CA1084903A - Anaesthetic steroids - Google Patents

Anaesthetic steroids

Info

Publication number: CA1084903A
Authority: CA; Canada
Prior art keywords: group; beta; alpha; hydroxy; preparation
Prior art date: 1976-01-06
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

CA269,161A

Other languages

English (en)

French (fr)

Inventor

Gordon H. Phillipps

Peter J. May

Barry E. Ayres

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.)

Glaxo Laboratories Ltd

Original Assignee

Glaxo Laboratories 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.)

1976-01-06

Filing date

1977-01-05

Publication date

1980-09-02

1977-01-05 Application filed by Glaxo Laboratories Ltd filed Critical Glaxo Laboratories Ltd

1980-09-02 Application granted granted Critical

1980-09-02 Publication of CA1084903A publication Critical patent/CA1084903A/en

Status Expired legal-status Critical Current

Links

150000003431 steroids Chemical class 0.000 title claims description 31
230000003444 anaesthetic effect Effects 0.000 title abstract description 19
150000001875 compounds Chemical class 0.000 claims abstract description 174
125000001424 substituent group Chemical group 0.000 claims abstract description 12
150000001441 androstanes Chemical class 0.000 claims abstract description 7
238000002360 preparation method Methods 0.000 claims description 155
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 75
238000000034 method Methods 0.000 claims description 74
-1 (N,N-disubstituted)amino ester Chemical class 0.000 claims description 70
238000006243 chemical reaction Methods 0.000 claims description 60
239000002253 acid Substances 0.000 claims description 52
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 46
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 45
150000003839 salts Chemical class 0.000 claims description 40
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 36
229910052705 radium Inorganic materials 0.000 claims description 33
230000008569 process Effects 0.000 claims description 31
125000000217 alkyl group Chemical group 0.000 claims description 30
229910052701 rubidium Inorganic materials 0.000 claims description 30
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 28
239000007858 starting material Substances 0.000 claims description 27
229920006395 saturated elastomer Polymers 0.000 claims description 23
150000001412 amines Chemical class 0.000 claims description 17
239000012458 free base Substances 0.000 claims description 15
229910052739 hydrogen Inorganic materials 0.000 claims description 15
239000001257 hydrogen Substances 0.000 claims description 15
125000004432 carbon atom Chemical group C* 0.000 claims description 14
230000009467 reduction Effects 0.000 claims description 12
KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 claims description 10
229910052757 nitrogen Inorganic materials 0.000 claims description 10
125000003118 aryl group Chemical group 0.000 claims description 9
125000000623 heterocyclic group Chemical group 0.000 claims description 8
125000004423 acyloxy group Chemical group 0.000 claims description 7
125000003545 alkoxy group Chemical group 0.000 claims description 7
229910052801 chlorine Inorganic materials 0.000 claims description 7
125000004433 nitrogen atom Chemical group N* 0.000 claims description 7
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 6
229910003827 NRaRb Inorganic materials 0.000 claims description 6
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 6
KQTIIICEAUMSDG-UHFFFAOYSA-N tricarballylic acid Chemical compound OC(=O)CC(C(O)=O)CC(O)=O KQTIIICEAUMSDG-UHFFFAOYSA-N 0.000 claims description 6
125000003277 amino group Chemical group 0.000 claims description 5
238000005886 esterification reaction Methods 0.000 claims description 5
125000005843 halogen group Chemical group 0.000 claims description 5
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 4
125000002618 bicyclic heterocycle group Chemical group 0.000 claims description 4
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 4
125000004093 cyano group Chemical group *C#N 0.000 claims description 4
125000000392 cycloalkenyl group Chemical group 0.000 claims description 4
125000000753 cycloalkyl group Chemical group 0.000 claims description 4
HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 claims description 4
230000032050 esterification Effects 0.000 claims description 4
229910052751 metal Inorganic materials 0.000 claims description 4
239000002184 metal Substances 0.000 claims description 4
125000002911 monocyclic heterocycle group Chemical group 0.000 claims description 4
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
125000000858 thiocyanato group Chemical group *SC#N 0.000 claims description 4
125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 3
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 3
229910019142 PO4 Inorganic materials 0.000 claims description 3
125000003342 alkenyl group Chemical group 0.000 claims description 3
QZLYKIGBANMMBK-UGCZWRCOSA-N androstane group Chemical group [C@@H]12CCC[C@@]1(C)CC[C@H]1[C@H]2CC[C@H]2CCCC[C@]12C QZLYKIGBANMMBK-UGCZWRCOSA-N 0.000 claims description 3
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
125000001309 chloro group Chemical group Cl* 0.000 claims description 3
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 3
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 3
230000018044 dehydration Effects 0.000 claims description 3
238000006297 dehydration reaction Methods 0.000 claims description 3
229910052731 fluorine Inorganic materials 0.000 claims description 3
JFCQEDHGNNZCLN-UHFFFAOYSA-N glutaric acid Chemical compound OC(=O)CCCC(O)=O JFCQEDHGNNZCLN-UHFFFAOYSA-N 0.000 claims description 3
229910052740 iodine Inorganic materials 0.000 claims description 3
150000002923 oximes Chemical class 0.000 claims description 3
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
150000003566 thiocarboxylic acids Chemical class 0.000 claims description 3
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 2
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims description 2
KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 claims description 2
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 claims description 2
JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 claims description 2
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims description 2
GTZCVFVGUGFEME-UHFFFAOYSA-N aconitic acid Chemical compound OC(=O)CC(C(O)=O)=CC(O)=O GTZCVFVGUGFEME-UHFFFAOYSA-N 0.000 claims description 2
230000010933 acylation Effects 0.000 claims description 2
238000005917 acylation reaction Methods 0.000 claims description 2
125000005194 alkoxycarbonyloxy group Chemical group 0.000 claims description 2
125000004414 alkyl thio group Chemical group 0.000 claims description 2
125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims description 2
235000010323 ascorbic acid Nutrition 0.000 claims description 2
125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 claims description 2
230000020176 deacylation Effects 0.000 claims description 2
238000005947 deacylation reaction Methods 0.000 claims description 2
238000006704 dehydrohalogenation reaction Methods 0.000 claims description 2
238000010511 deprotection reaction Methods 0.000 claims description 2
238000006073 displacement reaction Methods 0.000 claims description 2
238000006266 etherification reaction Methods 0.000 claims description 2
125000005745 ethoxymethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])* 0.000 claims description 2
125000001153 fluoro group Chemical group F* 0.000 claims description 2
238000007038 hydrochlorination reaction Methods 0.000 claims description 2
125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 2
QHCCDDQKNUYGNC-UHFFFAOYSA-N n-ethylbutan-1-amine Chemical compound CCCCNCC QHCCDDQKNUYGNC-UHFFFAOYSA-N 0.000 claims description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 2
239000010452 phosphate Substances 0.000 claims description 2
229910021653 sulphate ion Inorganic materials 0.000 claims description 2
229940095064 tartrate Drugs 0.000 claims description 2
239000000126 substance Substances 0.000 claims 4
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 3
JWMFYGXQPXQEEM-NUNROCCHSA-N 5β-pregnane Chemical compound C([C@H]1CC2)CCC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H](CC)[C@@]2(C)CC1 JWMFYGXQPXQEEM-NUNROCCHSA-N 0.000 claims 3
CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims 2
125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 1
125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 1
XVOUMQNXTGKGMA-OWOJBTEDSA-N (E)-glutaconic acid Chemical class OC(=O)C\C=C\C(O)=O XVOUMQNXTGKGMA-OWOJBTEDSA-N 0.000 claims 1
125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 claims 1
241000284466 Antarctothoa delta Species 0.000 claims 1
AFVFQIVMOAPDHO-UHFFFAOYSA-M Methanesulfonate Chemical compound CS([O-])(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 claims 1
229940022663 acetate Drugs 0.000 claims 1
229940091179 aconitate Drugs 0.000 claims 1
229940072107 ascorbate Drugs 0.000 claims 1
239000011668 ascorbic acid Substances 0.000 claims 1
239000011203 carbon fibre reinforced carbon Substances 0.000 claims 1
229940018560 citraconate Drugs 0.000 claims 1
HNEGQIOMVPPMNR-IHWYPQMZSA-N citraconic acid Chemical compound OC(=O)C(/C)=C\C(O)=O HNEGQIOMVPPMNR-IHWYPQMZSA-N 0.000 claims 1
229940001468 citrate Drugs 0.000 claims 1
125000003700 epoxy group Chemical group 0.000 claims 1
229940001447 lactate Drugs 0.000 claims 1
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 claims 1
238000004519 manufacturing process Methods 0.000 claims 1
KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 claims 1
JOXIMZWYDAKGHI-UHFFFAOYSA-M toluene-4-sulfonate Chemical compound CC1=CC=C(S([O-])(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-M 0.000 claims 1
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims 1
150000003128 pregnanes Chemical class 0.000 abstract description 6
241000284708 Sarcophaga alpha Species 0.000 abstract 1
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 310
239000000243 solution Substances 0.000 description 192
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 140
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 139
235000019439 ethyl acetate Nutrition 0.000 description 103
229940093499 ethyl acetate Drugs 0.000 description 103
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 93
239000000203 mixture Substances 0.000 description 83
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 78
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 63
230000000875 corresponding effect Effects 0.000 description 53
150000001860 citric acid derivatives Chemical class 0.000 description 37
239000011541 reaction mixture Substances 0.000 description 37
229910000030 sodium bicarbonate Inorganic materials 0.000 description 37
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 36
235000017557 sodium bicarbonate Nutrition 0.000 description 35
238000002425 crystallisation Methods 0.000 description 33
239000002904 solvent Substances 0.000 description 32
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 31
239000003208 petroleum Substances 0.000 description 31
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 30
238000001704 evaporation Methods 0.000 description 29
230000008020 evaporation Effects 0.000 description 29
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 28
239000000047 product Substances 0.000 description 28
239000000284 extract Substances 0.000 description 27
229960001407 sodium bicarbonate Drugs 0.000 description 27
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 26
239000007787 solid Substances 0.000 description 26
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 24
FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 24
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 23
239000002244 precipitate Substances 0.000 description 22
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 21
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 21
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 21
238000001914 filtration Methods 0.000 description 21
229960000443 hydrochloric acid Drugs 0.000 description 20
238000012746 preparative thin layer chromatography Methods 0.000 description 19
VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 18
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 18
239000000460 chlorine Substances 0.000 description 18
238000010992 reflux Methods 0.000 description 18
229910052938 sodium sulfate Inorganic materials 0.000 description 18
235000011152 sodium sulphate Nutrition 0.000 description 18
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 17
239000006260 foam Substances 0.000 description 17
235000011167 hydrochloric acid Nutrition 0.000 description 17
LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 15
239000002585 base Substances 0.000 description 15
229960001701 chloroform Drugs 0.000 description 13
238000007429 general method Methods 0.000 description 13
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
229960000583 acetic acid Drugs 0.000 description 12
239000000463 material Substances 0.000 description 12
239000012279 sodium borohydride Substances 0.000 description 12
229910000033 sodium borohydride Inorganic materials 0.000 description 12
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 11
230000008025 crystallization Effects 0.000 description 11
206010002091 Anaesthesia Diseases 0.000 description 10
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
238000001949 anaesthesia Methods 0.000 description 10
230000037005 anaesthesia Effects 0.000 description 10
239000007864 aqueous solution Substances 0.000 description 10
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 10
PNVPNXKRAUBJGW-UHFFFAOYSA-N (2-chloroacetyl) 2-chloroacetate Chemical compound ClCC(=O)OC(=O)CCl PNVPNXKRAUBJGW-UHFFFAOYSA-N 0.000 description 9
229910000019 calcium carbonate Inorganic materials 0.000 description 9
239000003054 catalyst Substances 0.000 description 9
238000004440 column chromatography Methods 0.000 description 9
239000010410 layer Substances 0.000 description 9
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 9
230000035484 reaction time Effects 0.000 description 9
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical class CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 9
238000000605 extraction Methods 0.000 description 8
239000012362 glacial acetic acid Substances 0.000 description 8
239000000741 silica gel Substances 0.000 description 8
229910002027 silica gel Inorganic materials 0.000 description 8
235000009518 sodium iodide Nutrition 0.000 description 8
YASYEJJMZJALEJ-UHFFFAOYSA-N Citric acid monohydrate Chemical compound O.OC(=O)CC(O)(C(O)=O)CC(O)=O YASYEJJMZJALEJ-UHFFFAOYSA-N 0.000 description 7
QCOGKXLOEWLIDC-UHFFFAOYSA-N N-methylbutylamine Chemical compound CCCCNC QCOGKXLOEWLIDC-UHFFFAOYSA-N 0.000 description 7
239000012267 brine Substances 0.000 description 7
229960004106 citric acid Drugs 0.000 description 7
229960002303 citric acid monohydrate Drugs 0.000 description 7
230000000694 effects Effects 0.000 description 7
CSNNHWWHGAXBCP-UHFFFAOYSA-L magnesium sulphate Substances [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 7
239000012044 organic layer Substances 0.000 description 7
239000000377 silicon dioxide Substances 0.000 description 7
239000011780 sodium chloride Substances 0.000 description 7
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 7
238000004809 thin layer chromatography Methods 0.000 description 7
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
230000015572 biosynthetic process Effects 0.000 description 6
150000002148 esters Chemical class 0.000 description 6
229910052943 magnesium sulfate Inorganic materials 0.000 description 6
239000011734 sodium Substances 0.000 description 6
238000003756 stirring Methods 0.000 description 6
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 5
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical group 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
XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 5
229910052783 alkali metal Inorganic materials 0.000 description 5
239000000706 filtrate Substances 0.000 description 5
235000019253 formic acid Nutrition 0.000 description 5
150000004820 halides Chemical class 0.000 description 5
229910052708 sodium Inorganic materials 0.000 description 5
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
238000005406 washing Methods 0.000 description 5
RSRDWHPVTMQUGZ-OZIWPBGVSA-N 1-[(8r,9s,10s,13s,14s,17s)-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]ethanone Chemical class C1CC2CCCC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 RSRDWHPVTMQUGZ-OZIWPBGVSA-N 0.000 description 4
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-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
230000002378 acidificating effect Effects 0.000 description 4
150000001299 aldehydes Chemical class 0.000 description 4
150000001340 alkali metals Chemical class 0.000 description 4
229940124326 anaesthetic agent Drugs 0.000 description 4
WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 description 4
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 4
238000004587 chromatography analysis Methods 0.000 description 4
239000013078 crystal Substances 0.000 description 4
239000002024 ethyl acetate extract Substances 0.000 description 4
125000001475 halogen functional group Chemical group 0.000 description 4
239000005457 ice water Substances 0.000 description 4
150000002576 ketones Chemical class 0.000 description 4
AMXOYNBUYSYVKV-UHFFFAOYSA-M lithium bromide Chemical compound [Li+].[Br-] AMXOYNBUYSYVKV-UHFFFAOYSA-M 0.000 description 4
235000019341 magnesium sulphate Nutrition 0.000 description 4
239000012528 membrane Substances 0.000 description 4
VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 4
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
ZMZDMBWJUHKJPS-UHFFFAOYSA-N thiocyanic acid Chemical compound SC#N ZMZDMBWJUHKJPS-UHFFFAOYSA-N 0.000 description 4
238000010626 work up procedure Methods 0.000 description 4
IZCOHUBVLOVWBV-PTSGMJDFSA-N (5s,8s,9s,10s,13s,14s,17s)-10,13-dimethyl-17-(2-methyl-1,3-dioxolan-2-yl)-1,4,5,6,7,8,9,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-11-one Chemical compound CC1([C@@H]2[C@]3(CC(=O)[C@@H]4[C@@]5(C)CC=CC[C@@H]5CC[C@H]4[C@@H]3CC2)C)OCCO1 IZCOHUBVLOVWBV-PTSGMJDFSA-N 0.000 description 3
WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 3
125000004493 2-methylbut-1-yl group Chemical group CC(C*)CC 0.000 description 3
JWMFYGXQPXQEEM-GCOKGBOCSA-N 5α-pregnane Chemical compound C([C@@H]1CC2)CCC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H](CC)[C@@]2(C)CC1 JWMFYGXQPXQEEM-GCOKGBOCSA-N 0.000 description 3
KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 3
239000000061 acid fraction Substances 0.000 description 3
239000012445 acidic reagent Substances 0.000 description 3
125000001231 benzoyloxy group Chemical group C(C1=CC=CC=C1)(=O)O* 0.000 description 3
239000011230 binding agent Substances 0.000 description 3
WEHWNAOGRSTTBQ-UHFFFAOYSA-N dipropylamine Chemical compound CCCNCCC WEHWNAOGRSTTBQ-UHFFFAOYSA-N 0.000 description 3
125000004185 ester group Chemical group 0.000 description 3
150000002431 hydrogen Chemical group 0.000 description 3
238000002347 injection Methods 0.000 description 3
239000007924 injection Substances 0.000 description 3
239000000543 intermediate Substances 0.000 description 3
150000002500 ions Chemical class 0.000 description 3
PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 3
230000007935 neutral effect Effects 0.000 description 3
239000012074 organic phase Substances 0.000 description 3
KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 3
ARJOQCYCJMAIFR-UHFFFAOYSA-N prop-2-enoyl prop-2-enoate Chemical compound C=CC(=O)OC(=O)C=C ARJOQCYCJMAIFR-UHFFFAOYSA-N 0.000 description 3
238000000746 purification Methods 0.000 description 3
238000001953 recrystallisation Methods 0.000 description 3
239000000523 sample Substances 0.000 description 3
OZZVGLMCYPJACF-UHFFFAOYSA-M sodium 2-hydroxypropane-1,2,3-tricarboxylic acid iodide Chemical compound C(CC(O)(C(=O)O)CC(=O)O)(=O)O.[I-].[Na+] OZZVGLMCYPJACF-UHFFFAOYSA-M 0.000 description 3
239000004094 surface-active agent Substances 0.000 description 3
239000003981 vehicle Substances 0.000 description 3
KQGXQUZDMSFMNG-UHFFFAOYSA-N 2-bromopropanoyl 2-bromopropanoate Chemical compound CC(Br)C(=O)OC(=O)C(C)Br KQGXQUZDMSFMNG-UHFFFAOYSA-N 0.000 description 2
IJBSTWJYAQXFIX-UHFFFAOYSA-N 2-chlorobutanoyl 2-chlorobutanoate Chemical compound CCC(Cl)C(=O)OC(=O)C(Cl)CC IJBSTWJYAQXFIX-UHFFFAOYSA-N 0.000 description 2
IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 2
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
229910015900 BF3 Inorganic materials 0.000 description 2
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
239000004215 Carbon black (E152) Substances 0.000 description 2
BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
VYBKVMASRYQQDW-KPTKGFLISA-N NCC(=O)OCC([C@H]1CC[C@H]2[C@@H]3CC[C@H]4CCCC[C@]4(C)[C@H]3CC[C@]12C)=O Chemical compound NCC(=O)OCC([C@H]1CC[C@H]2[C@@H]3CC[C@H]4CCCC[C@]4(C)[C@H]3CC[C@]12C)=O VYBKVMASRYQQDW-KPTKGFLISA-N 0.000 description 2
GQPLMRYTRLFLPF-UHFFFAOYSA-N Nitrous Oxide Chemical compound [O-][N+]#N GQPLMRYTRLFLPF-UHFFFAOYSA-N 0.000 description 2
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 2
OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
239000003377 acid catalyst Substances 0.000 description 2
238000005903 acid hydrolysis reaction Methods 0.000 description 2
150000007513 acids Chemical class 0.000 description 2
150000001350 alkyl halides Chemical class 0.000 description 2
125000004691 alkyl thio carbonyl group Chemical group 0.000 description 2
235000019270 ammonium chloride Nutrition 0.000 description 2
150000008064 anhydrides Chemical class 0.000 description 2
239000011260 aqueous acid Substances 0.000 description 2
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
125000002619 bicyclic group Chemical group 0.000 description 2
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
239000003153 chemical reaction reagent Substances 0.000 description 2
239000007810 chemical reaction solvent Substances 0.000 description 2
239000003638 chemical reducing agent Substances 0.000 description 2
239000012043 crude product Substances 0.000 description 2
FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 2
238000010790 dilution Methods 0.000 description 2
239000012895 dilution Substances 0.000 description 2
FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 2
239000012467 final product Substances 0.000 description 2
229930195733 hydrocarbon Natural products 0.000 description 2
150000002430 hydrocarbons Chemical class 0.000 description 2
150000003840 hydrochlorides Chemical class 0.000 description 2
230000007062 hydrolysis Effects 0.000 description 2
238000006460 hydrolysis reaction Methods 0.000 description 2
230000006698 induction Effects 0.000 description 2
239000002198 insoluble material Substances 0.000 description 2
229910052741 iridium Inorganic materials 0.000 description 2
GKOZUEZYRPOHIO-UHFFFAOYSA-N iridium atom Chemical compound [Ir] GKOZUEZYRPOHIO-UHFFFAOYSA-N 0.000 description 2
229910052742 iron Inorganic materials 0.000 description 2
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 2
ACKFDYCQCBEDNU-UHFFFAOYSA-J lead(2+);tetraacetate Chemical compound [Pb+2].CC([O-])=O.CC([O-])=O.CC([O-])=O.CC([O-])=O ACKFDYCQCBEDNU-UHFFFAOYSA-J 0.000 description 2
QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 2
WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 description 2
125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
229910052763 palladium Inorganic materials 0.000 description 2
235000021317 phosphate Nutrition 0.000 description 2
235000015497 potassium bicarbonate Nutrition 0.000 description 2
229910000028 potassium bicarbonate Inorganic materials 0.000 description 2
239000011736 potassium bicarbonate Substances 0.000 description 2
229910000027 potassium carbonate Inorganic materials 0.000 description 2
235000011181 potassium carbonates Nutrition 0.000 description 2
TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 2
229910000029 sodium carbonate Inorganic materials 0.000 description 2
239000011343 solid material Substances 0.000 description 2
239000001117 sulphuric acid Substances 0.000 description 2
235000011149 sulphuric acid Nutrition 0.000 description 2
239000000725 suspension Substances 0.000 description 2
150000003573 thiols Chemical class 0.000 description 2
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
CYTQBVOFDCPGCX-UHFFFAOYSA-N trimethyl phosphite Chemical compound COP(OC)OC CYTQBVOFDCPGCX-UHFFFAOYSA-N 0.000 description 2
RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
238000001665 trituration Methods 0.000 description 2
239000008096 xylene Substances 0.000 description 2
VCGRFBXVSFAGGA-UHFFFAOYSA-N (1,1-dioxo-1,4-thiazinan-4-yl)-[6-[[3-(4-fluorophenyl)-5-methyl-1,2-oxazol-4-yl]methoxy]pyridin-3-yl]methanone Chemical compound CC=1ON=C(C=2C=CC(F)=CC=2)C=1COC(N=C1)=CC=C1C(=O)N1CCS(=O)(=O)CC1 VCGRFBXVSFAGGA-UHFFFAOYSA-N 0.000 description 1
XMXYYMGLZNWCIW-HDDQBELSSA-N (3r,5s,8s,9s,10s,13s,14s,16r,17s)-17-acetyl-3-hydroxy-10,13,16-trimethyl-1,2,3,4,5,6,7,8,9,12,14,15,16,17-tetradecahydrocyclopenta[a]phenanthren-11-one Chemical compound C([C@@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2C[C@@H](C)[C@H](C(C)=O)[C@@]2(C)CC1=O XMXYYMGLZNWCIW-HDDQBELSSA-N 0.000 description 1
AHRWWYGWQKBKBF-MUGXHADPSA-N (5s,8s,9s,10s,13s,14s,17s)-17-acetyl-10,13-dimethyl-2,4,5,6,7,8,9,12,14,15,16,17-dodecahydro-1h-cyclopenta[a]phenanthrene-3,11-dione Chemical compound C([C@@H]1CC2)C(=O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H](C(=O)C)[C@@]2(C)CC1=O AHRWWYGWQKBKBF-MUGXHADPSA-N 0.000 description 1
DUHUCHOQIDJXAT-VEFHSKDMSA-N (5s,8s,9s,10s,13s,14s,17s)-17-acetyl-3-hydroxy-10,13-dimethyl-1,2,3,4,5,6,7,8,9,12,14,15,16,17-tetradecahydrocyclopenta[a]phenanthren-11-one Chemical compound C([C@@H]1CC2)C(O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H](C(=O)C)[C@@]2(C)CC1=O DUHUCHOQIDJXAT-VEFHSKDMSA-N 0.000 description 1
BCEYQEFOOCHLOD-WFFZUPQVSA-N (8s,9s,10r,13s,14s,17s)-17-acetyl-6,10,13-trimethyl-2,8,9,12,14,15,16,17-octahydro-1h-cyclopenta[a]phenanthrene-3,11-dione Chemical compound C1=C(C)C2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2=O BCEYQEFOOCHLOD-WFFZUPQVSA-N 0.000 description 1
UKGJZDSUJSPAJL-YPUOHESYSA-N (e)-n-[(1r)-1-[3,5-difluoro-4-(methanesulfonamido)phenyl]ethyl]-3-[2-propyl-6-(trifluoromethyl)pyridin-3-yl]prop-2-enamide Chemical compound CCCC1=NC(C(F)(F)F)=CC=C1\C=C\C(=O)N[C@H](C)C1=CC(F)=C(NS(C)(=O)=O)C(F)=C1 UKGJZDSUJSPAJL-YPUOHESYSA-N 0.000 description 1
VEFLKXRACNJHOV-UHFFFAOYSA-N 1,3-dibromopropane Chemical compound BrCCCBr VEFLKXRACNJHOV-UHFFFAOYSA-N 0.000 description 1
KVGFSSYSDMZJJN-NRYGDNMDSA-N 1-[(5r,8r,9s,10s,13s,14s,17s)-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]-2,2-dihydroxyethanone Chemical compound C1CCC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)C(=O)C(O)O)[C@@H]4[C@@H]3CC[C@H]21 KVGFSSYSDMZJJN-NRYGDNMDSA-N 0.000 description 1
UUFQTNFCRMXOAE-UHFFFAOYSA-N 1-methylmethylene Chemical compound C[CH] UUFQTNFCRMXOAE-UHFFFAOYSA-N 0.000 description 1
150000000315 19-norandrostanes Chemical class 0.000 description 1
RIZUCYSQUWMQLX-UHFFFAOYSA-N 2,3-dimethylbenzoic acid Chemical compound CC1=CC=CC(C(O)=O)=C1C RIZUCYSQUWMQLX-UHFFFAOYSA-N 0.000 description 1
OAVBKHDCXXETQR-UHFFFAOYSA-N 2-chloropropanoyl 2-chloropropanoate Chemical compound CC(Cl)C(=O)OC(=O)C(C)Cl OAVBKHDCXXETQR-UHFFFAOYSA-N 0.000 description 1
YGYGASJNJTYNOL-CQSZACIVSA-N 3-[(4r)-2,2-dimethyl-1,1-dioxothian-4-yl]-5-(4-fluorophenyl)-1h-indole-7-carboxamide Chemical compound C1CS(=O)(=O)C(C)(C)C[C@@H]1C1=CNC2=C(C(N)=O)C=C(C=3C=CC(F)=CC=3)C=C12 YGYGASJNJTYNOL-CQSZACIVSA-N 0.000 description 1
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 1
DUHUCHOQIDJXAT-OLVMNOGESA-N 3-hydroxy-(3-α,5-α)-Pregnane-11,20-dione Chemical compound C([C@@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H](C(=O)C)[C@@]2(C)CC1=O DUHUCHOQIDJXAT-OLVMNOGESA-N 0.000 description 1
VJPPLCNBDLZIFG-ZDUSSCGKSA-N 4-[(3S)-3-(but-2-ynoylamino)piperidin-1-yl]-5-fluoro-2,3-dimethyl-1H-indole-7-carboxamide Chemical compound C(C#CC)(=O)N[C@@H]1CN(CCC1)C1=C2C(=C(NC2=C(C=C1F)C(=O)N)C)C VJPPLCNBDLZIFG-ZDUSSCGKSA-N 0.000 description 1
UZOFELREXGAFOI-UHFFFAOYSA-N 4-methylpiperidine Chemical compound CC1CCNCC1 UZOFELREXGAFOI-UHFFFAOYSA-N 0.000 description 1
XMRPGKVKISIQBV-BJMCWZGWSA-N 5alpha-pregnane-3,20-dione Chemical compound C([C@@H]1CC2)C(=O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H](C(=O)C)[C@@]2(C)CC1 XMRPGKVKISIQBV-BJMCWZGWSA-N 0.000 description 1
XVMSFILGAMDHEY-UHFFFAOYSA-N 6-(4-aminophenyl)sulfonylpyridin-3-amine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=N1 XVMSFILGAMDHEY-UHFFFAOYSA-N 0.000 description 1
CYJRNFFLTBEQSQ-UHFFFAOYSA-N 8-(3-methyl-1-benzothiophen-5-yl)-N-(4-methylsulfonylpyridin-3-yl)quinoxalin-6-amine Chemical compound CS(=O)(=O)C1=C(C=NC=C1)NC=1C=C2N=CC=NC2=C(C=1)C=1C=CC2=C(C(=CS2)C)C=1 CYJRNFFLTBEQSQ-UHFFFAOYSA-N 0.000 description 1
ZRPZPNYZFSJUPA-UHFFFAOYSA-N ARS-1620 Chemical compound Oc1cccc(F)c1-c1c(Cl)cc2c(ncnc2c1F)N1CCN(CC1)C(=O)C=C ZRPZPNYZFSJUPA-UHFFFAOYSA-N 0.000 description 1
QNAYBMKLOCPYGJ-UHFFFAOYSA-N Alanine Chemical class CC([NH3+])C([O-])=O QNAYBMKLOCPYGJ-UHFFFAOYSA-N 0.000 description 1
229910000761 Aluminium amalgam Inorganic materials 0.000 description 1
239000005711 Benzoic acid Substances 0.000 description 1
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
229910021595 Copper(I) iodide Inorganic materials 0.000 description 1
ZNZYKNKBJPZETN-WELNAUFTSA-N Dialdehyde 11678 Chemical compound N1C2=CC=CC=C2C2=C1[C@H](C[C@H](/C(=C/O)C(=O)OC)[C@@H](C=C)C=O)NCC2 ZNZYKNKBJPZETN-WELNAUFTSA-N 0.000 description 1
BUDQDWGNQVEFAC-UHFFFAOYSA-N Dihydropyran Chemical compound C1COC=CC1 BUDQDWGNQVEFAC-UHFFFAOYSA-N 0.000 description 1
229910017147 Fe(CO)5 Inorganic materials 0.000 description 1
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 1
208000008454 Hyperhidrosis Diseases 0.000 description 1
150000000994 L-ascorbates Chemical class 0.000 description 1
239000002841 Lewis acid Substances 0.000 description 1
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
241001465754 Metazoa Species 0.000 description 1
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical class CS(O)(=O)=O AFVFQIVMOAPDHO-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
AYCPARAPKDAOEN-LJQANCHMSA-N N-[(1S)-2-(dimethylamino)-1-phenylethyl]-6,6-dimethyl-3-[(2-methyl-4-thieno[3,2-d]pyrimidinyl)amino]-1,4-dihydropyrrolo[3,4-c]pyrazole-5-carboxamide Chemical compound C1([C@H](NC(=O)N2C(C=3NN=C(NC=4C=5SC=CC=5N=C(C)N=4)C=3C2)(C)C)CN(C)C)=CC=CC=C1 AYCPARAPKDAOEN-LJQANCHMSA-N 0.000 description 1
238000007126 N-alkylation reaction Methods 0.000 description 1
229920000388 Polyphosphate Polymers 0.000 description 1
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical group [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
206010039897 Sedation Diseases 0.000 description 1
XSTXAVWGXDQKEL-UHFFFAOYSA-N Trichloroethylene Chemical group ClC=C(Cl)Cl XSTXAVWGXDQKEL-UHFFFAOYSA-N 0.000 description 1
229910052770 Uranium Inorganic materials 0.000 description 1
HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
VJDDQSBNUHLBTD-GGWOSOGESA-N [(e)-but-2-enoyl] (e)-but-2-enoate Chemical compound C\C=C\C(=O)OC(=O)\C=C\C VJDDQSBNUHLBTD-GGWOSOGESA-N 0.000 description 1
150000001242 acetic acid derivatives Chemical class 0.000 description 1
125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 description 1
150000008065 acid anhydrides Chemical class 0.000 description 1
230000009471 action Effects 0.000 description 1
125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 1
150000001298 alcohols Chemical class 0.000 description 1
150000008044 alkali metal hydroxides Chemical class 0.000 description 1
229910001516 alkali metal iodide Inorganic materials 0.000 description 1
229910052784 alkaline earth metal Inorganic materials 0.000 description 1
125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
238000005804 alkylation reaction Methods 0.000 description 1
229910000147 aluminium phosphate Inorganic materials 0.000 description 1
GRKUXCWELVWVMZ-UHFFFAOYSA-N amino acetate Chemical class CC(=O)ON GRKUXCWELVWVMZ-UHFFFAOYSA-N 0.000 description 1
125000004103 aminoalkyl group Chemical group 0.000 description 1
229910021529 ammonia Inorganic materials 0.000 description 1
239000000538 analytical sample Substances 0.000 description 1
230000002052 anaphylactic effect Effects 0.000 description 1
239000012736 aqueous medium Substances 0.000 description 1
125000004429 atom Chemical group 0.000 description 1
230000008901 benefit Effects 0.000 description 1
235000010233 benzoic acid Nutrition 0.000 description 1
238000005574 benzylation reaction Methods 0.000 description 1
229910052794 bromium Inorganic materials 0.000 description 1
125000001246 bromo group Chemical group Br* 0.000 description 1
229910052799 carbon Inorganic materials 0.000 description 1
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
150000001735 carboxylic acids Chemical class 0.000 description 1
230000003197 catalytic effect Effects 0.000 description 1
150000001768 cations Chemical class 0.000 description 1
239000003874 central nervous system depressant Substances 0.000 description 1
229940089960 chloroacetate Drugs 0.000 description 1
FOCAUTSVDIKZOP-UHFFFAOYSA-N chloroacetic acid Chemical class OC(=O)CCl FOCAUTSVDIKZOP-UHFFFAOYSA-N 0.000 description 1
AOGYCOYQMAVAFD-UHFFFAOYSA-N chlorocarbonic acid Chemical compound OC(Cl)=O AOGYCOYQMAVAFD-UHFFFAOYSA-N 0.000 description 1
WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 description 1
239000012141 concentrate Substances 0.000 description 1
238000001816 cooling Methods 0.000 description 1
LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 1
125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
DEZRYPDIMOWBDS-UHFFFAOYSA-N dcm dichloromethane Chemical compound ClCCl.ClCCl DEZRYPDIMOWBDS-UHFFFAOYSA-N 0.000 description 1
238000007257 deesterification reaction Methods 0.000 description 1
230000001419 dependent effect Effects 0.000 description 1
125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
LMBWSYZSUOEYSN-UHFFFAOYSA-N diethyldithiocarbamic acid Chemical compound CCN(CC)C(S)=S LMBWSYZSUOEYSN-UHFFFAOYSA-N 0.000 description 1
125000005594 diketone group Chemical group 0.000 description 1
150000002009 diols Chemical class 0.000 description 1
229950004394 ditiocarb Drugs 0.000 description 1
239000003937 drug carrier Substances 0.000 description 1
238000001035 drying Methods 0.000 description 1
238000006735 epoxidation reaction Methods 0.000 description 1
IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 1
125000001033 ether group Chemical group 0.000 description 1
FCZCIXQGZOUIDN-UHFFFAOYSA-N ethyl 2-diethoxyphosphinothioyloxyacetate Chemical compound CCOC(=O)COP(=S)(OCC)OCC FCZCIXQGZOUIDN-UHFFFAOYSA-N 0.000 description 1
NBEMQPLNBYYUAZ-UHFFFAOYSA-N ethyl acetate;propan-2-one Chemical compound CC(C)=O.CCOC(C)=O NBEMQPLNBYYUAZ-UHFFFAOYSA-N 0.000 description 1
125000004494 ethyl ester group Chemical group 0.000 description 1
239000011737 fluorine Substances 0.000 description 1
238000009472 formulation Methods 0.000 description 1
125000004438 haloalkoxy group Chemical group 0.000 description 1
229910052736 halogen Inorganic materials 0.000 description 1
150000002367 halogens Chemical class 0.000 description 1
BCQZXOMGPXTTIC-UHFFFAOYSA-N halothane Chemical compound FC(F)(F)C(Cl)Br BCQZXOMGPXTTIC-UHFFFAOYSA-N 0.000 description 1
229960003132 halothane Drugs 0.000 description 1
125000001145 hydrido group Chemical group *[H] 0.000 description 1
125000001183 hydrocarbyl group Chemical group 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
238000007327 hydrogenolysis reaction Methods 0.000 description 1
230000003301 hydrolyzing effect Effects 0.000 description 1
150000002466 imines Chemical class 0.000 description 1
230000001939 inductive effect Effects 0.000 description 1
239000012442 inert solvent Substances 0.000 description 1
229910052500 inorganic mineral Inorganic materials 0.000 description 1
238000010255 intramuscular injection Methods 0.000 description 1
239000007927 intramuscular injection Substances 0.000 description 1
238000001990 intravenous administration Methods 0.000 description 1
238000010253 intravenous injection Methods 0.000 description 1
PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
125000002346 iodo group Chemical group I* 0.000 description 1
238000002955 isolation Methods 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
150000003893 lactate salts Chemical class 0.000 description 1
JNODQFNWMXFMEV-UHFFFAOYSA-N latrepirdine Chemical compound C1N(C)CCC2=C1C1=CC(C)=CC=C1N2CCC1=CC=C(C)N=C1 JNODQFNWMXFMEV-UHFFFAOYSA-N 0.000 description 1
150000007517 lewis acids Chemical class 0.000 description 1
229910052744 lithium Inorganic materials 0.000 description 1
150000002688 maleic acid derivatives Chemical class 0.000 description 1
125000005905 mesyloxy group Chemical group 0.000 description 1
TWXDDNPPQUTEOV-FVGYRXGTSA-N methamphetamine hydrochloride Chemical compound Cl.CN[C@@H](C)CC1=CC=CC=C1 TWXDDNPPQUTEOV-FVGYRXGTSA-N 0.000 description 1
GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 description 1
VRWLBMGRSLQKSU-UHFFFAOYSA-N methanol;pyridine Chemical compound OC.C1=CC=NC=C1 VRWLBMGRSLQKSU-UHFFFAOYSA-N 0.000 description 1
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
DVSDBMFJEQPWNO-UHFFFAOYSA-N methyllithium Chemical compound C[Li] DVSDBMFJEQPWNO-UHFFFAOYSA-N 0.000 description 1
125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
235000010755 mineral Nutrition 0.000 description 1
239000011707 mineral Substances 0.000 description 1
238000002156 mixing Methods 0.000 description 1
125000002950 monocyclic group Chemical group 0.000 description 1
150000004682 monohydrates Chemical class 0.000 description 1
239000012452 mother liquor Substances 0.000 description 1
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
239000001272 nitrous oxide Substances 0.000 description 1
230000003287 optical effect Effects 0.000 description 1
150000007530 organic bases Chemical class 0.000 description 1
239000012430 organic reaction media Substances 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
239000008194 pharmaceutical composition Substances 0.000 description 1
239000000546 pharmaceutical excipient Substances 0.000 description 1
150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
239000011574 phosphorus Substances 0.000 description 1
229910052698 phosphorus Inorganic materials 0.000 description 1
229910000073 phosphorus hydride Inorganic materials 0.000 description 1
125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
239000002798 polar solvent Substances 0.000 description 1
239000001205 polyphosphate Substances 0.000 description 1
235000011176 polyphosphates Nutrition 0.000 description 1
LZMJNVRJMFMYQS-UHFFFAOYSA-N poseltinib Chemical compound C1CN(C)CCN1C(C=C1)=CC=C1NC1=NC(OC=2C=C(NC(=O)C=C)C=CC=2)=C(OC=C2)C2=N1 LZMJNVRJMFMYQS-UHFFFAOYSA-N 0.000 description 1
229910052700 potassium Chemical group 0.000 description 1
239000011591 potassium Chemical group 0.000 description 1
229960003975 potassium Drugs 0.000 description 1
229940086066 potassium hydrogencarbonate Drugs 0.000 description 1
ZNNZYHKDIALBAK-UHFFFAOYSA-M potassium thiocyanate Chemical compound [K+].[S-]C#N ZNNZYHKDIALBAK-UHFFFAOYSA-M 0.000 description 1
229940116357 potassium thiocyanate Drugs 0.000 description 1
230000002035 prolonged effect Effects 0.000 description 1
OVARTBFNCCXQKS-UHFFFAOYSA-N propan-2-one;hydrate Chemical compound O.CC(C)=O OVARTBFNCCXQKS-UHFFFAOYSA-N 0.000 description 1
125000006239 protecting group Chemical group 0.000 description 1
239000012047 saturated solution Substances 0.000 description 1
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
150000003335 secondary amines Chemical class 0.000 description 1
125000000467 secondary amino group Chemical group [H]N([*:1])[*:2] 0.000 description 1
230000036280 sedation Effects 0.000 description 1
239000000932 sedative agent Substances 0.000 description 1
229940125723 sedative agent Drugs 0.000 description 1
229940096017 silver fluoride Drugs 0.000 description 1
REYHXKZHIMGNSE-UHFFFAOYSA-M silver monofluoride Chemical compound [F-].[Ag+] REYHXKZHIMGNSE-UHFFFAOYSA-M 0.000 description 1
XGVXKJKTISMIOW-ZDUSSCGKSA-N simurosertib Chemical compound N1N=CC(C=2SC=3C(=O)NC(=NC=3C=2)[C@H]2N3CCC(CC3)C2)=C1C XGVXKJKTISMIOW-ZDUSSCGKSA-N 0.000 description 1
BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
238000000638 solvent extraction Methods 0.000 description 1
241000894007 species Species 0.000 description 1
235000015096 spirit Nutrition 0.000 description 1
230000000707 stereoselective effect Effects 0.000 description 1
239000012258 stirred mixture Substances 0.000 description 1
125000000547 substituted alkyl group Chemical group 0.000 description 1
150000003890 succinate salts Chemical class 0.000 description 1
150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
150000003892 tartrate salts Chemical class 0.000 description 1
150000003512 tertiary amines Chemical class 0.000 description 1
125000001302 tertiary amino group Chemical group 0.000 description 1
QERYCTSHXKAMIS-UHFFFAOYSA-N thiophene-2-carboxylic acid Chemical compound OC(=O)C1=CC=CS1 QERYCTSHXKAMIS-UHFFFAOYSA-N 0.000 description 1
201000005060 thrombophlebitis Diseases 0.000 description 1
125000005424 tosyloxy group Chemical group S(=O)(=O)(C1=CC=C(C)C=C1)O* 0.000 description 1
UBOXGVDOUJQMTN-UHFFFAOYSA-N trichloroethylene Natural products ClCC(Cl)Cl UBOXGVDOUJQMTN-UHFFFAOYSA-N 0.000 description 1
GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 1
239000003643 water by type Substances 0.000 description 1
239000011701 zinc Substances 0.000 description 1
229910052725 zinc Inorganic materials 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J43/00—Normal steroids having a nitrogen-containing hetero ring spiro-condensed or not condensed with the cyclopenta(a)hydrophenanthrene skeleton
- C07J43/003—Normal steroids having a nitrogen-containing hetero ring spiro-condensed or not condensed with the cyclopenta(a)hydrophenanthrene skeleton not condensed
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P23/00—Anaesthetics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P23/00—Anaesthetics
- A61P23/02—Local anaesthetics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J13/00—Normal steroids containing carbon, hydrogen, halogen or oxygen having a carbon-to-carbon double bond from or to position 17
- C07J13/005—Normal steroids containing carbon, hydrogen, halogen or oxygen having a carbon-to-carbon double bond from or to position 17 with double bond in position 16 (17)
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J17/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, having an oxygen-containing hetero ring not condensed with the cyclopenta(a)hydrophenanthrene skeleton
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J3/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by one carbon atom
- C07J3/005—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by one carbon atom the carbon atom being part of a carboxylic function
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J31/00—Normal steroids containing one or more sulfur atoms not belonging to a hetero ring
- C07J31/006—Normal steroids containing one or more sulfur atoms not belonging to a hetero ring not covered by C07J31/003
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J41/00—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring
- C07J41/0033—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005
- C07J41/0088—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005 containing unsubstituted amino radicals
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J41/00—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring
- C07J41/0033—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005
- C07J41/0094—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005 containing nitrile radicals, including thiocyanide radicals
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J5/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane and substituted in position 21 by only one singly bound oxygen atom, i.e. only one oxygen bound to position 21 by a single bond
- C07J5/0007—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane and substituted in position 21 by only one singly bound oxygen atom, i.e. only one oxygen bound to position 21 by a single bond not substituted in position 17 alfa
- C07J5/0015—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane and substituted in position 21 by only one singly bound oxygen atom, i.e. only one oxygen bound to position 21 by a single bond not substituted in position 17 alfa not substituted in position 16
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J63/00—Steroids in which the cyclopenta(a)hydrophenanthrene skeleton has been modified by expansion of only one ring by one or two atoms
- C07J63/008—Expansion of ring D by one atom, e.g. D homo steroids
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J7/00—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms
- C07J7/0005—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms not substituted in position 21
- C07J7/001—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms not substituted in position 21 substituted in position 20 by a keto group
- C07J7/0015—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms not substituted in position 21 substituted in position 20 by a keto group not substituted in position 17 alfa
- C07J7/0025—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms not substituted in position 21 substituted in position 20 by a keto group not substituted in position 17 alfa substituted in position 16
- C07J7/003—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms not substituted in position 21 substituted in position 20 by a keto group not substituted in position 17 alfa substituted in position 16 by a saturated or unsaturated hydrocarbon group
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J71/00—Steroids in which the cyclopenta(a)hydrophenanthrene skeleton is condensed with a heterocyclic ring
- C07J71/0005—Oxygen-containing hetero ring
- C07J71/001—Oxiranes

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
General Health & Medical Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Life Sciences & Earth Sciences (AREA)
Anesthesiology (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
Pharmacology & Pharmacy (AREA)
Animal Behavior & Ethology (AREA)
Neurosurgery (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Biomedical Technology (AREA)
Toxicology (AREA)
Neurology (AREA)
Steroid Compounds (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

CA269,161A 1976-01-06 1977-01-05 Anaesthetic steroids Expired CA1084903A (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
GB357/76		1976-01-06
GB357/76A GB1570394A (en)	1976-01-06	1976-01-06	11-acyloxy-3-hydroxy steroids

Publications (1)

Publication Number	Publication Date
CA1084903A true CA1084903A (en)	1980-09-02

Family

ID=9702974

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA269,161A Expired CA1084903A (en)	1976-01-06	1977-01-05	Anaesthetic steroids

Country Status (12)

Country	Link
JP (1)	JPS5285159A (da)
AU (1)	AU513579B2 (da)
BE (1)	BE850108A (da)
CA (1)	CA1084903A (da)
DE (1)	DE2700267A1 (da)
DK (1)	DK3577A (da)
FR (1)	FR2361419A1 (da)
GB (1)	GB1570394A (da)
NL (1)	NL7700054A (da)
NZ (1)	NZ183004A (da)
SE (1)	SE7700098L (da)
ZA (1)	ZA7759B (da)

Families Citing this family (28)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
CZ300694A3 (en) *	1993-12-02	1996-05-15	Akzo Nobel Nv	Substituted 2beta-morpholinandrostane derivatives, process of their preparation, their use for preparing pharmaceutical preparations and pharmaceutical compositions containing thereof
GB0105772D0 (en) *	2001-03-08	2001-04-25	Sterix Ltd	Use
CA3152410A1 (en)	2011-10-14	2013-04-18	Sage Therapeutics, Inc.	3,3-disubstituted 19-nor pregnane compounds, compositions, and uses thereof for the treatment of cns related disorders
SMT202000008T1 (it)	2012-01-23	2020-03-13	Sage Therapeutics Inc	Formulazione di steroide neuroattivo comprendente un complesso di allopregnanolone e solfobutil eter beta-ciclodestrina
PL2887944T3 (pl)	2012-08-21	2022-02-21	Sage Therapeutics, Inc.	Allopregnanolon do leczenia lekoopornego stanu padaczkowego
WO2014169831A1 (en)	2013-04-17	2014-10-23	Sage Therapeutics, Inc.	19-nor c3,3-disubstituted c21-c-bound heteroaryl steroids and methods of use thereof
CN113527400B (zh)	2013-04-17	2024-06-28	萨奇治疗股份有限公司	19-去甲c3,3-二取代的c21-n-吡唑基类固醇及其使用方法
RU2019126333A (ru)	2013-04-17	2019-10-08	Сейдж Терапьютикс, Инк.	19-нор нейроактивные стероиды и способы их применения
US20160068563A1 (en)	2013-04-17	2016-03-10	Boyd L. Harrison	19-nor neuroactive steroids and methods of use thereof
WO2015010054A2 (en) *	2013-07-19	2015-01-22	Sage Therapeutics, Inc.	Neuroactive steroids, compositions, and uses thereof
AU2014308621C1 (en)	2013-08-23	2022-01-06	Sage Therapeutics, Inc.	Neuroactive steroids, compositions, and uses thereof
WO2015195962A1 (en)	2014-06-18	2015-12-23	Sage Therapeutics, Inc.	Neuroactive steroids, compositions, and uses thereof
JOP20200195A1 (ar)	2014-09-08	2017-06-16	Sage Therapeutics Inc	سترويدات وتركيبات نشطة عصبياً، واستخداماتها
SMT202000414T1 (it)	2014-10-16	2020-09-10	Sage Therapeutics Inc	Composizioni e metodi per trattare disturbi del snc
MX2021004492A (es)	2014-10-16	2022-12-05	Sage Therapeutics Inc	Composiciones para el tratamiento de trastornos del snc.
ME03749B (me)	2014-11-27	2021-04-20	Sage Therapeutics Inc	KOMPOZICIJE I POSTUPCIZA LEČENJE POREMEĆAJA CNS-a
DK3250210T3 (da)	2015-01-26	2021-03-08	Sage Therapeutics Inc	Sammensætninger og fremgangsmåder til behandling af cns-forstyrrelser
JP6875996B2 (ja)	2015-02-20	2021-05-26	セージセラピューティクス，インコーポレイテッド	神経刺激性ステロイド、組成物、およびその使用
CN107743376B (zh)	2015-06-10	2021-06-25	波士顿科学医学有限公司	通过评估响应于激发辐射的光致发光的身体物质检测
RU2766155C2 (ru)	2016-03-08	2022-02-08	Сейдж Терапьютикс, Инк.	Нейроактивные стероиды, их композиции и применения
WO2018013613A1 (en)	2016-07-11	2018-01-18	Sage Therapeutics, Inc.	C17, c20, and c21 substituted neuroactive steroids and their methods of use
CA3030420C (en) *	2016-07-11	2025-11-18	Sage Therapeutics, Inc.	C7, C12 AND C16 SUBSTITUTED NEUROACTIVE STEROIDS AND ASSOCIATED METHODS OF USE
US20220315621A1 (en) *	2017-12-22	2022-10-06	Sage Therapeutics, Inc.	Compositions and methods for treating cns disorders
IL312610B2 (en)	2018-12-05	2026-05-01	Sage Therapeutics Llc	Neuroactive steroids and methods of using them
CN114206900A (zh)	2019-05-31	2022-03-18	萨奇治疗股份有限公司	神经活性类固醇及其组合物
EP3990468A1 (en) *	2019-06-27	2022-05-04	Sage Therapeutics, Inc.	Compounds for treating cns disorders
WO2020264495A1 (en) *	2019-06-27	2020-12-30	Sage Therapeutics, Inc.	Compositions and methods for treating cns disorders
TWI896547B (zh)	2019-06-27	2025-09-11	美商賽吉醫療公司	用於治療cns病症之組合物及方法

1976
- 1976-01-06 GB GB357/76A patent/GB1570394A/en not_active Expired
1977
- 1977-01-05 SE SE7700098A patent/SE7700098L/ not_active Application Discontinuation
- 1977-01-05 FR FR7700171A patent/FR2361419A1/fr active Granted
- 1977-01-05 BE BE173855A patent/BE850108A/xx not_active IP Right Cessation
- 1977-01-05 CA CA269,161A patent/CA1084903A/en not_active Expired
- 1977-01-05 DK DK3577A patent/DK3577A/da not_active Application Discontinuation
- 1977-01-05 DE DE19772700267 patent/DE2700267A1/de not_active Ceased
- 1977-01-05 NL NL7700054A patent/NL7700054A/xx not_active Application Discontinuation
- 1977-01-05 AU AU21065/77A patent/AU513579B2/en not_active Expired
- 1977-01-05 ZA ZA00770059A patent/ZA7759B/xx unknown
- 1977-01-05 JP JP30477A patent/JPS5285159A/ja active Pending
- 1977-01-06 NZ NZ183004A patent/NZ183004A/xx unknown

Also Published As

Publication number	Publication date
NZ183004A (en)	1980-03-05
FR2361419A1 (fr)	1978-03-10
AU2106577A (en)	1978-07-13
FR2361419B1 (da)	1980-04-04
JPS5285159A (en)	1977-07-15
ZA7759B (en)	1978-02-22
GB1570394A (en)	1980-07-02
NL7700054A (nl)	1977-07-08
AU513579B2 (en)	1980-12-11
DE2700267A1 (de)	1977-07-14
DK3577A (da)	1977-07-07
BE850108A (fr)	1977-07-05
SE7700098L (sv)	1977-07-07

Legal Events

Date	Code	Title	Description
1997-09-02	MKEX	Expiry

Publication	Publication Date	Title
US4192871A (en)	1980-03-11	Chemical compounds
GB1570394A (en)	1980-07-02	11-acyloxy-3-hydroxy steroids
DE3783007T2 (de)	1993-07-01	9-alpha-hydroxysteroide, verfahren zu ihrer herstellung und verfahren zur herstellung der entsprechenden 9(11)-dehydro-derivate.
EP0147361B1 (de)	1989-02-08	11 Beta-Aryl-Estradiene, deren Herstellung und diese enthaltende pharmazeutische Präparate
GB1581234A (en)	1980-12-10	11a - amino - 3a - hydroxysteroids
EP0116974B1 (de)	1986-10-29	11-Beta-Aryl-Estradiene, Verfahren zu deren Herstellung und diese enthaltende pharmazeutische Präparate
DE69500542T2 (de)	1998-01-02	11,21-Bisphenyl-19-nor-pregnan Derivate
GB1581235A (en)	1980-12-10	11a-amino-3a-hydroxy-steroids
NZ245520A (en)	1995-02-24	17-spirofuran-3'-ylidene steroids; preparatory processes, use, and pharmaceutical compositions
US4197296A (en)	1980-04-08	Androstanes
DE3102397A1 (de)	1981-12-24	17(alpha)-acyloxy-5(beta)-corticoide und 17(alpha)-acyloxy-5(alpha)-corticoide
EP0051762B1 (de)	1984-12-19	11-Methylen-delta-15-Steroide, Verfahren zu ihrer Herstellung und diese enthaltende pharmazeutische Präparate
US3463776A (en)	1969-08-26	Steroidal 6-cyclopropyl-4-en-3-ones and process for preparing same
EP0104387A1 (de)	1984-04-04	11-Beta-Aryl-17-alpha-alkinyl-17-beta-hydroxy-4,9(10)-estradien-3-on-Derivate, deren Herstellung und diese enthaltende pharmazeutische Präparate
WO1987005028A1 (en)	1987-08-27	Anti-inflammatory carboxy pregnane derivatives
US4110326A (en)	1978-08-29	Acylated diepoxy-androstane and a process for the preparation thereof
CS203912B2 (en)	1981-03-31	Process for preparing derivatives of estradiene
US3969345A (en)	1976-07-13	20β,21-Epoxy-3α-hydroxy-5α-pregnanes and derivatives thereof
EP0014005B1 (en)	1983-08-03	Novel alkylated pregnanes, processes for their preparation and pharmaceutical compositions containing same
EP0591268A1 (de)	1994-04-13	Verfahren zur herstellung von 6-methylensteroiden
EP0032261A1 (en)	1981-07-22	Novel bis- and mono-quaternary ammonium derivatives of 2-beta, 16-beta-dipiperidino-5-alpha-androstanes, processes for their preparation and pharmaceutical preparations
DE2309328A1 (de)	1973-10-04	3-keto-7(alpha,beta)-nied.-alkyldelta hoch 5-steroide und verfahren zu ihrer herstellung
US3242169A (en)	1966-03-22	6alpha-dimethylaminomethyl-3-oxo-delta4-steroids and method for producing same
DE2047071C3 (de)	1979-11-15	pregnadiene, Verfahren zu ihrer Herstellung sowie diese enthaltende Arzneimittel
EP0017094A1 (de)	1980-10-15	11-Methylensteroide, Verfahren zu ihrer Herstellung und diese enthaltende pharmazeutische Präparate