AP653A - Androstane and pregnane series for allosteric modulations of gaba receptor. - Google Patents

Androstane and pregnane series for allosteric modulations of gaba receptor. Download PDF

Info

Publication number: AP653A
Authority: AP; ARIPO
Prior art keywords: pregnan; hydroxy; dihydroxy; trifluoromethyl; compounds
Prior art date: 1994-11-23

Application number

APAP/P/1997/000998A

Other languages

English (en)

Other versions

AP9700998A0 (en

Inventor

Nancy C Lan

Kelvin W Gee

Michael B Bolger

Hassan F Tahir

Robetrt Purdy

Ravindra Upasani

Original Assignee

Cocensys Inc

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.)

1994-11-23

Filing date

1995-11-22

Publication date

1998-07-21

1995-11-22 Application filed by Cocensys Inc filed Critical Cocensys Inc

1997-07-31 Publication of AP9700998A0 publication Critical patent/AP9700998A0/xx

1998-07-21 Application granted granted Critical

1998-07-21 Publication of AP653A publication Critical patent/AP653A/en

Links

102000005915 GABA Receptors Human genes 0.000 title description 8
108010005551 GABA Receptors Proteins 0.000 title description 8
150000003128 pregnanes Chemical class 0.000 title description 4
QZLYKIGBANMMBK-UGCZWRCOSA-N 5α-Androstane Chemical compound C([C@@H]1CC2)CCC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CCC[C@@]2(C)CC1 QZLYKIGBANMMBK-UGCZWRCOSA-N 0.000 title description 2
230000003281 allosteric effect Effects 0.000 title description 2
150000001875 compounds Chemical class 0.000 claims abstract description 164
238000000034 method Methods 0.000 claims abstract description 37
208000019901 Anxiety disease Diseases 0.000 claims abstract description 17
230000036506 anxiety Effects 0.000 claims abstract description 17
208000019022 Mood disease Diseases 0.000 claims abstract description 8
206010002091 Anaesthesia Diseases 0.000 claims abstract description 6
230000037005 anaesthesia Effects 0.000 claims abstract description 6
230000000694 effects Effects 0.000 claims description 50
241001465754 Metazoa Species 0.000 claims description 28
239000003814 drug Substances 0.000 claims description 23
159000000000 sodium salts Chemical class 0.000 claims description 20
206010036618 Premenstrual syndrome Diseases 0.000 claims description 15
208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 claims description 7
206010022437 insomnia Diseases 0.000 claims description 7
HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 claims description 6
MSJMDZAOKORVFC-SEPHDYHBSA-L disodium fumarate Chemical compound [Na+].[Na+].[O-]C(=O)\C=C\C([O-])=O MSJMDZAOKORVFC-SEPHDYHBSA-L 0.000 claims description 5
239000003937 drug carrier Substances 0.000 claims description 4
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
239000003085 diluting agent Substances 0.000 claims description 2
239000008194 pharmaceutical composition Substances 0.000 claims description 2
230000001939 inductive effect Effects 0.000 claims 2
238000004519 manufacturing process Methods 0.000 claims 1
239000000203 mixture Substances 0.000 abstract description 100
206010010904 Convulsion Diseases 0.000 abstract description 14
239000002555 ionophore Substances 0.000 abstract description 3
230000000236 ionophoric effect Effects 0.000 abstract description 3
239000000243 solution Substances 0.000 description 137
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 110
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 96
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 83
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 67
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 65
RJKFOVLPORLFTN-LEKSSAKUSA-N Progesterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 RJKFOVLPORLFTN-LEKSSAKUSA-N 0.000 description 55
ODLHGICHYURWBS-LKONHMLTSA-N trappsol cyclo Chemical compound CC(O)COC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)COCC(O)C)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1COCC(C)O ODLHGICHYURWBS-LKONHMLTSA-N 0.000 description 54
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 48
238000006243 chemical reaction Methods 0.000 description 47
239000007787 solid Substances 0.000 description 47
150000003431 steroids Chemical class 0.000 description 47
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 42
238000012360 testing method Methods 0.000 description 41
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 40
BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 40
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 36
239000000047 product Substances 0.000 description 35
239000002904 solvent Substances 0.000 description 34
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 30
235000019439 ethyl acetate Nutrition 0.000 description 29
239000000186 progesterone Substances 0.000 description 28
229960003387 progesterone Drugs 0.000 description 28
239000012043 crude product Substances 0.000 description 27
HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 23
RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 23
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 22
238000003756 stirring Methods 0.000 description 22
229940079593 drug Drugs 0.000 description 21
-1 steroid compounds Chemical class 0.000 description 21
OGNSCSPNOLGXSM-UHFFFAOYSA-N (+/-)-DABA Natural products NCCC(N)C(O)=O OGNSCSPNOLGXSM-UHFFFAOYSA-N 0.000 description 20
229960003692 gamma aminobutyric acid Drugs 0.000 description 20
206010001497 Agitation Diseases 0.000 description 19
241000699670 Mus sp. Species 0.000 description 19
210000004556 brain Anatomy 0.000 description 19
150000002148 esters Chemical class 0.000 description 19
239000012044 organic layer Substances 0.000 description 19
229910000030 sodium bicarbonate Inorganic materials 0.000 description 19
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
239000001257 hydrogen Substances 0.000 description 18
229910052739 hydrogen Inorganic materials 0.000 description 18
229910000027 potassium carbonate Inorganic materials 0.000 description 18
125000000304 alkynyl group Chemical group 0.000 description 17
230000027455 binding Effects 0.000 description 17
238000009739 binding Methods 0.000 description 17
125000004435 hydrogen atom Chemical group [H]* 0.000 description 17
239000010410 layer Substances 0.000 description 17
239000000651 prodrug Substances 0.000 description 17
229940002612 prodrug Drugs 0.000 description 17
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 16
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 15
239000012267 brine Substances 0.000 description 15
229910052943 magnesium sulfate Inorganic materials 0.000 description 15
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 15
125000000217 alkyl group Chemical group 0.000 description 14
230000000949 anxiolytic effect Effects 0.000 description 14
239000003153 chemical reaction reagent Substances 0.000 description 14
238000010828 elution Methods 0.000 description 14
238000002474 experimental method Methods 0.000 description 14
WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 14
201000009916 Postpartum depression Diseases 0.000 description 13
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 13
239000002253 acid Substances 0.000 description 13
125000003342 alkenyl group Chemical group 0.000 description 13
AURFZBICLPNKBZ-SYBPFIFISA-N brexanolone 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 AURFZBICLPNKBZ-SYBPFIFISA-N 0.000 description 13
239000003981 vehicle Substances 0.000 description 13
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 12
239000001961 anticonvulsive agent Substances 0.000 description 12
239000002249 anxiolytic agent Substances 0.000 description 12
238000004587 chromatography analysis Methods 0.000 description 12
150000003146 progesterones Chemical class 0.000 description 12
230000004044 response Effects 0.000 description 12
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 11
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 11
241000700159 Rattus Species 0.000 description 11
235000019270 ammonium chloride Nutrition 0.000 description 11
238000004440 column chromatography Methods 0.000 description 11
206010015037 epilepsy Diseases 0.000 description 11
239000000741 silica gel Substances 0.000 description 11
229910002027 silica gel Inorganic materials 0.000 description 11
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 10
230000001773 anti-convulsant effect Effects 0.000 description 10
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 9
CWRVKFFCRWGWCS-UHFFFAOYSA-N Pentrazole Chemical compound C1CCCCC2=NN=NN21 CWRVKFFCRWGWCS-UHFFFAOYSA-N 0.000 description 9
238000003556 assay Methods 0.000 description 9
238000001035 drying Methods 0.000 description 9
239000012528 membrane Substances 0.000 description 9
239000002207 metabolite Substances 0.000 description 9
239000011734 sodium Substances 0.000 description 9
239000011780 sodium chloride Substances 0.000 description 9
125000001424 substituent group Chemical group 0.000 description 9
208000024891 symptom Diseases 0.000 description 9
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 compound 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 8
MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 8
229960003965 antiepileptics Drugs 0.000 description 8
125000003118 aryl group Chemical group 0.000 description 8
229940125717 barbiturate Drugs 0.000 description 8
229940049706 benzodiazepine Drugs 0.000 description 8
238000003818 flash chromatography Methods 0.000 description 8
238000000338 in vitro Methods 0.000 description 8
239000007858 starting material Substances 0.000 description 8
QMGVPVSNSZLJIA-FVWCLLPLSA-N strychnine Chemical compound O([C@H]1CC(N([C@H]2[C@H]1[C@H]1C3)C=4C5=CC=CC=4)=O)CC=C1CN1[C@@H]3[C@]25CC1 QMGVPVSNSZLJIA-FVWCLLPLSA-N 0.000 description 8
230000007704 transition Effects 0.000 description 8
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 8
VTBHBNXGFPTBJL-UHFFFAOYSA-N 4-tert-butyl-1-sulfanylidene-2,6,7-trioxa-1$l^{5}-phosphabicyclo[2.2.2]octane Chemical compound C1OP2(=S)OCC1(C(C)(C)C)CO2 VTBHBNXGFPTBJL-UHFFFAOYSA-N 0.000 description 7
VTBHBNXGFPTBJL-DLSVHHIMSA-N 4-tert-butyl-1-sulfanylidene-2,6,7-trioxa-1$l^{5}-phosphabicyclo[2.2.2]octane Chemical compound C1OP2(=[35S])OCC1(C(C)(C)C)CO2 VTBHBNXGFPTBJL-DLSVHHIMSA-N 0.000 description 7
CYKYBWRSLLXBOW-GDYGHMJCSA-N 5-alpha-THDOC Chemical compound C1[C@H](O)CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)C(=O)CO)[C@@H]4[C@@H]3CC[C@H]21 CYKYBWRSLLXBOW-GDYGHMJCSA-N 0.000 description 7
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 7
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 7
150000007513 acids Chemical class 0.000 description 7
231100000673 dose–response relationship Toxicity 0.000 description 7
229940093499 ethyl acetate Drugs 0.000 description 7
239000007789 gas Substances 0.000 description 7
230000003054 hormonal effect Effects 0.000 description 7
210000000287 oocyte Anatomy 0.000 description 7
229960001412 pentobarbital Drugs 0.000 description 7
238000002360 preparation method Methods 0.000 description 7
230000001225 therapeutic effect Effects 0.000 description 7
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 6
LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 6
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
150000001557 benzodiazepines Chemical class 0.000 description 6
HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 6
125000004122 cyclic group Chemical group 0.000 description 6
IYGYMKDQCDOMRE-UHFFFAOYSA-N d-Bicucullin Natural products CN1CCC2=CC=3OCOC=3C=C2C1C1OC(=O)C2=C1C=CC1=C2OCO1 IYGYMKDQCDOMRE-UHFFFAOYSA-N 0.000 description 6
238000001914 filtration Methods 0.000 description 6
235000013305 food Nutrition 0.000 description 6
230000005764 inhibitory process Effects 0.000 description 6
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 6
239000007788 liquid Substances 0.000 description 6
239000000463 material Substances 0.000 description 6
235000013336 milk Nutrition 0.000 description 6
239000008267 milk Substances 0.000 description 6
210000004080 milk Anatomy 0.000 description 6
230000001537 neural effect Effects 0.000 description 6
108020003175 receptors Proteins 0.000 description 6
238000001953 recrystallisation Methods 0.000 description 6
230000002787 reinforcement Effects 0.000 description 6
ZESRJSPZRDMNHY-YFWFAHHUSA-N 11-deoxycorticosterone Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 ZESRJSPZRDMNHY-YFWFAHHUSA-N 0.000 description 5
FALRKNHUBBKYCC-UHFFFAOYSA-N 2-(chloromethyl)pyridine-3-carbonitrile Chemical compound ClCC1=NC=CC=C1C#N FALRKNHUBBKYCC-UHFFFAOYSA-N 0.000 description 5
KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 5
230000009471 action Effects 0.000 description 5
125000003545 alkoxy group Chemical group 0.000 description 5
239000003179 convulsant agent Substances 0.000 description 5
230000036461 convulsion Effects 0.000 description 5
238000001816 cooling Methods 0.000 description 5
ZESRJSPZRDMNHY-UHFFFAOYSA-N de-oxy corticosterone Natural products O=C1CCC2(C)C3CCC(C)(C(CC4)C(=O)CO)C4C3CCC2=C1 ZESRJSPZRDMNHY-UHFFFAOYSA-N 0.000 description 5
229940119740 deoxycorticosterone Drugs 0.000 description 5
239000003480 eluent Substances 0.000 description 5
230000001965 increasing effect Effects 0.000 description 5
239000007924 injection Substances 0.000 description 5
238000002347 injection Methods 0.000 description 5
150000002500 ions Chemical class 0.000 description 5
210000002569 neuron Anatomy 0.000 description 5
239000002858 neurotransmitter agent Substances 0.000 description 5
231100000252 nontoxic Toxicity 0.000 description 5
230000003000 nontoxic effect Effects 0.000 description 5
230000003389 potentiating effect Effects 0.000 description 5
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
102000005962 receptors Human genes 0.000 description 5
238000010992 reflux Methods 0.000 description 5
230000001105 regulatory effect Effects 0.000 description 5
150000003839 salts Chemical class 0.000 description 5
ZDQYSKICYIVCPN-UHFFFAOYSA-L sodium succinate (anhydrous) Chemical group [Na+].[Na+].[O-]C(=O)CCC([O-])=O ZDQYSKICYIVCPN-UHFFFAOYSA-L 0.000 description 5
229940014800 succinic anhydride Drugs 0.000 description 5
UWTUEMKLYAGTNQ-OWOJBTEDSA-N (e)-1,2-dibromoethene Chemical group Br\C=C\Br UWTUEMKLYAGTNQ-OWOJBTEDSA-N 0.000 description 4
IYGYMKDQCDOMRE-QRWMCTBCSA-N Bicculine Chemical compound O([C@H]1C2C3=CC=4OCOC=4C=C3CCN2C)C(=O)C2=C1C=CC1=C2OCO1 IYGYMKDQCDOMRE-QRWMCTBCSA-N 0.000 description 4
DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 4
QMGVPVSNSZLJIA-UHFFFAOYSA-N Nux Vomica Natural products C1C2C3C4N(C=5C6=CC=CC=5)C(=O)CC3OCC=C2CN2C1C46CC2 QMGVPVSNSZLJIA-UHFFFAOYSA-N 0.000 description 4
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
LHNKBXRFNPMIBR-UHFFFAOYSA-N Picrotoxin Natural products CC(C)(O)C1(O)C2OC(=O)C1C3(O)C4OC4C5C(=O)OC2C35C LHNKBXRFNPMIBR-UHFFFAOYSA-N 0.000 description 4
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 4
PPTYJKAXVCCBDU-UHFFFAOYSA-N Rohypnol Chemical compound N=1CC(=O)N(C)C2=CC=C([N+]([O-])=O)C=C2C=1C1=CC=CC=C1F PPTYJKAXVCCBDU-UHFFFAOYSA-N 0.000 description 4
108010085012 Steroid Receptors Proteins 0.000 description 4
241001279009 Strychnos toxifera Species 0.000 description 4
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 4
125000002252 acyl group Chemical group 0.000 description 4
230000003444 anaesthetic effect Effects 0.000 description 4
HNYOPLTXPVRDBG-UHFFFAOYSA-M barbiturate Chemical compound O=C1CC(=O)[N-]C(=O)N1 HNYOPLTXPVRDBG-UHFFFAOYSA-M 0.000 description 4
AACMFFIUYXGCOC-UHFFFAOYSA-N bicuculline Natural products CN1CCc2cc3OCOc3cc2C1C4OCc5c6OCOc6ccc45 AACMFFIUYXGCOC-UHFFFAOYSA-N 0.000 description 4
229910052799 carbon Inorganic materials 0.000 description 4
239000000284 extract Substances 0.000 description 4
125000000350 glycoloyl group Chemical group O=C([*])C([H])([H])O[H] 0.000 description 4
125000002887 hydroxy group Chemical group [H]O* 0.000 description 4
125000002768 hydroxyalkyl group Chemical group 0.000 description 4
238000011534 incubation Methods 0.000 description 4
230000003993 interaction Effects 0.000 description 4
DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 4
230000001404 mediated effect Effects 0.000 description 4
210000004914 menses Anatomy 0.000 description 4
230000004048 modification Effects 0.000 description 4
238000012986 modification Methods 0.000 description 4
239000003921 oil Substances 0.000 description 4
235000019198 oils Nutrition 0.000 description 4
230000036961 partial effect Effects 0.000 description 4
VJKUPQSHOVKBCO-AHMKVGDJSA-N picrotoxin Chemical compound O=C([C@@]12O[C@@H]1C[C@]1(O)[C@@]32C)O[C@@H]3[C@H]2[C@@H](C(=C)C)[C@@H]1C(=O)O2.O=C([C@@]12O[C@@H]1C[C@]1(O)[C@@]32C)O[C@@H]3[C@H]2[C@@H](C(C)(O)C)[C@@H]1C(=O)O2 VJKUPQSHOVKBCO-AHMKVGDJSA-N 0.000 description 4
229960005235 piperonyl butoxide Drugs 0.000 description 4
229910052700 potassium Inorganic materials 0.000 description 4
239000011591 potassium Substances 0.000 description 4
150000003254 radicals Chemical class 0.000 description 4
239000011541 reaction mixture Substances 0.000 description 4
230000009467 reduction Effects 0.000 description 4
239000011877 solvent mixture Substances 0.000 description 4
102000005969 steroid hormone receptors Human genes 0.000 description 4
229960005453 strychnine Drugs 0.000 description 4
239000000126 substance Substances 0.000 description 4
208000011580 syndromic disease Diseases 0.000 description 4
FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 4
238000012549 training Methods 0.000 description 4
MWKJTNBSKNUMFN-UHFFFAOYSA-N trifluoromethyltrimethylsilane Chemical compound C[Si](C)(C)C(F)(F)F MWKJTNBSKNUMFN-UHFFFAOYSA-N 0.000 description 4
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
241000557626 Corvus corax Species 0.000 description 3
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 3
238000005481 NMR spectroscopy Methods 0.000 description 3
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
238000000692 Student's t-test Methods 0.000 description 3
KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 3
241000269370 Xenopus <genus> Species 0.000 description 3
150000001241 acetals Chemical class 0.000 description 3
239000004480 active ingredient Substances 0.000 description 3
239000013543 active substance Substances 0.000 description 3
239000000556 agonist Substances 0.000 description 3
HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 3
238000010171 animal model Methods 0.000 description 3
229940125681 anticonvulsant agent Drugs 0.000 description 3
125000003710 aryl alkyl group Chemical group 0.000 description 3
230000003542 behavioural effect Effects 0.000 description 3
230000009286 beneficial effect Effects 0.000 description 3
239000006227 byproduct Substances 0.000 description 3
125000004432 carbon atom Chemical group C* 0.000 description 3
210000004027 cell Anatomy 0.000 description 3
235000012000 cholesterol Nutrition 0.000 description 3
DGBIGWXXNGSACT-UHFFFAOYSA-N clonazepam Chemical compound C12=CC([N+](=O)[O-])=CC=C2NC(=O)CN=C1C1=CC=CC=C1Cl DGBIGWXXNGSACT-UHFFFAOYSA-N 0.000 description 3
229960003120 clonazepam Drugs 0.000 description 3
230000002596 correlated effect Effects 0.000 description 3
239000013078 crystal Substances 0.000 description 3
230000007423 decrease Effects 0.000 description 3
238000013461 design Methods 0.000 description 3
AAOVKJBEBIDNHE-UHFFFAOYSA-N diazepam Chemical compound N=1CC(=O)N(C)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 AAOVKJBEBIDNHE-UHFFFAOYSA-N 0.000 description 3
HDFFVHSMHLDSLO-UHFFFAOYSA-M dibenzyl phosphate Chemical compound C=1C=CC=CC=1COP(=O)([O-])OCC1=CC=CC=C1 HDFFVHSMHLDSLO-UHFFFAOYSA-M 0.000 description 3
UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
208000035475 disorder Diseases 0.000 description 3
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 3
238000001704 evaporation Methods 0.000 description 3
230000008020 evaporation Effects 0.000 description 3
229960002200 flunitrazepam Drugs 0.000 description 3
238000004128 high performance liquid chromatography Methods 0.000 description 3
230000000147 hypnotic effect Effects 0.000 description 3
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
229910052744 lithium Inorganic materials 0.000 description 3
RMGJCSHZTFKPNO-UHFFFAOYSA-M magnesium;ethene;bromide Chemical compound [Mg+2].[Br-].[CH-]=C RMGJCSHZTFKPNO-UHFFFAOYSA-M 0.000 description 3
238000005259 measurement Methods 0.000 description 3
230000008450 motivation Effects 0.000 description 3
150000007524 organic acids Chemical class 0.000 description 3
230000003647 oxidation Effects 0.000 description 3
238000007254 oxidation reaction Methods 0.000 description 3
125000004430 oxygen atom Chemical group O* 0.000 description 3
239000008188 pellet Substances 0.000 description 3
IBALRBWGSVJPAP-HEHNFIMWSA-N progabide Chemical compound C=1C(F)=CC=C(O)C=1C(=N/CCCC(=O)N)/C1=CC=C(Cl)C=C1 IBALRBWGSVJPAP-HEHNFIMWSA-N 0.000 description 3
229960002752 progabide Drugs 0.000 description 3
230000011514 reflex Effects 0.000 description 3
SQGYOTSLMSWVJD-UHFFFAOYSA-N silver(1+) nitrate Chemical compound [Ag+].[O-]N(=O)=O SQGYOTSLMSWVJD-UHFFFAOYSA-N 0.000 description 3
239000012279 sodium borohydride Substances 0.000 description 3
229910000033 sodium borohydride Inorganic materials 0.000 description 3
239000000725 suspension Substances 0.000 description 3
238000012353 t test Methods 0.000 description 3
FKHIFSZMMVMEQY-UHFFFAOYSA-N talc Chemical compound [Mg+2].[O-][Si]([O-])=O FKHIFSZMMVMEQY-UHFFFAOYSA-N 0.000 description 3
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 3
238000005303 weighing Methods 0.000 description 3
YWYQTGBBEZQBGO-QARKZGPCSA-N (8r,9s,10s,13s,14s,17s)-17-(1-hydroxyethyl)-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-3-ol Chemical compound C1CC2CC(O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(O)C)[C@@]1(C)CC2 YWYQTGBBEZQBGO-QARKZGPCSA-N 0.000 description 2
VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
VOXZDWNPVJITMN-ZBRFXRBCSA-N 17β-estradiol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 VOXZDWNPVJITMN-ZBRFXRBCSA-N 0.000 description 2
SVUOLADPCWQTTE-UHFFFAOYSA-N 1h-1,2-benzodiazepine Chemical compound N1N=CC=CC2=CC=CC=C12 SVUOLADPCWQTTE-UHFFFAOYSA-N 0.000 description 2
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 2
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 2
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
206010063659 Aversion Diseases 0.000 description 2
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 2
COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 2
FIPWRIJSWJWJAI-UHFFFAOYSA-N Butyl carbitol 6-propylpiperonyl ether Chemical compound C1=C(CCC)C(COCCOCCOCCCC)=CC2=C1OCO2 FIPWRIJSWJWJAI-UHFFFAOYSA-N 0.000 description 2
102000029816 Collagenase Human genes 0.000 description 2
108060005980 Collagenase Proteins 0.000 description 2
OMFXVFTZEKFJBZ-UHFFFAOYSA-N Corticosterone Natural products O=C1CCC2(C)C3C(O)CC(C)(C(CC4)C(=O)CO)C4C3CCC2=C1 OMFXVFTZEKFJBZ-UHFFFAOYSA-N 0.000 description 2
229920000858 Cyclodextrin Polymers 0.000 description 2
HDFFVHSMHLDSLO-UHFFFAOYSA-N Dibenzyl phosphate Chemical compound C=1C=CC=CC=1COP(=O)(O)OCC1=CC=CC=C1 HDFFVHSMHLDSLO-UHFFFAOYSA-N 0.000 description 2
108010010803 Gelatin Proteins 0.000 description 2
239000004471 Glycine Substances 0.000 description 2
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 2
IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
239000004698 Polyethylene Substances 0.000 description 2
239000012891 Ringer solution Substances 0.000 description 2
241000283984 Rodentia Species 0.000 description 2
206010039897 Sedation Diseases 0.000 description 2
VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 2
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
229930006000 Sucrose Natural products 0.000 description 2
206010043994 Tonic convulsion Diseases 0.000 description 2
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 2
229960004373 acetylcholine Drugs 0.000 description 2
230000000049 anti-anxiety effect Effects 0.000 description 2
230000003466 anti-cipated effect Effects 0.000 description 2
239000000935 antidepressant agent Substances 0.000 description 2
229940005530 anxiolytics Drugs 0.000 description 2
239000007864 aqueous solution Substances 0.000 description 2
239000012300 argon atmosphere Substances 0.000 description 2
230000037007 arousal Effects 0.000 description 2
150000007514 bases Chemical class 0.000 description 2
230000006399 behavior Effects 0.000 description 2
IYGYMKDQCDOMRE-ZWKOTPCHSA-N bicuculline Chemical compound O([C@H]1[C@@H]2C3=CC=4OCOC=4C=C3CCN2C)C(=O)C2=C1C=CC1=C2OCO1 IYGYMKDQCDOMRE-ZWKOTPCHSA-N 0.000 description 2
230000004071 biological effect Effects 0.000 description 2
239000011203 carbon fibre reinforced carbon Substances 0.000 description 2
239000000969 carrier Substances 0.000 description 2
239000003054 catalyst Substances 0.000 description 2
210000003169 central nervous system Anatomy 0.000 description 2
229960002424 collagenase Drugs 0.000 description 2
230000001143 conditioned effect Effects 0.000 description 2
230000000875 corresponding effect Effects 0.000 description 2
OMFXVFTZEKFJBZ-HJTSIMOOSA-N corticosterone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@H](CC4)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 OMFXVFTZEKFJBZ-HJTSIMOOSA-N 0.000 description 2
239000013058 crude material Substances 0.000 description 2
239000010779 crude oil Substances 0.000 description 2
125000004093 cyano group Chemical group *C#N 0.000 description 2
230000001419 dependent effect Effects 0.000 description 2
230000000994 depressogenic effect Effects 0.000 description 2
239000007933 dermal patch Substances 0.000 description 2
125000004663 dialkyl amino group Chemical group 0.000 description 2
229910000397 disodium phosphate Inorganic materials 0.000 description 2
230000035622 drinking Effects 0.000 description 2
230000001037 epileptic effect Effects 0.000 description 2
125000003700 epoxy group Chemical group 0.000 description 2
229930182833 estradiol Natural products 0.000 description 2
229960005309 estradiol Drugs 0.000 description 2
230000002964 excitative effect Effects 0.000 description 2
125000000524 functional group Chemical group 0.000 description 2
239000008273 gelatin Substances 0.000 description 2
229920000159 gelatin Polymers 0.000 description 2
235000019322 gelatine Nutrition 0.000 description 2
235000011852 gelatine desserts Nutrition 0.000 description 2
239000003862 glucocorticoid Substances 0.000 description 2
125000005843 halogen group Chemical group 0.000 description 2
239000000017 hydrogel Substances 0.000 description 2
239000012535 impurity Substances 0.000 description 2
238000001727 in vivo Methods 0.000 description 2
239000012442 inert solvent Substances 0.000 description 2
238000001990 intravenous administration Methods 0.000 description 2
238000002955 isolation Methods 0.000 description 2
125000000468 ketone group Chemical group 0.000 description 2
150000002576 ketones Chemical class 0.000 description 2
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
229910052751 metal Inorganic materials 0.000 description 2
239000002184 metal Substances 0.000 description 2
MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 2
125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 2
239000002808 molecular sieve Substances 0.000 description 2
238000012544 monitoring process Methods 0.000 description 2
125000006372 monohalo methyl group Chemical group 0.000 description 2
125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 2
239000012452 mother liquor Substances 0.000 description 2
PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 2
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
230000010807 negative regulation of binding Effects 0.000 description 2
239000012074 organic phase Substances 0.000 description 2
125000002524 organometallic group Chemical group 0.000 description 2
230000027758 ovulation cycle Effects 0.000 description 2
229910052760 oxygen Inorganic materials 0.000 description 2
239000012071 phase Substances 0.000 description 2
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
239000008389 polyethoxylated castor oil Substances 0.000 description 2
229920000573 polyethylene Polymers 0.000 description 2
230000001242 postsynaptic effect Effects 0.000 description 2
230000035935 pregnancy Effects 0.000 description 2
238000003825 pressing Methods 0.000 description 2
102000003998 progesterone receptors Human genes 0.000 description 2
108090000468 progesterone receptors Proteins 0.000 description 2
BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
229920006395 saturated elastomer Polymers 0.000 description 2
230000036280 sedation Effects 0.000 description 2
229910052708 sodium Inorganic materials 0.000 description 2
239000001632 sodium acetate Substances 0.000 description 2
235000017281 sodium acetate Nutrition 0.000 description 2
URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 2
239000001488 sodium phosphate Substances 0.000 description 2
239000011550 stock solution Substances 0.000 description 2
UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
238000007920 subcutaneous administration Methods 0.000 description 2
239000005720 sucrose Substances 0.000 description 2
238000010189 synthetic method Methods 0.000 description 2
OSBSFAARYOCBHB-UHFFFAOYSA-N tetrapropylammonium Chemical compound CCC[N+](CCC)(CCC)CCC OSBSFAARYOCBHB-UHFFFAOYSA-N 0.000 description 2
230000001256 tonic effect Effects 0.000 description 2
PYOKUURKVVELLB-UHFFFAOYSA-N trimethyl orthoformate Chemical compound COC(OC)OC PYOKUURKVVELLB-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
210000004291 uterus Anatomy 0.000 description 2
229940072690 valium Drugs 0.000 description 2
238000010626 work up procedure Methods 0.000 description 2
229910009112 xH2O Inorganic materials 0.000 description 2
VOTJVLLIYSMTJZ-JIWXIQHESA-N (3r,5s,8r,9s,10s,13s,14s)-10,13-dimethyl-17-methylidene-1,2,3,4,5,6,7,8,9,11,12,14,15,16-tetradecahydrocyclopenta[a]phenanthren-3-ol Chemical compound C1[C@H](O)CC[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=C)[C@@H]4[C@@H]3CC[C@H]21 VOTJVLLIYSMTJZ-JIWXIQHESA-N 0.000 description 1
YXUSFCXFYLGFOR-UOUDCZANSA-N (3r,5s,8r,9s,10s,13s,14s,17s)-17-(2-hydroxypropan-2-yl)-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-3-ol 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(C)(O)C)[C@@]2(C)CC1 YXUSFCXFYLGFOR-UOUDCZANSA-N 0.000 description 1
UWTUEMKLYAGTNQ-UPHRSURJSA-N (z)-1,2-dibromoethene Chemical compound Br\C=C/Br UWTUEMKLYAGTNQ-UPHRSURJSA-N 0.000 description 1
BCVYKUKJDBUDKS-BIBIXIOVSA-N 1-[(5S,8R,9S,10S,13S,14S,17S)-10,13-dimethylspiro[1,2,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydrocyclopenta[a]phenanthrene-3,2'-1,3-dioxolane]-17-yl]ethanone Chemical compound C1COC2(C[C@@H]3CC[C@H]4[C@@H]5CC[C@H](C(C)=O)[C@]5(CC[C@@H]4[C@]3(CC2)C)C)O1 BCVYKUKJDBUDKS-BIBIXIOVSA-N 0.000 description 1
HXXNSZGESRDYFE-VDBGNAEESA-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-hydroxyethanone Chemical compound C1CCC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)C(=O)CO)[C@@H]4[C@@H]3CC[C@H]21 HXXNSZGESRDYFE-VDBGNAEESA-N 0.000 description 1
238000004293 19F NMR spectroscopy Methods 0.000 description 1
CTPDSKVQLSDPLC-UHFFFAOYSA-N 2-(oxolan-2-ylmethoxy)ethanol Chemical compound OCCOCC1CCCO1 CTPDSKVQLSDPLC-UHFFFAOYSA-N 0.000 description 1
MFYSUUPKMDJYPF-UHFFFAOYSA-N 2-[(4-methyl-2-nitrophenyl)diazenyl]-3-oxo-n-phenylbutanamide Chemical compound C=1C=CC=CC=1NC(=O)C(C(=O)C)N=NC1=CC=C(C)C=C1[N+]([O-])=O MFYSUUPKMDJYPF-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
JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-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
UXFIKVWAAMKFQE-UHFFFAOYSA-N 5-chloropent-1-yne Chemical compound ClCCCC#C UXFIKVWAAMKFQE-UHFFFAOYSA-N 0.000 description 1
QGXBDMJGAMFCBF-HLUDHZFRSA-N 5α-Androsterone Chemical compound C1[C@H](O)CC[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CC[C@H]21 QGXBDMJGAMFCBF-HLUDHZFRSA-N 0.000 description 1
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 1
229920001817 Agar Polymers 0.000 description 1
GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 description 1
UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
108091006146 Channels Proteins 0.000 description 1
108010062745 Chloride Channels Proteins 0.000 description 1
102000011045 Chloride Channels Human genes 0.000 description 1
206010053398 Clonic convulsion Diseases 0.000 description 1
206010010071 Coma Diseases 0.000 description 1
206010012373 Depressed level of consciousness Diseases 0.000 description 1
QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical compound [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 description 1
VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
239000005977 Ethylene Substances 0.000 description 1
KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 1
102000004300 GABA-A Receptors Human genes 0.000 description 1
108090000839 GABA-A Receptors Proteins 0.000 description 1
239000007995 HEPES buffer Substances 0.000 description 1
229910004373 HOAc Inorganic materials 0.000 description 1
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
206010022998 Irritability Diseases 0.000 description 1
229930194542 Keto Natural products 0.000 description 1
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
240000007472 Leucaena leucocephala Species 0.000 description 1
235000010643 Leucaena leucocephala Nutrition 0.000 description 1
239000012359 Methanesulfonyl chloride Substances 0.000 description 1
VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 description 1
208000019695 Migraine disease Diseases 0.000 description 1
206010027603 Migraine headaches Diseases 0.000 description 1
241000699666 Mus <mouse, genus> Species 0.000 description 1
206010049816 Muscle tightness Diseases 0.000 description 1
208000002033 Myoclonus Diseases 0.000 description 1
LFTLOKWAGJYHHR-UHFFFAOYSA-N N-methylmorpholine N-oxide Chemical compound CN1(=O)CCOCC1 LFTLOKWAGJYHHR-UHFFFAOYSA-N 0.000 description 1
208000005736 Nervous System Malformations Diseases 0.000 description 1
102000019315 Nicotinic acetylcholine receptors Human genes 0.000 description 1
108050006807 Nicotinic acetylcholine receptors Proteins 0.000 description 1
GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
229910019142 PO4 Inorganic materials 0.000 description 1
235000019483 Peanut oil Nutrition 0.000 description 1
229930182555 Penicillin Natural products 0.000 description 1
JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
206010034759 Petit mal epilepsy Diseases 0.000 description 1
CXOFVDLJLONNDW-UHFFFAOYSA-N Phenytoin Chemical compound N1C(=O)NC(=O)C1(C=1C=CC=CC=1)C1=CC=CC=C1 CXOFVDLJLONNDW-UHFFFAOYSA-N 0.000 description 1
229920005372 Plexiglas® Polymers 0.000 description 1
208000028017 Psychotic disease Diseases 0.000 description 1
230000010799 Receptor Interactions Effects 0.000 description 1
235000021355 Stearic acid Nutrition 0.000 description 1
208000013200 Stress disease Diseases 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
241000269368 Xenopus laevis Species 0.000 description 1
208000003554 absence epilepsy Diseases 0.000 description 1
150000008065 acid anhydrides Chemical class 0.000 description 1
230000002378 acidificating effect Effects 0.000 description 1
230000010933 acylation Effects 0.000 description 1
238000005917 acylation reaction Methods 0.000 description 1
239000008272 agar Substances 0.000 description 1
235000010419 agar Nutrition 0.000 description 1
229960003305 alfaxalone Drugs 0.000 description 1
125000001931 aliphatic group Chemical group 0.000 description 1
125000004183 alkoxy alkyl group Chemical group 0.000 description 1
125000004849 alkoxymethyl group Chemical group 0.000 description 1
150000001371 alpha-amino acids Chemical class 0.000 description 1
235000008206 alpha-amino acids Nutrition 0.000 description 1
VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 1
150000001412 amines Chemical class 0.000 description 1
239000003708 ampul Substances 0.000 description 1
238000004458 analytical method Methods 0.000 description 1
150000001441 androstanes Chemical class 0.000 description 1
150000008064 anhydrides Chemical class 0.000 description 1
150000001450 anions Chemical class 0.000 description 1
239000005557 antagonist Substances 0.000 description 1
230000001430 anti-depressive effect Effects 0.000 description 1
230000002243 anti-metrazol Effects 0.000 description 1
229940005513 antidepressants Drugs 0.000 description 1
238000013459 approach Methods 0.000 description 1
125000004104 aryloxy group Chemical group 0.000 description 1
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
210000003050 axon Anatomy 0.000 description 1
125000005335 azido alkyl group Chemical group 0.000 description 1
230000008901 benefit Effects 0.000 description 1
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
150000005347 biaryls Chemical group 0.000 description 1
230000033228 biological regulation Effects 0.000 description 1
230000015572 biosynthetic process Effects 0.000 description 1
230000037396 body weight Effects 0.000 description 1
UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 1
229910010277 boron hydride Inorganic materials 0.000 description 1
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
125000001246 bromo group Chemical group Br* 0.000 description 1
239000000872 buffer Substances 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
239000001110 calcium chloride Substances 0.000 description 1
229910001628 calcium chloride Inorganic materials 0.000 description 1
OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 1
239000002775 capsule Substances 0.000 description 1
125000002837 carbocyclic group Chemical group 0.000 description 1
RBHJBMIOOPYDBQ-UHFFFAOYSA-N carbon dioxide;propan-2-one Chemical compound O=C=O.CC(C)=O RBHJBMIOOPYDBQ-UHFFFAOYSA-N 0.000 description 1
150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
239000001913 cellulose Substances 0.000 description 1
229920002678 cellulose Polymers 0.000 description 1
208000015114 central nervous system disease Diseases 0.000 description 1
238000005119 centrifugation Methods 0.000 description 1
210000003710 cerebral cortex Anatomy 0.000 description 1
230000008859 change Effects 0.000 description 1
238000012512 characterization method Methods 0.000 description 1
150000005829 chemical entities Chemical class 0.000 description 1
238000001311 chemical methods and process Methods 0.000 description 1
239000003638 chemical reducing agent Substances 0.000 description 1
239000003795 chemical substances by application Substances 0.000 description 1
230000002566 clonic effect Effects 0.000 description 1
229940110456 cocoa butter Drugs 0.000 description 1
235000019868 cocoa butter Nutrition 0.000 description 1
230000001276 controlling effect Effects 0.000 description 1
238000007796 conventional method Methods 0.000 description 1
238000002425 crystallisation Methods 0.000 description 1
230000008025 crystallization Effects 0.000 description 1
125000004966 cyanoalkyl group Chemical group 0.000 description 1
125000000753 cycloalkyl group Chemical group 0.000 description 1
229940097362 cyclodextrins Drugs 0.000 description 1
210000000172 cytosol Anatomy 0.000 description 1
238000001514 detection method Methods 0.000 description 1
238000011161 development Methods 0.000 description 1
229960003529 diazepam Drugs 0.000 description 1
235000005911 diet Nutrition 0.000 description 1
230000037213 diet Effects 0.000 description 1
FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 1
230000029087 digestion Effects 0.000 description 1
229940043279 diisopropylamine Drugs 0.000 description 1
238000007865 diluting Methods 0.000 description 1
150000002009 diols Chemical class 0.000 description 1
238000010494 dissociation reaction Methods 0.000 description 1
230000005593 dissociations Effects 0.000 description 1
230000001490 effect on brain Effects 0.000 description 1
230000002500 effect on skin Effects 0.000 description 1
239000000839 emulsion Substances 0.000 description 1
230000002255 enzymatic effect Effects 0.000 description 1
230000001076 estrogenic effect Effects 0.000 description 1
230000012173 estrus Effects 0.000 description 1
FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 1
JHYNXXDQQHTCHJ-UHFFFAOYSA-M ethyl(triphenyl)phosphanium;bromide Chemical compound [Br-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(CC)C1=CC=CC=C1 JHYNXXDQQHTCHJ-UHFFFAOYSA-M 0.000 description 1
238000011156 evaluation Methods 0.000 description 1
230000000763 evoking effect Effects 0.000 description 1
230000021824 exploration behavior Effects 0.000 description 1
238000000605 extraction Methods 0.000 description 1
239000000706 filtrate Substances 0.000 description 1
CTIKAHQFRQTTAY-UHFFFAOYSA-N fluoro(trimethyl)silane Chemical compound C[Si](C)(C)F CTIKAHQFRQTTAY-UHFFFAOYSA-N 0.000 description 1
210000003194 forelimb Anatomy 0.000 description 1
238000004817 gas chromatography Methods 0.000 description 1
238000002290 gas chromatography-mass spectrometry Methods 0.000 description 1
238000007429 general method Methods 0.000 description 1
239000003365 glass fiber Substances 0.000 description 1
YQEMORVAKMFKLG-UHFFFAOYSA-N glycerine monostearate Natural products CCCCCCCCCCCCCCCCCC(=O)OC(CO)CO YQEMORVAKMFKLG-UHFFFAOYSA-N 0.000 description 1
UHUSDOQQWJGJQS-UHFFFAOYSA-N glycerol 1,2-dioctadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(CO)OC(=O)CCCCCCCCCCCCCCCCC UHUSDOQQWJGJQS-UHFFFAOYSA-N 0.000 description 1
SVUQHVRAGMNPLW-UHFFFAOYSA-N glycerol monostearate Natural products CCCCCCCCCCCCCCCCC(=O)OCC(O)CO SVUQHVRAGMNPLW-UHFFFAOYSA-N 0.000 description 1
244000144993 groups of animals Species 0.000 description 1
150000004820 halides Chemical class 0.000 description 1
125000004994 halo alkoxy alkyl group Chemical group 0.000 description 1
125000001188 haloalkyl group Chemical group 0.000 description 1
229910052736 halogen Inorganic materials 0.000 description 1
150000002367 halogens Chemical class 0.000 description 1
125000004970 halomethyl group Chemical group 0.000 description 1
YVXHZKKCZYLQOP-UHFFFAOYSA-N hept-1-yne Chemical compound CCCCCC#C YVXHZKKCZYLQOP-UHFFFAOYSA-N 0.000 description 1
125000005842 heteroatom Chemical group 0.000 description 1
KDCIHNCMPUBDKT-UHFFFAOYSA-N hexane;propan-2-one Chemical compound CC(C)=O.CCCCCC KDCIHNCMPUBDKT-UHFFFAOYSA-N 0.000 description 1
230000003284 homeostatic effect Effects 0.000 description 1
229940088597 hormone Drugs 0.000 description 1
239000005556 hormone Substances 0.000 description 1
108091008039 hormone receptors Proteins 0.000 description 1
150000004678 hydrides Chemical class 0.000 description 1
150000002430 hydrocarbons Chemical group 0.000 description 1
230000007062 hydrolysis Effects 0.000 description 1
238000006460 hydrolysis reaction Methods 0.000 description 1
239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
230000002102 hyperpolarization Effects 0.000 description 1
125000001841 imino group Chemical group [H]N=* 0.000 description 1
238000011065 in-situ storage Methods 0.000 description 1
229910052816 inorganic phosphate Inorganic materials 0.000 description 1
230000003834 intracellular effect Effects 0.000 description 1
238000007918 intramuscular administration Methods 0.000 description 1
239000008101 lactose Substances 0.000 description 1
JEHCHYAKAXDFKV-UHFFFAOYSA-J lead tetraacetate Chemical compound CC(=O)O[Pb](OC(C)=O)(OC(C)=O)OC(C)=O JEHCHYAKAXDFKV-UHFFFAOYSA-J 0.000 description 1
239000002502 liposome Substances 0.000 description 1
238000004811 liquid chromatography Methods 0.000 description 1
239000008297 liquid dosage form Substances 0.000 description 1
239000006194 liquid suspension Substances 0.000 description 1
239000012280 lithium aluminium hydride Substances 0.000 description 1
ARNWQMJQALNBBV-UHFFFAOYSA-N lithium carbide Chemical compound [Li+].[Li+].[C-]#[C-] ARNWQMJQALNBBV-UHFFFAOYSA-N 0.000 description 1
239000007937 lozenge Substances 0.000 description 1
235000019359 magnesium stearate Nutrition 0.000 description 1
235000019341 magnesium sulphate Nutrition 0.000 description 1
VXWPONVCMVLXBW-UHFFFAOYSA-M magnesium;carbanide;iodide Chemical compound [CH3-].[Mg+2].[I-] VXWPONVCMVLXBW-UHFFFAOYSA-M 0.000 description 1
DQEUYIQDSMINEY-UHFFFAOYSA-M magnesium;prop-1-ene;bromide Chemical compound [Mg+2].[Br-].[CH2-]C=C DQEUYIQDSMINEY-UHFFFAOYSA-M 0.000 description 1
239000003550 marker Substances 0.000 description 1
230000007246 mechanism Effects 0.000 description 1
230000028161 membrane depolarization Effects 0.000 description 1
150000002739 metals Chemical class 0.000 description 1
QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
239000003094 microcapsule Substances 0.000 description 1
239000004005 microsphere Substances 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
239000002395 mineralocorticoid Substances 0.000 description 1
238000002156 mixing Methods 0.000 description 1
230000036651 mood Effects 0.000 description 1
125000001624 naphthyl group Chemical group 0.000 description 1
239000007922 nasal spray Substances 0.000 description 1
229940097496 nasal spray Drugs 0.000 description 1
230000008587 neuronal excitability Effects 0.000 description 1
230000001962 neuropharmacologic effect Effects 0.000 description 1
102000027246 neurosteroid receptors Human genes 0.000 description 1
108091008567 neurosteroid receptors Proteins 0.000 description 1
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
229910052757 nitrogen Inorganic materials 0.000 description 1
231100000344 non-irritating Toxicity 0.000 description 1
230000009871 nonspecific binding Effects 0.000 description 1
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
239000004006 olive oil Substances 0.000 description 1
235000008390 olive oil Nutrition 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
150000002891 organic anions Chemical class 0.000 description 1
238000006053 organic reaction Methods 0.000 description 1
230000002611 ovarian Effects 0.000 description 1
KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 1
150000002923 oximes Chemical class 0.000 description 1
150000002924 oxiranes Chemical class 0.000 description 1
239000001301 oxygen Substances 0.000 description 1
239000000312 peanut oil Substances 0.000 description 1
239000001814 pectin Substances 0.000 description 1
235000010987 pectin Nutrition 0.000 description 1
229920001277 pectin Polymers 0.000 description 1
229940049954 penicillin Drugs 0.000 description 1
238000003359 percent control normalization Methods 0.000 description 1
230000010412 perfusion Effects 0.000 description 1
230000035699 permeability Effects 0.000 description 1
230000003285 pharmacodynamic effect Effects 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
229960002695 phenobarbital Drugs 0.000 description 1
DDBREPKUVSBGFI-UHFFFAOYSA-N phenobarbital Chemical compound C=1C=CC=CC=1C1(CC)C(=O)NC(=O)NC1=O DDBREPKUVSBGFI-UHFFFAOYSA-N 0.000 description 1
229960002036 phenytoin Drugs 0.000 description 1
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
239000010452 phosphate Substances 0.000 description 1
239000008363 phosphate buffer Substances 0.000 description 1
LFGREXWGYUGZLY-UHFFFAOYSA-N phosphoryl Chemical compound [P]=O LFGREXWGYUGZLY-UHFFFAOYSA-N 0.000 description 1
230000036470 plasma concentration Effects 0.000 description 1
229920001223 polyethylene glycol Polymers 0.000 description 1
229920000642 polymer Polymers 0.000 description 1
235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
229920000053 polysorbate 80 Polymers 0.000 description 1
LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
239000000843 powder Substances 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
230000003518 presynaptic effect Effects 0.000 description 1
230000008569 process Effects 0.000 description 1
IBALRBWGSVJPAP-UHFFFAOYSA-N progabide Chemical compound C=1C(F)=CC=C(O)C=1C(=NCCCC(=O)N)C1=CC=C(Cl)C=C1 IBALRBWGSVJPAP-UHFFFAOYSA-N 0.000 description 1
239000000583 progesterone congener Substances 0.000 description 1
235000018102 proteins Nutrition 0.000 description 1
102000004169 proteins and genes Human genes 0.000 description 1
108090000623 proteins and genes Proteins 0.000 description 1
238000000746 purification Methods 0.000 description 1
238000011002 quantification Methods 0.000 description 1
239000000018 receptor agonist Substances 0.000 description 1
229940044601 receptor agonist Drugs 0.000 description 1
239000002464 receptor antagonist Substances 0.000 description 1
239000002469 receptor inverse agonist Substances 0.000 description 1
238000009877 rendering Methods 0.000 description 1
230000028527 righting reflex Effects 0.000 description 1
125000006413 ring segment Chemical group 0.000 description 1
238000009738 saturating Methods 0.000 description 1
238000000926 separation method Methods 0.000 description 1
230000035939 shock Effects 0.000 description 1
238000000526 short-path distillation Methods 0.000 description 1
239000000377 silicon dioxide Substances 0.000 description 1
230000007958 sleep Effects 0.000 description 1
IIZZSPOBOIMENB-UHFFFAOYSA-M sodium 2-[N-(3-carboxypropyl)-C-(4-chlorophenyl)carbonimidoyl]-4-fluorophenolate Chemical compound [Na+].ClC1=CC=C(C=C1)C(C1=C(C=CC(=C1)F)O)=NCCCC(=O)[O-] IIZZSPOBOIMENB-UHFFFAOYSA-M 0.000 description 1
WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
239000004299 sodium benzoate Substances 0.000 description 1
235000010234 sodium benzoate Nutrition 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
AEQFSUDEHCCHBT-UHFFFAOYSA-M sodium valproate Chemical compound [Na+].CCCC(C([O-])=O)CCC AEQFSUDEHCCHBT-UHFFFAOYSA-M 0.000 description 1
241000894007 species Species 0.000 description 1
230000009870 specific binding Effects 0.000 description 1
238000002798 spectrophotometry method Methods 0.000 description 1
238000001228 spectrum Methods 0.000 description 1
238000013222 sprague-dawley male rat Methods 0.000 description 1
238000012453 sprague-dawley rat model Methods 0.000 description 1
238000007619 statistical method Methods 0.000 description 1
208000005809 status epilepticus Diseases 0.000 description 1
239000008117 stearic acid Substances 0.000 description 1
239000003270 steroid hormone Substances 0.000 description 1
230000004936 stimulating effect Effects 0.000 description 1
230000000638 stimulation Effects 0.000 description 1
229960005322 streptomycin Drugs 0.000 description 1
230000035882 stress Effects 0.000 description 1
238000006467 substitution reaction Methods 0.000 description 1
239000001384 succinic acid Substances 0.000 description 1
BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
239000011593 sulfur Chemical group 0.000 description 1
229910052717 sulfur Chemical group 0.000 description 1
125000004434 sulfur atom Chemical group 0.000 description 1
239000006228 supernatant Substances 0.000 description 1
239000000829 suppository Substances 0.000 description 1
230000000946 synaptic effect Effects 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
229940037128 systemic glucocorticoids Drugs 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
235000012222 talc Nutrition 0.000 description 1
230000002123 temporal effect Effects 0.000 description 1
238000002560 therapeutic procedure Methods 0.000 description 1
150000003548 thiazolidines Chemical class 0.000 description 1
230000035922 thirst Effects 0.000 description 1
208000028500 tonic seizure Diseases 0.000 description 1
238000011200 topical administration Methods 0.000 description 1
230000032258 transport Effects 0.000 description 1
238000006692 trifluoromethylation reaction Methods 0.000 description 1
125000004385 trihaloalkyl group Chemical group 0.000 description 1
BPLKQGGAXWRFOE-UHFFFAOYSA-M trimethylsulfoxonium iodide Chemical compound [I-].C[S+](C)(C)=O BPLKQGGAXWRFOE-UHFFFAOYSA-M 0.000 description 1
XMQSELBBYSAURN-UHFFFAOYSA-M triphenyl(propyl)phosphanium;bromide Chemical compound [Br-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(CCC)C1=CC=CC=C1 XMQSELBBYSAURN-UHFFFAOYSA-M 0.000 description 1
238000001665 trituration Methods 0.000 description 1
125000004417 unsaturated alkyl group Chemical group 0.000 description 1
229930195735 unsaturated hydrocarbon Natural products 0.000 description 1
210000002700 urine Anatomy 0.000 description 1
229940102566 valproate Drugs 0.000 description 1
210000003462 vein Anatomy 0.000 description 1
229920002554 vinyl polymer Polymers 0.000 description 1
239000011345 viscous material Substances 0.000 description 1
238000005406 washing Methods 0.000 description 1
239000001993 wax Substances 0.000 description 1
239000002023 wood Substances 0.000 description 1

Classifications

- 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
- C07J41/005—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005 the 17-beta position being substituted by an uninterrupted chain of only two carbon atoms, e.g. pregnane derivatives
- 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
- A61P25/00—Drugs for disorders of the nervous system
- 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
- A61P25/08—Antiepileptics; Anticonvulsants
- 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
- A61P25/08—Antiepileptics; Anticonvulsants
- A61P25/12—Antiepileptics; Anticonvulsants for grand-mal
- 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
- A61P25/22—Anxiolytics
- 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
- A61P25/24—Antidepressants
- 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
- 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
- C07J7/002—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 not substituted in position 16
- 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
- C07J7/0065—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 an OH group free esterified or etherified
- C07J7/007—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 an OH group free esterified or etherified not substituted in position 17 alfa
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J9/00—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of more than two carbon atoms, e.g. cholane, cholestane, coprostane

Landscapes

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

APAP/P/1997/000998A 1994-11-23 1995-11-22 Androstane and pregnane series for allosteric modulations of gaba receptor. AP653A (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US34692694A	1994-11-23	1994-11-23
PCT/US1995/015210 WO1996016076A1 (en)	1994-11-23	1995-11-22	Androstane and pregnane series for allosteric modulation of gaba receptor

Publications (2)

Publication Number	Publication Date
AP9700998A0 AP9700998A0 (en)	1997-07-31
AP653A true AP653A (en)	1998-07-21

Family

ID=23361616

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
APAP/P/1997/000998A AP653A (en)	1994-11-23	1995-11-22	Androstane and pregnane series for allosteric modulations of gaba receptor.

Country Status (27)

Country	Link
EP (1)	EP0808325B1 (de)
JP (1)	JPH10509458A (de)
KR (1)	KR100394548B1 (de)
CN (1)	CN1171114A (de)
AP (1)	AP653A (de)
AT (1)	ATE198753T1 (de)
AU (1)	AU707486B2 (de)
BR (1)	BR9509764A (de)
CA (1)	CA2205919A1 (de)
CZ (1)	CZ292881B6 (de)
DE (1)	DE69519945T2 (de)
DK (1)	DK0808325T3 (de)
ES (1)	ES2155543T3 (de)
FI (1)	FI972202L (de)
GE (1)	GEP20002033B (de)
GR (1)	GR3035562T3 (de)
HU (1)	HUT77087A (de)
IL (1)	IL116108A (de)
IS (1)	IS4488A (de)
MX (1)	MX9703826A (de)
NO (1)	NO308950B1 (de)
NZ (1)	NZ298567A (de)
PL (1)	PL182898B1 (de)
PT (1)	PT808325E (de)
RU (1)	RU2176248C2 (de)
UA (1)	UA48154C2 (de)
WO (1)	WO1996016076A1 (de)

Families Citing this family (73)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5767117A (en) *	1994-11-18	1998-06-16	The General Hospital Corporation	Method for treating vascular headaches
US6780853B1 (en)	1995-06-06	2004-08-24	Euro-Celtique S.A.	Neuroactive steroids of the androstane and pregnane series
ATE284895T1 (de) *	1995-06-06	2005-01-15	Euro Celtique Sa	Neuroaktive steroide der androstan- und pregnanreihe
US20010051599A1 (en)	1997-05-02	2001-12-13	Michael Z. Kagan	Pregnan-3-ol-20-ones
CN1270718C (zh)	1998-03-11	2006-08-23	托布乔恩·贝克斯托罗姆	表别孕烷醇酮在制备治疗甾族化合物诱导的疾病的药物中的应用
US8771740B2 (en)	1999-12-20	2014-07-08	Nicholas J. Kerkhof	Process for producing nanoparticles by spray drying
WO2001045674A1 (en)	1999-12-20	2001-06-28	Cocensys, Inc.	Process for producing nanometer particles by fluid bed spray-drying
AR031473A1 (es) *	2000-11-20	2003-09-24	Lundbeck & Co As H	Intensificadores de gaba en el tratamiento de enfermedades relacionadas con una reducida actividad neuroesteroide
WO2006012563A2 (en) *	2004-07-23	2006-02-02	The Regents Of The University Of California	Method for the treatment and diagnosis of certain psychiatric disorders related to the menstrual cycle
RU2413516C2 (ru) *	2004-11-18	2011-03-10	Умекрин Аб	Гамк-стероидные антагонисты и их применение в лечении нарушений цнс
EP2258359A3 (de)	2005-08-26	2011-04-06	Braincells, Inc.	Neurogenese durch Modulation des Muscarinrezeptors mit Sabcomelin
WO2007025177A2 (en)	2005-08-26	2007-03-01	Braincells, Inc.	Neurogenesis by muscarinic receptor modulation
EP2377530A3 (de)	2005-10-21	2012-06-20	Braincells, Inc.	Modulation von Neurogenese durch PDE-Hemmung
EP1942879A1 (de)	2005-10-31	2008-07-16	Braincells, Inc.	Gaba-rezeptor-vermittelte modulation von neurogenese
US20100216734A1 (en)	2006-03-08	2010-08-26	Braincells, Inc.	Modulation of neurogenesis by nootropic agents
EP2021000A2 (de)	2006-05-09	2009-02-11	Braincells, Inc.	Neurogenese mittels angiotensin-modulation
IN2014DN02014A (de)	2006-11-21	2015-07-10	Umecrine Ab
CN103880909A (zh) *	2008-05-20	2014-06-25	梅克芳股份公司	甾族化合物
CN101585862B (zh) *	2008-05-20	2014-12-17	梅克芳股份公司	甾族化合物
CN103819525A (zh) *	2008-05-20	2014-05-28	梅克芳股份公司	甾族化合物
WO2010099217A1 (en)	2009-02-25	2010-09-02	Braincells, Inc.	Modulation of neurogenesis using d-cycloserine combinations
US8362286B2 (en) *	2009-08-13	2013-01-29	Marinus Pharmaceuticals, Inc.	Method for making 3α-hydroxy, 3β- substituted-5α-pregnan-20-ones
CA2786330C (en)	2010-01-14	2013-11-19	Umecrine Mood Ab	A pharmaceutical composition comprising 3-beta-hydroxy-5-alpha-pregnan-20-one with improved storage and solubility properties
WO2011120044A1 (en) *	2010-03-26	2011-09-29	Duke University	Conjugated neuroactive steroid compositions and methods of use
JP2014521662A (ja) *	2011-07-29	2014-08-28	ザリージェンツオブザユニバーシティオブカリフォルニア	ＧＡＢＡＡ受容体のモジュレーターとしての新規な１７β−ヘテロアリール置換ステロイド
RS64332B1 (sr) *	2011-09-08	2023-08-31	Sage Therapeutics Inc	Neuroaktivni steroidi, kompozicije i njihova upotreba
WO2013043985A1 (en)	2011-09-23	2013-03-28	The Regents Of The University Of California	Edible oils to enhance delivery of orally administered steroids
CN113234114A (zh) *	2011-10-14	2021-08-10	萨奇治疗股份有限公司	3,3-二取代的19-去甲孕甾烷化合物、组合物、及其用途
CA2862076C (en)	2012-01-23	2020-04-21	Sage Therapeutics, Inc.	Neuroactive steroid formulations and methods of treating cns disorders
WO2014031792A2 (en)	2012-08-21	2014-02-27	Sage Therapeutics	Methods of treating epilepsy or tatus epilepticus
DK2925327T3 (da)	2012-11-30	2024-03-25	Univ California	Allopregnanolon til behandling, reduktion eller lindring af symptomer på fødselsdepression
DK3461834T3 (da)	2013-03-13	2021-08-23	Sage Therapeutics Inc	Neuroaktive steroider
ES2807264T3 (es) *	2013-04-17	2021-02-22	Sage Therapeutics Inc	Esteroides neuroactivos 19-nor para métodos de tratamiento
HRP20190232T1 (hr)	2013-04-17	2019-03-22	Sage Therapeutics, Inc.	19-nor c3,3-disupstituirani c21-n-pirazolil steroidi i postupci za njihovu upotrebu
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
WO2014169836A1 (en)	2013-04-17	2014-10-23	Sage Therapeutics, Inc.	19-nor neuroactive steroids and methods of use thereof
EP3868382A1 (de) *	2013-07-19	2021-08-25	Sage Therapeutics, Inc.	Neuroaktive steroide, zusammensetzungen und verwendungen davon
SI3488852T1 (sl)	2013-08-23	2021-07-30	Sage Therapeutics, Inc.	Nevroaktivni steroidi, sestavki in uporabe le-teh
US10246482B2 (en)	2014-06-18	2019-04-02	Sage Therapeutics, Inc.	Neuroactive steroids, compositions, and uses thereof
WO2015195967A1 (en)	2014-06-18	2015-12-23	Sage Therapeutics, Inc.	Oxysterols and methods of use thereof
EP3188734A4 (de)	2014-09-02	2018-01-10	The Texas A&M University System	Verfahren zur behandlung einer organophosphatvergiftung
JOP20200195A1 (ar)	2014-09-08	2017-06-16	Sage Therapeutics Inc	سترويدات وتركيبات نشطة عصبياً، واستخداماتها
PT3206493T (pt)	2014-10-16	2020-08-03	Sage Therapeutics Inc	Composições e métodos para tratamento de transtornos do snc
SG11201703073UA (en)	2014-10-16	2017-05-30	Sage Therapeutics Inc	Compositions and methods for treating cns disorders
US10774108B2 (en)	2014-11-27	2020-09-15	Sage Therapeutics, Inc.	Compositions and methods for treating CNS disorders
ES2857082T3 (es)	2015-01-26	2021-09-28	Sage Therapeutics Inc	Composiciones y métodos para el tratamiento de trastornos del SNC
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
MD3319612T2 (ro)	2015-07-06	2021-10-31	Sage Therapeutics Inc	Oxisteroli și metode de utilizare a acestora
KR102703602B1 (ko)	2015-07-06	2024-09-06	세이지 테라퓨틱스, 인크.	옥시스테롤 및 그의 사용 방법
HK1258616A1 (zh)	2016-03-08	2019-11-15	Sage Therapeutics, Inc.	神经活性类固醇、组合物、及其用途
HRP20220716T1 (hr)	2016-04-01	2022-09-02	Sage Therapeutics, Inc.	Oksisteroli i postupci za njihovu uporabu
WO2017193046A1 (en)	2016-05-06	2017-11-09	Sage Therapeutics, Inc.	Oxysterols and methods of use thereof
IL264129B2 (en)	2016-07-11	2024-05-01	Sage Therapeutics Inc	C17, c20, and c21 substituted neuroactive steroids and their methods of use
EP3481844B1 (de)	2016-07-11	2024-04-17	Sage Therapeutics, Inc.	C12-substituierte neuroaktive steroide und deren verfahren zur verwendung
PT3519422T (pt)	2016-09-30	2022-12-05	Sage Therapeutics Inc	Oxisteróis substituídos em c7 e métodos como moduladores nmda
KR20250054838A (ko)	2016-10-18	2025-04-23	세이지 테라퓨틱스, 인크.	옥시스테롤 및 그의 사용 방법
KR102583278B1 (ko)	2016-10-18	2023-09-27	세이지 테라퓨틱스, 인크.	옥시스테롤 및 그의 사용 방법
EP3632900A4 (de) *	2017-06-01	2021-03-24	Sumitomo Chemical Company Limited	Heterocyclische verbindung und zusammensetzung damit
JP7538040B2 (ja) *	2018-01-12	2024-08-21	セージセラピューティクス，インコーポレイテッド	ＣＮＳ障害の処置における使用のためのアザ、オキサ、およびチア－プレグナン－２０－オン－３α－オール化合物
US11542296B2 (en)	2018-04-23	2023-01-03	The Texas A&M University System	Neurosteroid compounds and methods for their preparation and use in treating central nervous system disorders
ES2966055T3 (es)	2018-10-12	2024-04-18	Sage Therapeutics Inc	Esteroides neuroactivos sustituidos en la posición 10 con un grupo cíclico para su uso en el tratamiento de trastornos del SNC
TW202521129A (zh)	2018-12-05	2025-06-01	美商賽吉醫療公司	神經活性類固醇及其使用方法
GB201820887D0 (en) *	2018-12-20	2019-02-06	Nzp Uk Ltd	Compounds
CN121652218A (zh) *	2019-01-08	2026-03-13	成都康弘药业集团股份有限公司	甾体类化合物、用途及其制备方法
AR119047A1 (es)	2019-05-31	2021-11-17	Sage Therapeutics Inc	Esteroides neuroactivos como moduladores de gabaa y su uso en el tratamiento de trastornos del snc
KR20220038680A (ko)	2019-06-27	2022-03-29	세이지 테라퓨틱스, 인크.	Cns 장애를 치료하기 위한 조성물 및 방법
CA3143545A1 (en) *	2019-06-27	2020-12-30	Sage Therapeutics, Inc.	Compounds for treating cns disorders
WO2021174205A1 (en) *	2020-02-27	2021-09-02	Brii Biosciences, Inc.	Prodrugs of neuroactive steroids
AU2021238346A1 (en) *	2020-03-18	2022-09-29	Sage Therapeutics, Inc.	Neuroactive steroids and their methods of use
CA3229865A1 (en) *	2021-08-20	2023-02-23	The University Of Mississippi	Allopregnanolone analogues for hiv viremia and neurotoxicity protection
WO2023060067A1 (en)	2021-10-04	2023-04-13	Marinus Pharmaceuticals, Inc.	Amorphous solid dispersion ganaxolone formulation
CN115974950A (zh) *	2022-12-23	2023-04-18	上海彩迩文生化科技有限公司	一种3-烷基化的甾体中间体及其制备和应用
CN117801047B (zh) *	2023-01-19	2024-12-20	北京华睿鼎信科技有限公司	神经甾体衍生物及其用途

Citations (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5120723A (en) *	1987-08-25	1992-06-09	University Of Southern California	Method, compositions, and compounds for modulating brain excitability
US5232917A (en) *	1987-08-25	1993-08-03	University Of Southern California	Methods, compositions, and compounds for allosteric modulation of the GABA receptor by members of the androstane and pregnane series

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US3953429A (en) *	1970-12-17	1976-04-27	Glaxo Laboratories Limited	Anaesthetic steroids of the androstance and pregnane series
JPH06510999A (ja) *	1991-09-13	1994-12-08	コセンシス・インコーポレイテッド	ステロイド結合部位を有する新規ＧＡＢＡ↓ａレセプター
US5371077A (en) *	1992-08-03	1994-12-06	William Marsh Rice University	Side chain derivatized 15-oxygenated sterols, methods of using them and a process for preparing them
AU698834B2 (en) *	1993-05-24	1998-11-12	Purdue Pharma Ltd.	Methods and compositions for inducing sleep

1995
- 1995-11-22 CN CN95197071A patent/CN1171114A/zh active Pending
- 1995-11-22 FI FI972202A patent/FI972202L/fi not_active IP Right Cessation
- 1995-11-22 CA CA002205919A patent/CA2205919A1/en not_active Abandoned
- 1995-11-22 DK DK95942879T patent/DK0808325T3/da active
- 1995-11-22 HU HU9701972A patent/HUT77087A/hu not_active Application Discontinuation
- 1995-11-22 EP EP95942879A patent/EP0808325B1/de not_active Expired - Lifetime
- 1995-11-22 RU RU97110790/04A patent/RU2176248C2/ru active
- 1995-11-22 AP APAP/P/1997/000998A patent/AP653A/en active
- 1995-11-22 PT PT95942879T patent/PT808325E/pt unknown
- 1995-11-22 KR KR1019970703470A patent/KR100394548B1/ko not_active Expired - Fee Related
- 1995-11-22 UA UA97063025A patent/UA48154C2/uk unknown
- 1995-11-22 MX MX9703826A patent/MX9703826A/es not_active IP Right Cessation
- 1995-11-22 WO PCT/US1995/015210 patent/WO1996016076A1/en not_active Ceased
- 1995-11-22 BR BR9509764A patent/BR9509764A/pt not_active Application Discontinuation
- 1995-11-22 AU AU44085/96A patent/AU707486B2/en not_active Ceased
- 1995-11-22 PL PL95320416A patent/PL182898B1/pl not_active IP Right Cessation
- 1995-11-22 JP JP8517059A patent/JPH10509458A/ja not_active Ceased
- 1995-11-22 DE DE69519945T patent/DE69519945T2/de not_active Expired - Fee Related
- 1995-11-22 NZ NZ298567A patent/NZ298567A/xx unknown
- 1995-11-22 CZ CZ19971553A patent/CZ292881B6/cs not_active IP Right Cessation
- 1995-11-22 GE GEAP19953794A patent/GEP20002033B/en unknown
- 1995-11-22 AT AT95942879T patent/ATE198753T1/de not_active IP Right Cessation
- 1995-11-22 ES ES95942879T patent/ES2155543T3/es not_active Expired - Lifetime
- 1995-11-23 IL IL11610895A patent/IL116108A/en not_active IP Right Cessation
1997
- 1997-05-21 NO NO972320A patent/NO308950B1/no unknown
- 1997-05-23 IS IS4488A patent/IS4488A/is unknown
2001
- 2001-03-13 GR GR20010400408T patent/GR3035562T3/el not_active IP Right Cessation

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5120723A (en) *	1987-08-25	1992-06-09	University Of Southern California	Method, compositions, and compounds for modulating brain excitability
US5232917A (en) *	1987-08-25	1993-08-03	University Of Southern California	Methods, compositions, and compounds for allosteric modulation of the GABA receptor by members of the androstane and pregnane series

Also Published As

Publication number	Publication date
CZ155397A3 (cs)	1998-03-18
KR100394548B1 (ko)	2004-02-05
JPH10509458A (ja)	1998-09-14
EP0808325A1 (de)	1997-11-26
BR9509764A (pt)	1998-07-07
DE69519945D1 (de)	2001-02-22
CN1171114A (zh)	1998-01-21
ATE198753T1 (de)	2001-02-15
PL182898B1 (pl)	2002-03-29
RU2176248C2 (ru)	2001-11-27
GR3035562T3 (en)	2001-06-29
ES2155543T3 (es)	2001-05-16
AU4408596A (en)	1996-06-17
NO972320D0 (no)	1997-05-21
IL116108A (en)	2002-08-14
MX9703826A (es)	1998-02-28
EP0808325A4 (de)	1997-12-17
IL116108A0 (en)	1996-01-31
NO308950B1 (no)	2000-11-20
AU707486B2 (en)	1999-07-08
UA48154C2 (uk)	2002-08-15
CA2205919A1 (en)	1996-05-30
DE69519945T2 (de)	2001-06-07
FI972202A7 (fi)	1997-07-17
CZ292881B6 (cs)	2003-12-17
EP0808325B1 (de)	2001-01-17
DK0808325T3 (da)	2001-01-29
PT808325E (pt)	2001-06-29
NO972320L (no)	1997-07-23
FI972202L (fi)	1997-07-17
GEP20002033B (en)	2000-04-10
NZ298567A (en)	2000-01-28
PL320416A1 (en)	1997-09-29
AP9700998A0 (en)	1997-07-31
FI972202A0 (fi)	1997-05-23
HUT77087A (hu)	1998-03-02
WO1996016076A1 (en)	1996-05-30
IS4488A (is)	1997-05-23

Publication	Publication Date	Title
AP653A (en)	1998-07-21	Androstane and pregnane series for allosteric modulations of gaba receptor.
US6143736A (en)	2000-11-07	Methods, compositions, and compounds for allosteric modulation of the GABA receptor by members of the androstane and pregnane series
EP1038880B1 (de)	2007-10-17	Androstane und Pregane zur allosterischen Modulation des GABA Rezeptors
CA2093808C (en)	2008-01-29	Methods, compositions, and compounds for allosteric modulation of the gaba receptor by members of the androstane and pregnane series
EP0837874B1 (de)	2004-12-15	Neuroaktive steroide der androstan- und pregnanreihe
US5120723A (en)	1992-06-09	Method, compositions, and compounds for modulating brain excitability
US5208227A (en)	1993-05-04	Method, compositions, and compounds for modulating brain excitability
US6780853B1 (en)	2004-08-24	Neuroactive steroids of the androstane and pregnane series
HK1014665B (en)	2001-07-20	Androstanes and pregnanes for allosteric modulation of gaba receptor
HK1005986B (en)	2001-08-10	Gaba receptor modulators
HK1055594A (en)	2004-01-16	Neuroactive 3.alpha.-hydroxy-steroids of the androstane and pregnane series