FI71748C - Foerfarande foer framstaellning av terapeutiskt aktiva softsteroider. - Google Patents

Foerfarande foer framstaellning av terapeutiskt aktiva softsteroider. Download PDF

Info

Publication number: FI71748C
Authority: FI; Finland
Prior art keywords: formula; compound; carboxylate; hydroxy; compounds
Prior art date: 1980-07-10

Application number

FI812175A

Other languages

English (en)

Finnish (fi)

Swedish (sv)

Other versions

FI71748B (fi

FI812175L (fi

Inventor

Nicholas Stephen Bodor

Original Assignee

Otsuka Pharma Co Ltd

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1980-07-10

Filing date

1981-07-09

Publication date

1987-02-09

1981-07-09 Application filed by Otsuka Pharma Co Ltd filed Critical Otsuka Pharma Co Ltd

1982-01-11 Publication of FI812175L publication Critical patent/FI812175L/fi

1986-10-31 Application granted granted Critical

1986-10-31 Publication of FI71748B publication Critical patent/FI71748B/fi

1987-02-09 Publication of FI71748C publication Critical patent/FI71748C/fi

Links

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UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 1
125000004772 dichloromethyl group Chemical group [H]C(Cl)(Cl)* 0.000 description 1
LGTLXDJOAJDFLR-UHFFFAOYSA-N diethyl chlorophosphate Chemical compound CCOP(Cl)(=O)OCC LGTLXDJOAJDFLR-UHFFFAOYSA-N 0.000 description 1
HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 1
201000010099 disease Diseases 0.000 description 1
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
239000003221 ear drop Substances 0.000 description 1
229940047652 ear drops Drugs 0.000 description 1
230000008030 elimination Effects 0.000 description 1
238000003379 elimination reaction Methods 0.000 description 1
239000003480 eluent Substances 0.000 description 1
229940095399 enema Drugs 0.000 description 1
PSLIMVZEAPALCD-UHFFFAOYSA-N ethanol;ethoxyethane Chemical compound CCO.CCOCC PSLIMVZEAPALCD-UHFFFAOYSA-N 0.000 description 1
150000002170 ethers Chemical class 0.000 description 1
XKMNGMFPBQNISY-UHFFFAOYSA-N ethoxyethane;hexane;oxolane Chemical compound CCOCC.C1CCOC1.CCCCCC XKMNGMFPBQNISY-UHFFFAOYSA-N 0.000 description 1
125000005745 ethoxymethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])* 0.000 description 1
239000003889 eye drop Substances 0.000 description 1
229940012356 eye drops Drugs 0.000 description 1
229960002011 fludrocortisone Drugs 0.000 description 1
229960003469 flumetasone Drugs 0.000 description 1
WXURHACBFYSXBI-GQKYHHCASA-N flumethasone Chemical compound C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@]1(F)[C@@H]2[C@@H]2C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]2(C)C[C@@H]1O WXURHACBFYSXBI-GQKYHHCASA-N 0.000 description 1
125000001153 fluoro group Chemical group F* 0.000 description 1
229960000618 fluprednisolone Drugs 0.000 description 1
JKFAIQOWCVVSKC-UHFFFAOYSA-N furazan Chemical compound C=1C=NON=1 JKFAIQOWCVVSKC-UHFFFAOYSA-N 0.000 description 1
239000003349 gelling agent Substances 0.000 description 1
ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 1
229940075507 glyceryl monostearate Drugs 0.000 description 1
150000002334 glycols Chemical class 0.000 description 1
125000005843 halogen group Chemical group 0.000 description 1
208000014617 hemorrhoid Diseases 0.000 description 1
125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
229960001524 hydrocortisone butyrate Drugs 0.000 description 1
XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
230000009610 hypersensitivity Effects 0.000 description 1
238000000338 in vitro Methods 0.000 description 1
238000001727 in vivo Methods 0.000 description 1
208000027866 inflammatory disease Diseases 0.000 description 1
230000002757 inflammatory effect Effects 0.000 description 1
238000001802 infusion Methods 0.000 description 1
230000002401 inhibitory effect Effects 0.000 description 1
239000007924 injection Substances 0.000 description 1
238000002347 injection Methods 0.000 description 1
239000011630 iodine Substances 0.000 description 1
150000002500 ions Chemical class 0.000 description 1
QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 description 1
CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 1
230000007803 itching Effects 0.000 description 1
239000008101 lactose Substances 0.000 description 1
229940039717 lanolin Drugs 0.000 description 1
239000007788 liquid Substances 0.000 description 1
229940057995 liquid paraffin Drugs 0.000 description 1
239000003589 local anesthetic agent Substances 0.000 description 1
239000006210 lotion Substances 0.000 description 1
239000007937 lozenge Substances 0.000 description 1
229920002521 macromolecule Polymers 0.000 description 1
238000004519 manufacturing process Methods 0.000 description 1
239000000463 material Substances 0.000 description 1
IBIKHMZPHNKTHM-RDTXWAMCSA-N merck compound 25 Chemical compound C1C[C@@H](C(O)=O)[C@H](O)CN1C(C1=C(F)C=CC=C11)=NN1C(=O)C1=C(Cl)C=CC=C1C1CC1 IBIKHMZPHNKTHM-RDTXWAMCSA-N 0.000 description 1
KJLLJBVWJUFUTE-YFWFAHHUSA-N methyl (8s,9s,10r,13s,14s,17s)-10,13-dimethyl-3-oxo-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthrene-17-carboxylate Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)OC)[C@@]1(C)CC2 KJLLJBVWJUFUTE-YFWFAHHUSA-N 0.000 description 1
229960001293 methylprednisolone acetate Drugs 0.000 description 1
125000004092 methylthiomethyl group Chemical group [H]C([H])([H])SC([H])([H])* 0.000 description 1
230000002906 microbiologic effect Effects 0.000 description 1
238000002156 mixing Methods 0.000 description 1
239000001788 mono and diglycerides of fatty acids Substances 0.000 description 1
230000036651 mood Effects 0.000 description 1
150000002780 morpholines Chemical class 0.000 description 1
230000003232 mucoadhesive effect Effects 0.000 description 1
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
239000002547 new drug Substances 0.000 description 1
125000004433 nitrogen atom Chemical group N* 0.000 description 1
ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
230000036407 pain Effects 0.000 description 1
229940056211 paraffin Drugs 0.000 description 1
239000012188 paraffin wax Substances 0.000 description 1
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
239000002304 perfume Substances 0.000 description 1
150000004965 peroxy acids Chemical class 0.000 description 1
230000002085 persistent effect Effects 0.000 description 1
239000000546 pharmaceutical excipient Substances 0.000 description 1
239000000825 pharmaceutical preparation Substances 0.000 description 1
229960005323 phenoxyethanol Drugs 0.000 description 1
WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
229940067107 phenylethyl alcohol Drugs 0.000 description 1
LFSXCDWNBUNEEM-UHFFFAOYSA-N phthalazine Chemical compound C1=NN=CC2=CC=CC=C21 LFSXCDWNBUNEEM-UHFFFAOYSA-N 0.000 description 1
231100000572 poisoning Toxicity 0.000 description 1
230000000607 poisoning effect Effects 0.000 description 1
229920001223 polyethylene glycol Polymers 0.000 description 1
229940068917 polyethylene glycols Drugs 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
239000011591 potassium Substances 0.000 description 1
229940019974 pramoxine hydrochloride Drugs 0.000 description 1
229940096112 prednisol Drugs 0.000 description 1
229960005205 prednisolone Drugs 0.000 description 1
OIGNJSKKLXVSLS-VWUMJDOOSA-N prednisolone Chemical compound O=C1C=C[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 OIGNJSKKLXVSLS-VWUMJDOOSA-N 0.000 description 1
238000012746 preparative thin layer chromatography Methods 0.000 description 1
IVRIRQXJSNCSPQ-UHFFFAOYSA-N propan-2-yl carbonochloridate Chemical compound CC(C)OC(Cl)=O IVRIRQXJSNCSPQ-UHFFFAOYSA-N 0.000 description 1
230000000069 prophylactic effect Effects 0.000 description 1
QQKDTTWZXHEGAQ-UHFFFAOYSA-N propyl carbonochloridate Chemical compound CCCOC(Cl)=O QQKDTTWZXHEGAQ-UHFFFAOYSA-N 0.000 description 1
201000007094 prostatitis Diseases 0.000 description 1
USPWKWBDZOARPV-UHFFFAOYSA-N pyrazolidine Chemical class C1CNNC1 USPWKWBDZOARPV-UHFFFAOYSA-N 0.000 description 1
JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 description 1
SBYHFKPVCBCYGV-UHFFFAOYSA-N quinuclidine Chemical compound C1CC2CCN1CC2 SBYHFKPVCBCYGV-UHFFFAOYSA-N 0.000 description 1
150000008584 quinuclidines Chemical class 0.000 description 1
239000012048 reactive intermediate Substances 0.000 description 1
210000000664 rectum Anatomy 0.000 description 1
230000009467 reduction Effects 0.000 description 1
208000023504 respiratory system disease Diseases 0.000 description 1
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
229910052938 sodium sulfate Inorganic materials 0.000 description 1
235000011152 sodium sulphate Nutrition 0.000 description 1
241000894007 species Species 0.000 description 1
239000008107 starch Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
239000002294 steroidal antiinflammatory agent Substances 0.000 description 1
125000004434 sulfur atom Chemical group 0.000 description 1
239000000829 suppository Substances 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
231100000057 systemic toxicity Toxicity 0.000 description 1
239000003826 tablet Substances 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
OULAJFUGPPVRBK-UHFFFAOYSA-N tetratriacontyl alcohol Natural products CCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCO OULAJFUGPPVRBK-UHFFFAOYSA-N 0.000 description 1
238000002560 therapeutic procedure Methods 0.000 description 1
230000008719 thickening Effects 0.000 description 1
239000012049 topical pharmaceutical composition Substances 0.000 description 1
238000012546 transfer Methods 0.000 description 1
125000005270 trialkylamine group Chemical group 0.000 description 1
125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 description 1
ILWRPSCZWQJDMK-UHFFFAOYSA-N triethylazanium;chloride Chemical compound Cl.CCN(CC)CC ILWRPSCZWQJDMK-UHFFFAOYSA-N 0.000 description 1
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
210000000689 upper leg Anatomy 0.000 description 1
229940070710 valerate Drugs 0.000 description 1
NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
235000015112 vegetable and seed oil Nutrition 0.000 description 1
239000008158 vegetable oil Substances 0.000 description 1
238000005406 washing Methods 0.000 description 1
230000004584 weight gain Effects 0.000 description 1
235000019786 weight gain Nutrition 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J3/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by one carbon atom
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J33/00—Normal steroids having a sulfur-containing hetero ring spiro-condensed or not condensed with the cyclopenta(a)hydrophenanthrene skeleton
- C07J33/002—Normal steroids having a sulfur-containing hetero ring spiro-condensed or not condensed with the cyclopenta(a)hydrophenanthrene skeleton not condensed
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J3/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by one carbon atom
- C07J3/005—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by one carbon atom the carbon atom being part of a carboxylic function
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J31/00—Normal steroids containing one or more sulfur atoms not belonging to a hetero ring
- C07J31/006—Normal steroids containing one or more sulfur atoms not belonging to a hetero ring not covered by C07J31/003
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J43/00—Normal steroids having a nitrogen-containing hetero ring spiro-condensed or not condensed with the cyclopenta(a)hydrophenanthrene skeleton
- C07J43/003—Normal steroids having a nitrogen-containing hetero ring spiro-condensed or not condensed with the cyclopenta(a)hydrophenanthrene skeleton not condensed

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
General Health & Medical Sciences (AREA)
Steroid Compounds (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

FI812175A 1980-07-10 1981-07-09 Foerfarande foer framstaellning av terapeutiskt aktiva softsteroider. FI71748C (fi)

Applications Claiming Priority (4)

Application Number	Priority Date	Filing Date
US16845380A	1980-07-10	1980-07-10
US16845380		1980-07-10
US26578581A	1981-05-21	1981-05-21
US26578581		1981-05-21

Publications (3)

Publication Number	Publication Date
FI812175L FI812175L (fi)	1982-01-11
FI71748B FI71748B (fi)	1986-10-31
FI71748C true FI71748C (fi)	1987-02-09

Family

ID=26864131

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
FI812175A FI71748C (fi)	1980-07-10	1981-07-09	Foerfarande foer framstaellning av terapeutiskt aktiva softsteroider.

Country Status (17)

Country	Link
KR (2)	KR860000266B1 (sr)
AT (1)	AT379816B (sr)
AU (1)	AU540898B2 (sr)
CA (1)	CA1174667A (sr)
CH (1)	CH648856A5 (sr)
DE (1)	DE3126732C2 (sr)
DK (1)	DK165837C (sr)
ES (2)	ES504340A0 (sr)
FI (1)	FI71748C (sr)
FR (1)	FR2486529A1 (sr)
GB (1)	GB2079755B (sr)
IT (1)	IT1205446B (sr)
NL (1)	NL192343C (sr)
NO (1)	NO163285C (sr)
PH (1)	PH25874A (sr)
PT (1)	PT73348B (sr)
SE (1)	SE449106B (sr)

Families Citing this family (27)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GB2137206B (en) *	1980-02-15	1985-04-03	Glaxo Group Ltd	Androstane 17-carbothioc acid derivatives
JPS6041607A (ja) *	1983-08-12	1985-03-05	Otsuka Pharmaceut Co Ltd	軟膏基剤
SE8501693D0 (sv) *	1985-04-04	1985-04-04	Draco Ab	Novel 16,17-acetalsubstituted androstane-17beta-carboxylic acid esters
IL78144A0 (en) *	1985-04-04	1986-07-31	Draco Ab	Novel androstane-17beta-carboxylic acid esters
DE3786174T2 (de) *	1987-10-13	1993-10-21	Nicholas S Bodor	Weiche steroide mit anti-entzündungswirkung.
DE4025342A1 (de) *	1990-08-10	1992-02-13	Hoechst Ag	In 17-stellung substituierte corticoid-17-alkylcarbonate, verfahren zu deren herstellung und diese enthaltende arzneimittel
AU8439998A (en) *	1997-06-30	1999-01-25	Glaxo Group Limited	Compounds
GB0019172D0 (en)	2000-08-05	2000-09-27	Glaxo Group Ltd	Novel compounds
US6777399B2 (en)	2000-08-05	2004-08-17	Smithkline Beecham Corporation	Anti-inflammatory androstane derivative compositions
US6858596B2 (en)	2000-08-05	2005-02-22	Smithkline Beecham Corporation	Formulation containing anti-inflammatory androstane derivative
SI1775305T1 (sl)	2000-08-05	2015-01-30	Glaxo Group Limited	S-fluorometil ester 6alfa,9alfa-difluoro-17alfa-((2-furanilkarboksil)oksi)- 11beta-hidroksi-16alfa-metil-3-okso-androst-1,4-dien-17-karbotiojske kisline kot protivnetno sredstvo
US6858593B2 (en)	2000-08-05	2005-02-22	Smithkline Beecham Corporation	Anti-inflammatory androstane derivative compositions
US6777400B2 (en)	2000-08-05	2004-08-17	Smithkline Beecham Corporation	Anti-inflammatory androstane derivative compositions
US6750210B2 (en)	2000-08-05	2004-06-15	Smithkline Beecham Corporation	Formulation containing novel anti-inflammatory androstane derivative
US6759398B2 (en)	2000-08-05	2004-07-06	Smithkline Beecham Corporation	Anti-inflammatory androstane derivative
US6787532B2 (en)	2000-08-05	2004-09-07	Smithkline Beecham Corporation	Formulation containing anti-inflammatory androstane derivatives
UA77656C2 (en)	2001-04-07	2007-01-15	Glaxo Group Ltd	S-fluoromethyl ester of 6-alpha, 9-alpha-difluoro-17-alpha-[(2-furanylcarbonyl)oxy]-11-beta-hydroxy-16- alpha-methyl-3-oxoandrosta-1,4-dien-17-beta-carbothioacid as anti-inflammatory agent
KR100831534B1 (ko)	2001-04-30	2008-05-22	글락소 그룹 리미티드	17.알파 위치에 시클릭 에스테르기를 지닌 항염증성의안드로스탄의 17.베타.-카르보티오에이트 에스테르 유도체
GB2389530B (en)	2002-06-14	2007-01-10	Cipla Ltd	Pharmaceutical compositions
UA82323C2 (uk) *	2002-08-09	2008-04-10	Меда Фарма Гмбх & Ко. Кг	Нова комбінація глюкокортикоїду та pde-інгібітору для лікування респіраторних захворювань, алергічних захворювань, астми та хронічних обструктивних легеневих захворювань
GB0316290D0 (en) *	2003-07-11	2003-08-13	Glaxo Group Ltd	Novel compounds
EP1841780B1 (en)	2005-01-10	2011-07-27	Glaxo Group Limited	Androstane 17-alpha-carbonate derivatives for use in the treatment of allergic and inflammatory conditions
TWI374147B (en) *	2006-01-27	2012-10-11	Sun Pharma Advance Res Company Ltd	Novel 11β-hydroxyandrosta-4-ene-3-ones
US7687484B2 (en) *	2006-05-25	2010-03-30	Bodor Nicholas S	Transporter enhanced corticosteroid activity
US7691811B2 (en) *	2006-05-25	2010-04-06	Bodor Nicholas S	Transporter-enhanced corticosteroid activity and methods and compositions for treating dry eye
CN101942001B (zh) *	2010-08-24	2013-02-06	山东省医药工业研究所	一种氯替泼诺的提纯方法
CN103183714A (zh) *	2011-12-29	2013-07-03	山东方明药业集团股份有限公司	一种氯替泼诺的合成方法

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GB1384372A (en) *	1971-01-20	1975-02-19	Glaxo Lab Ltd	Dereivatives of 17alpha-hydroxyandrost-4-ene-17beta-carboxylic acids
GB1438940A (en) *	1972-07-19	1976-06-09	Glaxo Lab Ltd	17beta-haloalkoxycarbonyl-17alpha-oxysteroids
GB1514476A (en) *	1974-08-30	1978-06-14	Glaxo Lab Ltd	Alkyl and haloalkyl androst-4-ene and androsta-1,4-diene-17beta-carboxylates
DE2735110A1 (de) *	1977-08-04	1979-02-15	Hoechst Ag	Corticoid-17-alkylcarbonate und verfahren zu ihrer herstellung
IT1114534B (it) *	1978-02-08	1986-01-27	Glaxo Group Ltd	Steroide anti-infiammatorio della serie dell'androstano composizioni che lo contengono e procedimento per produrlo
US4188385A (en) *	1978-04-05	1980-02-12	Syntex (U.S.A.) Inc.	Thioetianic acid derivatives
DE2817988A1 (de) *	1978-04-25	1979-11-08	Hoechst Ag	Corticoid 17-alkylcarbonate und verfahren zu deren herstellung

1981
- 1981-07-02 SE SE8104132A patent/SE449106B/sv not_active IP Right Cessation
- 1981-07-06 AU AU72591/81A patent/AU540898B2/en not_active Expired
- 1981-07-06 GB GB8120864A patent/GB2079755B/en not_active Expired
- 1981-07-07 DE DE3126732A patent/DE3126732C2/de not_active Expired
- 1981-07-08 PH PH25877A patent/PH25874A/en unknown
- 1981-07-08 CA CA000381293A patent/CA1174667A/en not_active Expired
- 1981-07-08 DK DK302181A patent/DK165837C/da not_active IP Right Cessation
- 1981-07-08 CH CH4497/81A patent/CH648856A5/de not_active IP Right Cessation
- 1981-07-09 IT IT05186/81A patent/IT1205446B/it active
- 1981-07-09 FI FI812175A patent/FI71748C/fi not_active IP Right Cessation
- 1981-07-09 NO NO812344A patent/NO163285C/no unknown
- 1981-07-10 FR FR8113607A patent/FR2486529A1/fr active Granted
- 1981-07-10 ES ES504340A patent/ES504340A0/es active Granted
- 1981-07-10 PT PT73348A patent/PT73348B/pt unknown
- 1981-07-10 AT AT0307081A patent/AT379816B/de not_active IP Right Cessation
- 1981-07-10 KR KR1019810002502A patent/KR860000266B1/ko not_active Expired
- 1981-07-10 NL NL8103315A patent/NL192343C/nl not_active IP Right Cessation
1982
- 1982-08-02 ES ES514633A patent/ES514633A0/es active Granted
1984
- 1984-09-25 KR KR1019840005874A patent/KR860000452B1/ko not_active Expired

Also Published As

Publication number	Publication date
DK165837C (da)	1993-06-21
ES8300785A1 (es)	1982-12-01
PT73348B (en)	1982-09-23
ES8306767A1 (es)	1983-06-16
DE3126732A1 (de)	1982-03-25
AU540898B2 (en)	1984-12-06
KR860000452B1 (ko)	1986-04-26
PH25874A (en)	1991-12-02
KR830006327A (ko)	1983-09-24
NL192343B (nl)	1997-02-03
ES514633A0 (es)	1983-06-16
DK165837B (da)	1993-01-25
IT1205446B (it)	1989-03-23
PT73348A (en)	1981-08-01
SE8104132L (sv)	1982-01-11
DK302181A (da)	1982-01-11
KR860000266B1 (ko)	1986-03-22
DE3126732C2 (de)	1987-04-30
AT379816B (de)	1986-03-10
CH648856A5 (de)	1985-04-15
NO163285C (no)	1990-05-02
IT8105186A0 (it)	1981-07-09
FR2486529A1 (fr)	1982-01-15
ATA307081A (de)	1985-07-15
NL192343C (nl)	1997-06-04
CA1174667A (en)	1984-09-18
GB2079755B (en)	1985-01-30
SE449106B (sv)	1987-04-06
NO812344L (no)	1982-01-11
KR850002759A (ko)	1985-05-15
ES504340A0 (es)	1982-12-01
GB2079755A (en)	1982-01-27
FI71748B (fi)	1986-10-31
FI812175L (fi)	1982-01-11
FR2486529B1 (sr)	1985-01-04
AU7259181A (en)	1982-01-14
NO163285B (no)	1990-01-22
NL8103315A (nl)	1982-02-01

Legal Events

Date	Code	Title	Description
2004-08-31	MA	Patent expired	Owner name: BODOR, NICHOLAS STEPHEN

Publication	Publication Date	Title
FI71748C (fi)	1987-02-09	Foerfarande foer framstaellning av terapeutiskt aktiva softsteroider.
US5981517A (en)	1999-11-09	Androstene derivatives
US4996335A (en)	1991-02-26	Soft steroids having anti-inflammatory activity
US20090258849A1 (en)	2009-10-15	Nitrooxy derivatives of glucocorticoids
CA2005214A1 (en)	1990-06-23	Phosphinic acid substituted steroids as inhibitors of steroid 5-reductase
MXPA01010213A (es)	2002-09-18	Compuestos farmaceuticos.
IE53753B1 (en)	1989-02-01	Novel 6a-methylprednisolone derivatives and their manufacture and use
EP0120557A2 (en)	1984-10-03	21-Hydroxycorticosteroid esters, and compositions containing them
WO1989003390A1 (en)	1989-04-20	Soft steroids having anti-inflammatory activity
JPS6411037B2 (sr)	1989-02-23
JPS63501292A (ja)	1988-05-19	テトラヒドロ脈管形成抑制ステロイド
CA1085820A (en)	1980-09-16	Method for the preparation of esters
EP0104746A1 (en)	1984-04-04	21-Hydroxycorticosteroid esters, and compositions containing them
CA1086305A (en)	1980-09-23	Depot-steroid esters
DK165880B (da)	1993-02-01	Androstan-17beta-carboxylsyreestere, fremgangsmaade til fremstilling heraf samt farmaceutisk praeparat indeholdende samme
US3663579A (en)	1972-05-16	Dimeric steroid-21-alkyl-carbonates and process for their manufacture
US6610675B1 (en)	2003-08-26	Inactive metabolite approach to soft drug design
NO791142L (no)	1979-10-08	Corticosteroid antiinflammatoriske midler
DK168631B1 (da)	1994-05-09	Corticoidderivater, fremgangsmåde til fremstilling af corticoidderivaterne, farmaceutisk præparat indeholdende corticoidderivaterne samt mellemprodukter
MX2008003029A (en)	2008-09-02	Nitrooxy derivatives op glucocorticoids
CS248729B2 (cs)	1987-02-12	Způsob výroby derivátů 6a-niethylkortikoidu