CN102482318B - 异噁唑烷衍生物 - Google Patents
异噁唑烷衍生物 Download PDFInfo
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- CN102482318B CN102482318B CN201080040085.6A CN201080040085A CN102482318B CN 102482318 B CN102482318 B CN 102482318B CN 201080040085 A CN201080040085 A CN 201080040085A CN 102482318 B CN102482318 B CN 102482318B
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- DRMJRHUMYBYDIX-UHFFFAOYSA-N n-[4-[5-(4-fluorophenyl)-3-methyl-2-methylsulfinylimidazol-4-yl]pyridin-2-yl]acetamide Chemical compound C1=NC(NC(=O)C)=CC(C=2N(C(=NC=2C=2C=CC(F)=CC=2)S(C)=O)C)=C1 DRMJRHUMYBYDIX-UHFFFAOYSA-N 0.000 description 1
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- KCEHVJZZIGJAAW-FERBBOLQSA-N olodaterol hydrochloride Chemical compound Cl.C1=CC(OC)=CC=C1CC(C)(C)NC[C@H](O)C1=CC(O)=CC2=C1OCC(=O)N2 KCEHVJZZIGJAAW-FERBBOLQSA-N 0.000 description 1
- 238000005580 one pot reaction Methods 0.000 description 1
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- 125000005981 pentynyl group Chemical group 0.000 description 1
- 239000012466 permeate Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- KFDKNTQGTAEZGC-UHFFFAOYSA-N phenanthrene-1-carboxylic acid Chemical compound C1=CC2=CC=CC=C2C2=C1C(C(=O)O)=CC=C2 KFDKNTQGTAEZGC-UHFFFAOYSA-N 0.000 description 1
- 229960003531 phenolsulfonphthalein Drugs 0.000 description 1
- 125000004344 phenylpropyl group Chemical group 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 239000003757 phosphotransferase inhibitor Substances 0.000 description 1
- 150000003053 piperidines Chemical class 0.000 description 1
- ISWRGOKTTBVCFA-UHFFFAOYSA-N pirfenidone Chemical compound C1=C(C)C=CC(=O)N1C1=CC=CC=C1 ISWRGOKTTBVCFA-UHFFFAOYSA-N 0.000 description 1
- 229960003073 pirfenidone Drugs 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 230000023603 positive regulation of transcription initiation, DNA-dependent Effects 0.000 description 1
- NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 description 1
- 229960004583 pranlukast Drugs 0.000 description 1
- UAJUXJSXCLUTNU-UHFFFAOYSA-N pranlukast Chemical compound C=1C=C(OCCCCC=2C=CC=CC=2)C=CC=1C(=O)NC(C=1)=CC=C(C(C=2)=O)C=1OC=2C=1N=NNN=1 UAJUXJSXCLUTNU-UHFFFAOYSA-N 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 229960002288 procaterol Drugs 0.000 description 1
- FKNXQNWAXFXVNW-BLLLJJGKSA-N procaterol Chemical compound N1C(=O)C=CC2=C1C(O)=CC=C2[C@@H](O)[C@@H](NC(C)C)CC FKNXQNWAXFXVNW-BLLLJJGKSA-N 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- CPNGPNLZQNNVQM-UHFFFAOYSA-N pteridine Chemical compound N1=CN=CC2=NC=CN=C21 CPNGPNLZQNNVQM-UHFFFAOYSA-N 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- KOUKXHPPRFNWPP-UHFFFAOYSA-N pyrazine-2,5-dicarboxylic acid;hydrate Chemical compound O.OC(=O)C1=CN=C(C(O)=O)C=N1 KOUKXHPPRFNWPP-UHFFFAOYSA-N 0.000 description 1
- 150000003217 pyrazoles Chemical class 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 150000003233 pyrroles Chemical class 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 229960002720 reproterol Drugs 0.000 description 1
- WVLAAKXASPCBGT-UHFFFAOYSA-N reproterol Chemical compound C1=2C(=O)N(C)C(=O)N(C)C=2N=CN1CCCNCC(O)C1=CC(O)=CC(O)=C1 WVLAAKXASPCBGT-UHFFFAOYSA-N 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
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- 206010039083 rhinitis Diseases 0.000 description 1
- 230000000630 rising effect Effects 0.000 description 1
- MNDBXUUTURYVHR-UHFFFAOYSA-N roflumilast Chemical compound FC(F)OC1=CC=C(C(=O)NC=2C(=CN=CC=2Cl)Cl)C=C1OCC1CC1 MNDBXUUTURYVHR-UHFFFAOYSA-N 0.000 description 1
- 229960002586 roflumilast Drugs 0.000 description 1
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- 229950011005 semapimod Drugs 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 208000017520 skin disease Diseases 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 235000009518 sodium iodide Nutrition 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- GNBVPFITFYNRCN-UHFFFAOYSA-M sodium thioglycolate Chemical compound [Na+].[O-]C(=O)CS GNBVPFITFYNRCN-UHFFFAOYSA-M 0.000 description 1
- 229940046307 sodium thioglycolate Drugs 0.000 description 1
- PODWXQQNRWNDGD-UHFFFAOYSA-L sodium thiosulfate pentahydrate Chemical compound O.O.O.O.O.[Na+].[Na+].[O-]S([S-])(=O)=O PODWXQQNRWNDGD-UHFFFAOYSA-L 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000013222 sprague-dawley male rat Methods 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000001384 succinic acid Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- ZMELOYOKMZBMRB-DLBZAZTESA-N talmapimod Chemical compound C([C@@H](C)N(C[C@@H]1C)C(=O)C=2C(=CC=3N(C)C=C(C=3C=2)C(=O)C(=O)N(C)C)Cl)N1CC1=CC=C(F)C=C1 ZMELOYOKMZBMRB-DLBZAZTESA-N 0.000 description 1
- 229950008389 talmapimod Drugs 0.000 description 1
- 229950011332 talnetant Drugs 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 210000004876 tela submucosa Anatomy 0.000 description 1
- 229960000195 terbutaline Drugs 0.000 description 1
- 229950002896 tetomilast Drugs 0.000 description 1
- DZLFLBLQUQXARW-UHFFFAOYSA-N tetrabutylammonium Chemical compound CCCC[N+](CCCC)(CCCC)CCCC DZLFLBLQUQXARW-UHFFFAOYSA-N 0.000 description 1
- 150000003527 tetrahydropyrans Chemical group 0.000 description 1
- PASYJVRFGUDDEW-WMUGRWSXSA-J tetrasodium;[[(2r,3s,5r)-5-(4-amino-2-oxopyrimidin-1-yl)-3-hydroxyoxolan-2-yl]methoxy-oxidophosphoryl] [[[(2r,3s,4r,5r)-5-(2,4-dioxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-oxidophosphoryl]oxy-oxidophosphoryl] phosphate Chemical group [Na+].[Na+].[Na+].[Na+].O=C1N=C(N)C=CN1[C@@H]1O[C@H](COP([O-])(=O)OP([O-])(=O)OP([O-])(=O)OP([O-])(=O)OC[C@@H]2[C@H]([C@@H](O)[C@@H](O2)N2C(NC(=O)C=C2)=O)O)[C@@H](O)C1 PASYJVRFGUDDEW-WMUGRWSXSA-J 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000005301 thienylmethyl group Chemical group [H]C1=C([H])C([H])=C(S1)C([H])([H])* 0.000 description 1
- 150000007970 thio esters Chemical class 0.000 description 1
- 125000001806 thionaphthenyl group Chemical group 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- 229960002203 tilactase Drugs 0.000 description 1
- 229960000257 tiotropium bromide Drugs 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical class CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- OYYDSUSKLWTMMQ-JKHIJQBDSA-N trospium Chemical compound [N+]12([C@@H]3CC[C@H]2C[C@H](C3)OC(=O)C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CCCC1 OYYDSUSKLWTMMQ-JKHIJQBDSA-N 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J71/00—Steroids in which the cyclopenta(a)hydrophenanthrene skeleton is condensed with a heterocyclic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J71/00—Steroids in which the cyclopenta(a)hydrophenanthrene skeleton is condensed with a heterocyclic ring
- C07J71/0036—Nitrogen-containing hetero ring
- C07J71/0057—Nitrogen and oxygen
- C07J71/0068—Nitrogen and oxygen at position 16(17)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/58—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/02—Nasal agents, e.g. decongestants
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/38—Drugs for disorders of the endocrine system of the suprarenal hormones
- A61P5/44—Glucocorticosteroids; Drugs increasing or potentiating the activity of glucocorticosteroids
Abstract
Description
Claims (11)
Priority Applications (1)
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CN201510690091.0A CN105175479B (zh) | 2009-09-11 | 2010-09-01 | 异噁唑烷衍生物 |
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EP09011665.8 | 2009-09-11 | ||
EP09011665 | 2009-09-11 | ||
PCT/EP2010/005366 WO2011029547A2 (en) | 2009-09-11 | 2010-09-01 | Pregnane derivatives condensed in the 16, 17 position with an n-substituted isoxazolidine ring as anti-inflammatory agents |
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CN201510690091.0A Division CN105175479B (zh) | 2009-09-11 | 2010-09-01 | 异噁唑烷衍生物 |
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CN102482318A CN102482318A (zh) | 2012-05-30 |
CN102482318B true CN102482318B (zh) | 2015-11-25 |
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CN201080040085.6A Withdrawn - After Issue CN102482318B (zh) | 2009-09-11 | 2010-09-01 | 异噁唑烷衍生物 |
CN201510690091.0A Active CN105175479B (zh) | 2009-09-11 | 2010-09-01 | 异噁唑烷衍生物 |
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CN201510690091.0A Active CN105175479B (zh) | 2009-09-11 | 2010-09-01 | 异噁唑烷衍生物 |
Country Status (28)
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US (1) | US8637662B2 (zh) |
EP (2) | EP2475676B1 (zh) |
JP (1) | JP2013504524A (zh) |
KR (1) | KR101451486B1 (zh) |
CN (2) | CN102482318B (zh) |
AR (2) | AR078164A1 (zh) |
AU (1) | AU2010294598B2 (zh) |
BR (1) | BR112012005503B1 (zh) |
CA (1) | CA2773594C (zh) |
CL (1) | CL2012000450A1 (zh) |
CO (1) | CO6511204A2 (zh) |
EA (1) | EA025191B1 (zh) |
GE (1) | GEP20146135B (zh) |
HK (2) | HK1218759A1 (zh) |
IL (1) | IL218539A (zh) |
JO (1) | JO3760B1 (zh) |
MA (1) | MA33561B1 (zh) |
ME (1) | ME01331B (zh) |
MX (1) | MX2012002967A (zh) |
MY (1) | MY164842A (zh) |
NZ (1) | NZ598662A (zh) |
PE (1) | PE20120894A1 (zh) |
SG (2) | SG179055A1 (zh) |
TN (1) | TN2012000077A1 (zh) |
TW (1) | TWI494318B (zh) |
UA (1) | UA108858C2 (zh) |
WO (1) | WO2011029547A2 (zh) |
ZA (1) | ZA201201705B (zh) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN105175479A (zh) * | 2009-09-11 | 2015-12-23 | 奇斯药制品公司 | 异噁唑烷衍生物 |
Families Citing this family (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
TW201139369A (en) * | 2010-02-05 | 2011-11-16 | Chiesi Farma Spa | Pyrrolidine derivatives |
CN103391945B (zh) | 2011-03-15 | 2016-11-09 | 奇斯药制品公司 | 异噁唑烷衍生物 |
RU2013141933A (ru) | 2011-03-15 | 2015-03-20 | КЬЕЗИ ФАРМАЧЕУТИЧИ С.п.А. | Производные изоксазолидина |
KR20140042886A (ko) | 2011-08-01 | 2014-04-07 | 키에시 파르마슈티시 엣스. 피. 에이. | 피롤리딘 고리를 갖는 16,17 위치에서 응축된 항염증용 스테로이드 |
US9155747B2 (en) | 2012-09-13 | 2015-10-13 | Chiesi Farmaceutici S.P.A. | Isoxazolidine derivatives |
HUE048020T2 (hu) | 2014-05-12 | 2020-05-28 | Verona Pharma Plc | Új kezelés |
HUE049480T2 (hu) | 2014-09-03 | 2020-09-28 | Rhizen Pharmaceuticals S A | Kezelési eljárás és kettõs specifitású PI3K Delta-Gamma kináz inhibitort és kortikoszteroidot tartalmazó készítmények |
CN104262440B (zh) * | 2014-09-10 | 2016-08-17 | 江西赣亮医药原料有限公司 | 一种16ɑ-羟基泼尼松龙的制备方法 |
CN109206471B (zh) * | 2017-06-30 | 2022-07-12 | 天津药业研究院股份有限公司 | 一种哈西奈德的制备方法 |
CN109575096B (zh) * | 2019-01-20 | 2021-01-01 | 湖南科瑞生物制药股份有限公司 | 一种制备16a-羟基泼尼松龙产品的新方法 |
CN112142820A (zh) * | 2019-06-29 | 2020-12-29 | 天津药业研究院股份有限公司 | 曲安奈德的合成方法 |
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US3996359A (en) * | 1972-05-19 | 1976-12-07 | Ab Bofors | Novel stereoisomeric component A of stereoisomeric mixtures of 2'-unsymmetrical 16,17-methylenedioxy steroid 21-acylates, compositions thereof, and method of treating therewith |
US4018774A (en) * | 1976-02-13 | 1977-04-19 | E. R. Squibb & Sons, Inc. | Steroidal [16α,17-d]isoxazolidines |
CN101282987A (zh) * | 2004-07-14 | 2008-10-08 | 诺瓦提斯公司 | 作为抗炎药物的糖皮质激素16α,17α-异唑烷类化合物 |
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DE1131213B (de) * | 1958-06-13 | 1962-06-14 | Syntex Sa | Verfahren zur Herstellung neuer Pregnanverbindungen |
US3048581A (en) * | 1960-04-25 | 1962-08-07 | Olin Mathieson | Acetals and ketals of 16, 17-dihydroxy steroids |
BR6678983D0 (pt) * | 1965-05-04 | 1973-09-18 | Merck & Co Inc | Processo para preparar 21-fosfato esteroides |
SE307576B (zh) * | 1966-01-27 | 1969-01-13 | Bofors Ab | |
IL31997A (en) * | 1968-05-03 | 1974-03-14 | Lepetit Spa | Process for the preparation of pregnano(17alpha,16alpha-d)oxazolines and 16alpha,21-dihydroxy-17alpha-aminopregnanes |
GB1302572A (zh) * | 1969-05-05 | 1973-01-10 | ||
SE378110B (zh) * | 1972-05-19 | 1975-08-18 | Bofors Ab | |
DE3133631A1 (de) * | 1981-08-21 | 1983-03-03 | Schering Ag, 1000 Berlin Und 4619 Bergkamen | Neue kortikoide ihre herstellung und verwendung |
US5200518A (en) * | 1991-02-21 | 1993-04-06 | Kangweon National University | Anti-inflammatory carboxycyclic acetal pregnane derivatives |
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CN105175479A (zh) * | 2009-09-11 | 2015-12-23 | 奇斯药制品公司 | 异噁唑烷衍生物 |
CN105175479B (zh) * | 2009-09-11 | 2017-06-09 | 奇斯药制品公司 | 异噁唑烷衍生物 |
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