GB1044304A

GB1044304A – Pregneno- and pregnadieno-[3,2-c]pyrazoles
– Google Patents

GB1044304A – Pregneno- and pregnadieno-[3,2-c]pyrazoles
– Google Patents
Pregneno- and pregnadieno-[3,2-c]pyrazoles

Info

Publication number
GB1044304A

GB1044304A
GB22828/63A
GB2282863A
GB1044304A
GB 1044304 A
GB1044304 A
GB 1044304A
GB 22828/63 A
GB22828/63 A
GB 22828/63A
GB 2282863 A
GB2282863 A
GB 2282863A
GB 1044304 A
GB1044304 A
GB 1044304A
Authority
GB
United Kingdom
Prior art keywords
fluoro
pregnadien
hydroxy
prepared
compounds
Prior art date
1962-06-20
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
GB22828/63A
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.)

Merck and Co Inc

Original Assignee
Merck and Co 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.)
1962-06-20
Filing date
1963-06-07
Publication date
1966-09-28

1963-06-07
Application filed by Merck and Co Inc
filed
Critical
Merck and Co Inc

1966-09-28
Publication of GB1044304A
publication
Critical
patent/GB1044304A/en

Status
Expired
legal-status
Critical
Current

Links

Espacenet

Global Dossier

Discuss

Classifications

C—CHEMISTRY; METALLURGY

C07—ORGANIC CHEMISTRY

C07D—HETEROCYCLIC COMPOUNDS

C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings

C07D231/54—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings condensed with carbocyclic rings or ring systems

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

A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone

A61K31/573—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone

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

C—CHEMISTRY; METALLURGY

C07—ORGANIC CHEMISTRY

C07J—STEROIDS

C07J17/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, having an oxygen-containing hetero ring not condensed with the cyclopenta(a)hydrophenanthrene skeleton

C—CHEMISTRY; METALLURGY

C07—ORGANIC CHEMISTRY

C07J—STEROIDS

C07J21/00—Normal steroids containing carbon, hydrogen, halogen or oxygen having an oxygen-containing hetero ring spiro-condensed with the cyclopenta(a)hydrophenanthrene skeleton

C07J21/005—Ketals

C07J21/008—Ketals at position 17

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

C07J7/004—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 substituted in position 17 alfa

C07J7/0045—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 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

C07J7/004—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 substituted in position 17 alfa

C07J7/005—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 substituted in position 17 alfa substituted in position 16

C07J7/0055—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 substituted in position 17 alfa substituted in position 16 by a saturated or unsaturated hydrocarbon group

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

C07J7/0075—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 substituted in position 17 alfa

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

C07J71/0005—Oxygen-containing hetero ring

C07J71/001—Oxiranes

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

C07J71/0042—Nitrogen only

C07J71/0047—Nitrogen only at position 2(3)

C—CHEMISTRY; METALLURGY

C07—ORGANIC CHEMISTRY

C07J—STEROIDS

C07J75/00—Processes for the preparation of steroids in general

Abstract

Novel steroid of the formulae or (wherein R2 is hydrogen, fluorine or methyl; R3 is hydrogen, a -fluorine, a – or b -methyl or methylene; R* is hydrogen, acyl, C1- 4 alkyl, hydroxyalkyl, phenylalkyl, cycloalkyl, phenyl, halophenyl, methylphenyl, alkoxyphenyl or nitrophenyl; and R4 is hydrogen, fluorine, hydroxy, acyloxy or dihydrogen phosphate or alkali metal salts thereof; and the D 6-double bond is optional) and their acid-addition salts are prepared by reacting steroids of the formulae wherein R5 is tetrahydropyranyl) with an alkyl formate and sodium hydride in an inert atmosphere to form the corresponding 2-hydroxymethylene derivatives optionally treating the 2-hydroxymethylene derivatives with a C1- 5 alkanol in the presence of an acid reagent to form 2-alkoxymethylene derivatives, treating these or the 2-hydroxymethylene derivatives with slightly more than one equivalent of a hydrazine compound R1NHNH2 (wherein R1 has any of the values of R* except acyl) and oxidizing the 20-hydroxy-17a -pyranyloxy-[3,2-c]-pyrazolo-steroids so obtained and hydrolysing off the tetrahydropyranyl group to give the required 17a – hydroxy – 17b – acetyl compounds, or hydrolysing the 17a ,20; 20,21-bis-methylenedioxy – [3,2 – c]pyrazolo – steroids so obtained to give the required 17a -hydroxy-17b -hydroxyacetyl compounds. The structure of the products i.e. whether they have structure A or structure B, depends on whether a 2-hydroxymethylene or 2-alkoxymethylene compound is reacted with the hydrazine, and also on the nature of R1. 21-Hydroxy products may be acylated or converted to 21-fluoro or 21-unsubstituted compounds by standard methods involving 21-mesylates and 21-iodo compounds. In these processes compounds wherein R1 is hydrogen are preferably protected by conversion to N-carbamyl derivatives, the N-carbamyl group being subsequently removed by treatment with nitrous acid. N-unsubstituted compounds may also be alkyled or acylated, and on heating N-acyl-21-acylates with aqueous acetic acid the N-acyl group is selectively removed. 21-Acyl groups may be removed with sodium methoxide in methanol. 21-Dihydrogen phosphate esters are prepared from the 21-iodo steroids, silver phosphate and phosphoric acid, and are converted to alkali metal salts with an alkali methoxide, from which the free di-hydrogen phosphate is regenerated by contact with an ion exchange resin. 17a ,20; 20,21-bismethylenedioxy steroid starting materials of the above formula are prepared from the corresponding steroids containing a dihydroxyacetone side chain and formaldehyde in the presence of a strong acid. 17a – Tetrahydropyranyloxy 20 – hydroxy steroid starting materials of the above formula are prepared from the corresponding free 20-keto-17a -ols and dihydropyran in the presence of an acidic reagent, with subsequent reduction e.g. with lithium aluminium hydride, and oxidation of the thus formed 3,20-diol. 17a ,20; 20,21 – bismethylenedioxy – 16a -fluoro – 4,6 – pregnadiene – 3,20 – dione is prepared by the sequence: 21-acetoxy-4,17(20)-pregnadien – 3 – one –> 21 – acetoxy – 16a -hydroxy – 4,17(20) – pregnadien – 3 – one –> 20-chloro – 21 – acetoxy – 4,16 – pregnadien – 3 – one –> 20,21 – epoxy – 4,16 – pregnadien – 3 – one –> 21 – acetoxy – 16a – fluoro – 4,17(20) – pregnadien – 3 – one –> 16a – fluoro – 17a – hydroxy-21 – acetoxy – 4 – pregnene – 3,20 – dione –> free 21 – ol –> 17a ,20; 20,21 – bismethylenedioxy-16a – fluoro – 4 – pregnene – 3,20 – dione –> required 4,6-pregnadiene. The sequence of the last 3 processes can be changed. Similarly are prepared 6a – methyl – and 6a – fluoro – 17a ,20; 20,21 – bismethylene – dioxy – 16a – fluoro – 4-pregnene – 3,20 – dione and the corresponding D 4,6 – compounds, the 6a – fluoro – 21 acetoxy-4,17(20) – pregnadien – 3 – one starting material being prepared by the sequence: progesterone –> methyl 3 – oxo 4,17(20) – pregnadien – 21 – oate –> 3 – enol ether –> methyl 6(a and b ) – fluoro – 3 – keto – 4,17(20) -pregnadien-21-oates -> required compound. The anti-inflammatory pyrazolo-steroids of the invention and their acid-addition salts may be made up into pharmaceutical compositions for topical use.

GB22828/63A
1962-06-20
1963-06-07
Pregneno- and pregnadieno-[3,2-c]pyrazoles

Expired

GB1044304A
(en)

Applications Claiming Priority (2)

Application Number
Priority Date
Filing Date
Title

US203748A

US3148183A
(en)

1962-06-20
1962-06-20
Delta4 and delta4, 6-17alpha-acyloxy-20-oxo-steroid-[3, 2-c] pyrazoles of the pregnane series

US26230463A

1963-03-04
1963-03-04

Publications (1)

Publication Number
Publication Date

GB1044304A
true

GB1044304A
(en)

1966-09-28

Family
ID=26898869
Family Applications (1)

Application Number
Title
Priority Date
Filing Date

GB22828/63A
Expired

GB1044304A
(en)

1962-06-20
1963-06-07
Pregneno- and pregnadieno-[3,2-c]pyrazoles

Country Status (7)

Country
Link

US
(1)

US3148183A
(en)

BE
(1)

BE633906A
(en)

BR
(1)

BR6349964D0
(en)

CH
(1)

CH462178A
(en)

DE
(1)

DE1468265A1
(en)

FR
(2)

FR1552757A
(en)

GB
(1)

GB1044304A
(en)

Cited By (1)

* Cited by examiner, † Cited by third party

Publication number
Priority date
Publication date
Assignee
Title

WO2010147947A2
(en)

2009-06-16
2010-12-23
Schering Corporation
NOVEL [3,2-c] HETEROARYL STEROIDS AS GLUCOCORTICOID RECEPTOR AGONISTS, COMPOSITIONS AND USES THEREOF

Families Citing this family (2)

* Cited by examiner, † Cited by third party

Publication number
Priority date
Publication date
Assignee
Title

GB1101117A
(en)

*

1964-02-01
1968-01-31
Ormonoterapia Richter Spa
Steroidal 2ª-carbonylhydrazones

US3530117A
(en)

*

1969-01-09
1970-09-22
Merck & Co Inc
Delta**4 and delta**4,6 – 17 – hydroxy – steroidal pyrazoles of the pregnane series

Family Cites Families (1)

* Cited by examiner, † Cited by third party

Publication number
Priority date
Publication date
Assignee
Title

US2945852A
(en)

*

1959-05-20
1960-07-19
Searle & Co
17-oxygenated 9alpha-substituted androstano [3, 2-c] pyrazoles and derivatives

0

BE
BE633906D
patent/BE633906A/xx
unknown

1962

1962-06-20
US
US203748A
patent/US3148183A/en
not_active
Expired – Lifetime

1963

1963-06-07
GB
GB22828/63A
patent/GB1044304A/en
not_active
Expired

1963-06-14
DE
DE19631468265
patent/DE1468265A1/en
active
Pending

1963-06-18
BR
BR149964/63A
patent/BR6349964D0/en
unknown

1963-06-19
FR
FR938682A
patent/FR1552757A/fr
not_active
Expired

1963-06-20
CH
CH773463A
patent/CH462178A/en
unknown

1963-09-18
FR
FR947928A
patent/FR4030M/fr
not_active
Expired

Cited By (1)

* Cited by examiner, † Cited by third party

Publication number
Priority date
Publication date
Assignee
Title

WO2010147947A2
(en)

2009-06-16
2010-12-23
Schering Corporation
NOVEL [3,2-c] HETEROARYL STEROIDS AS GLUCOCORTICOID RECEPTOR AGONISTS, COMPOSITIONS AND USES THEREOF

Also Published As

Publication number
Publication date

BE633906A
(en)

DE1468265A1
(en)

1969-11-20

US3148183A
(en)

1964-09-08

CH462178A
(en)

1968-09-15

BR6349964D0
(en)

1973-07-03

FR4030M
(en)

1966-03-28

FR1552757A
(en)

1969-01-10

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