Login| Sign Up| Help| Contact|

Patent Searching and Data


Title:
QUINONES FOR TREATMENT OF DISEASES
Document Type and Number:
WIPO Patent Application WO/2000/066528
Kind Code:
A2
Abstract:
Novel quinones are provided, as well as compositions comprising these novel quinones. Methods of using the novel quinones in treatment of various indications including cancer are also provided.

Inventors:
BLOKHIN ANDREI V (US)
FRYDMAN BENJAMIN (US)
MARTON LAURENCE J (US)
NEDER KAREN M (US)
SUN JERRY SHUNNENG (US)
Application Number:
PCT/US2000/011538
Publication Date:
November 09, 2000
Filing Date:
April 27, 2000
Export Citation:
Click for automatic bibliography generation   Help
Assignee:
SLIL BIOMEDICAL CORP (US)
BLOKHIN ANDREI V (US)
FRYDMAN BENJAMIN (US)
MARTON LAURENCE J (US)
NEDER KAREN M (US)
SUN JERRY SHUNNENG (US)
International Classes:
A61K31/122; A61K31/16; A61K31/165; A61K31/22; A61K31/222; A61K31/265; A61K31/275; A61K31/343; A61K31/353; A61K31/401; A61K31/409; A61K31/473; A61K31/496; A61K31/5355; A61K31/661; A61K31/704; A61K38/00; A61K47/48; A61P35/00; C07C45/00; C07C45/46; C07C46/00; C07C50/32; C07C67/343; C07D221/08; C07C69/24; C07C69/708; C07C69/96; C07C217/12; C07C219/34; C07C229/12; C07C229/22; C07C233/31; C07C237/22; C07C255/54; C07C301/00; C07C305/20; C07C323/22; C07D207/34; C07D209/44; C07D209/48; C07D219/10; C07D235/18; C07D235/20; C07D295/185; C07D307/79; C07D307/92; C07D311/92; C07D317/70; C07D487/22; C07D493/04; C07F9/09; C07F9/12; C07F9/655; C07H15/20; C07K5/027; C07K5/10; C07K5/103; C07K7/02; C07K7/06; (IPC1-7): C07C50/10; C07C50/32; A61P35/04; C07D219/10; C07H15/203; C07D235/12; C07C317/46; C07C219/34; C07C229/08; C07C237/12; C07C233/03; C07C233/05; C07F9/145; C07K7/06; C07K5/10; A61K38/00; C07C255/54; C07C235/20; C07D295/18; C07D311/92; C07D307/92; C07D487/22; C07D207/34; C07C211/10
Domestic Patent References:
WO1997031936A21997-09-04
WO1997031611A21997-09-04
WO1997008162A11997-03-06
Foreign References:
US4273706A1981-06-16
EP0255679A21988-02-10
US5763625A1998-06-09
Other References:
TAKUWA, AKIO ET AL: "Structural influences on the isomerization of 4-benzyl- and 4-allyl-1,2-naphthoquinones to quinone methides and their stereochemistry" J. CHEM. SOC., PERKIN TRANS. 1 (1986), (9), 1627-31, XP002142390
DATABASE CHEMABS [Online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; PERSHIN, G. N. ET AL: "Bonaphthon, a new antiviral chemotherapeutic agent" retrieved from STN Database accession no. 82:118979 XP002142391 & FARMAKOL. TOKSIKOL. (MOSCOW) (1975), 38(1), 69-73,
NELSON, WENDEL L. ET AL: "3,4-Catechol derivative of propranolol, a minor dihydroxylated metabolite" J. MED. CHEM. (1984), 27(7), 857-61, XP002142392
BULLOCK, F. J. ET AL: "Antiprotozoal quinones. II. Synthesis of 4-amino-1,2- naphthoquinones and related compounds as potential antimalarials" J. MED. CHEM. (1970), 13(1), 97-103, XP002142393
DUNN, W. J., III ET AL: "Structure-activity analyzed by pattern recognition: the asymmetric case" J. MED. CHEM. (1980), 23(6), 595-9, XP002142394
TAKUWA, AKIO ET AL: "Addition of alcohol to 1,2-naphthoquinone promoted by metal ions. Facile synthesis of 4-alkoxy-1,2-naphthoquinones" BULL. CHEM. SOC. JPN. (1986), 59(9), 2959-61, XP002142395
DATABASE CHEMABS [Online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; DOLAN, M. EILEEN ET AL: "Effects of 1,2-naphthoquinones on human tumor cell growth and lack of cross-resistance with other anticancer agents" retrieved from STN Database accession no. 129:156459 XP002142396 & ANTI-CANCER DRUGS (1998), 9(5), 437-448,
COTE, PHILIP N. ET AL: "Glucopyranosides derived from 2-hydroxy-1,4-naphthoquinones" CARBOHYD. RES., vol. 26, no. 1, 1973, pages 247-251, XP000925262
PLANCHON, SARAH M. ET AL: "Bcl-2 protects against.beta.-lapachone-mediated caspase 3 activation and apoptosis in human myeloid leukemia (HL-60) cells" ONCOL. REP., vol. 6, no. 3, 1999, pages 485-492, XP000957471
Attorney, Agent or Firm:
Cerpa, Robert K. (CA, US)
Goldin, Douglas Michael (J.A. Kemp & Co. 14 South Square Gray's Inn London WC1R 5LX, GB)
Download PDF:
View/Download PDF      PDF Help
Claims:
CLAIMS What is claimed is:
1. A compound of the formula: wherein A is selected from the group consisting ofOandCH2; wherein M, is selected from the group consisting of a single bond and C1C8 alkyl, ClC8 branched alkyl, C3Cg cycloalkyl, and C3C8 cycloaryl; wherein B is selected from the group consisting of CH2, O, C (=O)O; OC (=O), andN (R1), wherein R, is selected from the group consisting ofH, C,Cg alkyl, C,C8 branched alkyl, C3C8 cycloalkyl, and C3C8 cycloaryl; wherein M2 is selected from the group consisting of a single bond and C,C8 alkyl, C)Cs branched alkyl, C3C8 cycloalkyl, and C3Cg cycloaryl; wherein D is selected from the group consisting ofH,OH,N (R7) (R8), pentoses, hexoses, wherein R4 4 is selected from the group consisting ofH, C,C8 alkyl, CC8 branched alkyl, C3C8 cycloalkyl, C3C8 cycloaryl, N(R9)(R10), andCN; and wherein R7, R8, R9 and R10 are independently selected from the group consisting of H, ClC8 alkyl, C1C8 branched alkyl, C3C8 cycloalkyl, C3C8 cycloaryl, and.
2. A compound according to the formula wherein x is an integer between 1 and 2; and each K is independently selected from the group consisting of H. C IC 8 alkyl, CC8 alkenyl, CC8 alkanol, C,C8 alkoxy, and where zero or two, but no more than two, vicinal K's in the molecule represent single electrons which form a pi bond, thus forming a double bond together with the existing sigma bond between the two adjacent carbons bearing the two vicinal K's.
3. A compound of the formula wherein R is selected from the group consisting of C1C8 alkyl, C1C8 cycloalkyul, C3C8 cycloaryl, C,C8 branched alkyl, and C IC8 alkanol.
4. A compound of the formula wherein Y is selected from the group consisting ofH,F,Br,Cl, and1; and wherein G and G2 are independently selected from the group consisting of H, C1C8 alkyl, andC (=O)CHnx3n, where n is an integer from 0 to 3 and X is selected from the group consisting of F, Cl, Br, and I.
5. A compound of the formula wherein M is selected from the group consisting of O, C (=O)O,O(C=O) C (=O)N, andN (C=O).
6. A compound of the formula wherein x is an integer between 1 and 2; each B is independently selected from the group consisting of H, C lC8 alkyl, C3C8 cycloalkyl, C3C8 cycloaryl, CiC8 alkylC3Cg cycloalkyl, and CC8 alkylC3C8 cycloaryl; and each K is independently selected from the group consisting of H, OH, C1C8 alkyl, C,Cg alkenyl, C,C8 alkanol, C,C8 alkoxy, and where zero or two, but no more than two, vicinal K's in the molecule represent single electrons which form a pi bond, thus forming a double bond together with the existing sigma bond between the two adjacent carbons bearing the two vicinal K's.
7. A compound of the formula wherein each B is independently selected from the group consisting of H, C1C8cycloalkyl,C3C8cycloaryl,C1C8alkylC3C8cycloalkyl,andC3C8 ClC8 alkylC3C8 cycloaryl; and wherein R is selected from the group consisting of C1C8 alkyl and ClC8 alkanol.
8. A compound of the formula where Ms is C,C8 alkyl, y is an integer from 1 to 6, and L is selected from the group consisting ofOK, orN (K1K2) ; where K, and K2 are independently selected from the group consisting of H, C,C8 alkyl, C,C8 alkylCOOH, C,C,, alkylCOOC1C8 alkyl, C,Cg alkylN (G, G2), and C.C, andalkylN(G3)C1C8alkylN(G4G5); wherein each of G1, G2, G3, G4, and Gs is independently selected from the group consisting ofH and C,C8 alkyl.
9. A compound of the formula: where z is an integer between one and ten; G) o is selected from the group consisting of C,C8 alkyl; each M is independently selected from the group consisting of C1C8 alkyl ; V is selected from the group consisting ofC (=O)N andN (C=O) ; and T is selected from the group consisting of COOM8 andCONM9Mlo, where each of M8, M9 and Mio are independently selected from the group consisting of H and C,C8 alkyl.
10. A compound of the formula where M) 2 is selected from the group consisting of C1C8 alkyl.
11. A compound of the formula where M 14 and M15 are independently selected from the group consisting of C1C8 alkyl.
12. A compound of the formula where J is selected from the group consisting of C,C8 alkyl, C,C8 cycloalkyl, C3C8 cycloaryl, and CfCs branched alkyl.
13. A compound of the formula where Rs is the side chain of a naturallyoccuring amino acid, attached in S or R configuration.
14. A compound of the formula SLQUIN wherein S represents a single amino acid or a peptide of at least two amino acids; L is a linking group containing at least one carbon, oxygen, or nitrogen atom attached covalently to both S and QUIN, or a nonentity; and QUIN is a quinone, quinone derivative, hydroquinone, or hydroquinone derivative.
15. A compound according to claim 14, wherein S or a portion thereof, SL or a portion thereof, or both S or a portion thereof and then L or a portion thereof, are cleaved from the quinonecontaining remainder of the molecule by an enzyme.
16. A compound according to claim 15, wherein the enzyme is prostate specific antigen.
17. A compound according to claim 14, wherein L is0,NH, or NH(CC8 alkyl)O.
18. A compound according to claim 14, wherein L is NH(C6H4) CH2O(C=O)NH(CC8 alkyl)O.
19. A compound according to claim 14, wherein S is XSerLysLeuGln, wherein X is a protecting group or an aminoterminal capping group, and the side chains of Ser, Lys, and Gln may optionally be protected with protecting groups.
20. A compound of the formula SLQUIN wherein S represents a single amino acid or a peptide of at least two amino acids; L is a linking group containing at least one carbon, oxygen, or nitrogen atom attached covalently to both S and QUIN, or a nonentity; and QUIN is selected from the group consisting of the quinone compounds of claim 13 and the compounds.
21. A method for making a compound according to claim 14, comprising the steps of a) covalently linking L to S, and b) covalently linking L to QUIN, wherein steps a) and b) can be performed in either order or simultaneously.
22. A compound of the formula wherein x is an integer between 1 and 2; W is selected fromH,OH,OCC8 alkyl,OC,Cs alkylNH2, and OC,Cg alkylNHS, wherein S is a single amino acid or a peptide of two or more amino acids; and each K is independently selected from the group consisting of H, OH, ClC8 alkyl, Cicl alkenyl, Cicl alkanol, C,C8 alkoxy, and where zero or two, but no more than two, vicinal K's in the molecule represent single electrons which form a pi bond, thus forming a double bond together with the existing sigma bond between the two adjacent carbons bearing the two vicinal K's.
23. A compound according to claim 22 of the formula wherein W is selected fromH,OH,OC,Cg alkyl,OC,C8 alkylNH2, and OC,C8 alkylNHS, and wherein S is a single amino acid or a peptide of two or more amino acids.
24. A compound according to claim 22, wherein W isOCC8 alkylNHS, wherein S is a single amino acid or a peptide of two or more amino acids; wherein the groupNHforms an amide bond with the alphacarboxy group of S when S is a single amino acid and the groupNHforms an amide bond with the Cterminal alphacarboxy group of S when S is a peptide of two or more amino acids.
25. A compound according to claim 23, wherein W isOCiC8 alkylNHS, wherein S is a single amino acid or a peptide of two or more amino acids; wherein the groupNHforms an amide bond with the alphacarboxy group of S when S is a single amino acid and the groupNHforms an amide bond with the Cterminal alphacarboxy group of S when S is a peptide of two or more amino acids.
Description:
INTERNATIONALSEARCHREPORT,lnttlonal Appllcation No PCT/US00/11538 A.CLASSIFICATIONOFS ABJECTMATTER IPC7A61K38/00C07C255/54C07C235/20C07D295/18C07D311/92 C07D307/92C07D487/22C07D207/34C07C211/10 AccordingtoIntemationalPatentClassification(IPC)ortobothnati onalclassification and IPC B.FIELDSSEARCHED Minimumdocumentationsearched(classificationsystemfollowedbyc lassificationsymbols) Documentationsearchedotherthanminimumdocumentationtotheexten tthatsuchdocumentsareincludedinthefieldssearched Electronicdatabaseconsulted duringtheinternational search(nameofdatabaseand,wherepractical,searchterms used) C.DOCUMENTSCONSIDEREDTOBERELEVANT Category°Citationofdocument,withindication,whereappropriate ,oftherelevantpassagesRelevanttoclaimNo. XTAKUWA,AKIOETAL:"Structural1 influencesontheisomerizationof 4-benzyl-and4-allyl-1,2-naphthoquinones toquinonemethidesandtheir stereochemistry" J.CHEM.SOC.,PERKINTRANS.1(1986), (9),1627-31, XP002142390 page 1628 -/- ElFurtherdocumentsarelistedinthecontinuationofboxC.Patentfam ilymembersarelistedinannex. LJ LJ °Specialcategoriesofciteddocuments: 'T"later document published after the intemational filing date "A"document defining the general state of the art which is not o priority date and not in conflict with the application but consideredto be of particular relevance invention invention E-eariierdocumentbutpublishedonoraftertheintemational X-documentofparticularrelevance; theclaimedinvention filing date cannotbeconsiderednovelorcannotbeconsideredto "L'documentwhichmaythrowdoubtsonpriorityclaim(s)orinvdveanin ventivestepwhenthedocumentistakenalone whichiscitedtoestablishthepublicationdateofanother. y. document of particular relevance : the claimed invention citation or other special reason(asspecified)cannot be considered to involve an inventive step when the "O"document referringtoanoraldisclosure,use,exhibitionordocumentiscombin edwithoneormoreothersuchdocu- othermeansments,suchcombinationbeingobvioustoapersonskilled "P"documentpublishedpriortotheinternationalfilingdatebut in the art. laterthantheprioritydateclaimed"&'documentmemberofthesamepat entfamily DateoftheactualcompletionoftheintemationalsearchDateofmailin goftheinternationalsearchreport 26October2000 NameandmailingaddressoftheISAAuthorizedofficer EuropeanPatentOffice,P.B.5818Patentaan2 NL-2280HVRijswijk Tel.(+31-70)340-2040,Tx.31651po nez Fax:(+31-70)340-3016 DBQer, ! \ INTERNATIONAL SEARCH REPORT Int tlonal Appllcation No PCT/US00/11538 C.(Continuation)DOCUMENTSCONSIDEREDTOBERELEVANT CategoryCitationofdocument,withindication,whereappropriate,o ftherelevantpassagesRelevanttoclaimNo. XDATABASECHEMABS'Online!1 CHEMICALABSTRACTSSERVICE,COLUMBUS, OHIO,US; PERSHIN,G.N.ETAL:"Bonaphthon,anew antiviralchemotherapeuticagent" retrievedfromSTN Databaseaccessionno.82:118979 XP002142391 abstract &FARMAKOL.TOKSIKOL.(MOSCOW)(1975), 38(1),69-73, XNELSON,WENDELL.ETAL:"3,4-Catechol 1 derivativeofpropranolol,aminor dihydroxylatedmetabolite" J.MED.CHEM.(1984),27(7),857-61, XP002142392 page860-page861 XBULLOCK,F.J.ETAL:"Antiprotozoal 1 quinones.II.Synthesisof4-amino-1,2- naphthoquinonesandrelatedcompoundsas potentialantimalarials" J.MED.CHEM.(1970),13(1),97-103, XP002142393 page99;table1 XDUNN,W.J.,IIIETAL:1 "Structure-activityanalyzedbypattern recognition:theasymmetriccase" J.MED.CHEM.(1980),23(6),595-9, XP002142394 page596;table1 XTAKUWA,AKIOETAL:"Additionofalcohol 1 to1,2-naphthoquinonepromotedbymetal ions.Facilesynthesisof 4-alkoxy-1,2-naphthoquinones" BULL.CHEM.SOC.JPN.(1986),59(9), 2959-61, XP002142395 page2961 3 3 INTERNATIONALSEARCHREPORT | Int tlonalAppilrathnNb PCT/US00/11538 C.(Contlnuation) DOCUMENTS CONSIDEREDTOBERELEVANT Category°Citationofdocument,withindication,whereappropriate ,oftherelevantpassagesRelevanttoclaimNo. XDATABASECHEMABS'Online!1 CHEMICALABSTRACTSSERVICE,COLUMBUS, OHIO,US; DOLAN,M.EILEENETAL:"Effectsof 1,2-naphthoquinonesonhumantumorcell growthandlackofcross-resistancewith otheranticanceragents" retrievedfromSTN Databaseaccessionno.129:156459 XP002142396 abstract &ANTI-CANCERDRUGS(1998),9(5),437-448, XCOTE,PHILIPN.ETAL:"Glucopyranosides22-25 derivedfrom 2-hydroxy-1,4-naphthoquinones" CARBOHYD.RES., vol.26,no.1,1973,pages247-251, XP000925262 page248 XWO9708162A(DANAFARBERCANCERINSTINC22-25 ;PARDEEARTHUR(US);LICHIANGJ(US)) 6March1997(1997-03-06) page19 page20 page26 XUS5763625A(WITIAKDONALDTETAL)22-25 9June1998(1998-06-09) column17;claim1 XPLANCHON,SARAHM.ETAL:"Bcl-2 protects22-25 against.beta.-lapachone-mediatedcaspase3 activationandapoptosisinhumanmyeloid leukemia(HL-60)cells" ONCOL.REP., vol.6,no.3,1999,pages485-492, XP000957471 page490;table1 3 h.ernationalapplicationNo. INTERNATIONALSEARCHREPORTPCT/US00/11538 BoxIObservationswherecertainclaimswerefoundunsearchable(Cont inuationofitem1offirstsheet) ThisInternationalSearchReporthasnotbeenestablishedinrespecto fcertainclaimsunderArticle17(2)(a)forthefollowingreasons: 1.ClaimsNos.: becausetheyrelatetosubjectmatternotrequiredtobesearchedbythi sAuthority,namely: 2.ClaimsNos.: becausetheyrelatetopartsoftheInternationalApplicationthatdon otcomplywiththeprescribedrequirementstosuch anextentthatnomeaningfulInternationalSearchcanbecarriedout,s pecifically: 3.CClaims Nos.: becausetheyaredependentclaimsandarenotdraftedinaccordancewit hthesecondandthirdsentencesofRule6.4(a). Box11Observationswhereunityofinventionislacking(Continuation ofitem2offirstsheet) ThisInternationalSearchingAuthorityfoundmultipleinventionsin thisinternationalapplication,asfollows: seeadditionalsheet 1.! As allrequiredadditionalsearchfeesweretimelypaidbytheapplicant, thisInternationalSearchReportcoversall searchableclaims. 2.C As all searchableclaimscouldbesearchedwithouteffortjustifyinganaddi tionalfee,thisAuthoritydidnotinvitepayment ofanyadditionalfee. 3.As onlysomeoftherequiredadditionalsearchfeesweretimelypaidbythe applicant,thisInternationalSearchReport covers onlythoseclaimsforwhichfeeswerepaid,specificallyclaimsNos.: 10,11,13-25 4.Norequiredadditionalsearchfeesweretimelypaidbytheapplicant .Consequently,thisInternationalSearchReportis restrictedtotheinventionfirstmentionedintheclaims; it iscoveredbyclaimsNos.: RemarkonProtestThe additionalsearchfeeswereaccompaniedbytheapplicant'sprotest. u Noprotestaccompaniedthepaymentofadditionalsearchfees. au FURTHER INFORMATION CONTINUED FROM PCT/ISA/210 This International Searching Authority found multiple (groups of) inventions in this international application, as follows: 1. Claims: 1,5 An ortho quinone as depicted in claims 1 or 5.

2. Claims: 2,3 Compounds as depicted in claims 2 and 3 with a-S03Na group.

3. Claim: 4 Compounds as depicted in claim 4 with substituents Y and CH2N (-G1) (-G2).

4. Claims: 6,7 Compounds as depicted in claims 6 and 7 comprising a -OP (=O) (OB) 2 moiety.

5. Claim: 8 A compound as depicted in claim 8.

6. Claim: 9 A compound as depicted in claim 9.

7. Claims: 10,11 Compounds as depicted in claims 10 and 11.

8. Claim: 12 A compound as depicted in claim 12.

9. Claim: 13 A compound as depicted in claim 13 10. Claims: 14-21 A compound of formula S-L-Quin and a method for it's preparation.

FURTHER INFORMATION CONTINUED FROM PCT/ISA/210 11. Claims: 22-25 Compounds as depicted in claim 22, wherein W=H.

12. Claims: 22-25 Compounds as depicted in claim 22, wherein W represents any substituent mentioned in claim 22, but cannot be-H. INTERNATIONAL SEARCH REPORT Int lonal AppllcatlonNo Intormatlon on patent tamily members PatentdocumentPublication Patent family Publication c'citedinsearchreportdate member(s)date WO9731936A04-09-1997US 5824700 A 20-10-1998 US 5883270 A 16-03-1999 AU 1975497 A 16-09-1997 EP 0888326 A 07-01-1999 JP 2000506841 T 06-06-2000 US 5977187 A 02-11-1999 US 5969163 A 19-10-1999 WO9731611A04-09-1997AU 2193797 A 16-09-1997 EP 0886524 A 30-12-1998 US4273706A16-06-1981US 4204870 A 27-05-1980 EP0255679A10-02-1988US 4879243 A 07-11-1989 US 5141855 A 25-08-1992 CA 1311178 A 08-12-1992 DE 3783532 A 25-02-1993 DE 3783532 T 22-07-1993 JP 2009200 C 11-01-1996 JP 7043370 B 15-05-1995 JP 63100376 A 02-05-1988 CA 1298177 A 31-03-1992 EP 0255086 A 03-02-1988 EP 0255087 A 03-02-1988 EP 0255089 A 03-02-1988 JP 63042450 A 23-02-1988 JP 63082363 A 13-04-1988 JP 63212864 A 05-09-1988 WO9708162A06-03-1997AU 6901296 A 19-03-1997 US5763625A09-06-1998AU 5569896 A 18-11-1996 WO 9633988 A 31-10-1996




 
Previous Patent: DIBENZOYLMETHANE DERIVATIVES, PROCESS FOR THE PREPARATION OF THE SAME AND USES THEREOF

Next Patent: A PRODUCTION METHOD OF AROMATIC CARBOXYLIC ACIDS