DE2365999A1 - CYCLOPENTANES FOR THE PRODUCTION OF 15 SUBSTITUTE OMEGA-PENTANOR PROSTAGLANDINES - Google Patents
CYCLOPENTANES FOR THE PRODUCTION OF 15 SUBSTITUTE OMEGA-PENTANOR PROSTAGLANDINESInfo
- Publication number
- DE2365999A1 DE2365999A1 DE2365999A DE2365999A DE2365999A1 DE 2365999 A1 DE2365999 A1 DE 2365999A1 DE 2365999 A DE2365999 A DE 2365999A DE 2365999 A DE2365999 A DE 2365999A DE 2365999 A1 DE2365999 A1 DE 2365999A1
- Authority
- DE
- Germany
- Prior art keywords
- radical
- phenyl
- lower alkyl
- biphenyl
- cyclopentanes
- 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.)
- Withdrawn
Links
- 150000001940 cyclopentanes Chemical class 0.000 title description 2
- 238000004519 manufacturing process Methods 0.000 title description 2
- -1 alkyl radical Chemical class 0.000 claims description 21
- SXXLKZCNJHJYFL-UHFFFAOYSA-N 4,5,6,7-tetrahydro-[1,2]oxazolo[4,5-c]pyridin-5-ium-3-olate Chemical compound C1CNCC2=C1ONC2=O SXXLKZCNJHJYFL-UHFFFAOYSA-N 0.000 claims description 6
- 101000799461 Homo sapiens Thrombopoietin Proteins 0.000 claims description 6
- 102100034195 Thrombopoietin Human genes 0.000 claims description 6
- CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical compound [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 claims description 6
- 150000001875 compounds Chemical class 0.000 claims description 5
- 150000003254 radicals Chemical class 0.000 claims description 3
- WZKSXHQDXQKIQJ-UHFFFAOYSA-N F[C](F)F Chemical compound F[C](F)F WZKSXHQDXQKIQJ-UHFFFAOYSA-N 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 125000001424 substituent group Chemical group 0.000 claims description 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
- 150000003180 prostaglandins Chemical class 0.000 description 7
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical group C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 5
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 description 3
- YXVFYQXJAXKLAK-UHFFFAOYSA-N biphenyl-4-ol Chemical compound C1=CC(O)=CC=C1C1=CC=CC=C1 YXVFYQXJAXKLAK-UHFFFAOYSA-N 0.000 description 3
- 238000004587 chromatography analysis Methods 0.000 description 3
- 230000032050 esterification Effects 0.000 description 3
- 238000005886 esterification reaction Methods 0.000 description 3
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- RGSFGYAAUTVSQA-UHFFFAOYSA-N Cyclopentane Chemical compound C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 239000012442 inert solvent Substances 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- 238000005903 acid hydrolysis reaction Methods 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000004927 clay Substances 0.000 description 1
- DMEGYFMYUHOHGS-UHFFFAOYSA-N heptamethylene Natural products C1CCCCCC1 DMEGYFMYUHOHGS-UHFFFAOYSA-N 0.000 description 1
- VLKZOEOYAKHREP-UHFFFAOYSA-N hexane Substances CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- WPHGSKGZRAQSGP-UHFFFAOYSA-N methylenecyclohexane Natural products C1CCCC2CC21 WPHGSKGZRAQSGP-UHFFFAOYSA-N 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 229940094443 oxytocics prostaglandins Drugs 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
- C07D333/24—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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/38—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D307/54—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
-
- 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
- C07D317/44—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 ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D317/46—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 ortho- or peri-condensed with carbocyclic rings or ring systems condensed with one six-membered ring
- C07D317/48—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring
- C07D317/50—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to atoms of the carbocyclic ring
- C07D317/54—Radicals substituted by oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/54—Quaternary phosphonium compounds
- C07F9/5407—Acyclic saturated phosphonium compounds
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Heterocyclic Compounds Containing Sulfur Atoms (AREA)
- Heterocyclic Compounds That Contain Two Or More Ring Oxygen Atoms (AREA)
- Furan Compounds (AREA)
- Pyrane Compounds (AREA)
Description
RECHTSANWÄLTELAWYERS
ADELONSTRASSE 58 2365993ADELONSTRASSE 58 2365993
FRANKFURT AM MAIN 80FRANKFURT AM MAIN 80
Unsere Nr. 20 757 Pr/brOur no. 20 757 Pr / br
Pfizer Inc.
New York, N.Y.,V.St.A.Pfizer Inc.
New York, NY, V.St.A.
Cyclopentane zur Herstellung von 15-substituierten-(u-Pentanorprostaglandinen Cyclopentanes for the production of 15-substituted- (u-Pentanorprostaglandinen
Die Erfindung betrifft bestimmte Cyclopentanzwischenprodukte, die sich zur Herstellung neuer Analoge der natürlichen Prostaglandine eignen. Insbesondere betrifft sie Zwischenprodukte, die sich zur Herstellung neuer 15-substituierter u)-Pentanorprostaglandine eignen.The invention relates to certain cyclopentane intermediates, which can be used to produce new analogs of natural prostaglandins suitable. In particular, it relates to intermediates which can be used to prepare new 15-substituted u) -pentanorprostaglandins suitable.
Die erfindungsgemäßen Verbindungen besitzen folgende allgemeine FormelThe compounds according to the invention have the following general formula
H · ■ · .-■/""■■.H · ■ · .- ■ / "" ■■.
THPÖ* ' . IV THPÖ * '. IV
709819/0998709819/0998
worin A einen Rest der Formel Ar-(CH2) - oder -(CH2) -OR , wobei η eine ganze Zahl von 0 bis 5»wherein A is a radical of the formula Ar- (CH 2 ) - or - (CH 2 ) -OR, where η is an integer from 0 to 5 »
m eine ganze Zahl von 1 bis M,m is an integer from 1 to M,
R einen Niederalkylrest undR is a lower alkyl radical and
Ar einen α- oder ß-Furylrest, einen α- oder ß-Thienylrest, einen α- oder ß-Naphthylrest, einen Phenylrest, einen 3,4-Dimethoxyphenylrest, einen 3»1*-Methylendioxyphenyl- ' rest, einen 3,4,5-Trimethoxyphenylrest oder einen monosubstituierten Phenylrest bedeuten, wobei der Substituent ein Halogenatom, einen Trifluormethylrest, einen Phenylrest , einen Niederalkylrest oder einen Niederalkoxyrest darstellt, nu Ar is an α- or ß-furyl radical, an α- or ß-thienyl radical, an α- or ß-naphthyl radical, a phenyl radical, a 3,4-dimethoxyphenyl radical, a 3 » 1 * -methylenedioxyphenyl radical, a 3,4 , 5-trimethoxyphenyl radical or a monosubstituted phenyl radical, where the substituent represents a halogen atom, a trifluoromethyl radical, a phenyl radical, a lower alkyl radical or a lower alkoxy radical, nu
M = O, <- n oder ζ ,M = O, <- n or ζ,
^H %H -^ H % H -
W eine Einfachbindung oder eine Cis-Doppelbindung, Z eine Einfachbindung oder eine Trans-Doppelbindung, THP einen Tetrahydropyranylrest,W is a single bond or a cis double bond, Z is a single bond or a trans double bond, THP is a tetrahydropyranyl radical,
R1 einen p-Biphenylrest undR 1 is a p-biphenyl radical and
R ein Wasserstoffatom oder einen Niederalkylrest bedeuten.R represents a hydrogen atom or a lower alkyl radical.
Insbesondere betrifft die Erfindung Verbindungen der allgemeinen FormelIn particular, the invention relates to compounds of the general formula
THPOTHPO
709819/0998709819/0998
eine Verbindung der Formel:
HO
: Wa compound of the formula:
HO
: W
THPOTHPO
THPOTHPO
und eine Verbindung der Formel:and a compound of the formula:
THPOTHPO
worin A, R, Z, W, THP und R1 vorstehende Bedeutung haben.wherein A, R, Z, W, THP and R 1 have the preceding meaning.
Der Ausdruck "Prostaglandin der O-Reihe", beispielsweise PGEQ, bezieht sich auf Prostaglandin, worin die 5-6 und 13-1** Doppelbindungen gesättigt sind; d.h. PGEQ ist 5-6, 13-14, Tetrahydro PGEp· Außerdem beziehen sich im vorliegenden die Ausdrücke "1-Reihe" oder "2-Reihe" auf den Grad der ünsättigung in den Seitenketten.The term "O-series prostaglandin", for example PGE Q , refers to prostaglandin in which the 5-6 and 13-1 ** double bonds are saturated; ie PGE Q is 5-6, 13-14, Tetrahydro PGEp · In addition, as used herein, the terms "1-series" or "2-series" relate to the degree of unsaturation in the side chains.
Die erfindungsgemäßen p-Biphenylester lassen sich auf mehrere verschiedene Weisen herstellen. Diese unterscheiden sich untereinander dadurch, daß der p-Biphenylrest mit dem Prostaglandinvorläufer in unterschiedlichen Synthesestufen verknüpft wird.The p-biphenyl esters according to the invention can be divided into several create different ways. These differ from one another in that the p-biphenyl radical is linked to the prostaglandin precursor is linked in different synthesis stages.
7098 19/09987098 19/0998
-Jf--Jf-
Beispielsweise zeigt Schema A verschiedene Wege, die zu den p-Biphenylestern (PBE) führen.For example, Scheme A shows various routes leading to the p-biphenyl esters (PBE).
In jedem Falle wird die p-Biphenylgruppe durch Veresterung eingeführt, die am einfachsten dadurch erfolgt, daß man de^ri- entsprechenden frostaglandinvorläufer ■·..-. mit etwa 1 bis 10 Mol p-Phenylphenol in Gegenwart von 1 bis 2 Mol Dicyclohexyl carbodiimid in einem reaktionsinerten Lösungsmittel, typischerweise Methylenchlorid, behandelt. Es kann jedes Prostaglandinanalog als Substrat für die vorstehend genannte Veresterung verwendet werden, wie es im Schema A erläutert wird.In each case the p-biphenyl group is introduced by esterification, The easiest way to do this is to use the corresponding frostaglandin precursors ■ · ..-. with about 1 to 10 moles of p-phenylphenol in the presence of 1 to 2 moles of dicyclohexyl carbodiimide in a reaction inert solvent, typically methylene chloride. Anyone can do it Prostaglandin analog can be used as a substrate for the above-mentioned esterification, as illustrated in Scheme A.
Beispielsweise kann 9 durch vorstehend beschriebene VeresterungFor example, 9 can be obtained by esterification described above
dann in 9 PBE umgewandelt werden und 9 PBE kann/in 10 PBE umgewandelt werden. .then converted to 9 PFU and 9 PFU can / converted to 10 PFU will. .
SCHEMA ASCHEME A
- OH - OH
1^0' THPd' VR 1 ^ 0 'THPd' VR
$ PBS $ PBS
709819/0998709819/0998
-S--S-
Wie aus vorstehendem ersichtlich ist, können die p-Biphenylester.j wie 9 PBE und 10 PBE, als Substrate für die verschiedenen vorstehend beschriebenen Reduktionsscheinen zur Herstellung der Prostaglandinanaloge der 1- und 2-Reihe verwendet werden, um den entsprechenden p-Biphenylester der 1- und 2-Reihe herzustellen.As can be seen from the above, the p-Biphenylester.j such as 9 PFU and 10 PFU, as substrates for the various above described reduction coupons for the preparation of the prostaglandin analogs of the 1 and 2 series can be used to the corresponding To produce p-biphenyl esters of the 1- and 2-series.
Die Tetrahydropyranylgruppen lassen sich durch saure Hydrolyse entfernen. Es kann jede Säure verwendet werden, die keine Zersetzung des Moleküls im Laufe der Entfernung der Schutzgruppen verursacht» jedoch wird meistens 65#ige wäßrige Essigsäure verwendet. Das Produkt wird nach bekannten Verfahren gereinigt.The tetrahydropyranyl groups can be removed by acid hydrolysis. Any acid that does not decompose can be used of the molecule in the course of the removal of the protective groups but usually 65% aqueous acetic acid is used. The product is purified according to known methods.
Falls in den vorstehenden Verfahren die Reinigung durch Chromatographie erwünscht ist, lassen sich als geeignete Chromatographierträgerstoffe neutrale Tonerde und Silicagel verwenden, wobei Silicagel mit einer Körnchengröße von 7 4 bis 250 u im allgemeinen bevorzugt wird. Die Chromatographie wird zweckmäßigerweise in reaktionsinerten Lösungsmitteln, wie Äther, Äthylacetat, Benzol, Chloroform, Methylenchlorid, Cyclohexan oder η-Hexan, durchgeführt, wie in den nachfolgenden Beispielen erläutert wird.If in the above procedure purification by chromatography is desired, can be used as suitable chromatography carriers Use neutral clay and silica gel, with silica gel having a grain size of 7 4 to 250 u in general is preferred. The chromatography is expediently carried out in inert solvents such as ether, ethyl acetate, benzene, chloroform, methylene chloride, cyclohexane or η-hexane, as explained in the following examples.
Nachstehende Beispiele dienen der weiteren Erläuterung der Erfindung. In diesen Beispielen sind sämtliche Temperaturen in C angegeben und sämtliche Schmelz- und Siedepunkte sind nicht korrigiert. Weitere Beispiele für Synthesen von Prostaglandinanalogen, aus denen die erfindungsgemäßen p-Biphenylester hergestellt werden, werden in den Patentanmeldungen P 23 87 813 und P 23 34 9^5 beschrieben.The following examples serve to further illustrate the invention. In these examples all temperatures are given in C and all melting and boiling points are not corrected. Further examples of syntheses of prostaglandin analogs, from which the p-biphenyl esters according to the invention are produced are disclosed in patent applications P 23 87 813 and P 23 34 9 ^ 5.
709819/0998709819/0998
Be is p ie 1.1For example 1.1
p-Biphenyl-9-oxo-lla,l5a-bis-(tetrahydropyran-2-yloxy)-l6-phenyl-cis-5-trans-13-u)-tetranorprostadienoat p-Biphenyl-9-oxo-IIIa, 15a-bis (tetrahydropyran-2-yloxy) -16-phenyl-cis-5-trans-13-u) -tetranorprostadienoate
Eine Lösung von 9-Oxo-lla,15a-bis-(tetrahydropyran-2-yloxy)-l6-phenyl-cis-5-trans-13-u)-tetranorprostadiensäure
(10a)
(1 Äquivalent), p-Phenylphenol (10 Äquivalente) und Dicyclohexylcarbodiimid (1,25 Äquivalente) in Methylenchlorid wurde über
Nacht gerührt, eingeengt (im Vakuum) und durch Säulenchromatographie gereinigt, wobei p-Biphenyl-9-oxo-lla,15a-bis-(tetrahydropyran-2-yloxy)-l6-phenyl-cis-5-trans-13-«)-tetranorprostadienoat
erhalten wurde.A solution of 9-oxo-lla, 15a-bis (tetrahydropyran-2-yloxy) -l6-phenyl-cis-5-trans-13-u) -tetranorprostadienäure (10a)
(1 equivalent), p-phenylphenol (10 equivalents) and dicyclohexylcarbodiimide (1.25 equivalents) in methylene chloride was over
Stirred overnight, concentrated (in vacuo) and purified by column chromatography, p-biphenyl-9-oxo-IIIa, 15a-bis (tetrahydropyran-2-yloxy) -16-phenyl-cis-5-trans-13- «) tetranorprostadienoate was obtained.
p-Biphenyl-9a-hydroxy-lla,l5a-bis-(tetrahydropyran.-2-yloxy)-l6-phenyl-cis-5-trans-13-o)-tetranorprostadienoat p-Biphenyl-9a-hydroxy-lla, l5a-bis (tetrahydropyran.-2-yloxy) -16-phenyl-cis-5-trans-13-o) -tetranorprostadienoate
Eine Lösung von einem Äquivalent 9a-Hydroxy-lla,15a-bis-(tetrahydropyran-2-yloxy)-l6-phenyl-cis-5-trans-13-tt)-tetranorpro3tadiensäure
(9a), 10 Äquivalenten p-Phenylphenol und 1,25 Äquivalenten Dicyclohexylcarbodiimid in Methylenchlorid wurde über Nacht
gerührt, im Vakuum konzentriert und durch Säulenchromatographie gereinigt, wobei p-Biphenyl-9a-hydroxy-lla,15a-bis-(tetrahydropyran-2-yloxy)-l6-phenyl-cis-5-trans-13-u)-tetranorprostadienoat
erhalten wurde.A solution of one equivalent of 9a-hydroxy-IIIa, 15a-bis (tetrahydropyran-2-yloxy) -16-phenyl-cis-5-trans-13-tt) -tetranorpro3tadienoic acid (9a), 10 equivalents of p-phenylphenol and 1 .25 equivalents of dicyclohexylcarbodiimide in methylene chloride was left overnight
stirred, concentrated in vacuo and purified by column chromatography, p-biphenyl-9a-hydroxy-IIIa, 15a-bis (tetrahydropyran-2-yloxy) -16-phenyl-cis-5-trans-13-u) -tetranorprostadienoate being obtained became.
709819/0998709819/0998
Claims (1)
MCompound of the general formula:
M.
wobei η eine ganze Zahl von 0 bis 5»wherein A is a radical of the formula Ar- (CH 2 ) - or ""
where η is an integer from 0 to 5 »
3,4-Dimethoxyphenylrest, einen S^-Methylendioxyphenylrest, einen 3,4,5-Trimethoxyphenylrest oder einen monosubstituierten Phenylrest bedeuten, wobei der Substituent ein Halogenatom, einen Trifluormethylrest, einen Phenylrest, einen Niederalkylrest oder einen NiederalkoxyrestAr is an α- or ß-furyl radical, an α- or ß-thienyl radical, an α- or ß-naphthyl radical, a phenyl radical, a
3,4-Dimethoxyphenyl radical, an S ^ -Methylenedioxyphenylrest, a 3,4,5-Trimethoxyphenylrest or a monosubstituted phenyl radical, wherein the substituent is a halogen atom, a trifluoromethyl radical, a phenyl radical, a lower alkyl radical or a lower alkoxy radical
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US30481572A | 1972-11-08 | 1972-11-08 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE2365999A1 true DE2365999A1 (en) | 1977-05-12 |
Family
ID=23178143
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19732355042 Withdrawn DE2355042A1 (en) | 1972-11-08 | 1973-11-03 | NEW PROSTAGLANDIN ANALOGS AND PROCESS FOR THEIR PRODUCTION |
| DE2365999A Withdrawn DE2365999A1 (en) | 1972-11-08 | 1973-11-03 | CYCLOPENTANES FOR THE PRODUCTION OF 15 SUBSTITUTE OMEGA-PENTANOR PROSTAGLANDINES |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19732355042 Withdrawn DE2355042A1 (en) | 1972-11-08 | 1973-11-03 | NEW PROSTAGLANDIN ANALOGS AND PROCESS FOR THEIR PRODUCTION |
Country Status (24)
| Country | Link |
|---|---|
| JP (1) | JPS5644068B2 (en) |
| AR (2) | AR204816A1 (en) |
| AT (1) | AT347607B (en) |
| BE (1) | BE807047A (en) |
| CA (1) | CA1027559A (en) |
| CH (1) | CH601222A5 (en) |
| CS (1) | CS188175B2 (en) |
| DD (2) | DD113211A5 (en) |
| DE (2) | DE2355042A1 (en) |
| ES (2) | ES420326A1 (en) |
| FI (1) | FI58116C (en) |
| FR (2) | FR2205339B1 (en) |
| GB (1) | GB1456511A (en) |
| HU (2) | HU171945B (en) |
| IE (1) | IE39686B1 (en) |
| IL (1) | IL43553A (en) |
| IN (1) | IN139905B (en) |
| NL (1) | NL7315240A (en) |
| NO (2) | NO145437C (en) |
| PH (2) | PH15504A (en) |
| SE (2) | SE420198B (en) |
| SU (2) | SU538659A3 (en) |
| YU (2) | YU287973A (en) |
| ZA (1) | ZA738593B (en) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2361381A1 (en) * | 1972-07-13 | 1978-03-10 | Pfizer | (15)-(Hetero) aryl prostaglandin analogues - with long-lasting prostaglandin-like activity |
| US3929862A (en) * | 1974-01-08 | 1975-12-30 | Upjohn Co | Substituted tolylesters of PGF{HD 2{B {60 |
| US3998869A (en) * | 1974-11-14 | 1976-12-21 | The Upjohn Company | Substituted anilide esters of 16-substituted PGE2 |
| DE2737807A1 (en) * | 1976-08-27 | 1978-03-09 | Pfizer | C LOW 1 -P-BIPHENYLESTER OF OMEGA-PENTANORPROSTAGLANDINES |
| US6531504B2 (en) * | 2001-05-17 | 2003-03-11 | Allergan, Inc. | Prostanoic acid derivatives as agents for lowering intraocular pressure |
-
1973
- 1973-01-01 AR AR250900A patent/AR204816A1/en active
- 1973-11-01 GB GB5088973A patent/GB1456511A/en not_active Expired
- 1973-11-01 SE SE7314885A patent/SE420198B/en unknown
- 1973-11-02 IL IL43553A patent/IL43553A/en unknown
- 1973-11-03 DE DE19732355042 patent/DE2355042A1/en not_active Withdrawn
- 1973-11-03 DE DE2365999A patent/DE2365999A1/en not_active Withdrawn
- 1973-11-06 IN IN2443/CAL/73A patent/IN139905B/en unknown
- 1973-11-07 YU YU02879/73A patent/YU287973A/en unknown
- 1973-11-07 CA CA185,201A patent/CA1027559A/en not_active Expired
- 1973-11-07 AT AT937173A patent/AT347607B/en not_active IP Right Cessation
- 1973-11-07 FI FI3444/73A patent/FI58116C/en active
- 1973-11-07 NL NL7315240A patent/NL7315240A/xx not_active Application Discontinuation
- 1973-11-07 ES ES420326A patent/ES420326A1/en not_active Expired
- 1973-11-07 NO NO4290/73A patent/NO145437C/en unknown
- 1973-11-08 CS CS737670A patent/CS188175B2/en unknown
- 1973-11-08 ZA ZA738593A patent/ZA738593B/en unknown
- 1973-11-08 DD DD180196*A patent/DD113211A5/xx unknown
- 1973-11-08 HU HU73PI00000453A patent/HU171945B/en unknown
- 1973-11-08 JP JP12501173A patent/JPS5644068B2/ja not_active Expired
- 1973-11-08 PH PH15198A patent/PH15504A/en unknown
- 1973-11-08 DD DD174537A patent/DD111370A5/xx unknown
- 1973-11-08 CH CH1570273A patent/CH601222A5/xx not_active IP Right Cessation
- 1973-11-08 BE BE1005489A patent/BE807047A/en unknown
- 1973-11-08 IE IE2013/73A patent/IE39686B1/en unknown
- 1973-11-08 FR FR7339759A patent/FR2205339B1/fr not_active Expired
- 1973-11-08 HU HU73PI00000400A patent/HU171818B/en unknown
- 1973-11-11 SU SU1971421A patent/SU538659A3/en active
-
1974
- 1974-07-31 AR AR254983A patent/AR202311A1/en active
- 1974-10-03 NO NO743588A patent/NO146280C/en unknown
-
1975
- 1975-02-13 ES ES434687A patent/ES434687A1/en not_active Expired
- 1975-03-20 SU SU752115232A patent/SU1021340A3/en active
- 1975-08-18 FR FR7525565A patent/FR2275452A1/en active Granted
-
1976
- 1976-03-12 PH PH18199A patent/PH13794A/en unknown
-
1977
- 1977-04-15 SE SE7704369A patent/SE7704369L/en not_active Application Discontinuation
-
1980
- 1980-10-15 YU YU02644/80A patent/YU264480A/en unknown
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