Title:
HETEROCYCLIC COMPOUNDS AS ADENOSINE DEAMINASE INHIBITORS
Document Type and Number:
WIPO Patent Application WO/2000/055155
Kind Code:
A2
Abstract:
Heterocyclic compounds of formula (I) wherein B is (1) [wherein R¿1? is hydrogen or lower alkyl; R¿2? is hydrogen or lower alkyl; and X is hydrogen or hydroxy protective group], lower alkanoyl or hydroxyimino (lower) alkyl; A is lower alkylene; W is heterocyclic or carbocyclic group, each of which may have one or more substituent(s); Z is heterocyclic group selected from the group consisting of imidazolyl, triazolyl, imidazopyridyl and adenyl, each of which may have one or more subtituent (s); or a salt thereof, provided that when W is aryl which may have one or more substituent(s), then (i) Z is triazolyl, imidazopyridyl or adenyl, each of which may have one or more substituent(s); (ii) Z is imidazolyl which may have one or more substituent(s) and B is lower alkanoyl or hydroxyimino(lower) alkyl; or (iii) Z is imidazolyl which may have one or more substituent(s) and R¿1? and R¿2? are both lower alkyl; or pharmaceutically acceptable salts thereof, which are useful as a medicament.
Inventors:
TERASAKA TADASHI (JP)
SEKI NOBUO (JP)
TSUJI KIYOSHI (JP)
NAKANISHI ISAO (JP)
KINOSHITA TAKAYOSHI (JP)
NAKAMURA KATSUYA (JP)
SEKI NOBUO (JP)
TSUJI KIYOSHI (JP)
NAKANISHI ISAO (JP)
KINOSHITA TAKAYOSHI (JP)
NAKAMURA KATSUYA (JP)
Application Number:
PCT/JP2000/001316
Publication Date:
September 21, 2000
Filing Date:
March 03, 2000
Export Citation:
Assignee:
FUJISAWA PHARMACEUTICAL CO (JP)
TERASAKA TADASHI (JP)
SEKI NOBUO (JP)
TSUJI KIYOSHI (JP)
NAKANISHI ISAO (JP)
KINOSHITA TAKAYOSHI (JP)
NAKAMURA KATSUYA (JP)
TERASAKA TADASHI (JP)
SEKI NOBUO (JP)
TSUJI KIYOSHI (JP)
NAKANISHI ISAO (JP)
KINOSHITA TAKAYOSHI (JP)
NAKAMURA KATSUYA (JP)
International Classes:
A61K31/4174; C07D249/08; A61K31/4178; A61K31/4184; A61K31/4196; A61K31/428; A61K31/437; A61K31/4439; A61K31/695; A61P1/00; A61P1/04; A61P1/16; A61P3/10; A61P5/14; A61P7/04; A61P7/06; A61P9/10; A61P9/14; A61P11/00; A61P11/06; A61P13/12; A61P17/06; A61P17/16; A61P19/02; A61P19/04; A61P19/06; A61P19/08; A61P21/00; A61P21/04; A61P25/06; A61P27/02; A61P29/00; A61P35/02; A61P37/02; A61P37/06; A61P43/00; C07D233/90; C07D249/10; C07D401/14; C07D403/06; C07D403/14; C07D413/14; C07D417/06; C07D417/14; C07D471/04; C07D521/00; C07F7/18; (IPC1-7): C07D403/00
Domestic Patent References:
| WO1998002166A1 | 1998-01-22 | |||
| WO1997028803A1 | 1997-08-14 |
Foreign References:
| DE3416444A1 | 1985-11-07 | |||
| GB2050334A | 1981-01-07 | |||
| DE3224129A1 | 1983-12-29 | |||
| DE3234627A1 | 1984-03-22 | |||
| DE3321422A1 | 1984-12-20 | |||
| DE3139250A1 | 1983-04-21 |
Other References:
YONG-ZHONG ZHAO ET AL.: "Screening solution-phase combinatorial libraries using pulsed ultrafiltration electrospray mass spectrometry" JOURNAL OF MEDICINAL CHEMISTRY., vol. 40, no. 25, - 1997 pages 4006-4012, XP002144610 AMERICAN CHEMICAL SOCIETY. WASHINGTON., US ISSN: 0022-2623
CHEMICAL ABSTRACTS, vol. 129, no. 19, 9 November 1998 (1998-11-09) Columbus, Ohio, US; abstract no. 245403u, CURTIS, ARK ET AL.: "Adenosine deaminase inhibitors. Synthesis and biological evaluation of aralkyladenines (ARADS)." XP002144612 -& DATABASE CHEMICAL ABSTRACTS [Online] CA 129:245403, XP002144615 & BIOORG. MED. CHEM. LETT., vol. 8, no. 13, - 1998 pages 1639-1642,
PAOLO COZZI ET AL.: "Agents combining thromboxane receptor antagonism with thromboxane synthase inhibition: (((2-(1H-Imidazol-1-yl)ethylidene)amino)ox y)alkanoic acids" JOURNAL OF MEDICINAL CHEMISTRY., vol. 37, no. 21, - 1994 pages 3588-3604, XP002144611 AMERICAN CHEMICAL SOCIETY. WASHINGTON., US ISSN: 0022-2623
CHEMICAL ABSTRACTS, vol. 125, no. 7, 12 August 1996 (1996-08-12) Columbus, Ohio, US; abstract no. 86571w, ZHENG, HONGKUI ET AL.: "Synthesis and biological activities of Dicyclobutrazol." XP002144613 -& DATABASE CHEMICAL ABSTRACTS [Online] CA 125: 86571, XP002144616 & HUAXUE YANJIU YU YINGYONG, vol. 7, no. 2, - 1995 pages 202-205,
CHEMICAL ABSTRACTS, vol. 110, no. 23, 5 June 1989 (1989-06-05) Columbus, Ohio, US; abstract no. 212710, LIAO, LIANAN ET AL.: "Synthesis of 1-substituted 1-(1,2,4-triazol-1-yl)-3,3-dimethylbutan-2 -ones." XP002144614 -& DATABASE CHEMICAL ABSTACTS [Online] CA 110: 212710, XP002144617 & XIAMEN DAXUE XUEBAO, ZIRAN KEXUEBAN, vol. 27, no. 5, - 1988 pages 590-592,
CHEMICAL ABSTRACTS, vol. 129, no. 19, 9 November 1998 (1998-11-09) Columbus, Ohio, US; abstract no. 245403u, CURTIS, ARK ET AL.: "Adenosine deaminase inhibitors. Synthesis and biological evaluation of aralkyladenines (ARADS)." XP002144612 -& DATABASE CHEMICAL ABSTRACTS [Online] CA 129:245403, XP002144615 & BIOORG. MED. CHEM. LETT., vol. 8, no. 13, - 1998 pages 1639-1642,
PAOLO COZZI ET AL.: "Agents combining thromboxane receptor antagonism with thromboxane synthase inhibition: (((2-(1H-Imidazol-1-yl)ethylidene)amino)ox y)alkanoic acids" JOURNAL OF MEDICINAL CHEMISTRY., vol. 37, no. 21, - 1994 pages 3588-3604, XP002144611 AMERICAN CHEMICAL SOCIETY. WASHINGTON., US ISSN: 0022-2623
CHEMICAL ABSTRACTS, vol. 125, no. 7, 12 August 1996 (1996-08-12) Columbus, Ohio, US; abstract no. 86571w, ZHENG, HONGKUI ET AL.: "Synthesis and biological activities of Dicyclobutrazol." XP002144613 -& DATABASE CHEMICAL ABSTRACTS [Online] CA 125: 86571, XP002144616 & HUAXUE YANJIU YU YINGYONG, vol. 7, no. 2, - 1995 pages 202-205,
CHEMICAL ABSTRACTS, vol. 110, no. 23, 5 June 1989 (1989-06-05) Columbus, Ohio, US; abstract no. 212710, LIAO, LIANAN ET AL.: "Synthesis of 1-substituted 1-(1,2,4-triazol-1-yl)-3,3-dimethylbutan-2 -ones." XP002144614 -& DATABASE CHEMICAL ABSTACTS [Online] CA 110: 212710, XP002144617 & XIAMEN DAXUE XUEBAO, ZIRAN KEXUEBAN, vol. 27, no. 5, - 1988 pages 590-592,
Attorney, Agent or Firm:
Tabushi, Eiji (Ltd. Osaka Factory 1-6 Kashima 2-chome Yodogawa-ku, Osaka-shi Osaka, JP)
Download PDF:
Claims:
C L A I M S
| 1. | A compound of the formula [I]: wherein [wherein R1 is hydrogen or lower alkyl ; R2 is hydrogen or lower alkyl ; and X is hydrogen or hydroxy protective groups, lower alkanoyl or hydroxyimino (lower) alkyl ; A is lower alkylene; W is heterocyclic or carbocyclic group, each of which may have one or more substituent (s); Z is heterocyclic group selected from the group consisting of imidazolyl, triazolyl, imidazopyridyl and adenyl, each of which may have one or more substituent (s); or a salt thereof, provided that when W is aryl which may have one or more substituent (s), then (i) Z is triazolyl, imidazopyridyl or adenyl, each of which may have one or more substituent (s); (ii) Z is imidazolyl which may have one or more substituent (s) and B is lower alkanoyl or hydroxyimino (lower) alkyl ; or (iii) Z is imidazolyl which may have one or more substituent (s) and R1 and R2 are both lower alkyl. |
| 2. | A compound of claim 1, wherein A is ethylene ; W is Ncontaining heterocyclic group or aryl, each of which may have one or more substituent (s); and Z is imidazoly, triazolyl, imidazopyridyl or adenyl, each of which may have one or two substituent (s). |
| 3. | A compound of claim 2, wherein [wherein X and Ri are both hydrogen, and R2 is hydrogen or lower alkyl]; W is Ncontaining heterobicyclic group or aryl, each of which may have one or more substituent (s) selected from the group consisting of cyano, hydroxy, halogen, oxo, optionally substituted lower alkoxy, lower alkyl, optionally substituted amino, nitro and NHC (O)R3 [wherein R3 is lower alkyl, optionally substituted ar (lower) alkyl, ar (lower) alkylamino, aryl, heterocyclic (lower) alkyl, or heterocyclicthio (lower) alkyl, each of which may have one or more substituent (s)]; and Z is imidazolyl, triazolyl or imidazopyridyl, each of which may have one or two substituent (s) selected from the group consisting of carbamoyl, N substituted carbamoyl, lower alkoxycarbonyl and guanidinocarbonyl. |
| 4. | A compound of claim 3, wherein W is indolyl, benzothiazolyl, indazolyl, phenyl or naphthyl, each of which may have one or two substituent (s) selected from the group consisting of cyano, hydroxy, halogen, oxo, lower alkoxy, pheny (lower) alkoxy, halophenyl (lower) alkoxy, indolyl (lower) alkoxy which may have lower alkyl, lower alkyl, phenyl (lower) alkylamino, amino, nitro andNHC (O)R3 [wherein R3 is lower alkyl, phenyl (lower) alkyl, lower alkylphenyl (lower) alkyl, lower alkoxyphenyl (lower) alkyl, phenyl (lower) alkylamino, phenyl, benzimidazolyl (lower) alkyl which may have lower alkyl, pyridyl (lower) alkyl, benzothiazolylthio (lower) alkyl or indolyl (lower) alkyl which may have one or two oxo] ; and Z is imidazolyl, triazolyl or imidazopyridyl, each of which may have one substituent selected from the group consisting of carbamoyl, (lower) alkylcarbamoyl, (lower) alkoxycarbonyl and guanidinocarbonyl. |
| 5. | A compound of claim 4, wherein Z is imidazolyl which may have carbamoyl or guanidinocarbonyl ; triazolyl which may have carbamoyl, (lower) alkylcarbamoyl or lower alkoxycarbonyl ; or imidazopyridyl. |
| 6. | A compound of claim 5, wherein W is indolyl which may have one or two substituent (s) selected from the group consisting of cyano, hydroxy, halogen, oxo, lower alkoxy, phenyl (lower) alkoxy, halophenyl (lower) alkoxy, indolyl (lower) alkoxy which may have lower alkyl, lower alkyl, phenyl (lower) alkylamino, amino, nitro, andNHC (O) R3 [wherein R3 is lower alkyl, phenyl (lower) alkyl, lower alkylphenyl (lower) alkyl, lower alkoxyphenyl (lower) alkyl, phenyl (lower) alkylamino, phenyl, benzimidazolyl (lower) alkyl which may have lower alkyl, pyridyl (lower) alkyl, benzothiazolylthio (lower) alkyl or indolyl (lower) alkyl which may have one or two oxo]; benzothiazolyl which may have oxo ; indazolyl; phenyl which may have one or two halogen (s); or naphthyl ;. |
| 7. | A compound of claim 6, wherein W is indolyl which has one or two substituent (s) selected from the group consisting of lower alkyl, lower alkoxy and halophenyl (lower) alkoxy ; or benzothiazolyl which has one oxo ; and Z is imidazolyl which has carbamoyl. |
| 8. | A process for preparing a compound of the formula [I]: wherein [wherein R1 is hydrogen or lower alkyl ; R2 is hydrogen or lower alkyl; and X is hydrogen or hydroxy protective group], lower alkanoyl or hydroxyimino (lower) alkyl ; A is lower alkylene ; W is heterocyclic or carbocyclic group, each of which may have one or more substituent (s); Z is heterocyclic group selected from the group consisting of imidazolyl, triazolyl, imidazopyridyl and adenyl, each of which may have one or more substituent (s); or a salt thereof, provided that when W is aryl which may have one or more substituent (s), then (i) Z is triazolyl, imidazopyridyl or adenyl, each of which may have one or more substituent (s); (ii) Z is imidazolyl which may have one or more substituent (s) and B is lower alkanoyl or hydroxyimino (lower) alkyl ; or (iii) Z is imidazolyl which may have one or more substituent (s) and R1 and R2 are both lower alkyl. or a salt thereof, which comprises (1) reacting a compound of the formula: ZH or a salt thereof, with a compound of the following formula : wherein A, Rl, R2, W, X and Z are each as defined above, or its reactive derivative at the hydroxy group, or a salt thereof, to give a compound of the following formula: wherein A, Rl, R2, W, X and Z are each as defined above, or a salt thereof, or (2) subjecting a compound of the following formula : wherein A, R1, R2, W and Z are each as defined above, X1 is a hydroxy protective group, or a salt thereof to deprotection of the hydroxy protective group to give a compound of the following formula : wherein A, R1, R2, W and Z are each as defined above, or a salt thereof, or (3) subjecting a compound of the following formula : wherein A, R1, R2, X and Z are each as defined above, Mi is heterocyclic group or carbocyclic group, each of which has nitro, or a salt thereof to reduction reaction of the nitro group to give a compound of . the following formula : wherein A, Rl, R2, X and Z are each as defined above, W2 is heterocyclic group or carbocyclic group, each of which has amino, or a salt thereof, or (4) reacting a compound of the following formula : wherein A, Rl, R2, W2, X and Z are each as defined above, or its reactive derivateives at the amino group, or a salt thereof, with a compound of the following formula: R3COOH wherein R3 is lower alkyl, optionally substituted ar (lower) alkyl, ar (lower) alkylamino, heterocyclic (lower) alkyl or heterocyclicthio (lower) alkyl, each of which may have one or more substituent (s); or its reactive derivative at carboxy group, or a salt thereof, to give a compound of the following formula : wherein A, Rl, R2, X and Z are each as defined above, W3 is heterocyclic group or carbocyclic group, each of which has a group of the following formula : NHC (O)R3 (wherein R3 is as defined above) or a salt thereof, or (5) reacting a compound of the following formula : wherein R1, R2, A, W and X are each as defined above, Z1 is imidazolyl, triazolyl, imidazopyridyl or adenyl each of which has carboxy, or its reactive derivatives at the carboxy group, or a salt thereof, with guanidine or a salt thereof, to give a compound of the following formula : wherein Rl, R2 A, W and X are each as defined above, Z2 is imidazolyl, triazolyl, imidazopyridyl or adenyl, each of which has guanidinocarbonyl, or a salt thereof, or (6) subjecting a compound of the following formula : wherein Rl, R2, A, W, X and Z1 are each as defined above, or its reactive derivative at the carboxy group, or a salt thereof to amidation to give a compound of the following formula : wherein Rl, R2, A, W and X are each as defined above, Z3 is imidazolyl, triazolyl, imidazopyridyl or adenyl, each of which has carbamoyl, or a salt thereof. (7) reacting a compound of the following formula: wherein W2, A, X, Z, R1 and R2 are each as defined above, or its reactive derivatives at the amino group, or a salt thereof, with a compound of the following formula: R4CHO wherein R4 is lower alkyl, carbocyclic (lower) alkyl or heterocyclic (lower) alkyl, to give a compound of the following formula: wherein A, X, Z, R1 and R2 are each as defined above, and W4 is carbocyclic or heterocyclic group, each of which has (lower) alkylamino, carbocyclic (lower) alkylamino or heterocyclic (lower) alkylamino, or a salt thereof, or (8) subjecting a compound of the following formula: wherein A, X, Z, R1 and R2 are each as defined above, and W5 is carbocyclic or heterocyclic group, each of which has a hydroxy protective group, or a salt thereof, to deprotection of the hydroxy protective group, and then reacting the deprotected compound with a compound of the following formula: R5Y or R6 OR7 wherein R5 and R6 are lower alkyl, heterocyclic (lower) alkyl or carbocyclic (lower) alkyl, R7 is hydrogen or methanesufonyl, and Y is halogen, to give a compound of the following formula: wherein A, X, Z, R1 and R2 are each as defined above, and W6 is heterocyclic or carbocyclic group, each of which hasOR5 orOR6 [wherein R5 and R6 are each as defined above.], or a salt thereof, or (9) subjecting a compound of the following formula: wherein W, A and Z are each as defined above, R8 is hydrogen and Rg is lower alkyl, or a reactive derivatives at the hydroxy group, or a salt thereof, to oxidation reaction to give a compound of the following formula: wherein W, A, Z and R9 are each as defined above, or a salt thereof, or (10) reacting a compound of the following formula: wherein W, A, Z and Rg are each as defined above, or salt thereof, with hydroxylamine or a salt thereof, to give a compound of the following formula: wherein W, A, Z and Rg are each as defined above, or a salt thereof, or (11) reacting a compound of the following formula: wherein W, A, Z and Rg are each as defined above, or a salt thereof, with a compound of the following formula: RloY wherein Y is as defined above, and Rlo are lower alkyl, to give a compound of the following formula: wherein W, A, Z, Rg and R1o are each as defined above, or a salt thereof. |
| 9. | A pharmaceutical composition containing a compound of claim 1, as active ingredient, in association with a pharmaceutically acceptable carrier or excipient. |
| 10. | A compound of claim 1 for use as a medicament. |
| 11. | An Adenosine deaminase inhibiting agent comprising the compound of claim 1. |
| 12. | A method for treating and/or preventing autoimmune diseases; inflammatory conditions, organ or tissue alloor xenotransplant rejection; various leukemias; or diseases that arise from, or are aggravated by, insufficient blood flow through a particular organ or portion thereof, which comprises administering an effective amount of a compound of claim 1 to human beings or animals. |
| 13. | Use of a compound of claim 1 for the manufacture of a medicament for treating and/or preventing autoimmune diseases; inflammatory conditions; organ or tissue alloor xenotransplant rejection; various leukemias; or diseases that arise from, or are aggravated by, insufficient blood flow through a particular organ or portion thereof. |
Description:
INTERNATIONAL SEARCH REPORT IM lonal AppUcation No PCT/JP00/01316 A.CLASSIFICATIONOFSUBJECTMATTER IPC7221:00) AccordingtoInternationalPatentClassification(IPC)ortobothnat
ionalclassificationandIPC B.FIELDSSEARCHED Minimumdocumentationsearched(classificationsystemfollowedbyc
lassificationsymbols) Documentationsearchedotherthanminimumdocumentationtotheexten
tthatsuchdocumentsareincludedinthefieldssearched Electronicdatabaseconsulteduringtheinternationalsearch(nameo
fdatabaseand,wherepractical,searchtermsused) C.DOCUMENTSCONSIDEREDTOBERELEVANT Category Citationofdocument,withindication,whereappropriate,oftherele
vantpassagesRelevanttodaimNo. XCHEMICALABSTRACTS,vol.129,no.19,1,10,11 9November1998(1998-11-09) Columbus,Ohio,US; abstractno.245403u, CURTIS,ARKETAL.:"Adenosinedeaminase inhibitors.Synthesisandbiological evaluationofaralkyladenines(ARADS)." XP002144612 abstract -&DATABASECHEMICALABSTRACTS'Online! CA129:245403, XP002144615 compoundwithRN213018-04-3and-03-2 &BIOORG.MED.CHEM.LETT., vol.8,no.13,-1998pages1639-1642, ___ mFurtherdocumentsarelistedinthecontinuationofboxC.Patentfami
lymembersarelistedinannex. LU J ° Speciaicategoriesofciteddocuments: T'later document published aftertheintemationalfiling date 'A'document defining the general state of the art which is not or priority date and not in conflict with the appticat'ron but conskjered to be of particular relevance invention invention E-eariberdocumentbut published on or after the intemationai X-document of particular reEvance, the chimed invention filing date cannot be considered novel or cannot be considered to 'L'document which may throw doubts on priority claim (s) or involveaninventivestepwhenthe document is taken alone whichiscitedtoestablishthepublicationdateofanotheryameMofpar
ticularrelevance;thechimed invention citationorotherspecialreason(asspecfied)8 ;toinvove an inventNe stepwhenthe '0'documentreferringtoanoraldisclosure,use,exhibitionordocum
entiscombinedwithoneormoreothersuchdocu- othermeansments,suchcombinationbeingobvioustoapersonskilled ' ?' documentpublishedpriortotheintemationaifilingdatebutintheart
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ntfamily DateoftheaduaicompletionoftheinternationalsearchDateofmailin
goftheinternationalsearchreport 11September2000 NameandmailingaddressoftheISAAuthorizedofficer EuropeanPatentOffice,P.B.5818 Patentlaan2 NL-2280HVRijswijk 7 Tel.(+31-70)340-2040.Tx.31 651eponl, Fax:(+31-70) 340-Wl6 INTERNATIONALSEARCH REPORT p onal ApaiSlon No PCT/JP00/01316 C.(Conlnuatlon) DOCUMENTS CONSIDEREDTOBE RELEVANT CategoryCitationofdocument,withindication,whereappropnate,of
therelevantpassagesRelevanttodaimNo. XWO9802166A(THEBOARDOFGOVERNORSFOR1,10,11 HIGHEREDUCATION,STATEOFRHODEISLAND) 22January1998(1998-01-22) * completedocument * XWO9728803A(CYPROSPHARMACEUTICAL1,10,11 CORPORATION)14August1997(1997-08-14) * page17,34:compound27 * XPAOLOCOZZIETAL.:"Agentscombining1 thromboxanereceptorantagonismwith thromboxanesynthaseinhibition: (((2-(lH-Imidazol-1-yl) ethylidene)amino)ox y)alkanoicacids" JOURNALOFMEDICINALCHEMISTRY., vol.37,no.21,-1994pages3588-3604, XP002144611 AMERICANCHEMICALSOCIETY.WASHINGTON.,US ISSN:0022-2623 * page3599:compounds16cand16d * XCHEMICALABSTRACTS,vol.125,no.7,1 12August1996(1996-08-12) Columbus,Ohio,US; abstractno.86571w, ZHENG,HONGKUIETAL.:"Synthesisand biologicalactivitiesofDicyclobutrazol." XP002144613 abstract -&DATABASECHEMICALABSTRACTS'Online! CA125:86571, XP002144616 compoundwithRN63191-09-3 &HUAXUEYANJIUYUYINGYONG, vol.7,no.2,-1995pages202-205, XCHEMICALABSTRACTS,vol.110,no.23,1 5June1989(1989-06-05) Columbus,Ohio,US; abstractno.212710, LIAO,LIANANETAL.:"Synthesisof 1-substituted 1- (1,2,4-triazol-1-yl)-3, 3-dimethylbutan-2 -ones." XP002144614 abstract -&DATABASECHEMICALABSTACTS'Online! CA110:212710, XP002144617 compoundwithRN63190-87-4and-75-0 &XIAMENDAXUEXUEBAO,ZIRANKEXUEBAN, vol.27,no.5,-1988pages590-592, 7 7 INTERNATIONALSEARCHREPORT, ,------- PCT/JP00/01316 C.(Continuatton)DOCUMENTSCONSIDEREDTOBERELEVANT Citatíonofdocument,withindication,whereappropriate,oftherel
evantpassagesRelevanttodaimNo. XDE 3416444A(BASF AG)1 7November1985(1985-11-07) example2 XGB2050334A(IMPERIALCHEMICAL1 INDUSTRIESLTD) 7January1981(1981-01-07) tableI XDE 3224129A(BASF AG) 29December1983(1983-12-29) *example1,2,9,10,13,14,17,18,31, 32,38,42-44,46-49,51 * XDE 3234627A(BAYER AG) 1 22March1984(1984-03-22) * example1-7,9,10,12-14,16-18 * XDE 3321422A(BASF AG) 1 20December1984(1984-12-20) *example1D,2,3;page22:compounds1, 2,7,10 * XDE 3139250A(BASF AG) 1 21April1983(1983-04-21) * example1-3,6-19,24-28,30-36,40,41 * 7 Intemational Application No. PCT/1P 00 A1316 FURTHERINFORMATIONCONTINUEFROMPCT/) SA/ 210 ContinuationofBox1.2 ClaimsNos.:1-7,9-11,13(allpartially) Theinitialphaseofthesearchrevealedaverylargenumberofdocument
s relevanttotheissueofnovelty.Somanydocumentswereretrievedthat
itisimpossibletodeterminewhichpartsoftheclaim(s)maybesaidto definesubject-matterforwhichprotectionmightlegitimatelybesou
ght (Article6PCT). Forthesereasonsitappearsimpossibletoexecuteameaningfulsearch
and/ortoissueacompletesearchreportoverthewholebreadthofthe abovementionedclaims. Thesearchandthereportforthoseclaimscanonlybeconsidered completeforthecompoundsoftheworkingexamples. Theapplicant'sattentionisdrawntothefactthatclaims,orpartsof claims,relatingtoinventionsinrespectofwhichnointernational searchreporthasbeenestablishedneednotbethesubjectofan internationalpreliminaryexamination(Rule66.1(e)PCT).Theappli
cant isadvisedthattheEPOpolicywhenactingasanInternational PreliminaryExaminingAuthorityisnormallynottocarryouta preliminaryexaminationonmatterwhichhasnotbeensearched.Thisis
thecaseirrespectiveofwhetherornottheclaimsareamendedfollowin
g receiptofthesearchreportorduringanyChapterIIprocedure. INTERNATIONALSEARCHREPORT Irrt tlonal ApplicationNo lSormationon patonttamiw mombon PCT/JP 00/01316 PatentdocumentPublication Patent citedinsearchreportdate member (s)date WO9802166A22-01-1998US 5703084 A 30-12-1997 CA 2261591 A 22-01-1998 CN 1227489 A 01-09-1999 EP 0936911 A 25-08-1999EP 0936911 A 25-08-1999 WO9728803A14-08-1997CA 2199615 A 14-08-1997 AU 5522996 A 28-08-1997 EP 0871449 A 21-10-1998 DE3416444A07-11-1985AT 42097 T 15-04-1989 DE 3569374 D 18-05-1989 EP 0163895 A 11-12-1985 IL 75017 A 31-07-1989 JP 61010566 A 18-01-1986 US 4748250 A 31-05-1988US 4748250 A 31-05-1988 GB2050334A07-01-1981NONE DE3224129A29-12-1983AT 55996 T 15-09-1990 AU 564930 B 03-09-1987 AU 1636383 A 05-01-1984 BR 8303462 A 07-02-1984 CA 1207328A,C 08-07-1986 CA 1255684 A 13-06-1989 CS 236888 B 15-05-1985 DD 210193 A 06-06-1984 DE 3381836 D 04-10-1990 DK 298483 A 30-12-1983 EG 16282 A 30-06-1990 EP 0097881 A 11-01-1984 ES 523658 D 16-06-1984 ES 8405772 A 01-10-1984 GR 78609 A 27-09-1984 HU 192150 B 28-05-1987 IL 69079 A 30-09-1986 JP 59021668 A 03-02-1984 NZ 204707 A 12-11-1986 PT 76897A,B 01-07-1983 TR 22729 A 24-05-1988 US 4747869 A 31-05-1988 ZA 8304710 A 28-03-1984 DE3234627A22-03-1984AT 24500 T 15-01-1987 AU 559068 B 19-02-1987 AU 1924283 A 22-03-1984 BR 8305021 A 08-05-1984 CA 1209151 A 05-08-1986 DD 210833 A 27-06-1984 DE 3368620 D 05-02-1987 DK 424483 A 19-03-1984 EP 0103798 A 28-03-1984 ES 525690 D 01-06-1984 ES 8405382 A 16-09-1984 GR 79670 A 31-10-1984 HU 40885A,B 30-03-1987 IE 55944 B 27-02-1991 IL 69730 A 30-11-1987 JP 59076066 A 28-04-1984 INTERNATIONALSEARCHREPORT InttlonalApplicationNo IMormation on patent tamily membos PCT/JP 00/01316 PatentdocumentPublicabon Patent family Publicabon citedinsearchreportdate member (s)date DE3234627ANZ 205606A11-04-1986 PT 77313A,801-10-1983 TR 21592A12-11-1984 US 4603140A29-07-1986 ZA 8306893A30-05-1984 DE3321422A20-12-1984AT 55602T15-09-1990 DE 3482977D20-09-1990 EP 0129186A27-12-1984 DE3139250A21-04-1983EP 0076446A13-04-1983 JP 58069802A26-04-1983