCCCCC(=O)OCC)C(=O)N(C)C1=O JWKLFXRLBZAPRK-UHFFFAOYSA-N 0.000 description 1
SGCSAWOTNMPCGD-UHFFFAOYSA-N ethyl 7-[2,5-dioxo-3-(3-oxooctyl)imidazolidin-4-yl]heptanoate Chemical compound CCCCCC(=O)CCN1C(CCCCCCC(=O)OCC)C(=O)NC1=O SGCSAWOTNMPCGD-UHFFFAOYSA-N 0.000 description 1
GFSKDNLWYHCQGB-UHFFFAOYSA-N ethyl 7-[2,5-dioxo-3-(5-phenylpentyl)imidazolidin-4-yl]heptanoate Chemical compound O=C1NC(=O)C(CCCCCCC(=O)OCC)N1CCCCCC1=CC=CC=C1 GFSKDNLWYHCQGB-UHFFFAOYSA-N 0.000 description 1
XCITXJMUTZPPHL-UHFFFAOYSA-N ethyl 7-[3-[3-(oxan-2-yloxy)octyl]-2,5-dioxoimidazolidin-4-yl]heptanoate Chemical compound C1CCCOC1OC(CCCCC)CCN1C(CCCCCCC(=O)OCC)C(=O)NC1=O XCITXJMUTZPPHL-UHFFFAOYSA-N 0.000 description 1
VKRLCNBNMMXEPM-UHFFFAOYSA-N ethyl 7-[5-(dibutoxymethyl)-2,4-dioxoimidazolidin-1-yl]heptanoate Chemical compound CCCCOC(OCCCC)C1N(CCCCCCC(=O)OCC)C(=O)NC1=O VKRLCNBNMMXEPM-UHFFFAOYSA-N 0.000 description 1
239000000194 fatty acid Substances 0.000 description 1
229930195729 fatty acid Natural products 0.000 description 1
150000004665 fatty acids Chemical class 0.000 description 1
210000001105 femoral artery Anatomy 0.000 description 1
230000001605 fetal effect Effects 0.000 description 1
239000000796 flavoring agent Substances 0.000 description 1
235000019634 flavors Nutrition 0.000 description 1
238000006170 formylation reaction Methods 0.000 description 1
125000000524 functional group Chemical group 0.000 description 1
230000027119 gastric acid secretion Effects 0.000 description 1
210000001035 gastrointestinal tract Anatomy 0.000 description 1
239000008273 gelatin Substances 0.000 description 1
229920000159 gelatin Polymers 0.000 description 1
239000007903 gelatin capsule Substances 0.000 description 1
235000019322 gelatine Nutrition 0.000 description 1
235000011852 gelatine desserts Nutrition 0.000 description 1
235000011187 glycerol Nutrition 0.000 description 1
PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
229910052737 gold Inorganic materials 0.000 description 1
239000010931 gold Substances 0.000 description 1
150000004820 halides Chemical group 0.000 description 1
150000002367 halogens Chemical class 0.000 description 1
230000035876 healing Effects 0.000 description 1
150000002391 heterocyclic compounds Chemical class 0.000 description 1
GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 1
150000003840 hydrochlorides Chemical class 0.000 description 1
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
229910000041 hydrogen chloride Inorganic materials 0.000 description 1
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
238000005984 hydrogenation reaction Methods 0.000 description 1
230000003301 hydrolyzing effect Effects 0.000 description 1
XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
150000002440 hydroxy compounds Chemical class 0.000 description 1
125000004356 hydroxy functional group Chemical group O* 0.000 description 1
230000001631 hypertensive effect Effects 0.000 description 1
CUILPNURFADTPE-UHFFFAOYSA-N hypobromous acid Chemical class BrO CUILPNURFADTPE-UHFFFAOYSA-N 0.000 description 1
150000002463 imidates Chemical class 0.000 description 1
150000002464 imidothioesters Chemical class 0.000 description 1
238000011065 in-situ storage Methods 0.000 description 1
239000000411 inducer Substances 0.000 description 1
238000007918 intramuscular administration Methods 0.000 description 1
238000010255 intramuscular injection Methods 0.000 description 1
239000007927 intramuscular injection Substances 0.000 description 1
150000002500 ions Chemical class 0.000 description 1
150000002513 isocyanates Chemical class 0.000 description 1
238000002955 isolation Methods 0.000 description 1
150000004715 keto acids Chemical class 0.000 description 1
201000006370 kidney failure Diseases 0.000 description 1
150000002632 lipids Chemical class 0.000 description 1
238000004811 liquid chromatography Methods 0.000 description 1
229910052744 lithium Inorganic materials 0.000 description 1
208000007903 liver failure Diseases 0.000 description 1
231100000835 liver failure Toxicity 0.000 description 1
239000000314 lubricant Substances 0.000 description 1
230000003211 malignant effect Effects 0.000 description 1
239000000463 material Substances 0.000 description 1
MJGFBOZCAJSGQW-UHFFFAOYSA-N mercury sodium Chemical compound [Na].[Hg] MJGFBOZCAJSGQW-UHFFFAOYSA-N 0.000 description 1
229910052751 metal Inorganic materials 0.000 description 1
239000002184 metal Substances 0.000 description 1
150000004702 methyl esters Chemical class 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
239000010446 mirabilite Substances 0.000 description 1
239000007932 molded tablet Substances 0.000 description 1
210000002464 muscle smooth vascular Anatomy 0.000 description 1
208000010125 myocardial infarction Diseases 0.000 description 1
SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
230000009935 nitrosation Effects 0.000 description 1
238000007034 nitrosation reaction Methods 0.000 description 1
CMUOJBJRZUHRMU-UHFFFAOYSA-N nitrourea Chemical compound NC(=O)N[N+]([O-])=O CMUOJBJRZUHRMU-UHFFFAOYSA-N 0.000 description 1
GQPLMRYTRLFLPF-UHFFFAOYSA-N nitrous oxide Inorganic materials [O-][N+]#N GQPLMRYTRLFLPF-UHFFFAOYSA-N 0.000 description 1
239000007764 o/w emulsion Substances 0.000 description 1
TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
150000007530 organic bases Chemical class 0.000 description 1
239000012044 organic layer Substances 0.000 description 1
229910052763 palladium Inorganic materials 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
235000010603 pastilles Nutrition 0.000 description 1
230000000149 penetrating effect Effects 0.000 description 1
229940049954 penicillin Drugs 0.000 description 1
UCUUFSAXZMGPGH-UHFFFAOYSA-N penta-1,4-dien-3-one Chemical class C=CC(=O)C=C UCUUFSAXZMGPGH-UHFFFAOYSA-N 0.000 description 1
ANRIQLNBZQLTFV-DZUOILHNSA-N pentagastrin Chemical compound C([C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1[C]2C=CC=CC2=NC=1)NC(=O)CCNC(=O)OC(C)(C)C)CCSC)C(N)=O)C1=CC=CC=C1 ANRIQLNBZQLTFV-DZUOILHNSA-N 0.000 description 1
229960000444 pentagastrin Drugs 0.000 description 1
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
239000000825 pharmaceutical preparation Substances 0.000 description 1
125000004346 phenylpentyl group Chemical group C1(=CC=CC=C1)CCCCC* 0.000 description 1
230000001766 physiological effect Effects 0.000 description 1
239000000106 platelet aggregation inhibitor Substances 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
239000011591 potassium Substances 0.000 description 1
159000000001 potassium salts Chemical class 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
239000002243 precursor Substances 0.000 description 1
239000006041 probiotic Substances 0.000 description 1
235000018291 probiotics Nutrition 0.000 description 1
230000001737 promoting effect Effects 0.000 description 1
235000019260 propionic acid Nutrition 0.000 description 1
FKRCODPIKNYEAC-UHFFFAOYSA-N propionic acid ethyl ester Natural products CCOC(=O)CC FKRCODPIKNYEAC-UHFFFAOYSA-N 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
230000000541 pulsatile effect Effects 0.000 description 1
239000012429 reaction media Substances 0.000 description 1
210000000664 rectum Anatomy 0.000 description 1
230000033904 relaxation of vascular smooth muscle Effects 0.000 description 1
238000011160 research Methods 0.000 description 1
230000004044 response Effects 0.000 description 1
238000012552 review Methods 0.000 description 1
229910052703 rhodium Inorganic materials 0.000 description 1
239000010948 rhodium Substances 0.000 description 1
MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
238000006798 ring closing metathesis reaction Methods 0.000 description 1
229910052707 ruthenium Inorganic materials 0.000 description 1
150000003333 secondary alcohols Chemical class 0.000 description 1
208000015891 sexual disease Diseases 0.000 description 1
238000010898 silica gel chromatography Methods 0.000 description 1
229910001923 silver oxide Inorganic materials 0.000 description 1
229910001023 sodium amalgam Inorganic materials 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
239000012312 sodium hydride Substances 0.000 description 1
229910000104 sodium hydride Inorganic materials 0.000 description 1
159000000000 sodium salts Chemical class 0.000 description 1
RSIJVJUOQBWMIM-UHFFFAOYSA-L sodium sulfate decahydrate Chemical compound O.O.O.O.O.O.O.O.O.O.[Na+].[Na+].[O-]S([O-])(=O)=O RSIJVJUOQBWMIM-UHFFFAOYSA-L 0.000 description 1
239000001119 stannous chloride Substances 0.000 description 1
235000011150 stannous chloride Nutrition 0.000 description 1
239000012258 stirred mixture Substances 0.000 description 1
239000006190 sub-lingual tablet Substances 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
238000010254 subcutaneous injection Methods 0.000 description 1
239000007929 subcutaneous injection Substances 0.000 description 1
239000000758 substrate Substances 0.000 description 1
125000001273 sulfonato group Chemical group [O-]S(*)(=O)=O 0.000 description 1
239000004094 surface-active agent Substances 0.000 description 1
238000001356 surgical procedure Methods 0.000 description 1
208000011580 syndromic disease Diseases 0.000 description 1
238000001308 synthesis method Methods 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
WMOVHXAZOJBABW-UHFFFAOYSA-N tert-butyl acetate Chemical compound CC(=O)OC(C)(C)C WMOVHXAZOJBABW-UHFFFAOYSA-N 0.000 description 1
125000004187 tetrahydropyran-2-yl group Chemical group [H]C1([H])OC([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
125000001412 tetrahydropyranyl group Chemical class 0.000 description 1
125000003831 tetrazolyl group Chemical group 0.000 description 1
229940124597 therapeutic agent Drugs 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
KJAMZCVTJDTESW-UHFFFAOYSA-N tiracizine Chemical compound C1CC2=CC=CC=C2N(C(=O)CN(C)C)C2=CC(NC(=O)OCC)=CC=C21 KJAMZCVTJDTESW-UHFFFAOYSA-N 0.000 description 1
210000001519 tissue Anatomy 0.000 description 1
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
230000001256 tonic effect Effects 0.000 description 1
230000000699 topical effect Effects 0.000 description 1
150000003626 triacylglycerols Chemical class 0.000 description 1
210000002700 urine Anatomy 0.000 description 1
230000000304 vasodilatating effect Effects 0.000 description 1
230000024883 vasodilation Effects 0.000 description 1
235000013311 vegetables Nutrition 0.000 description 1
239000003981 vehicle Substances 0.000 description 1
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
229920002554 vinyl polymer Polymers 0.000 description 1
239000007762 w/o emulsion Substances 0.000 description 1
238000005303 weighing Methods 0.000 description 1
239000008096 xylene Substances 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
- C07D309/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
- C07D309/08—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D309/10—Oxygen atoms
- C07D309/12—Oxygen atoms only hydrogen atoms and one oxygen atom directly attached to ring carbon atoms, e.g. tetrahydropyranyl ethers
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D233/72—Two oxygen atoms, e.g. hydantoin
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D233/72—Two oxygen atoms, e.g. hydantoin
- C07D233/76—Two oxygen atoms, e.g. hydantoin with substituted hydrocarbon radicals attached to the third ring carbon atom
- C07D233/78—Radicals substituted by oxygen atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D233/86—Oxygen and sulfur atoms, e.g. thiohydantoin

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
General Health & Medical Sciences (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Bioinformatics & Cheminformatics (AREA)
Pharmacology & Pharmacy (AREA)
Engineering & Computer Science (AREA)
Animal Behavior & Ethology (AREA)
Chemical Kinetics & Catalysis (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Diabetes (AREA)
Hematology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Plural Heterocyclic Compounds (AREA)

JP6525277A 1976-06-03 1977-06-02 Heterocyclic compound Granted JPS52151168A (en)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
GB2287776		1976-06-03
GB5034076		1976-12-02
GB1214577		1977-03-23

Publications (2)

Publication Number	Publication Date
JPS52151168A JPS52151168A (en)	1977-12-15
JPS6222986B2 true JPS6222986B2 (ru)	1987-05-20

Family

ID=27256793

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
JP6525277A Granted JPS52151168A (en)	1976-06-03	1977-06-02	Heterocyclic compound

Country Status (12)

Country	Link
JP (1)	JPS52151168A (ru)
CA (1)	CA1176261A (ru)
CH (3)	CH645631A5 (ru)
DE (1)	DE2724948A1 (ru)
DK (1)	DK244577A (ru)
ES (5)	ES459412A1 (ru)
FI (1)	FI71930C (ru)
FR (1)	FR2362839A1 (ru)
HU (1)	HU183046B (ru)
NL (1)	NL7706064A (ru)
NZ (1)	NZ184281A (ru)
SE (2)	SE446336B (ru)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
JP3022878U (ja) *	1995-08-18	1996-04-02	有限会社春江加工	ミニディスク用ケース

Families Citing this family (16)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GB1602188A (en) *	1977-12-01	1981-11-11	Wellcome Found	Hydantoin derivatives
DK391678A (da) *	1977-09-05	1979-03-06	Wellcome Found	Nitrogen-heterocycliske forbindelser fremgangsmaade til deres fremstilling samt deres anvendelse
DK543178A (da) *	1977-12-01	1979-06-02	Wellcome Found	Thiodydantoinderivater
EP0003410B1 (en) *	1978-01-23	1982-10-06	Beecham Group Plc	Hydantoins and thiohydantoins, method for their preparation and pharmaceutical compositions containing them
EP0004723A1 (en) *	1978-03-30	1979-10-17	Beecham Group Plc	Deoxyhydantoins, processes for their preparation and pharmaceutical compositions containing them
GB1599740A (en) *	1978-05-31	1981-10-07	Wellcome Found	Hydantoin derivatives
AU4778279A (en) *	1978-06-15	1979-12-20	Beecham Group Limited	Prostaglandin analogues
AU4806979A (en) *	1978-06-15	1979-12-20	Beecham Group Limited	1,2,4 triazole derivatives
IL57504A0 (en) *	1978-06-15	1979-10-31	Beecham Group Ltd	Prostagandin analogues,their preparation and pharmaceutical compositions containing
EP0006352A1 (en) *	1978-06-15	1980-01-09	Beecham Group Plc	Hydantoins and thiohydantoins, process for their preparation and pharmaceutical compositions containing them
IL59065A0 (en) *	1979-01-18	1980-05-30	Beecham Group Ltd	Hydantoin derivatives,their preparation pharmaceutical compositons containing them
JPS55151569A (en) *	1979-05-09	1980-11-26	Wellcome Found	Optically active heterocyclic compounds* their synthesis and medical blend containing them
US4684735A (en) *	1985-07-01	1987-08-04	Stauffer Chemical Company	Promotion of raney nickel hydrogenation catalyst
HUP0402486A3 (en) *	2001-11-30	2007-05-02	Lilly Co Eli	Nitrogen containing heterocyclic compounds as peroxisome proliferator activated receptor agonists, their use and pharmaceutical compositions cointaining them
US7179820B2 (en) *	2003-06-06	2007-02-20	Allergan, Inc.	Piperidinyl prostaglandin E analogs
AU2004245122A1 (en) *	2003-06-06	2004-12-16	Allergan, Inc.	Piperidinyl prostaglandin E analogs

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GB1524818A (en) *	1974-11-29	1978-09-13	Beecham Group Ltd	12-azaprostaglandins

1977
- 1977-06-02 JP JP6525277A patent/JPS52151168A/ja active Granted
- 1977-06-02 DK DK244577A patent/DK244577A/da not_active Application Discontinuation
- 1977-06-02 NL NL7706064A patent/NL7706064A/xx not_active Application Discontinuation
- 1977-06-02 SE SE7706428A patent/SE446336B/xx unknown
- 1977-06-02 CH CH679677A patent/CH645631A5/de not_active IP Right Cessation
- 1977-06-02 NZ NZ184281A patent/NZ184281A/xx unknown
- 1977-06-02 FR FR7716849A patent/FR2362839A1/fr active Granted
- 1977-06-02 DE DE19772724948 patent/DE2724948A1/de not_active Ceased
- 1977-06-02 FI FI771763A patent/FI71930C/fi not_active IP Right Cessation
- 1977-06-02 ES ES459412A patent/ES459412A1/es not_active Expired
- 1977-06-02 HU HU77WE560A patent/HU183046B/hu unknown
- 1977-06-02 CA CA000280455A patent/CA1176261A/en not_active Expired
1978
- 1978-06-01 ES ES470428A patent/ES470428A1/es not_active Expired
1979
- 1979-02-28 ES ES478156A patent/ES478156A1/es not_active Expired
- 1979-06-28 ES ES482010A patent/ES482010A1/es not_active Expired
1980
- 1980-03-25 ES ES489883A patent/ES489883A0/es active Granted
1982
- 1982-05-19 SE SE8203161A patent/SE8203161L/sv not_active Application Discontinuation
1984
- 1984-02-07 CH CH57784A patent/CH646426A5/de not_active IP Right Cessation
- 1984-02-07 CH CH576/84A patent/CH647511A5/de not_active IP Right Cessation

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
JP3022878U (ja) *	1995-08-18	1996-04-02	有限会社春江加工	ミニディスク用ケース

Also Published As

Publication number	Publication date
CH647511A5 (en)	1985-01-31
DK244577A (da)	1977-12-04
JPS52151168A (en)	1977-12-15
CH646426A5 (en)	1984-11-30
FI71930B (fi)	1986-11-28
SE8203161L (sv)	1982-05-19
HU183046B (en)	1984-04-28
SE446336B (sv)	1986-09-01
NL7706064A (nl)	1977-12-06
FI71930C (fi)	1987-03-09
CA1176261A (en)	1984-10-16
ES8103057A1 (es)	1981-02-16
FI771763A (fi)	1977-12-04
SE7706428L (sv)	1977-12-04
FR2362839B1 (ru)	1980-02-01
ES482010A1 (es)	1980-08-16
ES489883A0 (es)	1981-02-16
ES459412A1 (es)	1978-11-01
ES478156A1 (es)	1979-11-01
DE2724948A1 (de)	1977-12-15
FR2362839A1 (fr)	1978-03-24
ES470428A1 (es)	1979-09-01
NZ184281A (en)	1980-04-28
CH645631A5 (en)	1984-10-15

Publication	Publication Date	Title
USRE33024E (en)	1989-08-15	Bronchodilating 8-hydroxy-5-(1R)-1-hydroxy-2-(N-((1R)-2-(p-methoxyphenyl)-1-methylethyl)-amino)ethyl) carbostyril and intermediates thereof
JPS6222986B2 (ru)	1987-05-20
JP2564462B2 (ja)	1996-12-18	新規アリールアルキル（チオ）アミド化合物
US4948809A (en)	1990-08-14	Sulphonylalkylamines, processes for the preparation thereof and pharmaceutical compositions containing them
JP2002526442A (ja)	2002-08-20	プロスタグランジンｅ２アンタゴニストの新規用途
FR2698873A1 (fr)	1994-06-10	Benzocycloheptènes, benzoxépines et benzothiépines activateurs des canaux potassiques, procédé de préparation, composition pharmaceutique les contenant.
US6057357A (en)	2000-05-02	Peripherally selective kappa opioid agonists
JPS6210508B2 (ru)	1987-03-06
JPH05396B2 (ru)	1993-01-05
JP2656594B2 (ja)	1997-09-24	ジアミン化合物、その製法及び該化合物を含有する高血圧症及び炎症を治療するための医薬
US4204068A (en)	1980-05-20	Nitrogen heterocycles
KR840001552B1 (ko)	1984-10-05	시클로헥센 유도체의 제조방법
JPH0253430B2 (ru)	1990-11-16
BG100070A (bg)	1996-05-31	Инхибитори на 5-липоксигеназата
JPH01165554A (ja)	1989-06-29	置換ヒドロキシルアミン
JPH0261950B2 (ru)	1990-12-21
JPH054383B2 (ru)	1993-01-19
US4470986A (en)	1984-09-11	Certain imidazo (1,5-A) pyridine aliphatic carboxylic acid derivatives and their use as selective thromboxane inhibitors
EP0001238B1 (en)	1984-07-04	Hydantoin derivatives, their synthesis, pharmaceutical formulations and intermediates in their preparation
US4337262A (en)	1982-06-29	Hydantoin derivatives, pharmaceutical compounds and methods of use
JPH0536436B2 (ru)	1993-05-31
SU867304A3 (ru)	1981-09-23	Способ получени производных N-фенил-N-(4-пиперидинил)амида или их солей
US3972994A (en)	1976-08-03	Disubstituted azabicycloalkanes
JP2661841B2 (ja)	1997-10-08	インドリン誘導体
RU2181722C2 (ru)	2002-04-27	Способ получения и промежуточные соединения для получения ингибиторов 5-липоксигеназы

JPS6222986B2 - - Google Patents

Info

Links

Classifications

Landscapes

Applications Claiming Priority (3)

Publications (2)

Family

ID=27256793

Family Applications (1)

Country Status (12)

Cited By (1)

Families Citing this family (16)

Family Cites Families (1)

Cited By (1)

Also Published As

Similar Documents