GB1269657A - Prostaglandin analogues, their preparation and pharmaceutical compositions containing them - Google Patents

Prostaglandin analogues, their preparation and pharmaceutical compositions containing them

Info

Publication number
GB1269657A
GB1269657A GB38073/69A GB3807369A GB1269657A GB 1269657 A GB1269657 A GB 1269657A GB 38073/69 A GB38073/69 A GB 38073/69A GB 3807369 A GB3807369 A GB 3807369A GB 1269657 A GB1269657 A GB 1269657A
Authority
GB
United Kingdom
Prior art keywords
oxa
endo
hex
oxobicyclo
derivatives
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
GB38073/69A
Inventor
Norman Allan Nelson
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
Priority to BE754114D priority Critical patent/BE754114A/en
Application filed by Upjohn Co filed Critical Upjohn Co
Priority to GB38073/69A priority patent/GB1269657A/en
Priority to ZA704099A priority patent/ZA704099B/en
Priority to NL7010617A priority patent/NL7010617A/xx
Priority to DE19702036471 priority patent/DE2036471A1/de
Priority to HUUO67A priority patent/HU162688B/hu
Priority to HUUO66A priority patent/HU162687B/hu
Priority to SE7010366A priority patent/SE383513B/en
Priority to FR7027783A priority patent/FR2059574B1/fr
Priority to CH303273A priority patent/CH571487A5/xx
Priority to JP45065821A priority patent/JPS5028950B1/ja
Priority to CH1147370A priority patent/CH571486A5/xx
Publication of GB1269657A publication Critical patent/GB1269657A/en
Priority to JP47056175A priority patent/JPS503311B1/ja
Priority to US461498A priority patent/US3923864A/en
Priority to US461603A priority patent/US3922298A/en
Priority to US461508A priority patent/US3923861A/en
Priority to US461543A priority patent/US3920723A/en
Priority to US461583A priority patent/US3920724A/en
Priority to US461496A priority patent/US3923863A/en
Priority to US05/461,497 priority patent/US3944593A/en
Priority to US461489A priority patent/US3923862A/en
Priority to US461597A priority patent/US3923865A/en
Expired legal-status Critical Current

Links

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
    • C07C405/0008—Analogues having the carboxyl group in the side-chains replaced by other functional groups
    • C07C405/0016—Analogues having the carboxyl group in the side-chains replaced by other functional groups containing only hydroxy, etherified or esterified hydroxy groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C35/00—Compounds having at least one hydroxy or O-metal group bound to a carbon atom of a ring other than a six-membered aromatic ring
    • C07C35/22—Compounds having at least one hydroxy or O-metal group bound to a carbon atom of a ring other than a six-membered aromatic ring polycyclic, at least one hydroxy group bound to a condensed ring system
    • C07C35/23—Compounds having at least one hydroxy or O-metal group bound to a carbon atom of a ring other than a six-membered aromatic ring polycyclic, at least one hydroxy group bound to a condensed ring system with hydroxy on a condensed ring system having two rings
    • C07C35/27—Compounds having at least one hydroxy or O-metal group bound to a carbon atom of a ring other than a six-membered aromatic ring polycyclic, at least one hydroxy group bound to a condensed ring system with hydroxy on a condensed ring system having two rings the condensed ring system containing six carbon atoms
    • 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
    • C07C405/0008—Analogues having the carboxyl group in the side-chains replaced by other functional groups
    • C07C405/0025—Analogues having the carboxyl group in the side-chains replaced by other functional groups containing keto groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
    • C07D309/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
    • C07D309/08—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D309/10—Oxygen atoms
    • C07D309/12—Oxygen atoms only hydrogen atoms and one oxygen atom directly attached to ring carbon atoms, e.g. tetrahydropyranyl ethers
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
    • C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
    • C07D317/10—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings
    • C07D317/14—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D317/30—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals

Abstract

1,269,657. Prostaglandin derivatives. UPJOHN CO. 16 June, 1970 [29 July, 1969], No. 38073/69. Heading C2C. The invention comprises 3- or 4-oxa-PGE, 3- or 4-oxa PGF, 3- or 4-oxa PGA and 3- or 4-oxa PGB compounds of the formulµ 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, 2 or 3 bromine or 1, 2, 3 iodine atoms; R 2 is H, C 1-10 alkyl substituted with 0 to 3 fluorine atoms, or C 2-10 alkyl substituted with 4 or 5 fluorine atoms on the omega and omega-minus-one carbon atoms; R 3 and R 9 are H or C 1-4 alkyl, A is -CH 2 -CHR 4 - or trans -CH=CR 4 -, and V is -C n H 2n OCR 5 R 6 -, -C m H 2m OCR 5 R 6 -CR 7 R 8 -, cis or trans -CH=CH.C p H 2p OCR 5 R 6 -, cis or trans -CH=CH-C q H 2q -O-CR 5 R 6 -CR 7 R 8 -, -C#C-C p H 2p OCR 5 R 6 - or -C#C-CqH 2q O.CR 5 R 6 -CR 7 R 8 ; with the proviso that V is -C n H 2n -O-CR 5 R 6 - or -C m H 2m -O-CR 5 R 6 -CR 7 R 8 - when A is -CH 2 CHR 4 -; wherein R 4 , R 5 , R 6 , R 7 and R 8 are H or C 1-4 alkyl; wherein C n H 2n is C 1-10 alkylene, with 1 to 5 carbon atoms, inclusive, between -CHR 9 and -O-; wherein C m H 2m is C 1-9 alkylene, with 1 to 4 carbon atoms, inclusive, between -CHR 9 - and -O-; wherein C p H 2p is C 1-8 alkylene, with 1, 2 or 3 carbon atoms between -CHR 9 - and -O-; and wherein C q H 2q is C 1-7 alkylene with 1 or 2 carbon atoms between -CHR 9 and -O-; and wherein # indicates attachment of the group to the ring in alpha or beta configuration; including C 1-8 alkanoates, and pharmacologically acceptable salts thereof when R 1 is H. Esters of 3- or 4-oxa PGE derivatives of the above formula in which A is trans -CH=CR 4 are prepared by reacting compounds of the Formula LXXXII wherein R 10 is the same as R 1 except that it cannot be H, and R 13 is C 1-5 alkyl, in oxo or endo configuration with respect to the radical attached to the cyclopropane ring with water at temperatures of 0‹ to 60‹ C. The corresponding free acids are obtained by hydrolysing the thus obtained esters, and the corresponding compounds in which A is -CH 2 -CHR 4 by reducing compounds in which A is trans -CH=CR 4 -. 3-Oxa or 4-oxa PGF derivatives are made by the carbonyl reduction of the corresponding 3-oxa or 4-oxa PGE derivatives. 3-Oxa or 4-oxa PGA derivatives are obtained either by reacting the bicyclo-[3,1,0]-hexane derivatives of the above Formula LXXXII with combinations of water, bases characterized by their water solution having pH's of 8 to 12 and sufficient watersoluble organic diluents to form basic substantially homogeneous reaction mixtures at temperatures of 40‹ to 100‹ C., or by reacting the corresponding 3- or 4-oxa PGE or 3- or 4-oxa PGB derivatives with bases whose water solutions have pH's greater than 10. 3-Oxa and 4-oxa PGB derivatives are prepared by the acidic dehydration of the corresponding 3-oxa or 4-oxa PGE derivatives. The following intermediate compounds are also made: endo-6-(1,2-dihydroxyheptyl)-bicyclo [3,1,0] hexan-3-one and its acetonide, ethyl 3 - oxa - 7 - [endo - 6 - (1 - heptenyl) - 3 - oxobicyclo [3,1,0] hex - 2α - yl] heptanoate, ethyl 2,2 - dimethyl - 3 - oxa - 7 - [oxo - 6 - (1 - heptenyl) - 3 - oxobicycio [3,1,0] hex - 2 - yl] heptanoate, ethyl 3 - oxa - 7 - [endo - 6 - (1,2 - dihydroxyheptyl) - 3 - oxobicyclo - [3,1,0] hex-2α- yl] heptanoate acetonide, 3 - oxa - 7 - [endo-6- (1 - heptenyl) - 3 - oxobicyclo [3,1,0] hex - 2α- yl] heptanoic acid, 3 - oxa - 7 - [endo - 6 - (1- heptenyl) - 3 - hydroxybicyclo [3,1,0] hex-2α-yl] heptanoic acid and its ethyl ester, 3-oxa-7- [endo - 6 - (1,2 - dihydroxy - heptyl) 3 - oxabicyclo [3,1,0] hex - 2α - yl] heptanoic acid acetonide, #,#,# - trichloroethyl 3 - oxa - 7- [endo - 6 - (1 - heptenyl) - 3 - oxobicyclo [3,1,0] hex - 2α - yl] heptanoate, #,#,# - trichloroethyl 3 - oxo - 7 - [endo - 6 - (1,2 - dihydroxyheptyl)- 3 - oxobicyclo [3,1,0] hex - 2α - yl] heptanoate acetonide, ethyl 3 - oxa - 7 - [endo - 6 - (1,2- dihydroxyheptyl) - 3 - oxobicyclo [3,1,0] hex-2α- yl] heptanoate, ethyl 3-oxa-7-[endo-6-(1,2- dihydroxyheptyl) - 3 - oxobicyclo [3,1,0] hex- 2α - yl] - trans - 5 - heptenoate acetonide, ethyl 3 - oxa - 7 - [endo - 6 - (1,2 - dimesyloxyheptyl)- 3 - oxobicyclo [3,1,0] hex - 2α - yl] heptanoate, and 3 - oxa - 7 - [endo - 6 - (1 - hydroxy - 2- mesyloxyheptyl) - 3 - oxobicyclo [3,1,0] hex - 2α- yl] heptanoate. Pharmaceutical compositions, suitable for oral or parenteral administration and having prostaglandin-like activity, contain the above novel compounds or pharmaceutically acceptable salts thereof together with pharmaceutically acceptable carriers.
GB38073/69A 1969-07-29 1969-07-29 Prostaglandin analogues, their preparation and pharmaceutical compositions containing them Expired GB1269657A (en)

Priority Applications (22)

Application Number Priority Date Filing Date Title
BE754114D BE754114A (en) 1969-07-29 NEW COMPOUNDS OF THE PROSTAGLANDIN CLASS AND THEIR PREPARATION PROCESS
GB38073/69A GB1269657A (en) 1969-07-29 1969-07-29 Prostaglandin analogues, their preparation and pharmaceutical compositions containing them
ZA704099A ZA704099B (en) 1969-07-29 1970-06-16 Prostaglandin analogs and the process therefor
NL7010617A NL7010617A (en) 1969-07-29 1970-07-17
DE19702036471 DE2036471A1 (en) 1969-07-29 1970-07-23
HUUO67A HU162688B (en) 1969-07-29 1970-07-24
HUUO66A HU162687B (en) 1969-07-29 1970-07-24
SE7010366A SE383513B (en) 1969-07-29 1970-07-28 PROCEDURE FOR PREPARATION IN POSITIONS 7 AND 15 EV. SUBSTITUTED PROSTAGLANDINESTERS AND FREE ACIDS OF TYPE 3-OXA-PGA WITH BLOOD PRESSURE-LOWING PROPERTIES.
FR7027783A FR2059574B1 (en) 1969-07-29 1970-07-28
CH1147370A CH571486A5 (en) 1969-07-29 1970-07-29
JP45065821A JPS5028950B1 (en) 1969-07-29 1970-07-29
CH303273A CH571487A5 (en) 1969-07-29 1970-07-29
JP47056175A JPS503311B1 (en) 1969-07-29 1972-06-07
US461597A US3923865A (en) 1969-07-29 1974-04-17 4-Oxa prostaglandin F{62 -type compounds
US461508A US3923861A (en) 1969-07-29 1974-04-17 3-Oxa prostaglandin F{331 -type compounds
US461603A US3922298A (en) 1969-07-29 1974-04-17 3-Oxa prostaglandin B-type compounds
US461498A US3923864A (en) 1969-07-29 1974-04-17 3-Oxa prostaglandin A-type compounds
US461543A US3920723A (en) 1969-07-29 1974-04-17 4-oxaprostaglandin e-type compounds
US461583A US3920724A (en) 1969-07-29 1974-04-17 4-oxa prostaglandin f ' -type compounds
US461496A US3923863A (en) 1969-07-29 1974-04-17 4-Oxa prostaglandin A-type compounds
US05/461,497 US3944593A (en) 1969-07-29 1974-04-17 3-Oxa prostaglandin E-type compounds
US461489A US3923862A (en) 1969-07-29 1974-04-17 4-Oxa prostaglandin {62 -type compounds

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
GB38073/69A GB1269657A (en) 1969-07-29 1969-07-29 Prostaglandin analogues, their preparation and pharmaceutical compositions containing them

Publications (1)

Publication Number Publication Date
GB1269657A true GB1269657A (en) 1972-04-06

Family

ID=10400988

Family Applications (1)

Application Number Title Priority Date Filing Date
GB38073/69A Expired GB1269657A (en) 1969-07-29 1969-07-29 Prostaglandin analogues, their preparation and pharmaceutical compositions containing them

Country Status (10)

Country Link
JP (2) JPS5028950B1 (en)
BE (1) BE754114A (en)
CH (2) CH571486A5 (en)
DE (1) DE2036471A1 (en)
FR (1) FR2059574B1 (en)
GB (1) GB1269657A (en)
HU (2) HU162687B (en)
NL (1) NL7010617A (en)
SE (1) SE383513B (en)
ZA (1) ZA704099B (en)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4181725A (en) * 1977-05-02 1980-01-01 The Regents Of The University Of Michigan Method for alleviating psoriasis
US5891910A (en) * 1987-07-17 1999-04-06 Schering Aktiengesellschaft 9-halogen-(Z) prostaglandin derivatives, process for their production and their use as pharmaceutical agents
US6225347B1 (en) 1987-07-17 2001-05-01 Schering Aktiengesellschaft 9-halogen-(Z)-prostaglandin derivatives, process for their production and their use as pharmaceutical agents

Families Citing this family (21)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3923863A (en) * 1969-07-29 1975-12-02 Upjohn Co 4-Oxa prostaglandin A-type compounds
US3923862A (en) * 1969-07-29 1975-12-02 Upjohn Co 4-Oxa prostaglandin {62 -type compounds
US3920723A (en) * 1969-07-29 1975-11-18 Upjohn Co 4-oxaprostaglandin e-type compounds
US3923861A (en) * 1969-07-29 1975-12-02 Upjohn Co 3-Oxa prostaglandin F{331 -type compounds
US3923864A (en) * 1969-07-29 1975-12-02 Upjohn Co 3-Oxa prostaglandin A-type compounds
US3944593A (en) * 1969-07-29 1976-03-16 The Upjohn Company 3-Oxa prostaglandin E-type compounds
US3922298A (en) * 1969-07-29 1975-11-25 Upjohn Co 3-Oxa prostaglandin B-type compounds
US3923865A (en) * 1969-07-29 1975-12-02 Upjohn Co 4-Oxa prostaglandin F{62 -type compounds
US3920724A (en) * 1969-07-29 1975-11-18 Upjohn Co 4-oxa prostaglandin f ' -type compounds
US3936487A (en) * 1970-06-17 1976-02-03 The Upjohn Company 3-Oxa prostaglandin Fα-type compounds
DE2258668C3 (en) * 1971-12-03 1981-08-06 Syntex Corp., Panama-City New prostaglandins, processes for their production and pharmaceuticals containing them
US4001296A (en) * 1973-05-21 1977-01-04 The Upjohn Company 5-Oxa prostaglandin E1 analogs
US3980692A (en) * 1973-05-21 1976-09-14 The Upjohn Company 5-Oxa-17,18-dehydroprostaglandin-E1 -type analogs
US3981902A (en) * 1973-05-21 1976-09-21 The Upjohn Company 5-Oxa-17,18-dehydroprostaglandin-F1.sub.α -type analogs
US3931279A (en) * 1973-05-21 1976-01-06 The Upjohn Company 5-Oxa prostaglandin F2.sub.α analogs
JPS5215047U (en) * 1975-07-22 1977-02-02
JPS5235356A (en) * 1975-09-13 1977-03-17 Toyo Seisakusho:Kk Manufacturing method of heat recovery device using heat pipe
JPS5491311U (en) * 1977-12-10 1979-06-28
JPS60238552A (en) * 1984-05-09 1985-11-27 日本軽金属株式会社 Curtain wall
JPS6443107U (en) * 1987-09-08 1989-03-15
JPH0380812U (en) * 1989-08-16 1991-08-19

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4181725A (en) * 1977-05-02 1980-01-01 The Regents Of The University Of Michigan Method for alleviating psoriasis
US5891910A (en) * 1987-07-17 1999-04-06 Schering Aktiengesellschaft 9-halogen-(Z) prostaglandin derivatives, process for their production and their use as pharmaceutical agents
US6225347B1 (en) 1987-07-17 2001-05-01 Schering Aktiengesellschaft 9-halogen-(Z)-prostaglandin derivatives, process for their production and their use as pharmaceutical agents

Also Published As

Publication number Publication date
JPS5028950B1 (en) 1975-09-19
DE2036471A1 (en) 1971-02-11
BE754114A (en) 1971-01-29
ZA704099B (en) 1971-03-31
CH571486A5 (en) 1976-01-15
SE383513B (en) 1976-03-15
HU162687B (en) 1973-03-28
HU162688B (en) 1973-03-28
JPS503311B1 (en) 1975-02-03
NL7010617A (en) 1971-02-02
FR2059574B1 (en) 1974-03-22
CH571487A5 (en) 1976-01-15
FR2059574A1 (en) 1971-06-04

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