WO1982001002A1 - 7-oxoprostacyclin derivatives and process for the preparation thereof - Google Patents

7-oxoprostacyclin derivatives and process for the preparation thereof Download PDF

Info

Publication number: WO1982001002A1
Authority: WO; WIPO (PCT)
Prior art keywords: radical; chain; solution; acid; oxoprostacyclin
Prior art date: 1980-09-18

Application number

PCT/EP1981/000148

Other languages

English (en)

French (fr)

Inventor

Ag Schering

Original Assignee

Nickolson R

Casals Stenzel J

Vorbrueggen H

Mannesmann G

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.)

1980-09-18

Filing date

1981-09-17

Publication date

1982-04-01

1981-09-17 Application filed by Nickolson R, Casals Stenzel J, Vorbrueggen H, Mannesmann G filed Critical Nickolson R

1981-09-17 Priority to DE8181903255T priority Critical patent/DE3172032D1/de

1981-09-17 Priority to AT81903255T priority patent/ATE15194T1/de

1982-04-01 Publication of WO1982001002A1 publication Critical patent/WO1982001002A1/en

1982-05-14 Priority to FI821707A priority patent/FI66367C/fi

1982-05-14 Priority to NO821620A priority patent/NO158098C/no

1982-05-17 Priority to DK220982A priority patent/DK220982A/da

Links

ZHIHHYNLWRXTTN-GJUFTPBXSA-N (5z)-5-[(3ar,4r,5r,6as)-5-hydroxy-4-[(e,3s)-3-hydroxyoct-1-enyl]-3-oxo-4,5,6,6a-tetrahydro-3ah-cyclopenta[b]furan-2-ylidene]pentanoic acid Chemical class O1\C(=C/CCCC(O)=O)C(=O)[C@@H]2[C@@H](/C=C/[C@@H](O)CCCCC)[C@H](O)C[C@@H]21 ZHIHHYNLWRXTTN-GJUFTPBXSA-N 0.000 title claims abstract description 10
238000000034 method Methods 0.000 title claims description 15
230000008569 process Effects 0.000 title claims description 6
238000002360 preparation method Methods 0.000 title claims description 4
125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 18
125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 12
229920006395 saturated elastomer Polymers 0.000 claims abstract description 8
208000001953 Hypotension Diseases 0.000 claims abstract description 5
125000000623 heterocyclic group Chemical group 0.000 claims abstract description 5
208000021822 hypotensive Diseases 0.000 claims abstract description 5
230000001077 hypotensive effect Effects 0.000 claims abstract description 5
125000003107 substituted aryl group Chemical group 0.000 claims abstract description 5
BDHFUVZGWQCTTF-UHFFFAOYSA-N sulfonic acid Chemical compound OS(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-N 0.000 claims abstract description 3
-1 alkyl radical Chemical class 0.000 claims description 118
150000001875 compounds Chemical class 0.000 claims description 101
239000000203 mixture Substances 0.000 claims description 58
150000004702 methyl esters Chemical class 0.000 claims description 50
239000002253 acid Substances 0.000 claims description 29
125000004432 carbon atom Chemical group C* 0.000 claims description 29
150000003839 salts Chemical class 0.000 claims description 21
150000003254 radicals Chemical class 0.000 claims description 14
JPJALAQPGMAKDF-UHFFFAOYSA-N selenium dioxide Chemical compound O=[Se]=O JPJALAQPGMAKDF-UHFFFAOYSA-N 0.000 claims description 12
125000005843 halogen group Chemical group 0.000 claims description 9
125000001424 substituent group Chemical group 0.000 claims description 8
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
125000003118 aryl group Chemical group 0.000 claims description 5
150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 4
239000000825 pharmaceutical preparation Substances 0.000 claims description 4
238000002560 therapeutic procedure Methods 0.000 claims description 4
238000011282 treatment Methods 0.000 claims description 4
239000003795 chemical substances by application Substances 0.000 claims description 3
125000004430 oxygen atom Chemical group O* 0.000 claims description 3
125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 3
125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 3
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical class OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 claims description 3
125000000753 cycloalkyl group Chemical group 0.000 claims description 2
241001465754 Metazoa Species 0.000 claims 3
125000004183 alkoxy alkyl group Chemical group 0.000 claims 2
125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 1
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims 1
125000001589 carboacyl group Chemical group 0.000 claims 1
239000002552 dosage form Substances 0.000 claims 1
229960001123 epoprostenol Drugs 0.000 abstract description 8
230000009471 action Effects 0.000 abstract description 6
150000003180 prostaglandins Chemical class 0.000 abstract description 5
229940094443 oxytocics prostaglandins Drugs 0.000 abstract description 4
150000001735 carboxylic acids Chemical class 0.000 abstract description 3
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 abstract description 2
210000004204 blood vessel Anatomy 0.000 abstract description 2
230000000916 dilatatory effect Effects 0.000 abstract description 2
239000001301 oxygen Substances 0.000 abstract description 2
229910052760 oxygen Inorganic materials 0.000 abstract description 2
125000000008 (C1-C10) alkyl group Chemical group 0.000 abstract 2
KAQKFAOMNZTLHT-VVUHWYTRSA-N epoprostenol Chemical compound O1C(=CCCCC(O)=O)C[C@@H]2[C@@H](/C=C/[C@@H](O)CCCCC)[C@H](O)C[C@@H]21 KAQKFAOMNZTLHT-VVUHWYTRSA-N 0.000 abstract 2
239000001257 hydrogen Substances 0.000 abstract 2
229910052739 hydrogen Inorganic materials 0.000 abstract 2
125000006832 (C1-C10) alkylene group Chemical group 0.000 abstract 1
125000006374 C2-C10 alkenyl group Chemical group 0.000 abstract 1
125000003601 C2-C6 alkynyl group Chemical group 0.000 abstract 1
101100294115 Caenorhabditis elegans nhr-4 gene Proteins 0.000 abstract 1
239000002220 antihypertensive agent Substances 0.000 abstract 1
125000005346 substituted cycloalkyl group Chemical group 0.000 abstract 1
239000000243 solution Substances 0.000 description 160
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 146
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 81
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 69
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 60
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 52
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 51
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 45
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 38
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 36
229910052943 magnesium sulfate Inorganic materials 0.000 description 30
235000019341 magnesium sulphate Nutrition 0.000 description 30
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 29
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 27
238000006243 chemical reaction Methods 0.000 description 27
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 26
229910052786 argon Inorganic materials 0.000 description 26
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 24
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 21
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 21
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
239000000741 silica gel Substances 0.000 description 21
229910002027 silica gel Inorganic materials 0.000 description 21
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 20
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 18
239000012074 organic phase Substances 0.000 description 16
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 15
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 14
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 14
239000012071 phase Substances 0.000 description 14
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 12
239000012043 crude product Substances 0.000 description 12
229960000583 acetic acid Drugs 0.000 description 11
239000008346 aqueous phase Substances 0.000 description 11
HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 11
YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 10
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
238000010828 elution Methods 0.000 description 10
239000002904 solvent Substances 0.000 description 10
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
125000000217 alkyl group Chemical group 0.000 description 9
239000002244 precipitate Substances 0.000 description 9
239000007858 starting material Substances 0.000 description 9
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 8
229910052740 iodine Inorganic materials 0.000 description 8
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 7
150000007513 acids Chemical class 0.000 description 7
239000007864 aqueous solution Substances 0.000 description 7
239000012362 glacial acetic acid Substances 0.000 description 7
239000011630 iodine Substances 0.000 description 7
150000003815 prostacyclins Chemical class 0.000 description 7
KAQKFAOMNZTLHT-OZUDYXHBSA-N prostaglandin I2 Chemical compound O1\C(=C/CCCC(O)=O)C[C@@H]2[C@@H](/C=C/[C@@H](O)CCCCC)[C@H](O)C[C@@H]21 KAQKFAOMNZTLHT-OZUDYXHBSA-N 0.000 description 7
239000000725 suspension Substances 0.000 description 7
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 6
210000001772 blood platelet Anatomy 0.000 description 6
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 6
229960001760 dimethyl sulfoxide Drugs 0.000 description 6
150000002009 diols Chemical class 0.000 description 6
239000000284 extract Substances 0.000 description 6
238000010992 reflux Methods 0.000 description 6
229910000030 sodium bicarbonate Inorganic materials 0.000 description 6
235000017557 sodium bicarbonate Nutrition 0.000 description 6
229910052938 sodium sulfate Inorganic materials 0.000 description 6
235000011152 sodium sulphate Nutrition 0.000 description 6
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 5
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 5
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 5
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 5
229910052731 fluorine Inorganic materials 0.000 description 5
239000011737 fluorine Substances 0.000 description 5
230000005764 inhibitory process Effects 0.000 description 5
230000007935 neutral effect Effects 0.000 description 5
238000000746 purification Methods 0.000 description 5
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 4
BUDQDWGNQVEFAC-UHFFFAOYSA-N Dihydropyran Chemical compound C1COC=CC1 BUDQDWGNQVEFAC-UHFFFAOYSA-N 0.000 description 4
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
235000011054 acetic acid Nutrition 0.000 description 4
239000002585 base Substances 0.000 description 4
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical group OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 4
230000036772 blood pressure Effects 0.000 description 4
239000000460 chlorine Substances 0.000 description 4
229910052801 chlorine Inorganic materials 0.000 description 4
238000001816 cooling Methods 0.000 description 4
XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 4
239000012259 ether extract Substances 0.000 description 4
FFUAGWLWBBFQJT-UHFFFAOYSA-N hexamethyldisilazane Chemical compound C[Si](C)(C)N[Si](C)(C)C FFUAGWLWBBFQJT-UHFFFAOYSA-N 0.000 description 4
239000012442 inert solvent Substances 0.000 description 4
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 4
150000002576 ketones Chemical class 0.000 description 4
238000004519 manufacturing process Methods 0.000 description 4
239000011541 reaction mixture Substances 0.000 description 4
229910052708 sodium Inorganic materials 0.000 description 4
239000011734 sodium Substances 0.000 description 4
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 4
LOYZVRIHVZEDMW-UHFFFAOYSA-N 1-bromo-3-methylbut-2-ene Chemical compound CC(C)=CCBr LOYZVRIHVZEDMW-UHFFFAOYSA-N 0.000 description 3
GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 3
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
230000002776 aggregation Effects 0.000 description 3
238000004220 aggregation Methods 0.000 description 3
150000001298 alcohols Chemical class 0.000 description 3
125000003545 alkoxy group Chemical group 0.000 description 3
150000001412 amines Chemical class 0.000 description 3
238000004587 chromatography analysis Methods 0.000 description 3
238000004440 column chromatography Methods 0.000 description 3
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 3
238000004821 distillation Methods 0.000 description 3
230000032050 esterification Effects 0.000 description 3
238000005886 esterification reaction Methods 0.000 description 3
150000002148 esters Chemical class 0.000 description 3
125000004494 ethyl ester group Chemical group 0.000 description 3
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
150000004679 hydroxides Chemical class 0.000 description 3
239000005457 ice water Substances 0.000 description 3
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
210000000056 organ Anatomy 0.000 description 3
239000003960 organic solvent Substances 0.000 description 3
238000012746 preparative thin layer chromatography Methods 0.000 description 3
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
MYHXHCUNDDAEOZ-FOSBLDSVSA-N prostaglandin A2 Chemical compound CCCCC[C@H](O)\C=C\[C@H]1C=CC(=O)[C@@H]1C\C=C/CCCC(O)=O MYHXHCUNDDAEOZ-FOSBLDSVSA-N 0.000 description 3
230000009467 reduction Effects 0.000 description 3
239000011780 sodium chloride Substances 0.000 description 3
AGBWDHTZUCGTAI-UHFFFAOYSA-N 1-(cycloundecen-1-yl)-3-diazocycloundecene Chemical compound [N-]=[N+]=C1CCCCCCCCC(C=2CCCCCCCCCC=2)=C1 AGBWDHTZUCGTAI-UHFFFAOYSA-N 0.000 description 2
HUHXLHLWASNVDB-UHFFFAOYSA-N 2-(oxan-2-yloxy)oxane Chemical compound O1CCCCC1OC1OCCCC1 HUHXLHLWASNVDB-UHFFFAOYSA-N 0.000 description 2
HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
SMNDYUVBFMFKNZ-UHFFFAOYSA-N 2-furoic acid Chemical group OC(=O)C1=CC=CO1 SMNDYUVBFMFKNZ-UHFFFAOYSA-N 0.000 description 2
MLOSJPZSZWUDSK-UHFFFAOYSA-N 4-carboxybutyl(triphenyl)phosphanium;bromide Chemical compound [Br-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(CCCCC(=O)O)C1=CC=CC=C1 MLOSJPZSZWUDSK-UHFFFAOYSA-N 0.000 description 2
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
239000005711 Benzoic acid Chemical group 0.000 description 2
FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 2
VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
102000016736 Cyclin Human genes 0.000 description 2
108050006400 Cyclin Proteins 0.000 description 2
YVHAIVPPUIZFBA-UHFFFAOYSA-N Cyclopentylacetic acid Chemical compound OC(=O)CC1CCCC1 YVHAIVPPUIZFBA-UHFFFAOYSA-N 0.000 description 2
ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
YZGQDNOIGFBYKF-UHFFFAOYSA-N Ethoxyacetic acid Chemical compound CCOCC(O)=O YZGQDNOIGFBYKF-UHFFFAOYSA-N 0.000 description 2
IYXGSMUGOJNHAZ-UHFFFAOYSA-N Ethyl malonate Chemical compound CCOC(=O)CC(=O)OCC IYXGSMUGOJNHAZ-UHFFFAOYSA-N 0.000 description 2
DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
RRHGJUQNOFWUDK-UHFFFAOYSA-N Isoprene Chemical compound CC(=C)C=C RRHGJUQNOFWUDK-UHFFFAOYSA-N 0.000 description 2
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical group OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 2
241000283973 Oryctolagus cuniculus Species 0.000 description 2
XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 2
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
239000004133 Sodium thiosulphate Substances 0.000 description 2
HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 2
NDHMOBCVFGMXRK-FVCCEPFGSA-N [(3ar,4r,5r,6as)-4-formyl-2-oxo-3,3a,4,5,6,6a-hexahydrocyclopenta[b]furan-5-yl] benzoate Chemical compound O([C@H]1[C@@H]([C@H]2CC(=O)O[C@H]2C1)C=O)C(=O)C1=CC=CC=C1 NDHMOBCVFGMXRK-FVCCEPFGSA-N 0.000 description 2
150000000475 acetylene derivatives Chemical class 0.000 description 2
239000013543 active substance Substances 0.000 description 2
125000002252 acyl group Chemical group 0.000 description 2
WNLRTRBMVRJNCN-UHFFFAOYSA-N adipic acid Chemical group OC(=O)CCCCC(O)=O WNLRTRBMVRJNCN-UHFFFAOYSA-N 0.000 description 2
229910052783 alkali metal Inorganic materials 0.000 description 2
229910000288 alkali metal carbonate Inorganic materials 0.000 description 2
150000008041 alkali metal carbonates Chemical class 0.000 description 2
229910052784 alkaline earth metal Inorganic materials 0.000 description 2
125000003342 alkenyl group Chemical group 0.000 description 2
229940006138 antiglaucoma drug and miotics prostaglandin analogues Drugs 0.000 description 2
AYJRCSIUFZENHW-UHFFFAOYSA-L barium carbonate Chemical compound [Ba+2].[O-]C([O-])=O AYJRCSIUFZENHW-UHFFFAOYSA-L 0.000 description 2
235000010233 benzoic acid Nutrition 0.000 description 2
230000015572 biosynthetic process Effects 0.000 description 2
230000017531 blood circulation Effects 0.000 description 2
239000012267 brine Substances 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
AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 2
239000000920 calcium hydroxide Substances 0.000 description 2
229910001861 calcium hydroxide Inorganic materials 0.000 description 2
230000000747 cardiac effect Effects 0.000 description 2
LJOODBDWMQKMFB-UHFFFAOYSA-N cyclohexylacetic acid Chemical compound OC(=O)CC1CCCCC1 LJOODBDWMQKMFB-UHFFFAOYSA-N 0.000 description 2
GHVNFZFCNZKVNT-UHFFFAOYSA-N decanoic acid Chemical compound CCCCCCCCCC(O)=O GHVNFZFCNZKVNT-UHFFFAOYSA-N 0.000 description 2
150000005690 diesters Chemical class 0.000 description 2
POULHZVOKOAJMA-UHFFFAOYSA-N dodecanoic acid Chemical compound CCCCCCCCCCCC(O)=O POULHZVOKOAJMA-UHFFFAOYSA-N 0.000 description 2
239000003814 drug Substances 0.000 description 2
125000004185 ester group Chemical group 0.000 description 2
125000001033 ether group Chemical group 0.000 description 2
238000006266 etherification reaction Methods 0.000 description 2
238000001704 evaporation Methods 0.000 description 2
239000000706 filtrate Substances 0.000 description 2
230000027119 gastric acid secretion Effects 0.000 description 2
229910052736 halogen Inorganic materials 0.000 description 2
150000002367 halogens Chemical group 0.000 description 2
125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 2
125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
230000007062 hydrolysis Effects 0.000 description 2
238000006460 hydrolysis reaction Methods 0.000 description 2
150000007529 inorganic bases Chemical class 0.000 description 2
238000010253 intravenous injection Methods 0.000 description 2
KQNPFQTWMSNSAP-UHFFFAOYSA-N isobutyric acid Chemical compound CC(C)C(O)=O KQNPFQTWMSNSAP-UHFFFAOYSA-N 0.000 description 2
TWBYWOBDOCUKOW-UHFFFAOYSA-N isonicotinic acid Chemical group OC(=O)C1=CC=NC=C1 TWBYWOBDOCUKOW-UHFFFAOYSA-N 0.000 description 2
JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
150000002596 lactones Chemical class 0.000 description 2
230000002045 lasting effect Effects 0.000 description 2
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
230000003387 muscular Effects 0.000 description 2
229910052757 nitrogen Inorganic materials 0.000 description 2
FBUKVWPVBMHYJY-UHFFFAOYSA-N nonanoic acid Chemical compound CCCCCCCCC(O)=O FBUKVWPVBMHYJY-UHFFFAOYSA-N 0.000 description 2
WWZKQHOCKIZLMA-UHFFFAOYSA-N octanoic acid Chemical compound CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 description 2
125000004043 oxo group Chemical group O=* 0.000 description 2
WQEPLUUGTLDZJY-UHFFFAOYSA-N pentadecanoic acid Chemical compound CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 description 2
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 2
LCPDWSOZIOUXRV-UHFFFAOYSA-N phenoxyacetic acid Chemical compound OC(=O)COC1=CC=CC=C1 LCPDWSOZIOUXRV-UHFFFAOYSA-N 0.000 description 2
XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 description 2
159000000001 potassium salts Chemical class 0.000 description 2
238000011321 prophylaxis Methods 0.000 description 2
235000019260 propionic acid Nutrition 0.000 description 2
IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 2
239000012279 sodium borohydride Substances 0.000 description 2
229910000033 sodium borohydride Inorganic materials 0.000 description 2
JHJLBTNAGRQEKS-UHFFFAOYSA-M sodium bromide Chemical compound [Na+].[Br-] JHJLBTNAGRQEKS-UHFFFAOYSA-M 0.000 description 2
239000012312 sodium hydride Substances 0.000 description 2
229910000104 sodium hydride Inorganic materials 0.000 description 2
AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 2
235000019345 sodium thiosulphate Nutrition 0.000 description 2
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
239000007787 solid Substances 0.000 description 2
230000000638 stimulation Effects 0.000 description 2
150000003512 tertiary amines Chemical class 0.000 description 2
FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 2
SZHOJFHSIKHZHA-UHFFFAOYSA-N tridecanoic acid Chemical compound CCCCCCCCCCCCC(O)=O SZHOJFHSIKHZHA-UHFFFAOYSA-N 0.000 description 2
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 2
ADZJWYULTMTLQZ-UHFFFAOYSA-N tritylphosphane;hydrobromide Chemical compound [Br-].C=1C=CC=CC=1C(C=1C=CC=CC=1)([PH3+])C1=CC=CC=C1 ADZJWYULTMTLQZ-UHFFFAOYSA-N 0.000 description 2
ZDPHROOEEOARMN-UHFFFAOYSA-N undecanoic acid Chemical compound CCCCCCCCCCC(O)=O ZDPHROOEEOARMN-UHFFFAOYSA-N 0.000 description 2
NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 2
239000011701 zinc Substances 0.000 description 2
229910052725 zinc Inorganic materials 0.000 description 2
ALFAIYBMQQREFH-UHFFFAOYSA-N (2-oxo-3,3a,4,5,6,6a-hexahydrocyclopenta[b]furan-5-yl) benzoate Chemical compound C1C2CC(=O)OC2CC1OC(=O)C1=CC=CC=C1 ALFAIYBMQQREFH-UHFFFAOYSA-N 0.000 description 1
JCULBPXRQGDFMI-GLEOKDIPSA-N (3ar,4r,5r,6as)-4-[(1e,3s,6z)-7-chloro-3-(oxan-2-yloxy)octa-1,6-dienyl]-5-(oxan-2-yloxy)-3,3a,4,5,6,6a-hexahydro-2h-cyclopenta[b]furan-2-ol Chemical compound O([C@@H](CC/C=C(Cl)/C)\C=C\[C@@H]1[C@H]2CC(O)O[C@H]2C[C@H]1OC1OCCCC1)C1CCCCO1 JCULBPXRQGDFMI-GLEOKDIPSA-N 0.000 description 1
HQAVBWYYWCZPAX-FBXXZOPISA-N (3ar,4r,5r,6as)-4-[(1e,3s,6z)-7-chloro-3-hydroxyocta-1,6-dienyl]-5-hydroxy-3,3a,4,5,6,6a-hexahydrocyclopenta[b]furan-2-one Chemical compound O1C(=O)C[C@@H]2[C@@H](/C=C/[C@@H](O)CC/C=C(Cl)/C)[C@H](O)C[C@@H]21 HQAVBWYYWCZPAX-FBXXZOPISA-N 0.000 description 1
SELGCCAETSODQB-FNLFQXNBSA-N (3ar,4r,5r,6as)-5-hydroxy-4-[(e,3s)-3-hydroxyoct-1-en-5-ynyl]-3,3a,4,5,6,6a-hexahydrocyclopenta[b]furan-2-one Chemical compound O1C(=O)C[C@@H]2[C@@H](/C=C/[C@@H](O)CC#CCC)[C@H](O)C[C@@H]21 SELGCCAETSODQB-FNLFQXNBSA-N 0.000 description 1
125000004178 (C1-C4) alkyl group Chemical group 0.000 description 1
WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
WGWXMHNNMYQQSA-UHFFFAOYSA-N 1-(triphenyl-$l^{5}-phosphanylidene)hept-4-yn-2-one Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=CC(=O)CC#CCC)C1=CC=CC=C1 WGWXMHNNMYQQSA-UHFFFAOYSA-N 0.000 description 1
AZUYLZMQTIKGSC-UHFFFAOYSA-N 1-[6-[4-(5-chloro-6-methyl-1H-indazol-4-yl)-5-methyl-3-(1-methylindazol-5-yl)pyrazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]prop-2-en-1-one Chemical compound ClC=1C(=C2C=NNC2=CC=1C)C=1C(=NN(C=1C)C1CC2(CN(C2)C(C=C)=O)C1)C=1C=C2C=NN(C2=CC=1)C AZUYLZMQTIKGSC-UHFFFAOYSA-N 0.000 description 1
125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 description 1
125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
XYHKNCXZYYTLRG-UHFFFAOYSA-N 1h-imidazole-2-carbaldehyde Chemical compound O=CC1=NC=CN1 XYHKNCXZYYTLRG-UHFFFAOYSA-N 0.000 description 1
IJAFXNYUNXJAQB-UHFFFAOYSA-N 2-(3-methylbut-2-enyl)propanedioic acid Chemical compound CC(C)=CCC(C(O)=O)C(O)=O IJAFXNYUNXJAQB-UHFFFAOYSA-N 0.000 description 1
OXQGTIUCKGYOAA-UHFFFAOYSA-N 2-Ethylbutanoic acid Chemical compound CCC(CC)C(O)=O OXQGTIUCKGYOAA-UHFFFAOYSA-N 0.000 description 1
NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
FXKMTSIKHBYZSZ-UHFFFAOYSA-N 2-chloroethanesulfonic acid Chemical compound OS(=O)(=O)CCCl FXKMTSIKHBYZSZ-UHFFFAOYSA-N 0.000 description 1
KVVDRQDTODKIJD-UHFFFAOYSA-N 2-cyclopropylacetic acid Chemical compound OC(=O)CC1CC1 KVVDRQDTODKIJD-UHFFFAOYSA-N 0.000 description 1
125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 description 1
125000005916 2-methylpentyl group Chemical group 0.000 description 1
WLJVXDMOQOGPHL-PPJXEINESA-N 2-phenylacetic acid Chemical compound O[14C](=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-PPJXEINESA-N 0.000 description 1
VRDBIJCCXDEZJN-UHFFFAOYSA-N 2-piperidin-1-ylacetic acid Chemical compound OC(=O)CN1CCCCC1 VRDBIJCCXDEZJN-UHFFFAOYSA-N 0.000 description 1
125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 1
WADSJYLPJPTMLN-UHFFFAOYSA-N 3-(cycloundecen-1-yl)-1,2-diazacycloundec-2-ene Chemical compound C1CCCCCCCCC=C1C1=NNCCCCCCCC1 WADSJYLPJPTMLN-UHFFFAOYSA-N 0.000 description 1
GWYFCOCPABKNJV-UHFFFAOYSA-M 3-Methylbutanoic acid Natural products CC(C)CC([O-])=O GWYFCOCPABKNJV-UHFFFAOYSA-M 0.000 description 1
ZRPLANDPDWYOMZ-UHFFFAOYSA-N 3-cyclopentylpropionic acid Chemical group OC(=O)CCC1CCCC1 ZRPLANDPDWYOMZ-UHFFFAOYSA-N 0.000 description 1
125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 1
OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
RJWBTWIBUIGANW-UHFFFAOYSA-N 4-chlorobenzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=C(Cl)C=C1 RJWBTWIBUIGANW-UHFFFAOYSA-N 0.000 description 1
125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
SJAZDJCBOMMENQ-UHFFFAOYSA-N 5-chlorohex-4-enoic acid Chemical compound CC(Cl)=CCCC(O)=O SJAZDJCBOMMENQ-UHFFFAOYSA-N 0.000 description 1
YJJLHGCCADOOPZ-UHFFFAOYSA-N 5-methylhex-4-enoic acid Chemical compound CC(C)=CCCC(O)=O YJJLHGCCADOOPZ-UHFFFAOYSA-N 0.000 description 1
OIXSONNHKLEYHU-UHFFFAOYSA-N 6-chloro-1-dimethoxyphosphorylhept-5-en-2-one Chemical compound COP(=O)(OC)CC(=O)CCC=C(C)Cl OIXSONNHKLEYHU-UHFFFAOYSA-N 0.000 description 1
FHJOKULWJSXCKI-UHFFFAOYSA-N 6-methyl-1-(triphenyl-$l^{5}-phosphanylidene)hept-5-en-2-one Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=CC(=O)CCC=C(C)C)C1=CC=CC=C1 FHJOKULWJSXCKI-UHFFFAOYSA-N 0.000 description 1
KPRGOTLNGIBVFL-GINZOMEDSA-N 7-ketodehydroepiandrosterone Chemical group C1[C@@H](O)CC[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3C(=O)C=C21 KPRGOTLNGIBVFL-GINZOMEDSA-N 0.000 description 1
206010004053 Bacterial toxaemia Diseases 0.000 description 1
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
206010006482 Bronchospasm Diseases 0.000 description 1
SNRDFPUMRHPUCQ-UHFFFAOYSA-N CS(=O)C[Na] Chemical compound CS(=O)C[Na] SNRDFPUMRHPUCQ-UHFFFAOYSA-N 0.000 description 1
239000005632 Capric acid (CAS 334-48-5) Substances 0.000 description 1
239000005635 Caprylic acid (CAS 124-07-2) Substances 0.000 description 1
241000700198 Cavia Species 0.000 description 1
XJUZRXYOEPSWMB-UHFFFAOYSA-N Chloromethyl methyl ether Chemical compound COCCl XJUZRXYOEPSWMB-UHFFFAOYSA-N 0.000 description 1
206010011091 Coronary artery thrombosis Diseases 0.000 description 1
206010012735 Diarrhoea Diseases 0.000 description 1
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 1
VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
206010061216 Infarction Diseases 0.000 description 1
208000035945 Labour pain Diseases 0.000 description 1
239000005639 Lauric acid Substances 0.000 description 1
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 1
FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
SGXDXUYKISDCAZ-UHFFFAOYSA-N N,N-diethylglycine Chemical compound CCN(CC)CC(O)=O SGXDXUYKISDCAZ-UHFFFAOYSA-N 0.000 description 1
VIWZVFVJPXTXPA-UHFFFAOYSA-N N-(2-Carboxymethyl)-morpholine Chemical compound OC(=O)CN1CCOCC1 VIWZVFVJPXTXPA-UHFFFAOYSA-N 0.000 description 1
MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
229910019213 POCl3 Inorganic materials 0.000 description 1
239000005643 Pelargonic acid Substances 0.000 description 1
208000005764 Peripheral Arterial Disease Diseases 0.000 description 1
208000030831 Peripheral arterial occlusive disease Diseases 0.000 description 1
241000700159 Rattus Species 0.000 description 1
208000006011 Stroke Diseases 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
239000005864 Sulphur Substances 0.000 description 1
DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 1
208000007536 Thrombosis Diseases 0.000 description 1
GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
206010047139 Vasoconstriction Diseases 0.000 description 1
WBFSXDGXZIQQTN-PFPAMLNPSA-N [(3ar,4r,5r,6as)-4-[(1e)-7-methyl-3-oxoocta-1,6-dienyl]-2-oxo-3,3a,4,5,6,6a-hexahydrocyclopenta[b]furan-5-yl] benzoate Chemical compound O([C@H]1[C@@H]([C@H]2CC(=O)O[C@H]2C1)/C=C/C(=O)CCC=C(C)C)C(=O)C1=CC=CC=C1 WBFSXDGXZIQQTN-PFPAMLNPSA-N 0.000 description 1
QDOJCJUAIARWNR-UOJBZKOCSA-N [(3ar,4r,5r,6as)-4-[(1e,3s,6z)-7-chloro-3-hydroxyocta-1,6-dienyl]-2-oxo-3,3a,4,5,6,6a-hexahydrocyclopenta[b]furan-5-yl] benzoate Chemical compound O([C@H]1[C@@H]([C@H]2CC(=O)O[C@H]2C1)/C=C/[C@@H](O)CC/C=C(Cl)/C)C(=O)C1=CC=CC=C1 QDOJCJUAIARWNR-UOJBZKOCSA-N 0.000 description 1
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
150000008065 acid anhydrides Chemical class 0.000 description 1
239000003377 acid catalyst Substances 0.000 description 1
239000001361 adipic acid Substances 0.000 description 1
235000011037 adipic acid Nutrition 0.000 description 1
239000002671 adjuvant Substances 0.000 description 1
125000001931 aliphatic group Chemical group 0.000 description 1
229910001854 alkali hydroxide Inorganic materials 0.000 description 1
150000008044 alkali metal hydroxides Chemical class 0.000 description 1
150000001340 alkali metals Chemical class 0.000 description 1
229910001860 alkaline earth metal hydroxide Inorganic materials 0.000 description 1
150000001342 alkaline earth metals Chemical class 0.000 description 1
125000002947 alkylene group Chemical group 0.000 description 1
HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
229910021529 ammonia Inorganic materials 0.000 description 1
230000003266 anti-allergic effect Effects 0.000 description 1
239000007900 aqueous suspension Substances 0.000 description 1
206010003119 arrhythmia Diseases 0.000 description 1
SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
239000002876 beta blocker Substances 0.000 description 1
229940097320 beta blocking agent Drugs 0.000 description 1
GWYFCOCPABKNJV-UHFFFAOYSA-N beta-methyl-butyric acid Natural products CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 description 1
DOZNIPMBQBZWNB-UHFFFAOYSA-N bis(2-chloroethyl)sulfamic acid Chemical compound ClCCN(S(=O)(=O)O)CCCl DOZNIPMBQBZWNB-UHFFFAOYSA-N 0.000 description 1
AZWXAPCAJCYGIA-UHFFFAOYSA-N bis(2-methylpropyl)alumane Chemical compound CC(C)C[AlH]CC(C)C AZWXAPCAJCYGIA-UHFFFAOYSA-N 0.000 description 1
ZVKZVKWNVILEOS-UHFFFAOYSA-N bis(2-methylpropyl)sulfamic acid Chemical compound CC(C)CN(S(O)(=O)=O)CC(C)C ZVKZVKWNVILEOS-UHFFFAOYSA-N 0.000 description 1
230000037396 body weight Effects 0.000 description 1
238000009835 boiling Methods 0.000 description 1
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
229910052794 bromium Inorganic materials 0.000 description 1
125000001246 bromo group Chemical group Br* 0.000 description 1
230000007885 bronchoconstriction Effects 0.000 description 1
QDHFHIQKOVNCNC-UHFFFAOYSA-N butane-1-sulfonic acid Chemical compound CCCCS(O)(=O)=O QDHFHIQKOVNCNC-UHFFFAOYSA-N 0.000 description 1
KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
125000004369 butenyl group Chemical group C(=CCC)* 0.000 description 1
125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
229910000019 calcium carbonate Inorganic materials 0.000 description 1
239000002775 capsule Substances 0.000 description 1
229910052799 carbon Inorganic materials 0.000 description 1
239000001569 carbon dioxide Substances 0.000 description 1
229910002092 carbon dioxide Inorganic materials 0.000 description 1
150000004649 carbonic acid derivatives Chemical class 0.000 description 1
239000003054 catalyst Substances 0.000 description 1
230000003727 cerebral blood flow Effects 0.000 description 1
239000007795 chemical reaction product Substances 0.000 description 1
125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 1
229940061627 chloromethyl methyl ether Drugs 0.000 description 1
230000002301 combined effect Effects 0.000 description 1
208000029078 coronary artery disease Diseases 0.000 description 1
208000002528 coronary thrombosis Diseases 0.000 description 1
150000003983 crown ethers Chemical class 0.000 description 1
ZHGASCUQXLPSDT-UHFFFAOYSA-N cyclohexanesulfonic acid Chemical compound OS(=O)(=O)C1CCCCC1 ZHGASCUQXLPSDT-UHFFFAOYSA-N 0.000 description 1
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
YAIKGZQRXQYYJZ-UHFFFAOYSA-N cyclopentanesulfonic acid Chemical compound OS(=O)(=O)C1CCCC1 YAIKGZQRXQYYJZ-UHFFFAOYSA-N 0.000 description 1
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
YMGUBTXCNDTFJI-UHFFFAOYSA-N cyclopropanecarboxylic acid Chemical compound OC(=O)C1CC1 YMGUBTXCNDTFJI-UHFFFAOYSA-N 0.000 description 1
125000005265 dialkylamine group Chemical group 0.000 description 1
238000000502 dialysis Methods 0.000 description 1
BAQKWXACUNEBOT-UHFFFAOYSA-N dibutylsulfamic acid Chemical compound CCCCN(S(O)(=O)=O)CCCC BAQKWXACUNEBOT-UHFFFAOYSA-N 0.000 description 1
ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
QQXGDKTYCIVKKA-UHFFFAOYSA-N diethyl 2-(3-chlorobut-2-enyl)-2-methylpropanedioate Chemical compound CCOC(=O)C(C)(CC=C(C)Cl)C(=O)OCC QQXGDKTYCIVKKA-UHFFFAOYSA-N 0.000 description 1
UXBLYMUHQJDAFO-UHFFFAOYSA-N diethyl 2-(3-methylbut-2-enyl)propanedioate Chemical compound CCOC(=O)C(CC=C(C)C)C(=O)OCC UXBLYMUHQJDAFO-UHFFFAOYSA-N 0.000 description 1
UPQZOUHVTJNGFK-UHFFFAOYSA-N diethyl 2-methylpropanedioate Chemical compound CCOC(=O)C(C)C(=O)OCC UPQZOUHVTJNGFK-UHFFFAOYSA-N 0.000 description 1
NXFNZLHFBJYCPG-UHFFFAOYSA-N diethylsulfamic acid Chemical compound CCN(CC)S(O)(=O)=O NXFNZLHFBJYCPG-UHFFFAOYSA-N 0.000 description 1
SIPUZPBQZHNSDW-UHFFFAOYSA-N diisobutylaluminium hydride Substances CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 1
VONWDASPFIQPDY-UHFFFAOYSA-N dimethyl methylphosphonate Chemical compound COP(C)(=O)OC VONWDASPFIQPDY-UHFFFAOYSA-N 0.000 description 1
YGNOYUCUPMACDT-UHFFFAOYSA-N dimethylsulfamic acid Chemical compound CN(C)S(O)(=O)=O YGNOYUCUPMACDT-UHFFFAOYSA-N 0.000 description 1
KPUWHANPEXNPJT-UHFFFAOYSA-N disiloxane Chemical group [SiH3]O[SiH3] KPUWHANPEXNPJT-UHFFFAOYSA-N 0.000 description 1
239000002934 diuretic Substances 0.000 description 1
229940030606 diuretics Drugs 0.000 description 1
239000008298 dragée Substances 0.000 description 1
239000003937 drug carrier Substances 0.000 description 1
230000000694 effects Effects 0.000 description 1
CCIVGXIOQKPBKL-UHFFFAOYSA-N ethanesulfonic acid Chemical compound CCS(O)(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-N 0.000 description 1
150000002170 ethers Chemical class 0.000 description 1
FPIQZBQZKBKLEI-UHFFFAOYSA-N ethyl 1-[[2-chloroethyl(nitroso)carbamoyl]amino]cyclohexane-1-carboxylate Chemical compound ClCCN(N=O)C(=O)NC1(C(=O)OCC)CCCCC1 FPIQZBQZKBKLEI-UHFFFAOYSA-N 0.000 description 1
239000002024 ethyl acetate extract Substances 0.000 description 1
125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
230000008020 evaporation Effects 0.000 description 1
125000001153 fluoro group Chemical group F* 0.000 description 1
125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 description 1
235000019253 formic acid Nutrition 0.000 description 1
ICGWWCLWBPLPDF-UHFFFAOYSA-N furan-2-ol Chemical compound OC1=CC=CO1 ICGWWCLWBPLPDF-UHFFFAOYSA-N 0.000 description 1
230000002496 gastric effect Effects 0.000 description 1
210000001156 gastric mucosa Anatomy 0.000 description 1
229960002449 glycine Drugs 0.000 description 1
235000013905 glycine and its sodium salt Nutrition 0.000 description 1
238000002615 hemofiltration Methods 0.000 description 1
229960002897 heparin Drugs 0.000 description 1
229920000669 heparin Polymers 0.000 description 1
MNWFXJYAOYHMED-UHFFFAOYSA-N heptanoic acid Chemical compound CCCCCCC(O)=O MNWFXJYAOYHMED-UHFFFAOYSA-N 0.000 description 1
125000005842 heteroatom Chemical group 0.000 description 1
JHBKYZNFFMIFDA-UHFFFAOYSA-N hex-3-ynoic acid Chemical compound CCC#CCC(O)=O JHBKYZNFFMIFDA-UHFFFAOYSA-N 0.000 description 1
125000006038 hexenyl group Chemical group 0.000 description 1
150000004678 hydrides Chemical class 0.000 description 1
229910000042 hydrogen bromide Inorganic materials 0.000 description 1
239000012433 hydrogen halide Substances 0.000 description 1
229910000039 hydrogen halide Inorganic materials 0.000 description 1
125000004356 hydroxy functional group Chemical group O* 0.000 description 1
210000003405 ileum Anatomy 0.000 description 1
239000011261 inert gas Substances 0.000 description 1
230000007574 infarction Effects 0.000 description 1
230000002401 inhibitory effect Effects 0.000 description 1
229910052500 inorganic mineral Inorganic materials 0.000 description 1
229910017053 inorganic salt Inorganic materials 0.000 description 1
210000004347 intestinal mucosa Anatomy 0.000 description 1
230000000302 ischemic effect Effects 0.000 description 1
239000012948 isocyanate Substances 0.000 description 1
150000002513 isocyanates Chemical class 0.000 description 1
210000003734 kidney Anatomy 0.000 description 1
239000004310 lactic acid Substances 0.000 description 1
235000014655 lactic acid Nutrition 0.000 description 1
229910052744 lithium Inorganic materials 0.000 description 1
210000004185 liver Anatomy 0.000 description 1
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
RMIODHQZRUFFFF-UHFFFAOYSA-N methoxyacetic acid Chemical compound COCC(O)=O RMIODHQZRUFFFF-UHFFFAOYSA-N 0.000 description 1
DRSDMCTUDRWIRA-UHFFFAOYSA-N methyl 5-chlorohex-4-enoate Chemical compound COC(=O)CCC=C(C)Cl DRSDMCTUDRWIRA-UHFFFAOYSA-N 0.000 description 1
NRJSHTINJMCKTR-UHFFFAOYSA-N methyl 5-methylhex-4-enoate Chemical compound COC(=O)CCC=C(C)C NRJSHTINJMCKTR-UHFFFAOYSA-N 0.000 description 1
QQBWOPCZBBALNP-UHFFFAOYSA-N methyl hex-3-ynoate Chemical compound CCC#CCC(=O)OC QQBWOPCZBBALNP-UHFFFAOYSA-N 0.000 description 1
XYDYWTJEGDZLTH-UHFFFAOYSA-N methylenetriphenylphosphorane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=C)C1=CC=CC=C1 XYDYWTJEGDZLTH-UHFFFAOYSA-N 0.000 description 1
235000010755 mineral Nutrition 0.000 description 1
239000011707 mineral Substances 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
238000002156 mixing Methods 0.000 description 1
230000004048 modification Effects 0.000 description 1
238000012986 modification Methods 0.000 description 1
FDUNKCCEGPJHLK-UHFFFAOYSA-N morpholine-2-sulfonic acid Chemical compound OS(=O)(=O)C1CNCCO1 FDUNKCCEGPJHLK-UHFFFAOYSA-N 0.000 description 1
230000002107 myocardial effect Effects 0.000 description 1
PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 1
125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
230000003472 neutralizing effect Effects 0.000 description 1
239000011664 nicotinic acid Chemical group 0.000 description 1
229960003512 nicotinic acid Drugs 0.000 description 1
235000001968 nicotinic acid Nutrition 0.000 description 1
229960002446 octanoic acid Drugs 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
150000007530 organic bases Chemical class 0.000 description 1
KVNYFPKFSJIPBJ-UHFFFAOYSA-N ortho-diethylbenzene Natural products CCC1=CC=CC=C1CC KVNYFPKFSJIPBJ-UHFFFAOYSA-N 0.000 description 1
210000000496 pancreas Anatomy 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
125000002255 pentenyl group Chemical group C(=CCCC)* 0.000 description 1
230000002093 peripheral effect Effects 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 description 1
IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
210000002381 plasma Anatomy 0.000 description 1
235000015497 potassium bicarbonate Nutrition 0.000 description 1
229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
239000011736 potassium bicarbonate Substances 0.000 description 1
229910000027 potassium carbonate Inorganic materials 0.000 description 1
235000011181 potassium carbonates Nutrition 0.000 description 1
239000011698 potassium fluoride Substances 0.000 description 1
235000003270 potassium fluoride Nutrition 0.000 description 1
TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
230000035935 pregnancy Effects 0.000 description 1
238000004321 preservation Methods 0.000 description 1
230000002035 prolonged effect Effects 0.000 description 1
HNDXKIMMSFCCFW-UHFFFAOYSA-N propane-2-sulphonic acid Chemical compound CC(C)S(O)(=O)=O HNDXKIMMSFCCFW-UHFFFAOYSA-N 0.000 description 1
125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
125000006239 protecting group Chemical group 0.000 description 1
230000002685 pulmonary effect Effects 0.000 description 1
230000036593 pulmonary vascular resistance Effects 0.000 description 1
238000000926 separation method Methods 0.000 description 1
230000035939 shock Effects 0.000 description 1
238000006884 silylation reaction Methods 0.000 description 1
239000011877 solvent mixture Substances 0.000 description 1
238000001228 spectrum Methods 0.000 description 1
208000010110 spontaneous platelet aggregation Diseases 0.000 description 1
230000006641 stabilisation Effects 0.000 description 1
238000003756 stirring Methods 0.000 description 1
239000001117 sulphuric acid Substances 0.000 description 1
235000011149 sulphuric acid Nutrition 0.000 description 1
230000009885 systemic effect Effects 0.000 description 1
239000003826 tablet Substances 0.000 description 1
TUNFSRHWOTWDNC-HKGQFRNVSA-N tetradecanoic acid Chemical compound CCCCCCCCCCCCC[14C](O)=O TUNFSRHWOTWDNC-HKGQFRNVSA-N 0.000 description 1
DHCDFWKWKRSZHF-UHFFFAOYSA-L thiosulfate(2-) Chemical compound [O-]S([S-])(=O)=O DHCDFWKWKRSZHF-UHFFFAOYSA-L 0.000 description 1
210000001519 tissue Anatomy 0.000 description 1
210000003437 trachea Anatomy 0.000 description 1
YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
229960004319 trichloroacetic acid Drugs 0.000 description 1
125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
229940005605 valeric acid Drugs 0.000 description 1
230000002792 vascular Effects 0.000 description 1
230000025033 vasoconstriction Effects 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/93—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems condensed with a ring other than six-membered
- C07D307/935—Not further condensed cyclopenta [b] furans or hydrogenated cyclopenta [b] furans
- 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
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C17/00—Preparation of halogenated hydrocarbons
- C07C17/07—Preparation of halogenated hydrocarbons by addition of hydrogen halides
- C07C17/08—Preparation of halogenated hydrocarbons by addition of hydrogen halides to unsaturated hydrocarbons
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C57/00—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms
- C07C57/02—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms with only carbon-to-carbon double bonds as unsaturation
- C07C57/03—Monocarboxylic acids
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C57/00—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms
- C07C57/02—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms with only carbon-to-carbon double bonds as unsaturation
- C07C57/13—Dicarboxylic acids
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C57/00—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms
- C07C57/52—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms containing halogen
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/93—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems condensed with a ring other than six-membered
- C07D307/935—Not further condensed cyclopenta [b] furans or hydrogenated cyclopenta [b] furans
- C07D307/937—Not further condensed cyclopenta [b] furans or hydrogenated cyclopenta [b] furans with hydrocarbon or substituted hydrocarbon radicals directly attached in position 2, e.g. prostacyclins
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
- C07F9/40—Esters thereof
- C07F9/4003—Esters thereof the acid moiety containing a substituent or a structure which is considered as characteristic
- C07F9/4015—Esters of acyclic unsaturated acids
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/535—Organo-phosphoranes
- C07F9/5352—Phosphoranes containing the structure P=C-

Definitions

alkyl groups represented by R 3 there come into consideration straight-chain or branched alkyl groups having from 1 to 10 carbon atoms, such as, for example, methyl, ethyl, propyl, butyl, isobutyl, tert.-butyl, pentyl, neopentyl, heptyl, hexyl or decyl radicals.
carboxylic acids may be mentioned by way of examples formic acid, acetic acid, propionic acid, butyric acid, isobutyric acid, valeric acid, isovaleric acid, caproic acid, oenanthic acid, caprylic acid, pelargonic acid, capric acid, undecylic acid, lauric acid, tridecylic acid, myristic acid, pentadecylic acid, tri-methylacetic acid, diethylacetic acid, tert.-butylacetic acid, cyclopropylacetic acid, cyclopentylacetic acid, cyclohexylacetic acid, cyclopropanecarboxylic acid, cyclohexanecarboxylic acid, phenylacetic acid, phenoxyacetic acid, methoxyacetic acid, ethoxyacetic acid, mono-, di- and tri-chloroacetic acid, aminoacetic acid, diethylaminoacetic acid, piperidinoacetic acid,
sterile, injectable, aqueous of oily solutions are used.
aqueous of oily solutions are used for parenteral administration.
oral administra tion for example tablets, dragees or capsules are suitable.
Example 2 Analogously to Example 1, 141 mg of the title compound are obtained starting from 480 mg of 19-methyl-l8,19-didehydroprostacyclin-11,15-diacetate methyl ester. IR: 2950, 1750, 1710, 1670, 1440, 1370, 1240/cm.

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
General Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Molecular Biology (AREA)
Biochemistry (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Pharmacology & Pharmacy (AREA)
Bioinformatics & Cheminformatics (AREA)
Animal Behavior & Ethology (AREA)
Engineering & Computer Science (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
General Chemical & Material Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

PCT/EP1981/000148 1980-09-18 1981-09-17 7-oxoprostacyclin derivatives and process for the preparation thereof WO1982001002A1 (en)

Priority Applications (5)

Application Number	Priority Date	Filing Date	Title
DE8181903255T DE3172032D1 (en)	1980-09-18	1981-09-17	7-oxoprostacyclin derivatives and process for the preparation thereof
AT81903255T ATE15194T1 (de)	1980-09-18	1981-09-17	7-oxoprostacyclin-derivate und verfahren zu deren herstellung.
FI821707A FI66367C (fi)	1980-09-18	1982-05-14	Foerfarande foer framstaellning av nya terapeutiskt anvaendbara 7-oxoprostacyklinderivat
NO821620A NO158098C (no)	1980-09-18	1982-05-14	Fremgangsmaate for fremstilling av terapeutisk aktive 7-oxoprostacycloderivater.
DK220982A DK220982A (da)	1980-09-18	1982-05-17	7-oxoprostacyklinderivater og fremgangsmaade til fremstilling deraf

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
DE3035454800918		1980-09-18
DE19803035454 DE3035454A1 (de)	1980-09-18	1980-09-18	7-oxoprostacyclinderivate und verfahren zu ihrer herstellung

Publications (1)

Publication Number	Publication Date
WO1982001002A1 true WO1982001002A1 (en)	1982-04-01

Family

ID=6112413

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
PCT/EP1981/000148 WO1982001002A1 (en)	1980-09-18	1981-09-17	7-oxoprostacyclin derivatives and process for the preparation thereof

Country Status (17)

Country	Link
US (1)	US4466969A (de)
EP (1)	EP0059756B1 (de)
JP (1)	JPH0314031B2 (de)
AU (1)	AU557398B2 (de)
BE (1)	BE890390A (de)
CA (1)	CA1220470A (de)
CS (1)	CS226440B2 (de)
DE (2)	DE3035454A1 (de)
DK (1)	DK220982A (de)
ES (1)	ES505576A0 (de)
FI (1)	FI66367C (de)
GR (1)	GR75350B (de)
HU (1)	HU200601B (de)
IE (1)	IE51792B1 (de)
IT (1)	IT1167504B (de)
WO (1)	WO1982001002A1 (de)
ZA (1)	ZA816516B (de)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
WO1985002187A1 (en) *	1983-11-10	1985-05-23	Schering Aktiengesellschaft	20-alkyl-7-oxoprostacycline derivatives and production process thereof
EP0205969A2 (de) *	1985-05-29	1986-12-30	CHINOIN Gyogyszer és Vegyészeti Termékek Gyára RT.	7-Oxo-PGI2-Ephedrinsalze, deren Herstellung und diese Verbindungen enthaltende pharmazeutsche Präparate
DE3610556A1 (de) *	1986-03-26	1987-10-01	Schering Ag	7-oxoprostacyclinderivate und verfahren zu ihrer herstellung

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5190973A (en) *	1983-11-10	1993-03-02	Schering Aktiengesellschaft	20-alkyl-7-oxoprostacyclin derivatives useful as pharmaceuticals
HU191264B (en) *	1984-01-13	1987-01-28	Chinoin Gyogyszer Es Vegyeszeti Termekek Gyara Rt,Hu	Process for production of derivatives of 7-oxo-prostacyclin with selective biological effect

Citations (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
EP0031426A1 (de) *	1979-11-12	1981-07-08	CHINOIN Gyogyszer és Vegyészeti Termékek Gyára RT.	7-Oxo-PGI2-derivate, Verfahren zu deren Herstellung sowie diese Verbindungen enthaltende pharmazeutische Präparate

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US4330553A (en) *	1979-11-12	1982-05-18	Chinoin Gyogyszer Es Vegyeszeti Termekek Gyara R.T.	7-Oxo-PGI2 -derivatives and process for the preparation thereof and pharmaceutical compositions containing same

1980
- 1980-09-18 DE DE19803035454 patent/DE3035454A1/de not_active Withdrawn
1981
- 1981-09-16 CA CA000386074A patent/CA1220470A/en not_active Expired
- 1981-09-16 GR GR66067A patent/GR75350B/el unknown
- 1981-09-17 HU HU813835A patent/HU200601B/hu not_active IP Right Cessation
- 1981-09-17 ES ES505576A patent/ES505576A0/es active Granted
- 1981-09-17 BE BE0/205991A patent/BE890390A/fr not_active IP Right Cessation
- 1981-09-17 EP EP81903255A patent/EP0059756B1/de not_active Expired
- 1981-09-17 US US06/385,414 patent/US4466969A/en not_active Expired - Fee Related
- 1981-09-17 AU AU78091/81A patent/AU557398B2/en not_active Ceased
- 1981-09-17 DE DE8181903255T patent/DE3172032D1/de not_active Expired
- 1981-09-17 JP JP56503683A patent/JPH0314031B2/ja not_active Expired - Lifetime
- 1981-09-17 IE IE2163/81A patent/IE51792B1/en unknown
- 1981-09-17 WO PCT/EP1981/000148 patent/WO1982001002A1/en active IP Right Grant
- 1981-09-17 CS CS816866A patent/CS226440B2/cs unknown
- 1981-09-18 ZA ZA816516A patent/ZA816516B/xx unknown
- 1981-09-18 IT IT24030/81A patent/IT1167504B/it active
1982
- 1982-05-14 FI FI821707A patent/FI66367C/fi not_active IP Right Cessation
- 1982-05-17 DK DK220982A patent/DK220982A/da not_active Application Discontinuation

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
EP0031426A1 (de) *	1979-11-12	1981-07-08	CHINOIN Gyogyszer és Vegyészeti Termékek Gyára RT.	7-Oxo-PGI2-derivate, Verfahren zu deren Herstellung sowie diese Verbindungen enthaltende pharmazeutische Präparate

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
WO1985002187A1 (en) *	1983-11-10	1985-05-23	Schering Aktiengesellschaft	20-alkyl-7-oxoprostacycline derivatives and production process thereof
EP0205969A2 (de) *	1985-05-29	1986-12-30	CHINOIN Gyogyszer és Vegyészeti Termékek Gyára RT.	7-Oxo-PGI2-Ephedrinsalze, deren Herstellung und diese Verbindungen enthaltende pharmazeutsche Präparate
EP0205969A3 (en) *	1985-05-29	1989-04-19	Chinoin Gyogyszer Es Vegyeszeti Termekek Gyara Rt.	7-oxo-pgi2-ephedrine salts, their preparation and pharmaceutical compositions containing them
DE3610556A1 (de) *	1986-03-26	1987-10-01	Schering Ag	7-oxoprostacyclinderivate und verfahren zu ihrer herstellung
WO1987005900A1 (en) *	1986-03-26	1987-10-08	Schering Aktiengesellschaft	7-oxoprostacycline derivatives and process for their manufacture

Also Published As

Publication number	Publication date
DE3035454A1 (de)	1982-04-22
FI821707A (fi)	1982-05-14
IT1167504B (it)	1987-05-13
JPH0314031B2 (de)	1991-02-25
JPS57501482A (de)	1982-08-19
CA1220470A (en)	1987-04-14
ES8205787A1 (es)	1982-08-16
CS226440B2 (en)	1984-03-19
EP0059756A1 (de)	1982-09-15
US4466969A (en)	1984-08-21
ZA816516B (en)	1982-09-29
EP0059756B1 (de)	1985-08-28
DK220982A (da)	1982-05-17
FI66367B (fi)	1984-06-29
DE3172032D1 (en)	1985-10-03
AU557398B2 (en)	1986-12-18
FI821707A0 (fi)	1982-05-14
AU7809181A (en)	1982-04-14
ES505576A0 (es)	1982-08-16
HU200601B (en)	1990-07-28
IT8124030A0 (it)	1981-09-18
GR75350B (de)	1984-07-13
FI66367C (fi)	1984-10-10
BE890390A (fr)	1982-03-17
IE51792B1 (en)	1987-04-01
IE812163L (en)	1982-03-18

Legal Events

Date	Code	Title	Description
1982-04-01	AK	Designated states	Designated state(s): AU DK FI HU JP NO SU US
1982-04-01	AL	Designated countries for regional patents	Designated state(s): AT CH DE FR GB LU NL SE
1982-05-04	WWE	Wipo information: entry into national phase	Ref document number: 1981903255 Country of ref document: EP
1982-05-14	WWE	Wipo information: entry into national phase	Ref document number: 821707 Country of ref document: FI
1982-09-15	WWP	Wipo information: published in national office	Ref document number: 1981903255 Country of ref document: EP
1984-10-10	WWG	Wipo information: grant in national office	Ref document number: 821707 Country of ref document: FI
1985-08-28	WWG	Wipo information: grant in national office	Ref document number: 1981903255 Country of ref document: EP

Publication	Publication Date	Title
US6225347B1 (en)	2001-05-01	9-halogen-(Z)-prostaglandin derivatives, process for their production and their use as pharmaceutical agents
US4708963A (en)	1987-11-24	Novel carbacyclins, their preparation and use
US4692464A (en)	1987-09-08	Novel prostacyclin derivatives and a process for the preparation thereof
US4191694A (en)	1980-03-04	Prostaglandin-I2 derivatives
US4073934A (en)	1978-02-14	Novel acetylenic prostaglandin analogs
US4699920A (en)	1987-10-13	9-halo-2-prostaglandin derivatives, processes for the preparation thereof and use thereof as medicinal agents
CS228916B2 (en)	1984-05-14	Method of preparing new derivatives of 9 alpha,6-nitril
IE45863B1 (en)	1982-12-15	Prostanoic acid derivatives and process for their preparation
US4235930A (en)	1980-11-25	Novel acetylenic prostaglandins and processes for the preparation thereof
US4466969A (en)	1984-08-21	7-Oxoprostacyclin derivatives and their use as hypotensives and bronchodilators
US4954524A (en)	1990-09-04	Carbacylcins, their preparation and use as medicinal agents
US4532236A (en)	1985-07-30	Certain prostacyclins and their blood-pressure-lowering and thrombocyte-aggregation-inhibiting compositions and methods
US5891910A (en)	1999-04-06	9-halogen-(Z) prostaglandin derivatives, process for their production and their use as pharmaceutical agents
WO1983003248A1 (en)	1983-09-29	Carbacycline, preparation and utilization thereof
IE49406B1 (en)	1985-10-02	New prostane derivatives and their manufacture and use
EP0057660A2 (de)	1982-08-11	Neue Prostacyclin-Derivate, Verfahren zu ihrer Herstellung sowie ihre Verwendung als Arzneimittel
US5053400A (en)	1991-10-01	Novel 9-substituted carbacyclin derivatives, processes for their preparation, and their use as medicinal agents
US5374654A (en)	1994-12-20	9-substituted carbacyclin derivatives, processes for their preparation, and their use as medicinal agents
US5157042A (en)	1992-10-20	3-oxa-5-fluoro-carbacyclins, their preparation and use as medicinal agents
US5190973A (en)	1993-03-02	20-alkyl-7-oxoprostacyclin derivatives useful as pharmaceuticals
US5104861A (en)	1992-04-14	7-oxoprostacyclin derivatives which are useful as pharmaceuticals
NZ223858A (en)	1990-11-27	6-oxo-prostaglandin-e 1 -derivatives and pharmaceutical compositions
US4094899A (en)	1978-06-13	Oxaprostaglandins
US5124343A (en)	1992-06-23	Carbacyclins, process for the preparation thereof, and use thereof as medicinal agents
Skuballa et al.	1980	Prostaglandin-I 2 derivatives