GB1269656A - Improvements in or relating to prostaglandin derivatives and the manufacture thereof - Google Patents
Improvements in or relating to prostaglandin derivatives and the manufacture thereofInfo
- Publication number
- GB1269656A GB1269656A GB3687169A GB3687169A GB1269656A GB 1269656 A GB1269656 A GB 1269656A GB 3687169 A GB3687169 A GB 3687169A GB 3687169 A GB3687169 A GB 3687169A GB 1269656 A GB1269656 A GB 1269656A
- Authority
- GB
- United Kingdom
- Prior art keywords
- alkyl
- compounds
- formula
- atoms
- alpha
- 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
Links
- 150000003180 prostaglandins Chemical class 0.000 title abstract 2
- 238000004519 manufacturing process Methods 0.000 title 1
- 125000000217 alkyl group Chemical group 0.000 abstract 11
- 239000002253 acid Substances 0.000 abstract 6
- 229910052739 hydrogen Inorganic materials 0.000 abstract 6
- 150000007513 acids Chemical class 0.000 abstract 5
- 150000001875 compounds Chemical class 0.000 abstract 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract 5
- 229910052799 carbon Inorganic materials 0.000 abstract 4
- 125000001309 chloro group Chemical group Cl* 0.000 abstract 4
- -1 3,3-difluorobutyl Chemical group 0.000 abstract 3
- 239000003085 diluting agent Substances 0.000 abstract 3
- 125000001153 fluoro group Chemical group F* 0.000 abstract 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 abstract 3
- 125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 abstract 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 abstract 2
- 125000003710 aryl alkyl group Chemical group 0.000 abstract 2
- 125000001246 bromo group Chemical group Br* 0.000 abstract 2
- 125000004432 carbon atom Chemical group C* 0.000 abstract 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 abstract 2
- 239000001257 hydrogen Substances 0.000 abstract 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 abstract 1
- 108700023418 Amidases Proteins 0.000 abstract 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical group C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 abstract 1
- 239000005977 Ethylene Substances 0.000 abstract 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 abstract 1
- 230000002378 acidificating effect Effects 0.000 abstract 1
- 125000005907 alkyl ester group Chemical group 0.000 abstract 1
- 125000002947 alkylene group Chemical group 0.000 abstract 1
- 102000005922 amidase Human genes 0.000 abstract 1
- 229940006138 antiglaucoma drug and miotics prostaglandin analogues Drugs 0.000 abstract 1
- 239000000969 carrier Substances 0.000 abstract 1
- 150000001768 cations Chemical class 0.000 abstract 1
- 230000018044 dehydration Effects 0.000 abstract 1
- 238000006297 dehydration reaction Methods 0.000 abstract 1
- 125000004969 haloethyl group Chemical group 0.000 abstract 1
- 238000010438 heat treatment Methods 0.000 abstract 1
- 230000003301 hydrolyzing effect Effects 0.000 abstract 1
- 125000002346 iodo group Chemical group I* 0.000 abstract 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 abstract 1
- 239000007788 liquid Substances 0.000 abstract 1
- 239000002184 metal Substances 0.000 abstract 1
- 229910052751 metal Inorganic materials 0.000 abstract 1
- 238000000034 method Methods 0.000 abstract 1
- 244000005700 microbiome Species 0.000 abstract 1
- 239000000203 mixture Substances 0.000 abstract 1
- 229940094443 oxytocics prostaglandins Drugs 0.000 abstract 1
- 238000007911 parenteral administration Methods 0.000 abstract 1
- 239000008194 pharmaceutical composition Substances 0.000 abstract 1
- 238000002360 preparation method Methods 0.000 abstract 1
- 230000002997 prostaglandinlike Effects 0.000 abstract 1
- 239000011541 reaction mixture Substances 0.000 abstract 1
- 150000003839 salts Chemical class 0.000 abstract 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 abstract 1
- 229910052725 zinc Inorganic materials 0.000 abstract 1
- 239000011701 zinc Substances 0.000 abstract 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C405/00—Compounds containing a five-membered ring having two side-chains in ortho position to each other, and having oxygen atoms directly attached to the ring in ortho position to one of the side-chains, one side-chain containing, not directly attached to the ring, a carbon atom having three bonds to hetero atoms with at the most one bond to halogen, and the other side-chain having oxygen atoms attached in gamma-position to the ring, e.g. prostaglandins ; Analogues or derivatives thereof
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
1,269,656. Prostaglandins. UPJOHN CO. 22 July, 1969 [29 July, 1968 (7)], No. 36871/69. Heading C2C. The invention comprises processes for the preparation of PGE compounds of the Formula VII and PGA compounds of the Formula IX wherein R 1 is H, C 1-8 alkyl, C 3-10 cycloalkyl C 7-12 aralkyl, phenyl, phenyl substituted with 1 to 3 chlorine atoms or C 1-4 alkyl, or ethyl substituted in the #-position with 3 chlorine atoms, 2 or 3 bromine atoms or 1, 2 or 3 iodine atoms; R 2 is H or C 1-8 alkyl substituted with 0 to 3 fluorine atoms, R 3 and R 4 are H or C 1-4 alkyl; C n H 2n is alkylene of 1 to 8 carbon atoms, substituted with 0 to 2 fluorine atoms; and # indicates attachment of C n H 2n COOR 1 to the ring is alpha or beta configuration and pharmaceutically acceptable salts thereof when R 1 is H, and the novel prostaglandin analogues of the formulµ wherein m is 1 to 6, p is 0 to 7, n is 1 to 8, a is 0 to 4, b is 5 to 7, e is 6 or 7, R 13 H, C 1-4 alkyl or a pharmacologically acceptable cation, 2 is ethylene substituted by 1 or 2 fluorine atoms, CH 3 or CH 3 CH 2 , or by one C 3-4 alkyl; Y is isobutyl, tert-butyl, 3,3-difluorobutyl, 4,4-difluorobutyl, or 4,4,4-trifluorobutyl, and where # indicates attachment of the group to the ring in alpha or beta configuration. PGE compounds of Formula VII above in which R 1 is other than hydrogen are obtained by reacting bis-sulphonic acid esters of Formula XXVII wherein R 7 is as R 1 above, except that H is not included and R 6 is C 1-5 alkyl or the corresponding endo form with water at 0‹ to 60‹ C. PGA compounds of Formula IX above in which R 1 is other than hydrogen are obtained by heating compounds of Formula XXVII above or the corresponding endo form in the range 40‹ to 100‹ C. with combinations of water; bases characterized by their water solution having pH's 8 to 12, and sufficiently inert watersoluble organic diluents to form a basic and substantially homogeneous reaction mixtures. PGA compounds may also be obtained by the acidic dehydration of the corresponding PGE compounds. The corresponding free acids are prepared by subjecting the corresponding C 1-8 alkyl esters of Formula VII or IX above to the acylase enzyme system of a microorganism species of subphylum 2 of Phylum III. Haloethyl esters, where R 1 is ethyl substituted in the #-position by 3 chloro, 2 or 3 bromo or 1, 2 or 3 iodo are converted to the corresponding free acids by treatment with zinc metal and C 2-6 alkanoic acids. Free acids of Formula VII may also be made by converting ketals of formula wherein R 6 is C 1-5 alkyl, R 8 is C 1-8 alkyl, C 3-10 cycloalkyl, C 7-12 aralkyl, phenyl or phenylsubstituted with 1 to 3 chloro or C 1-4 alkyl, R 12 is C 1-6 alkyl or the two R 12 linked together are 1,2-alkylene or 1,3-alkylene of 2-6 C atoms and # indicates attachment of the C n H2 2n COOR 8 to the ring is alpha or beta and the C(OSO 2 R 6 )R 4 -C(OSO 2 R 6 )R 2 R 3 is in oxo or endo configuration to ketals of the formula by treatment with water, saponifying the latter compounds to the free acid forms and then hydrolysing those acids to give the desired products. The alpha and beta isomers of compounds of Formula VII are isomerized to the beta and alpha isomers respectively by maintaining them in an inert liquid diluent at 0‹ to 80‹ C. in the presence of bases characterized by their water solutions having pH's below about 10. Racemic compounds of Formulµ VII and IX may be resolved in the normal manner. Pharmaceutical compositions, having prostaglandin-like activities, contain the above novel compounds and pharmaceutically acceptable diluents or carriers. The compositions may be in form suitable for oral or parenteral administration.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB3687169A GB1269656A (en) | 1969-07-22 | 1969-07-22 | Improvements in or relating to prostaglandin derivatives and the manufacture thereof |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB3687169A GB1269656A (en) | 1969-07-22 | 1969-07-22 | Improvements in or relating to prostaglandin derivatives and the manufacture thereof |
Publications (1)
Publication Number | Publication Date |
---|---|
GB1269656A true GB1269656A (en) | 1972-04-06 |
Family
ID=10391854
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
GB3687169A Expired GB1269656A (en) | 1969-07-22 | 1969-07-22 | Improvements in or relating to prostaglandin derivatives and the manufacture thereof |
Country Status (1)
Country | Link |
---|---|
GB (1) | GB1269656A (en) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2307529A1 (en) * | 1975-04-17 | 1976-11-12 | American Cyanamid Co | NEW 9-CETALS OF 11-HYDROXY-13-PROSTAGLANDINS, USEFUL IN PARTICULAR AS BRONCHODILATORS AND THEIR PREPARATION PROCESS |
-
1969
- 1969-07-22 GB GB3687169A patent/GB1269656A/en not_active Expired
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2307529A1 (en) * | 1975-04-17 | 1976-11-12 | American Cyanamid Co | NEW 9-CETALS OF 11-HYDROXY-13-PROSTAGLANDINS, USEFUL IN PARTICULAR AS BRONCHODILATORS AND THEIR PREPARATION PROCESS |
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