FORFARANDE FOR FRAMSTELLNING AV VISSA TERAPEUTISKT AKTIVA 9-OXO-1-PROSTANOLER

• Main Authors: G L WATKINS, E C J COFFEE, M P L CATON
• Format: Patent
• Language: Swedish
• Published: 18.01.1982
• Subjects: ACYCLIC OR CARBOCYCLIC COMPOUNDS; ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAININGELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN,SULFUR, SELENIUM OR TELLURIUM; CHEMISTRY; HETEROCYCLIC COMPOUNDS; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; ORGANIC CHEMISTRY; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS

1468830 Cyclopentanone derivatives MAY & BAKER Ltd 24 Jan 1975 [26 Jan 1974] 03730/74 Headings C2C and C2P [Also in Division C3] The invention comprises cyclopentanone derivatives of the Formula I wherein R1 is H or carboxylic acyl, and either (i) R2 is -CR2R4R5, wherein R3 and R4 each are H or C 1-4 alkyl; and R5 is H or C 1-10 alkyl, C 1-10 alkoxy, C 5-7 cycloalkyl, adamantyl or C 1-6 alkyl substituted by a C 1-6 alkoxy, C 5-7 cycloalkyl or adamantyl radical, or the group -CR3R4R5 together forms a C 5-7 cycloalkyl or adamantyl group, X is trans-CH=CH- or CH 2 CH 2 - and Y is carbonyl or wherein R6 is H or C 1-4 alkyl and R7 is H, or when R1 is carboxylic acyl, R7 is H or carboxylic acyl, or else (ii) R2 is -A-Z-R8, wherein A is C 1-12 alkylene, Z is a direct bond, O or S, and R8 is aryl or heterocyclyl group which may be substituted by one or more substituents selected from halogen, C 1-6 alkyl, C 1-6 alkoxy and trihalomethyl; X is CH 2 CH 2 or trans CH=CH, Y is carbonyl or or (iii) R2 is a group R8 and X and Y are simultaneously -CH 2 CH 2 - and carbonyl or ethylene and respectively, and their preparation. The compounds of Formula I above wherein R1 is H are prepared by hydrolysing compounds of the Formula V wherein the symbols R9 are identical alkyl radicals or together form an ethylene linkage optionally substituted by identical alkyl groups on each carbon atom, and R10 is H or when Y is wherein R6 is alkyl and R7 is H, the group -OR10 optionally represents a protected hydroxy group and the OH group forming part of is then optionally in the form of a Grignard intermediate complex. The following intermediates and starting materials are prepared: compounds of Formula V above; 1 - chloro - 2 - oxo - 5 - phenylpentane; ethyl 2-(2-phenylethyl)hexanoate, and 1-chloro-3-phenoxyacetone. Dimethyl 2 - cyclohexyl - 2 - oxoethylphosphonate, dimethyl 2 - oxo - 4 - phenylbutylphosphonate, dimethyl 2 - oxo - 3 - phenylpropylphosphonate, dimethyl 2 - oxo - 3 - (2 - phenylethyl)heptylphosphonate and dimethyl 3-methyl-2-oxobutylphosphonate are prepared by reacting dimethyl methylphosphonate with ethyl cyclohexanecarboxylate, ethyl 3-phenylpropionate, ethyl phenylacetate, ethyl 2 - (2 - phenylethyl)- hexanoate and ethyl isobutyrate respectively in the presence of butyl lithium. Butyrylmethylenetriphenylphosphorone is prepared by reacting sodium carbonate with (2- oxopentyl)triphenylphosphonium chloride, obtained from triphenylphosphine and 1-chloropentan - 2 - one. (3 - Ethoxypropionyl)methylenetriphenylphosphorone, (4 - ethoxy - 2 - oxobutyl)- triphenylphosphonium chloride, (4 - phenylbutanoyl)methylenetriphenylphosphorane, (5- phenylpentanoyl)triphenylphosphonium chloride, phenoxyacetylmethylenetriphenylphosphorane and (2 - oxo - 3 - phenoxypropyl)triphenylphosphonium chloride are prepared in a similar manner. Pharmaceutical compositions, suitable for oral rectal, nasal, vaginal and parenteral administration, contain the above cyclopentane derivatives and pharmaceutical carriers or coatings. The compounds possess pharmacological properties typical of the naturally occurring prostaglandins. British Patent Specification 1,398,073 is referred to.