WO1997032885B1 - Synthesis of isoimide of chlorins and bacteriochlorins and their use for diagnosis and treatment of cancer - Google Patents
Synthesis of isoimide of chlorins and bacteriochlorins and their use for diagnosis and treatment of cancerInfo
- Publication number
- WO1997032885B1 WO1997032885B1 PCT/US1997/003891 US9703891W WO9732885B1 WO 1997032885 B1 WO1997032885 B1 WO 1997032885B1 US 9703891 W US9703891 W US 9703891W WO 9732885 B1 WO9732885 B1 WO 9732885B1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- purpurin
- imide
- group
- alkyl
- derivative
- Prior art date
Links
- VZUHQRBBQSLSHS-SSZFMOIBSA-N Isoimide Chemical compound C1=CC(Br)=CC=C1\N=C/1C(CCCC2)=C2C(=O)O\1 VZUHQRBBQSLSHS-SSZFMOIBSA-N 0.000 title claims 3
- 206010028980 Neoplasm Diseases 0.000 title 1
- 150000004036 bacteriochlorins Chemical class 0.000 title 1
- 230000015572 biosynthetic process Effects 0.000 title 1
- 201000011510 cancer Diseases 0.000 title 1
- 150000004035 chlorins Chemical class 0.000 title 1
- 238000003745 diagnosis Methods 0.000 title 1
- 238000003786 synthesis reaction Methods 0.000 title 1
- 125000000217 alkyl group Chemical group 0.000 claims abstract 17
- 150000001875 compounds Chemical class 0.000 claims abstract 12
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims abstract 6
- 239000000126 substance Substances 0.000 claims abstract 6
- 125000000539 amino acid group Chemical group 0.000 claims abstract 5
- 125000003118 aryl group Chemical group 0.000 claims abstract 5
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract 5
- 239000001257 hydrogen Substances 0.000 claims abstract 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract 5
- 229920000768 polyamine Polymers 0.000 claims abstract 5
- 239000004721 Polyphenylene oxide Substances 0.000 claims abstract 3
- 125000002947 alkylene group Chemical group 0.000 claims abstract 3
- 229920000570 polyether Polymers 0.000 claims abstract 3
- 125000000547 substituted alkyl group Chemical group 0.000 claims abstract 3
- BBNQQADTFFCFGB-UHFFFAOYSA-N purpurin Chemical class C1=CC=C2C(=O)C3=C(O)C(O)=CC(O)=C3C(=O)C2=C1 BBNQQADTFFCFGB-UHFFFAOYSA-N 0.000 claims 24
- -1 imide derivative of purpurin Chemical class 0.000 claims 21
- 238000000034 method Methods 0.000 claims 15
- 238000004519 manufacturing process Methods 0.000 claims 8
- 150000008044 alkali metal hydroxides Chemical class 0.000 claims 7
- 150000003949 imides Chemical class 0.000 claims 6
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims 5
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 5
- BMVXCPBXGZKUPN-UHFFFAOYSA-N 1-hexanamine Chemical compound CCCCCCN BMVXCPBXGZKUPN-UHFFFAOYSA-N 0.000 claims 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims 4
- 125000003342 alkenyl group Chemical group 0.000 claims 4
- 125000003545 alkoxy group Chemical group 0.000 claims 4
- 125000004104 aryloxy group Chemical group 0.000 claims 4
- 150000001718 carbodiimides Chemical class 0.000 claims 4
- 229910052799 carbon Inorganic materials 0.000 claims 4
- 125000001475 halogen functional group Chemical group 0.000 claims 4
- 150000002678 macrocyclic compounds Chemical class 0.000 claims 4
- 150000008064 anhydrides Chemical group 0.000 claims 2
- BHPNXACHQYJJJS-UHFFFAOYSA-N bacteriochlorin Chemical compound N1C(C=C2N=C(C=C3NC(=C4)C=C3)CC2)=CC=C1C=C1CCC4=N1 BHPNXACHQYJJJS-UHFFFAOYSA-N 0.000 claims 2
- 125000004432 carbon atom Chemical group C* 0.000 claims 2
- 239000007795 chemical reaction product Substances 0.000 claims 2
- SURLGNKAQXKNSP-DBLYXWCISA-N chlorin Chemical compound C\1=C/2\N/C(=C\C3=N/C(=C\C=4NC(/C=C\5/C=CC/1=N/5)=CC=4)/C=C3)/CC\2 SURLGNKAQXKNSP-DBLYXWCISA-N 0.000 claims 2
- 125000001033 ether group Chemical group 0.000 claims 2
- 229920006395 saturated elastomer Polymers 0.000 claims 2
- 125000001424 substituent group Chemical group 0.000 claims 2
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical group C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 claims 1
- 150000004702 methyl esters Chemical class 0.000 claims 1
- 238000002428 photodynamic therapy Methods 0.000 abstract 1
Abstract
Compounds having utility as light absorbing compounds, especially in the area of photodynamic therapy. Such compounds have formula (I), where z is = 0 or NR14; R14 is alkyl or substituted alkyl, R1 is an amino acid group, a polyamine group, a polyether group or OR13 where R13 is alkyl; R4 through R11 are -H, -OH, alkyl, alkylene, -OR16 where R16 is H, alkyl or aryl, or a carbonyl containing group, provided that: R4 may be taken together with R5 to form =O; R6 may be taken together with R7 to form =O; R8 may be taken together with R9 to form =O; R10 may be taken together with R11 to form =O; and R4 and R7 may together form a chemical bond and R8 and R11 may together form a chemical bond; and R12 is hydrogen or lower alkyl; provided that if one z is 0, the other z is -NR14.
Claims
AMENDED CLAIMS
[received by the International Bureau on 9 September 1997 (09 09.97), original claims 1 , 2, 9, 1 1 , 17 and 19 amended; original claims 12, 15, 16, 18, 22, 23 and 25 cancelled, remaimng claims unchanged (6 pages) |
1. A method for the manufacture of an imide derivative of purpurin comprising: reacting hexylamine with a chlorin or bacteriochlorin having a macrocycle with a six membered anhydride ring fused thereto, said macrocycle containing a and b rings which may be saturated or unsaturated at R^ to R-j^ positions of the rings and which R4 and R-±ι positions may contain at least one group selected from the group consisting of hydrogen, hydroxy, formyl, substituted and unsubstituted alkyl, alkoxy, alkenyl, aryl and aryloxy wherein carbon containing groups may be substituted with a substituent selected from carboxyl, hydroxy, phosphoro, carboxy, halo, sulfo, amino and ether, to obtain a purpurin derivative; and reacting the purpurin derivative with a carbodiimide to obtain the imide derivative of purpurin.
2. The method of Claim 1, wherein the carbodiimide is dicyclohexylcarbodiimide.
3. The method of Claim 1, wherein the imide derivative is further reacted with an alkali metal hydroxide to obtain a purpurin imide of the formula:
4. The method of Claim 1, wherein the imide derivative is further reacted with an alkali metal hydroxide to obtain a cyclic imide.
5. An imide of purpurin manufactured in accordance with the method of Claim 1.
6. An imide of purpurin manufactured in accordance with the method of Claim 2.
7. A reaction product comprising an imide of purpurin manufactured in accordance with the method of Claim 3.
8. A reaction product comprising an imide of purpurin manufactured in accordance with the method of Claim 4.
9. A compound of the formula:
40
where z is = 0 or = NR14; R- is an amino acid group, a polyamine group, a polyether group or 0R13 where R13 is alkyl; R14 is alkyl, substituted alkyl, a polyamine group, or an amino acid group; R4 through Rl λ are -H, -OH, alkyl, alkoxy, alkenyl, alkylene, aryl, or aryloxy, or a carbonyl containing group, wherein carbon containing groups may be substituted with carbonyl, hydroxy, phosphoro, carboxy, halo, sulfo, amino and ether substituents, provided that; R4 may be taken together with R5 to form =0; R6 may be taken together with R7 to form =0; R8 may be taken together with R9 to form =0; R,Q may be taken together with R-j^ to form =0; and R4 and R7 may together form a chemical bond and Rg and R1;L may together form a chemical bond; and R12 is hydrogen or lower alkyl; provided that if one z is = 0, the other z is = NR14.
10. The compound of Claim 9 wherein Rj^ and R12 are -CH3.
11. The compound of Claim 9 wherein Rg is -COCHo .
13. The compound of Claim 9 having the formula:
where R is normal alkyl of 2 through 12 carbon atoms .
41
14 . The compound of Claim 9 having the formula ;
C02Pr
where R is normal alkyl of 2 through 12 carbon atoms.
17. The compound of Claim 9 wherein R-^ is H3C02C-.
19. A method for the manufacture of an isoimide derivati- purpurin comprising reacting a purpurin of the formula:
20. A method for the manufacture of purpurin imide comprising reacting the compound of Claim 9 with alkali metal hydroxide.
21. A method for the manufacture of purpurin imide comprising reacting the compound of Claim 10 with an alkali metal hydroxide.
24. A method for the manufacture of purpurin imide comprising reacting the compound of Claim 17 with an alkali metal hydroxide.
26. A method for the manufacture of purpurin imide comprising reacting the purpurin derivative from Claim 19 with alkali metal hydroxide.
27. A method for the manufacture of purpurin imide comprising reacting the purpurin derivative from Claim 19 with alkali metal hydroxide.
43
28. A method for the manufacture of an imide derivative of purpurin comprising: reacting hexylamine with a chlorin or bacteriochlorin having a macrocycle with a six membered anhydrid ring fused thereto, said macrocycle containing a and b rings which may be saturated or unsaturated at R4 to R-^ positions and which R4 to R-,-^ positions may contain at least one group selected from the group consisting of hydrogen, hydroxy, formal, substituted and unsubstituted alkyl, alkoxy, alkenyl, aryl and aryloxy, wherein carbon containing groups may be substituted with a substituent selected from carbonyl, hydroxy, phosphoro, carboxy, halo, sulfo, amino and ether, to obtain a purpurin derivative; and reacting the obtained purpurin derivative with a carbodiimide to obtain the imide derivative of purpurin.
44
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US08/613,134 | 1996-03-08 | ||
| US08/613,134 US5770730A (en) | 1996-03-08 | 1996-03-08 | Synthesis of carbodimide analogs of chlorins and bacteriochlorins and their use for diagnosis and treatment of cancer |
| US08/812,029 | 1997-03-06 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| WO1997032885A1 WO1997032885A1 (en) | 1997-09-12 |
| WO1997032885B1 true WO1997032885B1 (en) | 1997-11-06 |
| WO1997032885A9 WO1997032885A9 (en) | 1997-12-18 |
Family
ID=24456008
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/US1997/003891 WO1997032885A1 (en) | 1996-03-08 | 1997-03-07 | Synthesis of isoimide of chlorins and bacteriochlorins and their use for diagnosis and treatment of cancer |
Country Status (2)
| Country | Link |
|---|---|
| US (2) | US5770730A (en) |
| WO (1) | WO1997032885A1 (en) |
Families Citing this family (28)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| USRE38994E1 (en) | 1988-07-20 | 2006-02-28 | Health Research, Inc. | Pyropheophorbides conjugates and their use in photodynamic therapy |
| USRE39094E1 (en) | 1988-07-20 | 2006-05-09 | Health Research, Inc. | Pyropheophorbides and their use in photodynamic therapy |
| US5952366A (en) * | 1996-03-08 | 1999-09-14 | Health Research, Inc. | Alkyl ether analogs of chlorins having an N-substituted imide ring |
| DK0945454T3 (en) * | 1996-10-01 | 2003-10-27 | Wyeth Lederle Japan Ltd | Iminochlorin aspartic acid derivatives |
| CA2221912A1 (en) * | 1997-11-21 | 1999-05-21 | David Dolphin | Photosensitizers with improved biodistribution and light-absorbing properties |
| DE19814405C2 (en) | 1998-03-31 | 2000-03-02 | Schastak Astrid | Porphyrins and their use as photosensitizers |
| US6602274B1 (en) * | 1999-01-15 | 2003-08-05 | Light Sciences Corporation | Targeted transcutaneous cancer therapy |
| AU2412800A (en) * | 1999-01-15 | 2000-08-01 | Light Sciences Corporation | Noninvasive vascular therapy |
| US6454789B1 (en) * | 1999-01-15 | 2002-09-24 | Light Science Corporation | Patient portable device for photodynamic therapy |
| EP1131100B1 (en) * | 1999-01-15 | 2003-03-12 | Light Sciences Corporation | Therapeutic compositions for metabolic bone disorders or bone metastases comprising a photosensitizer and a bisphosphonate |
| US6376483B1 (en) | 1999-05-27 | 2002-04-23 | Miravant Pharmaceuticals, Inc. | Bacteriochlorins and bacteriopurpurins useful as photoselective compounds for photodynamic therapy and a process for their production |
| US6534040B2 (en) | 1999-12-23 | 2003-03-18 | Health Research, Inc. | Chlorin and bacteriochlorin-based aminophenyl DTPA and N2S2 conjugates for MR contrast media and radiopharmaceuticals |
| US7897140B2 (en) * | 1999-12-23 | 2011-03-01 | Health Research, Inc. | Multi DTPA conjugated tetrapyrollic compounds for phototherapeutic contrast agents |
| US7078014B2 (en) * | 1999-12-23 | 2006-07-18 | Health Research, Inc. | Method for using chlorin and bacteriochlorin-based aminophenyl DTPA and N2S2 conjugates for MR contrast media and radiopharmaceuticals |
| US7166719B2 (en) * | 2002-06-27 | 2007-01-23 | Health Research, Inc. | Fluorinated photosensitizers related to chlorins and bacteriochlorins for photodynamic therapy |
| US7097826B2 (en) | 1999-12-23 | 2006-08-29 | Health Research, Inc. | Chlorin and bacteriochlorin-based difunctional aminophenyl DTPA and N2S2 conjugates for MR contrast media and radiopharmaceuticals |
| JP2003519670A (en) * | 2000-01-12 | 2003-06-24 | ライト サイエンシーズ コーポレイション | New treatments for eye diseases |
| US6624187B1 (en) * | 2000-06-12 | 2003-09-23 | Health Research, Inc. | Long wave length absorbing bacteriochlorin alkyl ether analogs |
| WO2003061696A2 (en) * | 2002-01-23 | 2003-07-31 | Light Sciences Corporation | Systems and methods for photodynamic therapy |
| US7053210B2 (en) * | 2002-07-02 | 2006-05-30 | Health Research, Inc. | Efficient synthesis of pyropheophorbide a and its derivatives |
| IL152900A0 (en) * | 2002-11-17 | 2003-06-24 | Yeda Res & Dev | Water-soluble bacteriochlorophyll derivatives and their pharmaceutical uses |
| US7057100B2 (en) * | 2003-06-26 | 2006-06-06 | The J.C. Robinson Seed Co. | Inbred corn line W23129 |
| MXPA06014326A (en) * | 2004-06-07 | 2007-02-19 | Yeda Res & Dev | Cationic bacteriochlorophyll derivatives and uses thereof. |
| US7147840B2 (en) * | 2004-11-24 | 2006-12-12 | Health Research, Inc. | Oxo-bacteriopyropheophorbide-a carboxylic acid and esters thereof |
| EP1933941A2 (en) | 2005-08-25 | 2008-06-25 | Philip R. Houle | Treatment systems for delivery of sensitizer solutions |
| CN101980609B (en) * | 2008-02-19 | 2016-10-19 | 健康研究有限公司 | B-ring-reduced-D-ring-oxidized tetrapyrrole photosensitizers for photodynamic therapy and tumor imaging |
| US20110092961A1 (en) * | 2008-08-13 | 2011-04-21 | Searete Llc | Artificial cells |
| GB0819594D0 (en) | 2008-10-24 | 2008-12-03 | Univ Coimbrra | Process |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5002962A (en) * | 1988-07-20 | 1991-03-26 | Health Research, Inc. | Photosensitizing agents |
| US5591847A (en) * | 1994-05-23 | 1997-01-07 | Health Research, Inc. | Long wavelength absorbing photosensitizers related to purpurin-18, bacteriopurpurin-18 and related compounds with imide linkages |
-
1996
- 1996-03-08 US US08/613,134 patent/US5770730A/en not_active Expired - Fee Related
-
1997
- 1997-03-06 US US08/812,029 patent/US5864035A/en not_active Expired - Fee Related
- 1997-03-07 WO PCT/US1997/003891 patent/WO1997032885A1/en active Application Filing
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| WO1997032885B1 (en) | Synthesis of isoimide of chlorins and bacteriochlorins and their use for diagnosis and treatment of cancer | |
| CA1311239C (en) | Porphyrin derivatives, and their production and use | |
| Kato et al. | Facile carbon dioxide uptake by zinc (II)-tetraazacycloalkane complexes. 1. Syntheses, characterizations, and chemical properties of (monoalkyl carbonato)(tetraazacycloalkane) zinc (II) complexes | |
| US4877872A (en) | Production and use of dimers of hematoporophyrin, purpurins, chlorines and purpurin- and chlorin-complexes | |
| US5591847A (en) | Long wavelength absorbing photosensitizers related to purpurin-18, bacteriopurpurin-18 and related compounds with imide linkages | |
| Chang et al. | The porphinedione structure of heme d1. Synthesis and spectral properties of model compounds of the prosthetic group of dissimilatory nitrite reductase. | |
| NZ294203A (en) | Chlorin derivatives such as isobacteriochlorin or bacteriochlorin and their preparation | |
| Lee et al. | Use of the chlorophyll derivative, purpurin-18, for syntheses of sensitizers for use in photodynamic therapy | |
| WO1997032885A1 (en) | Synthesis of isoimide of chlorins and bacteriochlorins and their use for diagnosis and treatment of cancer | |
| WO1997032885A9 (en) | Synthesis of isoimide of chlorins and bacteriochlorins and their use for diagnosis and treatment of cancer | |
| Kasuga et al. | Cycloaddition of carbon dioxide to propylene oxide catalysed by tetra-t-butylphthalocyaninatoaluminium (III) chloride | |
| Tsuchida et al. | Synthesis and O2-binding properties of tetraphenylporphyrinatoiron (II) derivatives bearing a proximal imidazole covalently bound at the β-pyrrolic position | |
| Eckes et al. | Sensitization of the NIR emission of Nd (III) by the α4 atropoisomer of a meso-tetraphenyl porphyrin bearing four 8-hydroxyquinolinylamide chelates | |
| Sun et al. | Iron-promoted nitrene-extrusion reactions in 7-azanorbornadiene derivatives | |
| Gennari et al. | Peptide bond formation using an enzyme mimicking approach | |
| Hirota et al. | TERRECYCLIC ACID A, A NEW ANTIBIOTIC FROM ASPERGILLUS TERREUS II. STRUCTURE OF TERRECYCLIC ACID A | |
| Nemoto et al. | A New Water-soluble p-Boronophenylalanine Derivative for Neutron Capture Therapy. | |
| Bestmann et al. | Enzymatic Synthesis of Chiral C4 Building Blocks from meso‐Tartaric Acid | |
| Martin et al. | Synthesis and characterization of copper (II) and nickel (II) complexes of novel 18-membered tetraaza macrocyclic ligands | |
| Yashunsky et al. | Synthesis of meso-monosubstituted ethane-and trans-ethylenebis (porphyrins) | |
| Pearson | Protonation of tricarbonyldieneiron complexes: Acid-catalysed cyclization of tricarbonylmyrceneiron | |
| Akar et al. | Synthesis of meso‐tetra acid and ester functionalized calix [4] pyrroles | |
| Schlingmann et al. | Structure of Yellow Metal‐Free and Yellow Cobalt‐Containing Corrinoids | |
| Fuchs et al. | Selective ring-opening of 3, 4, 5-tri-O-acetyl-2, 6-anhydro-D-glycero-L-manno-heptaric anhydride with ammonia: the synthesis of 7-amino-2, 6-anhydro-7-deoxy-L-glycero-L-galacto-heptonic acid | |
| Helmreich et al. | Synthesis of novel pyropheophorbide a-fullerene conjugates |