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Title:
POLYAMINES AND THEIR USE IN THERAPY
Document Type and Number:
WIPO Patent Application WO/2000/066587
Kind Code:
A2
Abstract:
Novel conformationally restricted polyamine analogs are provided, as well as compositions comprising these novel polyamine analogs. Methods of using the novel polyamine analogs in treatment of diseases such as cancer are also provided. Also provided is a method of delivering these analogs specifically to tumor cells by covalently attaching polyamine analogs to porphyrin compounds, along with novel polyamine-porphyrin covalent conjugates.

Inventors:
FRYDMAN BENJAMIN (US)
MARTON LAURENCE J (US)
REDDY VENODHAR K (US)
VALASINAS ALDONIA (US)
BLOKHIN ANDREI V (US)
BASU HIRAK S (US)
Application Number:
PCT/US2000/011591
Publication Date:
November 09, 2000
Filing Date:
April 27, 2000
Export Citation:
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Assignee:
SLIL BIOMEDICAL CORP (US)
FRYDMAN BENJAMIN (US)
MARTON LAURENCE J (US)
REDDY VENODHAR K (US)
VALASINAS ALDONIA (US)
BLOKHIN ANDREI V (US)
BASU HIRAK S (US)
International Classes:
A61K31/13; A61K31/132; A61K31/137; A61K31/155; A61K31/40; A61K31/409; A61K47/48; A61P1/04; A61P9/10; A61P17/02; A61P17/06; A61P25/08; A61P25/28; A61P31/04; A61P33/00; A61P35/00; C07C45/46; C07C67/343; C07C211/18; C07C211/22; C07C211/23; C07C211/36; C07C215/14; C07C251/18; C07C257/18; C07D207/34; C07D219/10; C07D235/18; C07D295/185; C07D307/79; C07D307/92; C07D311/92; C07D317/70; C07D487/22; C07D493/04; C07K5/103; C07K7/06; A61K38/00; (IPC1-7): C07D487/22; C07C211/22; C07C211/23; C07C211/18; C07C215/14; C07C257/18; A61P35/00; A61K31/155; A61K31/13; A61K31/40
Domestic Patent References:
WO1995018091A11995-07-06
WO1997002027A11997-01-23
WO1996022962A11996-08-01
WO1998017624A11998-04-30
Foreign References:
US5541230A1996-07-30
US4590288A1986-05-20
US4092432A1978-05-30
DE1295826B1969-05-22
US5889061A1999-03-30
US5021571A1991-06-04
US4035174A1977-07-12
US4153567A1979-05-08
US5962533A1999-10-05
Other References:
PATENT ABSTRACTS OF JAPAN vol. 1996, no. 02, 29 February 1996 (1996-02-29) & JP 07 277964 A (NIPPON KAYAKU CO LTD), 24 October 1995 (1995-10-24)
PATENT ABSTRACTS OF JAPAN vol. 017, no. 327 (C-1073), 22 June 1993 (1993-06-22) & JP 05 032902 A (IDEMITSU PETROCHEM CO LTD;OTHERS: 01), 9 February 1993 (1993-02-09)
FISCHER, H. A.: "Synthesis of 3H-spermine" J. LABELLED COMPD., vol. 11, no. 1, 1975, pages 141-143, XP000956379
REDDY, VENODHAR K. ET AL: "Conformationally Restricted Analogs of 1N,12N-Bisethylspermine: Synthesis and Growth Inhibitory Effects on Human Tumor Cell Lines" J. MED. CHEM., vol. 41, no. 24, 1998, pages 4723-4732, XP000952845
GOTO, MASAFUMI ET AL: "Stereochemical studies of metal chelates. III. Preparation and stereochemistry of cobalt(III) complexes with C-substituted triethylenetetramines at the central ethylenediamine bridge" INORG. CHEM., vol. 8, no. 2, 1969, pages 358-366, XP000952924
ALFONSO, IGNACIO ET AL: "Sequential biocatalytic resolution of (.+-.)-trans-cyclohexane-1,2- diamine. Chemoenzymic synthesis of an optically active polyamine" CHEM. COMMUN. (CAMBRIDGE), no. 21, 1996, pages 2471-2472, XP000952857
NAGARAJAN, SRINIVASAN ET AL: "Chemistry of naturally occurring polyamines. 11. Unsaturated spermidine and spermine derivatives" J. ORG. CHEM., vol. 52, no. 22, 1987, pages 5044-5046, XP000952844
SNYDER, RONALD D. ET AL: "Effects of polyamine analogs on the extent and fidelity of in vitro polypeptide synthesis" BIOCHEM. BIOPHYS. RES. COMMUN., vol. 176, no. 3, 1991, pages 1383-1392, XP000952839
WUNZ, TIMOTHY P. ET AL: "New antitumor agents containing the anthracene nucleus" J. MED. CHEM., vol. 30, no. 8, 1987, pages 1313-1321, XP000867863
KOBIRO, KAZUYA ET AL: "Synthesis and molecular structures of nickel(II) alkyl-substituted cyclam complexes" INORG. CHEM., vol. 31, no. 4, 1992, pages 676-685, XP000957409
Attorney, Agent or Firm:
Cerpa, Robert K. (CA, US)
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Claims:
CLAIMS What is claimed is:
1. A conformationally restricted polyamine analog of the formula: ENHBABNHBABNHBABNHBABNHE wherein each A is independently selected from the group consisting of : a single bond, ClC6 alkyl, C2C6 alkenyl, C2C6 alkynyl, C3C6 cycloalkyl, C3C6 cycloaryl, and C3C6 cycloalkenyl; each B is independently selected from the group consisting of : a single bond, CC6 alkyl, and C2C6 alkenyl; and each E is independently selected from the group consisting of H, ClC6 alkyl, C2C6 alkenyl, C2C6 alkynyl, C3C6 cycloalkyl, C3C6 cycloaryl, and C3C6 cycloalkenyl; with the proviso that either at least one A moiety is selected from the group consisting of C2C6 alkenyl, C2C6 alkynyl, C3C6 cycloalkyl, C3C6 cycloaryl, and C3C6 cycloalkenyl, or at least one B moiety is selected from the group consisting of C2C6 alkenyl; and any salt or stereoisomer thereof.
2. A conformationally restricted polyamine analog according to claim 1, selected from the group consisting of , and any salt or stereoisomer thereof.
3. A conformationally restricted polyamine analog of the formula: ENHBABNHBABNHBABNH (BABNH) XE wherein each A is independently selected from the group consisting of : a single bond, CC6 alkyl, C2C6 alkenyl, C2C6 alkynyl, C3C6 cycloalkyl, C3C6 cycloaryl, and C3C6 cycloalkenyl; each B is independently selected from the group consisting of : a single bond, CC6 alkyl, and C2C6 alkenyl; each E is independently selected from the group consisting of H, CC6 alkyl, C2C6 alkenyl, C2C6 alkynyl, C3C6 cycloalkyl, C3C6 cycloaryl, and C3C6 cycloalkenyl; and x is an integer from 2 to 16; with the proviso that either at least one A moiety is selected from the group consisting of C2C6 alkenyl, C2C6 alkynyl, C3C6 cycloalkyl, C3C6 cycloaryl, and C3C6 cycloalkenyl, or at least one B moiety is selected from the group consisting of C2C6 alkenyl; and any salt or stereoisomer thereof.
4. A conformationally restricted polyamine analog according to claim 3, selected from the group consisting of : and any salt or stereoisomer thereof.
5. A polyamine analog of the formula: ENHBABNHBABNHBABNH (BABNH) XE wherein each A is independently selected from the group consisting of : a single bond, C2C6 alkenyl, C2C6 alkynyl, C3C6 cycloalkyl, C3C6 cycloaryl, and C3C6 cycloalkenyl; each B is independently selected from the group consisting of : a single bond, CiCe alkyi, and C2C6 alkenyl; each E is independently selected from the group consisting of CC6 alkyl, CC6 alkanol, C3C6 cycloalkanol, and C3C6 hydroxyaryl, with the proviso that at least one E moiety be selected from the group consisting of CC6 alkanol, C3C6 cycloalkanol, and C3C6 hydroxyaryl; and x is an integer from 0 to 16; and any salt or stereoisomer thereof.
6. A polyamine analog according to claim 5, selected from the group consisting of : and all salts and stereoisomers thereof.
7. A conformationally restricted polyamine analog of the formula: ENHDNHBABNHDNHE wherein each A is selected from the group consisting of C2C6 alkynyl; each B is independently selected from the group consisting of : a single bond, CC6 alkyl, and C2C6 alkenyl; each D is independently selected from the group consisting of CC6 alkyl, C2C6 alkenyl, C2C6 alkynyl, C3C6 cycloalkyl, C3C6 cycloalkenyl, and C3C6 cycloaryl; and each E is independently selected from the group consisting of H, CC6 alkyl, C2C6 alkenyl, C2C6 alkynyl, C3C6 cycloalkyl, C3C6 cycloaryl, and C3C6 cycloalkenyl; and any salt or stereoisomer thereof.
8. A conformationally restricted polyamine analog according to claim 7, selected from the group consisting of and any salt or stereoisomer thereof.
9. A conformationally restricted polyamine analog of the formula: ENHBABNHFNHBABNHE wherein F is selected from the group consisting of CC6 alkyl; each A is independently selected from the group consisting of: a single bond, CC6 alkyl; C2C6 alkenyl, C2C6 alkynyl, C3C6 cycloalkyl, C3C6 cycloaryl, and C3C6 cycloalkenyl; each B is independently selected from the group consisting of : a single bond, C lC6 alkyl, and C2C6 alkenyl; and each E is independently selected from the group consisting of H, CC6 alkyl, C2C6 alkenyl, C2C6 alkynyl, C3C6 cycloalkyl, C3C6 cycloaryl, and C3C6 cycloalkenyl; with the proviso that either at least one A moiety is selected from the group consisting of C2C6 alkenyl, C2C6 alkynyl, C3C6 cycloalkyl, C3C6 cycloaryl, and C3C6 cycloalkenyl, or at least one B moiety is selected from the group consisting of C2C6 alkenyl; and any salt or stereoisomer thereof.
10. A conformationally restricted polyamine analog according to claim 9, selected from the group consisting of and any salt or stereoisomer thereof.
11. A conformationally restricted polyamine analog of the formula: wherein A is independently selected from the group consisting of : a single bond, ClC6 alkyl; C2C6 alkenyl, C2C6 alkynyl, C3C6 cycloalkyl, C3C6 cycloaryl, and C3C6 cycloalkenyl; each B is independently selected from the group consisting of : a single bond, CC6 alkyl, and C2C6 alkenyl; with the proviso that A and both B moieties are not all a single bond; and any salt or stereoisomer thereof.
12. A conformationally restricted polyamine analog according to claim 11, selected from the group consisting of : and any salt or stereoisomer thereof.
13. A conformationally restricted polyamine analog of the formula: ENHDNHBABNHDNHE wherein A is selected from the group consisting of CC6 alkyl, C2C6 alkenyl, C2C6 alkynyl, C3C6 cycloalkyl, C3C6 cycloalkenyl, and C3C6 cycloaryl; each B is independently selected from the group consisting of : a single bond, CiCe alkyl, and C2C6 alkenyl; each D is independently selected from the group consisting of CC6 alkyl, C2C6 alkenyl, C2C6 alkynyl, C3C6 cycloalkyl, C3C6 cycloalkenyl, and C3C6 cycloaryl; and each E is independently selected from the group consisting of H and CC6 alkyl; with the proviso that either at least one A moiety is selected from the group consisting of C2C6 alkenyl, C2C6 alkynyl, C3C6 cycloalkyl, C3C6 cycloaryl, and C3C6 cycloalkenyl, or at least one B moiety is selected from the group consisting of C2C6 alkenyl; and the proviso that at least one E is selected from the group consisting of H or methyl; and any salt or stereoisomer thereof.
14. A conformationally restricted polyamine analog according to claim 13 of the formula and any salt or stereoisomer thereof.
15. A conformationally restricted polyamine analog of the formula: <BR> <BR> <BR> \N/\N/\A/\N/\N<BR> #N# #N# #A# #N# #N H H H H wherein A is transethene each B is independently selected from the group consisting of : a single bond, ClC6 alkyl, and C2C6 alkenyl; each D is independently selected from the group consisting of CC6 alkyl, C2C6 alkenyl, C2C6 alkynyl, C3C6 cycloalkyl, C3C6 cycloaryl, and C3C6 cycloalkenyl, with the proviso that D is not C3 alkyl; and each E is independently selected from the group consisting of H, C 1C6 alkyl, C2C6 alkenyl, C2C6 alkynyl, C3C6 cycloalkyl, C3C6 cycloaryl, and C3C6 cycloalkenyl; and any salt thereof.
16. The polyamine analog of claims 1,2,3,4,5,6,7,8,9,10,11,12,13,14, or 15, further comprising a pharmaceutically acceptable excipient.
17. A method of treating an indication in an individual comprising the step of administering to the individual a therapeutic amount of a polyamine analog of claims 1,2, 3,4,5,6,7,8,9,10,11,12,13,14, or 15.
18. The method of claim 17, wherein the individual is a human.
19. The method of claim 17, wherein the indication is a cancer.
20. The method of claim 19, wherein the cancer affects cells of the bladder, blood, brain, breast, colon, digestive tract, lung, ovaries, pancreas, prostate gland, or skin.
21. The method of claim 17, wherein the indication is Alzheimer's disease, epilepsy, multiple sclerosis, problems associated with tissue grafts and organ transplants, psoriasis, restenosis, stomach ulcers, or tissue overgrowth after surgery, or an infection or infestation of parasites, bacteria, fungi or insects.
22. A method of suppressing cell growth in an individual comprising the step of administering to the individual a therapeutic amount of a polyamine analog of claims 1,2, 3,4,5,6,7,8,9,10,11,12,13,14, or 15.
23. The method of claim 22, wherein the individual is a human.
24. A porphyrinpolyamine conjugate, comprising a polyamine compound covalently linked to a porphyrin compound.
25. A compound of claim 24, wherein the covalent link is an amide bond or a amine bond.
26. A compound according to claim 24 of the formula wherein at least one of JlJ8 is independently selected from the group consisting of KiGL (N (P)A).K2 where K, is independently selected from the group consisting of CC8 alkyl and where the valence to the left of Kl attaches to the porphyrin ring; G is O, (C=O),C (=O)O,O (C=O),O (C=O)O,0 (C=O)N,N (C=O)O, or a nonentity; L is C1C8 alkyl, C3Cg cycloalkyl, C3Cg cycloaryl, ClC8 alkoxy, CC8 alkylC3C8 cycloalkyl, cycloaryl,C1C8alkoxyC3C8cycloaryl,C3C8alkylC3C8 cycloalkylC3C8 cycloaryl, alkyl,C3C8cycloarylC1C8alkyl.cycloalkylC1C8 C3Cg cycloarylC18 alkoxy, C3Cg cycloarylC3C8 cycloalkyl, or a nonentity; each A is independently selected from the group consisting of C1C8 alkyl, C2C8 alkenyl, C2C8 alkynyl, C3Cg cycloalkyl, C3Cg cycloaryl, C3C8 cycloalkenyl, and C3C8 cycloalkynyl; P is selected from the group consisting of H and CC8 alkyl; n is an integer from 2 to 8; and K2 is independently selected from the group consisting of H, C1C8 alkyl, C2C8 alkenyl, C2Cg alkynyl, C3Cg cycloalkyl, C3Cg cycloaryl, C3Cg cycloalkenyl, C3Cg cycloalkynyl, ClC8 alkanol, C3Cg cycloalkanol, and C3C8 hydroxyaryl; where the remainder of the groups JIJ8 are each independently selected from the group consisting of H, K3, or K4COOH, where K3 is independently selected from the group consisting of CC8 alkyl, C2C8 alkenyl, C2Cg alkynyl, C3Cg cycloalkyl, C3Cg cycloaryl, C3C8cycloalkynyl,C3C8alkanol,C3C8cycloalkanol,andC3C8C3C8cycloalkenyl, hydroxyaryl; and K4 is independently selected from the group consisting of C1C8 alkyl, C2C8alkynyl,C3C8cycloalkyl,C3C8cycloaryl,C3C8cycloalkenyl,andC2C8alkenyl, C3C8cycloalkynyl; and any salt or stereoisomer thereof.
27. A compound according to claim 26, wherein Kl and each A are independently selected from the group consisting of C1C8 alkyl, K2 is independently selected from the group consisting of H and ClC8 alkyl, and the remainder of the groups JJ8 are each independently selected from the group consisting of H, K3, or K4COOH, where K3 and K4 are independently selected from the group consisting of C1C8 alkyl,.
28. A compound according to claim 27, wherein K1 isCH2CH2orCH2CH2CH2.
29. A compound according to claim 27, wherein n is 4.
30. A compound according to claim 27, wherein J3, J4, J7 and J8 are independently selected from the group consisting of ClC3 alkyl; J5 and J6 are independently selected from the group consisting of C1C3 alkyl and ClC3 alkylCOOH; and J, and J2 are independently selected from the group consisting of C1C3alkylGN(P1)A(NHA)n1K5; wherein G is (C=O) or a nonentity; Pl is H or ClC3 alkyl; each A is independently selected from the group consisting of CzC8 alkyl; nl is 3 or 4; and K5 is independently selected from the group consisting of H and C1C8 alkyl.
31. A method of treating an indication in an individual comprising the step of administering to the individual a therapeutic amount of a porphyrinpolyamine conjugate of claim 24.
Description:
INTERNATIONALSEARCHREPORT j-------------------) InettionafApplicationNo PCT/US00/11591 C.(Continuation)DOCUMENTSCONSIDEREDTOBERELEVANT CategoryCitation ofdocument,withindication,whereappropnate.oftherelevantpassa gesRelevanttoclaimNo. XWO9702027A(TEVAPHARMA;GILADGAD13,17,18 (IL);GILADVARDA(IL);STERLINGJEFFREY (I)23January1997(1997-01-23) page44 XWO9622962A(UNIVCOLUMBIA;NAKANISHI13,17,18 KOJI(US);HUANGDANWEN(US);CHOISEOKK) 1August1996(1996-08-01) page19 XPATENTABSTRACTSOFJAPAN13 vol.017,no.327(C-1073), 22June1993(1993-06-22) &JP05032902A(IDEMITSUPETROCHEMCO LTD;OTHERS:01), 9February1993(1993-02-09) abstract XUS4590288A(KLEMANNLAWRENCEP)13 20May1986(1986-05-20) column3-column6 XUS4092432A(BJORKLUNDCHRISTERJAMES13 AXELETAL)30May1978(1978-05-30) column4-column5;examples1-6 XDE1295826B(J.R.GEIGYAG,BASEL13 (SCHWEIZ)) column3;tables1,NR.7 XUS5889061A(MARTONLAURENCEJETAL)13,16-23 30March1999(1999-03-30) column19-column20;table1 column39;claims15-22 XUS5021571A(SRIVASTAVASURESHCET13,16-23 AL)4June1991(1991-06-04) column6 XWO9817624A(WISCONSINALUMNIRESFOUND)13,16-23 30April1998(1998-04-30) page29;table1 XUS4035174A(GRIERNATHANIELETAL)13 12July1977(1977-07-12) column18,line20 XUS4153567A(KLUGEREDWARDWETAL)13 8May1979(1979-05-08) column3,line55-line60 P,XUS5962533A(BERGERONJRRAYMONDJ)13,16-23 5October1999(1999-10-05) page7-page14;tables1,2 7 INTERNATIONAL SEARCH REPORT In. etional ApplicationNo PCT/US00/11591 C.(Continuation)DOCUMENTSCONSIDERED TO BE RELEVANT Category° Citation ofdocument,withindication,whereappropriate,oftherelevantpass agesRelevanttoclaimNo. XFISCHER,H.A.:"Synthesisof7,13 3H-spermine" J.LABELLEDCOMPD., vol.11,no.1,1975,pages141-143, XP000956379 page141-page143 XREDDY,VENODHARK.ETAL:7,13, "ConformationallyRestrictedAnalogsof16-23 1N,12N-Bisethylspermine:Synthesisand GrowthInhibitoryEffectsonHumanTumor CellLines" J.MED.CHEM., vol.41,no.24,1998,pages4723-4732, XP000952845 page4724;figure1 XGOTO,MASAFUMIETAL:"Stereochemical13 studiesofmetalchelates.III. Preparationandstereochemistryof cobalt(III)complexeswithC-substituted triethylenetetraminesatthecentral ethylenediaminebridge" INORG.CHEM., vol.8,no.2,1969,pages358-366, XP000952924 page361;figure1 XALFONSO,IGNACIOETAL:"Sequential13 biocatalyticresolutionof (.+-.)-trans-cyclohexane-1,2- diamine. Chemoenzymicsynthesisofanoptically activepolyamine" CHEM.COMMUN.(CAMBRIDGE), no.21,1996,pages2471-2472,XP000952857 page2472 XNAGARAJAN,SRINIVASANETAL:"Chemistry7,13 ofnaturallyoccurringpolyamines.11. Unsaturatedspermidineandspermine derivatives" J.ORG.CHEM., vol.52,no.22,1987,pages5044-5046, XP000952844 Scheme1 page5044 XSNYDER,RONALDD.ETAL:"Effectsof13 polyamineanalogsontheextentand fidelityofinvitropolypeptide synthesis" BIOCHEM.BIOPHYS.RES.COMMUN., vol.176,no.3,1991,pages1383-1392, XP000952839 page1385;table1 INTERNATIONALSEARCHREPORT j------------------. Int tional ApplicationNo PCT/US00/11591 C.(Continuation)DOCUMENTSCONSIDEREDTOBERELEVANT CategoryCitationofdocument,withindication,whereappropriate,o ftherelevantpassagesRelevant to claimNo. XWUNZ,TIMOTHYP.ETAL:"Newantitumor13 agentscontainingtheanthracenenucleus" J.MED.CHEM., vol.30,no.8,1987,pages1313-1321, XP000867863 scheme1 page1314 XKOBIRO,KAZUYAETAL:"Synthesisand13 molecularstructuresofnickel(II) alkyl-substitutedcyclamcomplexes" INORG.CHEM., vol.31,no.4,1992,pages676-685, XP000957409 page677 7 .emationalapplicationNo- PCT/US00/11591 INTERNATIONALSEARCHREPORT PCT/US 00/11591 Box IObservationswherecertainclaimswerefoundunsearchable(Continu ationofitem1offirstsheet) ThisInternationalSearchReporthasnotbeenestablishedinrespecto fcertainclaimsunderArticle17(2)(a)forthefollowingreasons: 1.FXIClaimsNos.: becausetheyrelatetosubjectmatternotrequiredtobesearchedbythi sAuthority,namely: Althoughclaims17-23,31aredirectedtoamethodoftreatmentofthe human/animalbody,thesearchhasbeencarriedoutandbasedonthealle ged effectsofthecompound/composition. 2.ClaimsNos.: becausetheyrelatetopartsoftheInternationalApplicationthatdon otcomplywiththeprescribedrequirementstosuch anextentthatnomeaningfulInternationalSearchcanbecarriedout,s pecifically: 3.ClaimsNos.: becausetheyaredependentclaimsandarenotdraftedinaccordancewit hthesecondandthirdsentencesofRule6.4(a). Box11Observationswhereunityofinventionislacking(Continuation ofitem2offirstsheet) ThisinternationalSearchingAuthorityfoundmultipleinventionsin thisinternationalapplication,asfollows: seeadditionalsheet 1.As allrequiredadditionalsearchfeesweretimelypaidbytheapplicant, thisinternationalSearchReportcoversall searchableclaims. 2.as aitsearchableclaimscouldbesearchedwithouteffortjustifyingana dditionalfee,thisAuthoritydidnotinvitepayment ofanyadditionalfee. 3.As onlysomeoftherequiredadditionalsearchfeesweretimelypaidbythe applicant,thisInternationalSearchReport coversonlythoseclaimsforwhichfeeswerepaid,specificallyclaims Nos.: 1-4,7,8,11-14,16-31(therof16-23and31onlypartially) 4.Norequiredadditionalsearchfeesweretimelypaidbytheapplicant .Consequently,thisInternationalSearchReportis restrictedtotheinventionfirstmentionedintheclaims;itiscovere dbyclaimsNos.: RemarkonProtest2 Theadditionalsearchfeeswereaccompaniedbytheapplicant'sprotes t. u FxlNoprotestaccompaniedthepaymentofadditionalsearchfees. U FURTHER INFORMATION CONTINUED FROM PCT/ISA/210 This International Searching Authority found multiple (groups of) inventions in this international application, as follows: 1. Claims: 1-4 (completely), 16-23 (in part) A compound according to the definition of claim 1.

2. Claims: 5,6 (completely), 16-23 (in part) A compound according to the definition of claim 5.

3. Claims: 7,8,13,14 (completely), 16-23 (in part) A compound according to definition of claim 7 or according to the definition of claim 13.

4. Claims: 9,10 (completely), 16-23 (in part) A compound according to definition of claim 9.

5. Claims: 11,12 (completely), 16-23 (in part) A compound according tothe definition of claim 11.

6. Claims: 15; 16-23 (in part) A compound according to the definition of claim 15.

7. Claims: 24-31 A porphyrin-polyamine conjugate and it's use. INTERNATIONALSEARCHREPORT i------------------t trn itional ApplicationNo Informationonpatentfamilymembers PCT/US 00/11591 PCT/US00/11591 Publication Patent f Publication citedinsearchreportdate member(s)date JP07277964A24-10-1995NONE WO9518091A06-07-1995AT 169614 T 15-08-1998 AU 690618 B 30-04-1998 AU 1274495 A 17-07-1995 BR 9405892 A 12-12-1995 CN 1121707 A 01-05-1996 DE 69412467 D 17-09-1998 DE 69412467 T 28-01-1999 DK 686143 T 17-05-1999 EP 0686143 A 13-12-1995 ES 2119371 T 01-10-1998 JP 8507548 T 13-08-1996 NZ 277503 A 27-07-1997 US 5627215 A 06-05-1997 US5541230A30-07-1996US 5880161 A 09-03-1999 WO9702027A23-01-1997US 5646188 A 08-07-1997 AU 6452596 A 05-02-1997 EP 0865276 A 23-09-1998 WO9622962A01-08-1996US 6001824 A 14-12-1999 AU 5168496 A 14-08-1996 JP05032902A09-02-1993NONE US4590288A20-05-1986NONE US4092432A30-05-1978SE 417569 B 30-03-1981 AR 216638 A 15-01-1980 AU 505423 B 22-11-1979 AU 1855076 A 20-04-1978 BR 7606992 A 06-09-1977 CA 1072008 A 19-02-1980 CH 625208 A 15-09-1981 DD 128387 A 16-11-1977 DE 2647915 A 05-05-1977 DK 473376A,B,23-04-1977 FR 2328399 A 20-05-1977 GB 1570517 A 02-07-1980 HU 176545 B 28-03-1981 IL 50649 A 30-06-1980 IN 143379 A 12-11-1977 IT 1121707 B 23-04-1986 JP 1119495 C 28-10-1982 JP 52051021 A 23-04-1977 JP 57007605 B 12-02-1982 MX 4511 E 02-06-1982 NL 7611508A,B,26-04-1977 SE 7511852 A 23-04-1977 SU 852169 A 30-07-1981 ZA 7606127 A 28-09-1977 DE1295826BNONE US5889061A30-03-1999NONE INTERNATIONALSEARCHREPORT Int tional ApplicationNo informationonpatentfamily members PCT/US 00/11591 PCT/US00/11591 PatentdocumentPublicationPatentfamily Publication citedinsearchreportdatemember(s)date US5021571A04-06-1991US5089663A18-02-1992 US5334729A02-08-1994 WO9817624A30-04-1998AU4900797A15-05-1998 EP0934249A11-08-1999 US4035174A12-07-1977US4049559A20-09-1977 US4153567A08-05-1979NONE US5962533A05-10-1999NONE




 
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