WO1993007150A1 - Tetraphenylporphyn derivatives - Google Patents
Tetraphenylporphyn derivatives Download PDFInfo
- Publication number
- WO1993007150A1 WO1993007150A1 PCT/EP1992/002283 EP9202283W WO9307150A1 WO 1993007150 A1 WO1993007150 A1 WO 1993007150A1 EP 9202283 W EP9202283 W EP 9202283W WO 9307150 A1 WO9307150 A1 WO 9307150A1
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- WIPO (PCT)
- Prior art keywords
- compound
- group
- formula
- alkylene
- hapten
- Prior art date
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- IQFXJRXOTKFGPN-UHFFFAOYSA-N CCN(CC)C=C Chemical compound CCN(CC)C=C IQFXJRXOTKFGPN-UHFFFAOYSA-N 0.000 description 1
- YXFVVABEGXRONW-UHFFFAOYSA-N Cc1ccccc1 Chemical compound Cc1ccccc1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/22—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains four or more hetero rings
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Definitions
- This invention relates generally to catalytic
- the invention also relates to
- tetraphenylporphyrin derivatives tetraphenylporphyrin derivatives, haptens containing them, antigens containing the haptens, and antibodies raised to the antigens, which have application in the processes.
- Metalloporphyrins are able to act as catalysts for many types of chemical reactions; especially oxidative
- substrate that is correctly orientated can be bound and reacted.
- Schwabacher et al managed to prepare antibodies to Fe 3+ and Co 3+ complexes of synthetic meso-tetra-kis (4-carboxyphenyl) porphine by coupling the complexes to keyhole limpet hemocyanin (KLH) or bovine serum albumin (BSA) and applying standard monoclonal techniques. However no further steps of the proposed process were carried out.
- KLH keyhole limpet hemocyanin
- BSA bovine serum albumin
- EP 0305870 discloses a similar concept, in general terms, in which an immunoproximity catalyst for chemical reactions is prepared by selecting a hapten which
- a transition state complex of the reactant and a catalyst corresponds to, but is different from, a transition state complex of the reactant and a catalyst.
- An immune response is then stimulated using an antigen derived from the hapten to produce antibodies to the hapten.
- the antibodies are then isolated.
- "Converting" haptens are then used to covalently bind the catalyst to the antibodies to produce "modified” antibodies.
- the modified antibodies are then isolated for use. These modified antibodies catalyze cleavage of bonds in the target molecules; much in the manner of an enzyme.
- the antibodies are said to speed up the reaction and to introduce site-specificity.
- the catalysts could be general acid-base catalysts, nucleophilic catalysts, electrophilic catalysts and metal catalysts. No specific mention is made of metalloporphyrins. Also, for many processes, the
- EP 0305870 does not disclose any specific process examples which illustrate that the modified
- PCT patent publication WO 92/01781 discloses a similar process in which metalloporphyrin derivatives are used as cofactors or catalysts. Also proposed in general terms are porphyrins derivativised with alkyl groups so that the resultant antibody would have alkyl or aryl binding sites. The derivatives are used to generate haptens that mimic the actual catalyst and the substrate in the relative
- the haptens are then used to generate antibodies which have binding sites complementary to the catalyst and the
- the antibodies need not have the catalyst covalently bound to them prior to use.
- this invention provides a compound of the formula I:
- each R 2 and R 2 ' is independently selected from -H, -F, -Cl, -Br, -CH 3 , -COOH, -SO 3 H, -NO 2 and phenyl;
- each R 3 and R 3 ' is independently selected from -H, -F, -Cl, -Br, -CH 3 , -O-C 1-6 -alkyl, -NO 2 , phenyl, -NH 2 , and
- At least one R 3 or R 3 ' is independently selected from (a) -NH-CO-alkylene-3N-imidazole or -NH-CO-alkylene-3- pyridine, in which each alkylene has 2 to 4 carbon atoms; and (b) -CO-alkylene-3N-imidazole or -CO-alkylene- 3-pyridine, in which each alkylene has 3 or 4 carbon atoms; or
- R 3 and R 3 ' on opposing phenyl groups, jointly form (c) -NH-CO-alkylene-3-pyridyl-5-alkylene-CO-NH- or -CO-alkylene-3-pyridyl-5-alkylene-CO-, in which each
- alkylene has 2 to 4 carbon atoms
- R 4 is a) a hydrogen atom; b) a linker group containing a reactive centre or group through which the compound of Formula I may be bonded to another compound; or c) a
- each R 8 and R 8 ' is independently -H, -F, -Cl, -Br or -CN;
- R 4 is a linker group b
- it is preferably of the formula -(CH 2 ) m -R 5 -(CH 2 ) n -(R 6 ) p -A in which R 5 is -(CO)-,
- R 6 is -O-, -S-, or -(NH)-, each of m, n and p independently is 0 or 1 and A is a reactive leaving group or centre or, when p is 1, A may also be a hydrogen atom.
- n and p are 0 and A is halogen, particularly Cl or Br.
- a particularly preferred linker group is -COCl, which may easily react with a functional group such as -OH or -NH 2 on another molecule to form the bridging group -CO-O- or -CO-NH-.
- R 4 is a removable protecting group c
- it is preferably a protecting group which will protect the >N-NH 2 group against oxidation by a reagent such as 2,3-dichloro- 5,6-dicyanobenzoquinone (DDQ) , and which is removable by hydrolysis under acid or alkaline conditions.
- DDQ 2,3-dichloro- 5,6-dicyanobenzoquinone
- a preferred protecting group is CF 3 -CO-, which may be removed by mild alkaline hydrolysis.
- R 1 is H, a group which increases the water solubility of the compound, or a functional group which permits the attachment of a carrier protein to the compound. More preferably, at least one R 1 is -NH-CO-CH 2 -CH 2 -COOH or
- R 2 and R 2 ' are all H.
- one R 3 or R 3 ', or one pair of R 3 and R 3 ' are selected from groups a), b) and c) as defined above for R 3 and R 3 '.
- the remaining R 3 and R 3 ' are preferably H.
- R 8 and R 8 ' are preferably H.
- the C 1-6 -alkyl may be any branched or unbranched alkyl group that contains up to 6 carbon atoms.
- Methyl is
- derivative of a desired substrate may be attached to the linker group.
- the invention also provides a compound of formula I, as defined above, for use in the preparation of a hapten that mimics a transition state of a metalloporphyrin catalyst and a substrate in a reaction.
- the invention also provides a process for the
- step a) the deprotection step will depend upon the nature of the protecting group, but is preferably carried out by acid or alkaline hydrolysis. Where the protecting group is CF 3 CO-, mild alkaline hydrolysis may be used; for example using EtOH/KOH or EtOH/Ca(OH) 2 at temperatures in the 65°C to 75°C.
- the precursor of the linker group may be, for example, X-(CH 2 ) m -R 5 -(CH 2 ) n -(R 6 ) p -A in which X is a reactive leaving group or atom, preferably Cl or Br, and the other symbols are as defined above.
- X is a reactive leaving group or atom, preferably Cl or Br, and the other symbols are as defined above.
- a suitable precursor is phosgene or diphosgene.
- step c) where the protecting group is CF 3 -CO-, the compound of formula III in which R 4 is hydrogen may be reacted with trifluoracetic anhydride in a polar non-aqueous solvent.
- the oxidation step ii) may be carried out using an oxidizing agent such as DDQ in an inert solvent, for example methylene chloride.
- the starting material of formula III may be prepared by reacting the corresponding porphyrin with O-m-toluene-sulphonylhydroxylamine as described in Callot, H.J.; 1979; Tetrahedron, 35, 1455-6.
- this invention provides a hapten comprising a metalloporphyrin cofactor bound to a residue of a substrate, the hapten mimicking a transition state of a metalloporphyrin catalyst and the substrate in a reaction, and in which the metalloporphyrin cofactor is of the formula II:
- R 1 , R 2 , R 2 ', R 3 , R 3 ', R 8 , and R 8 ' are as defined above for formula I;
- R 4 ' is a bridging group connecting the metalloporphyrin catalyst to the residue of the substrate.
- M is a metal ion having a co-ordination number of at least 4.
- the bridging group may be any suitable bridging group, with the proviso that it should be selected such that the spacial orientation of the metalloporphyrin cofactor with respect to the residue is as close as possible to that of the transition state formed by the corresponding
- the bridging group is of the formula
- R 6 is -O-, -S-, or -(NH)-
- m is 0 or 1
- n is 0 or 1
- p is 0 or 1.
- m, n and p are 0.
- the bridging group is -(SO 2 )-O- or
- bridging group projects axially from the centrally located amino group. Therefore the hapten can more closely mimic the relative positions of the
- R 3 or R 3 ' is independently selected from (a) -NH-CO-alkylene-3N-imidazole or -NH-CO-alkylene-3-pyridine, in which each alkylene has 2 to 4 carbon atoms; and (b) -CO-alkylene-3N-imidazole or -CO-alkylene-3-pyridine, in which each alkylene has 3 or 4 carbon atoms; or a pair of R 3 and R 3 ' on opposing phenyl groups jointly form (c) -NH-CO-alkylene-3-pyridyl-5-alkylene-CO-NH- or -CO-alkylene-3-pyridyl-5-alkylene-CO-, in which each
- alkylene has 2 to 4 carbon atoms; a nitrogen atom in the heterocyclic ring acts as a fifth ligand for the metal ion M.
- the side of the porphyrin that has the fifth ligand is shielded and cannot come into contact with antibodies raised to antigens containing the hapten.
- the substrate may be any molecule upon which an
- the residue is a group that corresponds to the substrate molecule and is bound to the bridging group.
- the residue may differ from the substrate in that it may contain an additional functional group through which it is bound to the bridging group.
- the residue may bind to the bridging group through an atom or functional group existing in the substrate. In either case, the residue is attached to the bridging group in such a way to mimic a transition state of the substrate in a reaction pathway with a metalloporphyrin catalyst.
- the substrate may contain a non-activated primary, secondary or tertiary carbon atom which is to be hydroxylated.
- the residue would then comprise the substrate molecule with a hydrogen removed from the carbon atom or with the hydrogen replaced by a functional group that is bonded to the bridging group.
- the substrate in the preparation of Ser 8 -cyclosporin A from cyclosporin A (CsA), the substrate would be cyclosporin A and the residue would be Ser 8 -cyclosporin A bonded to the bridging group though the OH of Ser 8 .
- the -O- of the hydroxy may be considered to be part of the residue or the bridging group.
- the residue may contain a group of the formula >N-alkylene'- in which the alkylene' may be any branched, unbranched, substituted or
- the substrate will be a group of the formula >N-alkyl.
- the residue may contain a group of the formula -O-alkylene'- in which alkylene' is as defined above.
- the substrate would then have a group of the formula -O-alkyl and the hapten would mimic a transition state in the dealkylation and hydroxylation of the -O-.
- -O-alkyl corresponds to the methoxy group on the carbon atom numbered 15.
- the residue would then be ascomycin but with one of the hydrogen atoms of the methoxy group replaced by a bond to the bridging group.
- the hapten would then mimic a transition state in the replacement of an alkoxy group with a hydroxy group on carbon atom 15 of ascomycin.
- the residue may contain an aromatic group of which a carbon atom is attached to the bridging group.
- the substrate would then also contain an aromatic group and the hapten would mimic a transition state in the hydroxylation of the aromatic ring.
- the residue may contain the group of the formula or
- R 12 and R 13 are each independently a substituted carbon atom
- the residue may contain the group
- R 14 is H or an unsubstituted or substituted alkyl group and R 14 ' is an unsubstituted or substituted alkyl group.
- the substrate would then contain a group
- the substituents on the groups R 14 and R 14 ' must permit the desaturation of the C-C bond and hence the removal of a hydrogen atom from one of the carbon atoms.
- Specific examples would be the desaturation of dihydro-MeBmt 1 cyclosporin A to cyclosporin A and the desaturation of valproic acid to 4, 5-dehydro-valproic acid.
- each of R 2 , R 2 ', R 3 and R 3 is H and a least one R 1 is -NH-CO-CH 2 -CH 2 -COOH or NH 2 and the others are H.
- -NH-CO-CH 2 -CH 2 -COOH or NH 2 facilitates coupling of a carrier protein to the hapten.
- solubility of the hapten can be increased.
- the solubility of the hapten can also be increased by substituting the para-position of the phenyl groups with carboxy or ester groups.
- the metal ion M is such that when it is coordinated in the hapten, it is inert; particularly to oxygen.
- the metal ion may be Ni 2+ , Zn 2+ or Sn 4+ .
- the invention provides an antigen comprising a hapten, as defined above, coupled to a carrier protein that is capable of causing an immunogenic response.
- the carrier protein may be connected to the porphyrin portion of the hapten; especially to one of the R 1 groups. Alternatively the carrier protein may be connected to the residue portion of the hapten.
- the carrier protein may be any suitable protein such as keyhole limpet hemocyanin
- KLH bovine serum albumin
- ovalbumin ovalbumin
- this invention provides an antibody, or a fragment thereof, that binds to a hapten as defined above.
- the antibody is produced by monoclonal techniques.
- the antibody, or fragment has the advantage that it has two binding pockets; one for the porphyrin portion and the other for the residue portion.
- this invention provides a process for the production of antibodies suitable for controlling reactions in which a substrate undergoes reaction in the presence of a metalloporphyrin catalyst to give rise to specific regioisomers or enantiomeric pure compounds, the process comprising:
- the antibodies are monoclonal antibodies.
- the process may further comprise the step of selecting the antibodies by binding them to haptens as defined above that have been immobilised in chromatography columns or bound to tracer proteins.
- this invention provides a process for the oxidation of a substrate, in the presence of a
- metalloporphyrin catalyst to produce a specific regioisomer or enantiomer; the process comprising:
- the metalloporphyrin catalyst is coordinated with a metal ion selected from Fe 3+ , Cr 3+ and Mn 3+ .
- N-amino-porphyrins of formula I may be synthesised by reacting tetraphenylporphyrin with O-m-toluenesulfonyl-hydroxylamine in a suitable solvent such as chloroform to produce N-aminotetraphenylchlorin.
- the N-aminotetraphenylchlorin may be isolated and purified using
- a suitable protecting group for example a trifluoroacetyl group, may then be introduced to protect the introduced amino group and the compound oxidized to give N- (protecting group) amino-tetraphenylporphyrin.
- the residue of the substrate may be produced by first synthesising or providing the desired product (ie, the substrate when reacted). This may be done using classical chemical pathways or by direct hydroxylation using a porphyrin catalyst.
- N-hydroxymethylleucine 4 -CsA may be produced by reacting CsA over a porphyrin catalyst in the presence of magnesium monoperoxyphthalate.
- the product is then covalently bonded to the bridging group of the aminoporphyrin, for example by condensation.
- the procedure adopted will depend upon the desired product but will be facilitated by the amination of the porphyrin.
- the adduct formed in the condensation step may be isolated and purified using chromatography.
- the adduct is then complexed with a suitable metal ion for example by dissolving a salt of the metal ion in a suitable solvent and refluxing with the adduct.
- a suitable metal ion coordinates between the introduced nitrogen and the three pyrrol nitrogen atoms of the porphyrin.
- haptens may be produced by similar methods.
- the following reaction scheme can be adopted:
- the antigen is produced by coupling to the hapten a carrier protein that renders the hapten/carrier protein complex immunogenic.
- the carrier protein may be covalently bound to the hapten by providing one of the R 1 groups in the form of an amino group; which then forms a bridge between the carrier protein and the hapten. Suitable procedures are disclosed in Richards et. al; 1990; Current Research in Photosynthesis, 3, 695-8.
- the advantage of coupling the carrier protein to the porphyrin portion of the hapten, as opposed to the residue portion, is its general applicability since the residue portion need not bear a further functional group for the attachment of the carrier protein. However if a functional group is present in the residue portion or can be introduced by synthesis, the carrier protein can be attached to it.
- Other procedures for binding carrier proteins to haptens are disclosed in Harada, A et al; 1990; Chemistry Letters, 917-918 and 1991; Chemistry Letters, 953- 956.
- the antigens may then be used to immunise mice.
- the spleen cells of the mice that give a good response are fused with myeloma cells to produce hybridomas.
- Those hybridomas that secrete monoclonal antibodies specific to the haptens are then selected.
- the haptens may also be used to isolate and purify the desired antibodies from the antibodies produced by the various hybridomas. This is a significant advantage since radiolabelled antibodies that bind the desired antibody need not be prepared. This can be done by selecting those antibodies which bind to the haptens; for example by
- the selected and purified antibodies may then be used in reactions to produce the desired product in a manner similar to that described in WO 92/01781.
- metalloporphyrin catalyst which can fit into the pocket of the antibody, is provided.
- the metalloporphyrin catalyst, the substrate and the antibodies are then combined.
- An oxygen source is then added under controlled conditions. If desired, the catalyst may be covalently bound to the
- the catalyst may be added separately from the antibody and allowed to bind to the antibody during the process.
- the substrate will be able to enter the cavity formed by the antibody and porphyrin only if it is in the correct orientation to the catalyst to produce the desired product.
- the D-Ala 8 of CsA may be converted to D-Ser 8 by using the following procedure.
- a catalyst, CsA and antibodies raised to the aminoporphyrin-bridging group-D-Ser 8 -CsA antigen are then mixed in a suitable solvent.
- An oxygen source is then added under controlled conditions.
- CsA with the correct orientation is able to enter the pocket of the antibody and offer the methyl group to be
- the N-methylgroup of leucine 4 of CsA may be converted to 4-N-hydromethylleucine by using the following procedure.
- a catalyst, CsA and antibodies raised to the aminoporphyrin-bridging group-N-hydromethylleucine 4 - CsA antigen are then mixed in a suitable solvent.
- An oxygen source is then added under controlled conditions.
- CsA with the correct orientation is able to enter the pocket of the antibody and bond offer the N-methyl group of leucine 4 to the metal-oxygen group of the porphyrin.
- the hydroxylated N-hydromethylleucine 4 -CsA is then removed.
- the source of oxygen atoms may be selected from H 2 O 2 , iodosobenzene, magnesium monoperoxyphthalate, NaOCl, KHSO 5 and the like.
- substrates that have more than one site that can be hydroxylated, dealkylated,
- epoxidated, desaturated and the like can be selectively attacked so that only the desired site is altered.
- substrates that have prochiral centres that, when reacted, can form diastereomers can be selectively reacted so that only one diastereomer forms.
- single enantiomer products can be produced from substrates that, when ordinarily reacted, form racemic mixtures.
- Example 1 Hapten formed from N-Amino-5,10,15,20-Tetraphenyl-21H,23H-Porphyrin-Derivative and
- N-Amino-tetraphenyl-chlorin from Tetraphenyl-porphyrin 10 g of Tetraphenylporphyrin is dissolved in 500 ml warm chloroform. The solution is then cooled to 20 °C and 9.8 g O-mesitylsulfonylhydroxylamine is added to it. The solution is then stirred for 20 hours at room temperature. The green reaction mixture is then heated to 60°C for 1 hour and 2N sodium carbonate with chloroform added. The crystalline residue (10 g) is then separated using column chromatography (500 g Alox N, Activity V). After elution with chloroform, 7.5 g of an adduct is obtained. 680 mg N-amino-tetraphenyl-chlorin is then eluted using a chloroform : Ethanol (ratio 100 : 0.6 to 1.0) mixture.
- N-amino-tetraphenyl-chlorin 631 mg N-amino-tetraphenyl-chlorin is dissolved in 30 ml of absolute dimethyl-formamide and 2 ml pyridine. 122 mg of 4-dimethyl-aminopyridine (1mM) is then added and a solution of 231 mg trifluoro acetic acid anhydride (1.1 mM) in 3 ml methylchloride at 20oC is added dropwise over 5 minutes. The solution is then stirred for 10 minutes. The reaction mixture is then evaporated and the residue is shaken with 2N sodium carbonate and chloroform and then washed once with water. 850 mg of N-trifluoroacetylamino-tetraphenyl-chlorin is obtained.
- a suspension of 400 mg of N-trifluoroacetylamino-tetraphenyl-porphyrin in 40 ml of ethanol is mixed with a solution of 0.5 g calcium hydroxide in 10 ml of ethanol.
- the mixture i s then sti rred for 30 minutes at 70 to 75 o C .
- the precipitate is then cooled to room temperature, filtered and washed with ethanol.
- the precipitate is then crystallised out of a chloroform-methanol mixture to give 280 mg of
- a solution of 44.9 mg of 97% diphosgene is mixed with 2 ml of dichloromethane.
- the resulting solution is cooled to 0 to 5oC and a solution of 244 mg of N-hydroxymethyl- leucine 4 -Cyclosporin A in 5 ml dichloromethane is then added dropwise over 15 minutes.
- the solution is then stirred at 0oC for 15 minutes and a solution of 126 N-amino- tetraphenyl-porphyrin and 25 mg of 4-dimethylaminopyridine in 1 ml pyridine and 8 ml dichloromethane is added rapidly.
- the reaction mixture is allowed to react for 2 hours at room temperature and then 2N sodium carbonate and dichloromethane is added.
- the residue (430 mg) is then purified using column chromatography (65 g Alox basic, activity II, chloroform). 340 mg of the condensation product is obtained.
- N-amino-tetraphenyl-porphyrin is produced in the same manner as described in Example 1, steps 1.1. to 1.4. 2.2. Condensation of Serine 8 -Cyclosporin A with
- the hapten obtained from step 2.3 is activated as its benzotriazole ester in dimethyl formamide (DMF) using bis[2-oxo-3-oxazolidinyl]phosphinic chloride (BOP)/hydroxybenzotriazol (HOBt). This is then added to a solution of protein (KLH, BSA or ovalbumin) in 2.5:1 DMSO:borate buffer at pH 8.5. A hapten:protein stoichiometry of 5:1 is used to prevent over-derivativisation and precipitation of the protein. After 4 hours, the reaction mixture is dialyzed against phosphate-buffered saline to remove organic solvents. A conjugate for each protein is obtained
- IRCF1 mice are anaesthetized and the peritoneal cavities surgically opened to access the spleen.
- the surface of the spleen is swabbed with an ethanolic solution containing KLH conjugate obtained from example 3.
- the mice are immunised in a similar manner on day 22. Serum titres are measured on day 27 by ELISA analysis against free hapten or BSA derivatives absorbed in wells of polystyrene
- the antibodies also have partial antibodies to microtitre plates.
- the antibodies also have partial antibodies to microtitre plates.
- the antibodies also have partial antibodies to microtitre plates.
- the antibodies also have partial antibodies to microtitre plates.
- the antibodies also have partial antibodies to microtitre plates.
- the antibodies also have partial antibodies to microtitre plates.
- the antibodies also have partial antibodies to microtitre plates.
- the antibodies also have partial antibodies to microtitre plates.
- BSA and KLH conjugates obtained from example 3 are added to Ribi adjuvant and 6 IRC1 mice are immunised using i.p. injections. On day 14, the mice are boosted with conjugate absorbed on bentonite and the serum sampled on day 17. Three mice showing high serum titres are boosted with further conjugate and are sacrificed on day 31. The spleens from two mice are used in standard fusion protocols using Sp2/0 myeloma cells and PEG. A stable clone which secretes antibody specific for the BSA conjugate is isolated.
- the antibodies may be selected and purified using free hapten immobilised in an affinity chromatograph.
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Peptides Or Proteins (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Abstract
Description
Claims
Priority Applications (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP92920263A EP0606295A1 (en) | 1991-10-04 | 1992-10-02 | Tetraphenylporphyn derivatives |
JP5506611A JPH06511245A (en) | 1991-10-04 | 1992-10-02 | Tetraphenylporphine derivative |
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DEP4132893.0 | 1991-10-04 | ||
DE4132893 | 1991-10-04 | ||
DE4141381 | 1991-12-16 | ||
DEP4141381.4 | 1991-12-16 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO1993007150A1 true WO1993007150A1 (en) | 1993-04-15 |
Family
ID=25907938
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/EP1992/002283 WO1993007150A1 (en) | 1991-10-04 | 1992-10-02 | Tetraphenylporphyn derivatives |
Country Status (5)
Country | Link |
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EP (1) | EP0606295A1 (en) |
JP (1) | JPH06511245A (en) |
AU (1) | AU2686592A (en) |
CA (1) | CA2116652A1 (en) |
WO (1) | WO1993007150A1 (en) |
Cited By (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5877165A (en) * | 1995-11-02 | 1999-03-02 | Brookhaven Science Associates | Boronated porhyrins and methods for their use |
EP1762248A1 (en) * | 2005-09-09 | 2007-03-14 | CORIT Consorzio per la Ricerca sul | Use of cobalt porphyrins in joint therapy with an immunosuppressant drug for treatment of transplant patients or autoimmune disorders |
CN103819480A (en) * | 2014-03-11 | 2014-05-28 | 沅江华龙催化科技有限公司 | Continuous production technology for tetra-aryl-bi-metal porphyrin |
CN103880851A (en) * | 2014-03-11 | 2014-06-25 | 沅江华龙催化科技有限公司 | Continuous production process of tetraaryl metal porphyrin |
CN103880852A (en) * | 2014-03-11 | 2014-06-25 | 沅江华龙催化科技有限公司 | Continuous production process of tetraaryl porphin |
CN111440352A (en) * | 2020-04-15 | 2020-07-24 | Tcl华星光电技术有限公司 | Magnetic polymer microsphere and preparation method thereof |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0305870A2 (en) * | 1987-09-02 | 1989-03-08 | Igen, Incorporated | Production of immunoproximity catalysts |
WO1992001781A1 (en) * | 1990-07-17 | 1992-02-06 | The Regents Of The University Of California | Antibody-mediated cofactor-driven reactions |
-
1992
- 1992-10-02 WO PCT/EP1992/002283 patent/WO1993007150A1/en not_active Application Discontinuation
- 1992-10-02 AU AU26865/92A patent/AU2686592A/en not_active Abandoned
- 1992-10-02 EP EP92920263A patent/EP0606295A1/en not_active Withdrawn
- 1992-10-02 CA CA002116652A patent/CA2116652A1/en not_active Abandoned
- 1992-10-02 JP JP5506611A patent/JPH06511245A/en active Pending
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0305870A2 (en) * | 1987-09-02 | 1989-03-08 | Igen, Incorporated | Production of immunoproximity catalysts |
WO1992001781A1 (en) * | 1990-07-17 | 1992-02-06 | The Regents Of The University Of California | Antibody-mediated cofactor-driven reactions |
Non-Patent Citations (4)
Title |
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Chemical Abstracts, volume 114, no. 11, 18 March 1991, (Columbus, Ohio, US), Keinan E. et al. : "Towards antibody mediated metallo-porphyrin chemistry ", see, abstract 97314p, & Pure Appl. Chem. 1990, 62(10), 2013-201 * |
J. Am. Chem. Soc., Vol. 111, 1989 Alan W. Schwabacher et al.: "Metalloselective Anti-Porphyrin Monoclonal Antibodies ", * |
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JPH06511245A (en) | 1994-12-15 |
AU2686592A (en) | 1993-05-03 |
EP0606295A1 (en) | 1994-07-20 |
CA2116652A1 (en) | 1993-04-15 |
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