GB869511A - Improvements in or relating to steroids and the manufacture thereof - Google Patents

Improvements in or relating to steroids and the manufacture thereof

Info

Publication number
GB869511A
GB869511A GB14103/59A GB1410359A GB869511A GB 869511 A GB869511 A GB 869511A GB 14103/59 A GB14103/59 A GB 14103/59A GB 1410359 A GB1410359 A GB 1410359A GB 869511 A GB869511 A GB 869511A
Authority
GB
United Kingdom
Prior art keywords
methyl
dihydroxy
dione
pregnadiene
pregnene
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired
Application number
GB14103/59A
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Pharmacia and Upjohn Co
Original Assignee
Upjohn Co
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.)
Filing date
Publication date
Application filed by Upjohn Co filed Critical Upjohn Co
Publication of GB869511A publication Critical patent/GB869511A/en
Expired legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J43/00—Normal steroids having a nitrogen-containing hetero ring spiro-condensed or not condensed with the cyclopenta(a)hydrophenanthrene skeleton
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J75/00—Processes for the preparation of steroids in general
    • 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

Abstract

The invention comprises compounds having the formulae: wherein R is hydrogen or the acyl radical of a hydrocarbon carboxylic acid of from 1-12 carbon atoms, inclusive; R1 is b -hydroxy or keto; X111 is hydrogen, bromine, iodine, fluorine or chlorine; Ac is the acyl radical of a carboxylic acid; M is hydrogen or an alkali metal and the lower alkyl contains 1-8 carbon atoms inclusive, X is chlorine or bromine, and wherein the carbon atoms joined by the dotted line are single or double bonded; and a process for preparing such compounds by treating the 3-enmine of 11-keto-16-dehydroprogesterone with a Grignard reagent and hydrolysing to form 11-keto-16-methylprogesterone IV; reacting IV with oxalic acid diester and a base, and with halogen to obtain 2,21-dialkoxyoxalyl-2,21,21-trihalo 11-keto-16a methylprogesterone VI; rearranging with a strong base and removing the 2-halo group to produce 3,11-diketo-16a -methyl-4,17(20)-[cis]pregnadien-21-oic acid alkyl ester VIII; forming the 3-ketal from VIII, reducing with LiA1H4 and hydrolysing gives 11b ,21-dihydroxy-16a - methyl-4,17(20)- [cis]- pregnadiene-3-one XI; dehydrogenating with SeO2 followed by oxidative hydroxylation gives 11b , 17a - dihydroxy-21- acyloxy-16a - methyl-1,4pregnadiene-3, 20-dione XIV; hydrolysing or oxidising XIV gives the corresponding 21hydroxy and 11-keto compounds; treating XIV with a dehydrating agent and a source of hypohalous acid gives 11b ,17a -dihydroxy-9a -halo-21- acyloxy-16a - methyl-1, 4- pregnadiene3,20-dione XVII; reacting this compound with a base gives the 9,11-epoxy compound which with HF gives the corresponding 9a -fluoro11b -hydroxy compound. Illustrative products of the invention are 11b ,17a ,21-trihydroxy16a -methyl-4-pregnene-3,20-dione and the 21-acetate thereof, 9a -fluor-11b ,17a ,21-trihydroxy-16a -methyl-4-pregnene-3, 20-dione and the 21-acetate thereof, the corresponding 1,4-pregnadienes,3,11-diketo- 16a -methyl- 4,17(20) [cis]-pregnadiene-21-oic acid methyl ester, 11-keto-16a -methylprogesterone and the 3-pyrrolidyl enamine thereof, 11b ,21-dihydroxy-16a -methyl-4,17(20)-[cis]-pregnadiene-3-one and the 3-pyrrolidyl enamine thereof and 11b ,21-dihydroxy- 16a - methyl- 1,4,17(20) - [cis]-pregnatriene-3-one. Specifications 761,490, 771,344, 779,002 and 781,712 are referred to.ALSO:Pharmaceutical compositions comprise 11b , 17a ,21 - trihydroxy - 16a - methyl - 4 - pregnene-3,20 - dione, 16a - methyl - 17a ,21 - dihydroxy - 4 - pregnene - 3,11,20 - trione, 11b ,17a ,21 - trihydroxy - 16a - methyl - 1,4 - pregnadiene - 3,20-dione, 16a -methyl-17a ,21-dihydroxy-1,4-pregnadiene - 3,11,20 - trione, 9a - fluoro - 11b ,17a , 21 - trihydroxy - 16a - methyl - 4 - pregnene - 3,20 - dione, 9a - fluoro - 16a - methyl - 17a ,21 - dihydroxy - 4 - pregnene - 3,11,20 - trione, 9a -fluoro - 11b ,17a ,21 - trihydroxy - 16a - methyl - 1,4 - pregnadiene - 3,20 - dione, 9a - fluoro - 16a - methyl - 17a ,21 - dihydroxy - 1,4 - pregnadiene - 3,11,20-dione and their 21-esters incorporated in an inert ointment, cream, lotion or spray. In addition, antibiotics, e.g. penicillins, neomycin, tetracycline, chloramphenicol and novobiocin, may be present. Specification 761,490, 771,344, 779,002 and 781,712 are referred to.
GB14103/59A 1958-05-26 1959-04-24 Improvements in or relating to steroids and the manufacture thereof Expired GB869511A (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US869511XA 1958-05-26 1958-05-26

Publications (1)

Publication Number Publication Date
GB869511A true GB869511A (en) 1961-05-31

Family

ID=22201934

Family Applications (1)

Application Number Title Priority Date Filing Date
GB14103/59A Expired GB869511A (en) 1958-05-26 1959-04-24 Improvements in or relating to steroids and the manufacture thereof

Country Status (1)

Country Link
GB (1) GB869511A (en)

Cited By (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101168555B (en) * 2006-10-27 2011-05-04 天津药业研究院有限公司 Preparation of medicine and derivative thereof
US8178679B2 (en) 2007-11-28 2012-05-15 Almirall, S.A. Derivatives of 4-(2-amino-1-hydroxyethyl)phenol as agonists of the β2 adrenergic receptors
US8242177B2 (en) 2005-05-20 2012-08-14 Almirall, S.A. Derivatives of 4-(2-amino-1-hydroxyethyl)phenol as agonists of the β2 adrenergic receptor
US8283342B2 (en) 2007-02-09 2012-10-09 Almirall S.A. Napadisylate salt of 5-(2-{[6-(2,2-difluoro-2-phenylethoxy) hexyl]amino}-1-hydroxyethyl)-8-hydroxyquinolin-2(1H)-one as agonist of the β2 adrenergic receptor
EP2556083A2 (en) * 2010-04-05 2013-02-13 Validus Biopharma, Inc. Non-hormonal steroid modulators of nf- kappa b for treatment of disease
US8507670B2 (en) 2006-08-22 2013-08-13 Ranbaxy Laboratories Limited Matrix metalloproteinase inhibitors
US8524908B2 (en) 2009-03-12 2013-09-03 Almirall, S.A. Process for manufacturing 5-(2-{[6-(2,2-difluoro-2-phenylethoxy)hexyl]amino}-1-hydroxyethyl)-8-hydroxyquinolin-2(1H)-one
US8563731B2 (en) 2008-12-22 2013-10-22 Almirall, S.A. Mesylate salt of 5-(2-{[6-(2,2-difluoro-2-phenylethoxy)hexyl]jamino}-1-hydroxyethyl)-8-hydroxyquinolin-2(1H)-one as agonist of the β2 adrenergic receptor
US9108918B2 (en) 2011-10-07 2015-08-18 Almirall, S.A. Process for preparing 5-(2-{[6-(2,2-difluoro-2-phenylethoxy)hexyl]amino}-1(R)-hydroxyethyl)-8-hydroxyquinolin-2(1H)-one via a novel intermediate
US9346759B2 (en) 2012-03-20 2016-05-24 Almirall, S.A. Polymorphic crystal forms of 5-(2-{[6-(2,2-difluoro-2-phenylethoxy)hexyl]amino}-1-(R)-hydroxyethyl)-8-hydroxyquinolin-2(1H)-one, heminapadisytlate as agonist of the β2 adrenergic receptor

Cited By (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8242177B2 (en) 2005-05-20 2012-08-14 Almirall, S.A. Derivatives of 4-(2-amino-1-hydroxyethyl)phenol as agonists of the β2 adrenergic receptor
US8420669B2 (en) 2005-05-20 2013-04-16 Laboratories Almirall, S.A. Derivatives of 4-(2-amino-1-hydroxyethyl)phenol as agonists of the BETA2 adrenergic receptor
US8507670B2 (en) 2006-08-22 2013-08-13 Ranbaxy Laboratories Limited Matrix metalloproteinase inhibitors
US8846910B2 (en) 2006-08-22 2014-09-30 Ranbaxy Laboratories Limited Matrix metalloproteinase inhibitors
US8816073B2 (en) 2006-08-22 2014-08-26 Ranbaxy Laboratories Limited Matrix metalloproteinase inhibitors
CN101168555B (en) * 2006-10-27 2011-05-04 天津药业研究院有限公司 Preparation of medicine and derivative thereof
US8283342B2 (en) 2007-02-09 2012-10-09 Almirall S.A. Napadisylate salt of 5-(2-{[6-(2,2-difluoro-2-phenylethoxy) hexyl]amino}-1-hydroxyethyl)-8-hydroxyquinolin-2(1H)-one as agonist of the β2 adrenergic receptor
US8178679B2 (en) 2007-11-28 2012-05-15 Almirall, S.A. Derivatives of 4-(2-amino-1-hydroxyethyl)phenol as agonists of the β2 adrenergic receptors
US8563731B2 (en) 2008-12-22 2013-10-22 Almirall, S.A. Mesylate salt of 5-(2-{[6-(2,2-difluoro-2-phenylethoxy)hexyl]jamino}-1-hydroxyethyl)-8-hydroxyquinolin-2(1H)-one as agonist of the β2 adrenergic receptor
US8524908B2 (en) 2009-03-12 2013-09-03 Almirall, S.A. Process for manufacturing 5-(2-{[6-(2,2-difluoro-2-phenylethoxy)hexyl]amino}-1-hydroxyethyl)-8-hydroxyquinolin-2(1H)-one
EP2556083A4 (en) * 2010-04-05 2013-12-04 Validus Biopharma Inc Non-hormonal steroid modulators of nf- kappa b for treatment of disease
EP2556083A2 (en) * 2010-04-05 2013-02-13 Validus Biopharma, Inc. Non-hormonal steroid modulators of nf- kappa b for treatment of disease
US10000525B2 (en) 2010-04-05 2018-06-19 Reveragen Biopharma, Inc. Non-hormonal steroid modulators of NF-κB for treatment of disease
US9108918B2 (en) 2011-10-07 2015-08-18 Almirall, S.A. Process for preparing 5-(2-{[6-(2,2-difluoro-2-phenylethoxy)hexyl]amino}-1(R)-hydroxyethyl)-8-hydroxyquinolin-2(1H)-one via a novel intermediate
US9346759B2 (en) 2012-03-20 2016-05-24 Almirall, S.A. Polymorphic crystal forms of 5-(2-{[6-(2,2-difluoro-2-phenylethoxy)hexyl]amino}-1-(R)-hydroxyethyl)-8-hydroxyquinolin-2(1H)-one, heminapadisytlate as agonist of the β2 adrenergic receptor

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