BRPI0407968A - derivados de oxamida úteis como inibidores de raf-quinase - Google Patents

derivados de oxamida úteis como inibidores de raf-quinase

Info

Publication number
BRPI0407968A
BRPI0407968A BRPI0407968-0A BRPI0407968A BRPI0407968A BR PI0407968 A BRPI0407968 A BR PI0407968A BR PI0407968 A BRPI0407968 A BR PI0407968A BR PI0407968 A BRPI0407968 A BR PI0407968A
Authority
BR
Brazil
Prior art keywords
kinase inhibitors
raf kinase
derivatives useful
oxamide derivatives
oxamide
Prior art date
Application number
BRPI0407968-0A
Other languages
English (en)
Inventor
Hans-Peter Buchstaller
Mathias Wiesner
Frank Zenke
Christiane Amendt
Matthias Grell
Christian Sirrenberg
Original Assignee
Merck Patent Gmbh
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Merck Patent Gmbh filed Critical Merck Patent Gmbh
Publication of BRPI0407968A publication Critical patent/BRPI0407968A/pt

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/81—Amides; Imides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/06—Antiasthmatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/08—Drugs for disorders of the urinary system of the prostate
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/12—Drugs for disorders of the urinary system of the kidneys
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/06—Antipsoriatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/02—Antineoplastic agents specific for leukemia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/04—Immunostimulants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/62—Oxygen or sulfur atoms
    • C07D213/63—One oxygen atom
    • C07D213/68—One oxygen atom attached in position 4
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links

Abstract

"DERIVADOS DE OXAMIDA úTEIS COMO INIBIDORES DE RAF-QUINASE". A presente invenção refere-se a derivados de oxamida de Fórmula (I), ao uso dos compostos de Fórmula (I) como inibidores de raf-quinase, ao uso dos compostos de Fórmula (I) para a produção de uma composição farmacêutica e a um método de tratamento que compreende administrar essa composição farmacêutica a um paciente.
BRPI0407968-0A 2003-03-24 2004-03-09 derivados de oxamida úteis como inibidores de raf-quinase BRPI0407968A (pt)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP03006702 2003-03-24
PCT/EP2004/002406 WO2004085399A1 (en) 2003-03-24 2004-03-09 Oxamide derivatives useful as raf-kinase inhibitors

Publications (1)

Publication Number Publication Date
BRPI0407968A true BRPI0407968A (pt) 2006-03-07

Family

ID=33040911

Family Applications (1)

Application Number Title Priority Date Filing Date
BRPI0407968-0A BRPI0407968A (pt) 2003-03-24 2004-03-09 derivados de oxamida úteis como inibidores de raf-quinase

Country Status (13)

Country Link
US (1) US20060189665A1 (pt)
EP (1) EP1606260A1 (pt)
JP (1) JP2006521304A (pt)
KR (1) KR20050110693A (pt)
CN (1) CN1764645A (pt)
AR (1) AR043757A1 (pt)
AU (1) AU2004224239A1 (pt)
BR (1) BRPI0407968A (pt)
CA (1) CA2520009A1 (pt)
MX (1) MXPA05010020A (pt)
PL (1) PL377124A1 (pt)
WO (1) WO2004085399A1 (pt)
ZA (1) ZA200508522B (pt)

Families Citing this family (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8124630B2 (en) 1999-01-13 2012-02-28 Bayer Healthcare Llc ω-carboxyaryl substituted diphenyl ureas as raf kinase inhibitors
WO2000041698A1 (en) 1999-01-13 2000-07-20 Bayer Corporation φ-CARBOXY ARYL SUBSTITUTED DIPHENYL UREAS AS p38 KINASE INHIBITORS
US20030216396A1 (en) 2002-02-11 2003-11-20 Bayer Corporation Pyridine, quinoline, and isoquinoline N-oxides as kinase inhibitors
EP2324825A1 (en) 2002-02-11 2011-05-25 Bayer Healthcare LLC Aryl ureas with angiogenesis inhibiting activity
UY28213A1 (es) 2003-02-28 2004-09-30 Bayer Pharmaceuticals Corp Nuevos derivados de cianopiridina útiles en el tratamiento de cáncer y otros trastornos.
AU2004247626B8 (en) 2003-05-15 2011-05-19 Arqule, Inc. Imidazothiazoles and imidazoxazole derivatives as inhibitors of p38
US8796250B2 (en) 2003-05-20 2014-08-05 Bayer Healthcare Llc Diaryl ureas for diseases mediated by PDGFR
BR122016015715B8 (pt) 2003-07-23 2021-05-25 Bayer Healthcare Llc composições farmacêuticas de metilamida de ácido 4[4-[3-(4-cloro-3-trifluorometilfenil)-ureido]-3-fluorofenóxi)-piridina-2-carboxílico
JP2007515412A (ja) * 2003-12-10 2007-06-14 メルク　パテント　ゲゼルシャフト　ミット　ベシュレンクテル　ハフトング ジアシルヒドラジン誘導体
US7829560B2 (en) 2004-07-08 2010-11-09 Arqule, Inc. 1,4-disubstituted naphthalenes as inhibitors of P38 MAP kinase
CA2584368A1 (en) 2004-10-19 2006-04-27 Arqule, Inc. Synthesis of imidazooxazole and imidazothiazole inhibitors of p38 map kinase
US7470693B2 (en) 2005-04-21 2008-12-30 Bristol-Myers Squibb Company Oxalamide derivatives as kinase inhibitors
US20130266636A1 (en) * 2010-08-12 2013-10-10 The Regents Of The University Of California Methods for blocking cell proliferation and treating diseases and conditions responsive to cell growth inhibition
CN102406644A (zh) * 2010-09-20 2012-04-11 北大方正集团有限公司 芳基脲衍生物用于制备治疗移植排斥药物的新用途
CN102406646B (zh) * 2010-09-20 2015-09-09 北大方正集团有限公司 芳基脲衍生物用于制备治疗移植排斥药物的用途
CN108484587A (zh) * 2018-06-03 2018-09-04 刘思良 一种Raf激酶抑制剂及其在癌症治疗中的应用

Family Cites Families (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR1434226A (fr) * 1964-02-10 1966-04-08 Ciba Geigy Nouveaux agents pesticides
GB1572527A (en) * 1977-05-05 1980-07-30 Ici Ltd Method of controlling pollen formation
ZA846616B (en) * 1983-08-26 1985-08-28 Ciba Geigy Ag Oxalyl anilides
DE3480199D1 (de) * 1983-08-26 1989-11-23 Ciba Geigy Ag Oxalic-acid anilides
DE3830054A1 (de) * 1988-09-03 1990-03-15 Boehringer Mannheim Gmbh Phenylamide - verfahren zu ihrer herstellung sowie diese verbindungen enthaltende arzneimittel
JP3354090B2 (ja) * 1996-09-30 2002-12-09 シエーリング アクチエンゲゼルシャフト 分化誘導剤
US6174905B1 (en) * 1996-09-30 2001-01-16 Mitsui Chemicals, Inc. Cell differentiation inducer
CZ299156B6 (cs) * 1997-12-22 2008-05-07 Bayer Corporation Substituované heterocyklické mocoviny, farmaceutické prípravky je obsahující a jejich použití
EP1140840B1 (en) * 1999-01-13 2006-03-22 Bayer Pharmaceuticals Corp. -g(v)-carboxyaryl substituted diphenyl ureas as raf kinase inhibitors
US7928239B2 (en) * 1999-01-13 2011-04-19 Bayer Healthcare Llc Inhibition of RAF kinase using quinolyl, isoquinolyl or pyridyl ureas
JP2001114753A (ja) * 1999-10-19 2001-04-24 Taisho Pharmaceut Co Ltd Ｎ−アリールチオオキサミド誘導体
US6867299B2 (en) * 2000-02-24 2005-03-15 Hoffmann-La Roche Inc. Oxamide IMPDH inhibitors
DE10117823A1 (de) * 2001-04-10 2002-10-17 Merck Patent Gmbh Oxalsäurederivate
DE10123574A1 (de) * 2001-05-08 2002-11-28 Schering Ag Selektive Anthranylamid-Derivate als VEGFR II Inhibitoren
JP4224979B2 (ja) * 2002-04-09 2009-02-18 大正製薬株式会社 インターロイキン１２抑制剤
AU2003246927A1 (en) * 2002-07-03 2004-01-23 Astex Technology Limited 3-`(hetero) arylmethoxy ! pyridines and their analogues as p38 map kinase inhibitors

Also Published As

Publication number Publication date
AU2004224239A1 (en) 2004-10-07
JP2006521304A (ja) 2006-09-21
US20060189665A1 (en) 2006-08-24
ZA200508522B (en) 2007-04-25
AR043757A1 (es) 2005-08-10
KR20050110693A (ko) 2005-11-23
EP1606260A1 (en) 2005-12-21
CA2520009A1 (en) 2004-10-07
WO2004085399A1 (en) 2004-10-07
MXPA05010020A (es) 2005-11-17
PL377124A1 (pl) 2006-01-23
CN1764645A (zh) 2006-04-26

Similar Documents

Publication Publication Date Title
BRPI0507198A (pt) derivados de bisariluréia
BR0315580A (pt) Derivados de metileno uréia
BRPI0515991A (pt) derivados de bisariluréia substituìda heterocìclica como inibidores de cinase
BRPI0514448A (pt) derivados do ácido bifenil-oxiacético para uso no tratamento de doenças respiratórias
BRPI0407968A (pt) derivados de oxamida úteis como inibidores de raf-quinase
BRPI0409227C1 (pt) composto, composição farmacêutica, uso de um composto e processo para a preparação de um composto de fórmula (i)
BRPI0514841A (pt) inibidores de piridila da sinalização de hedgehog, processo de preparação dos mesmos e composição compreendendo os referidos inibidores
BRPI0312464B8 (pt) compostos inibidores de tirosina quinases, composições farmacêuticas compreendendo os mesmos, processos para fabricação e usos dos mesmos
MY148429A (en) Novel 1,4-benzothiepin-1,1-dioxide derivatives which are substituted with benzyl groups, method for producing drugs containing said compounds and use thereof
ATE307810T1 (de) Imidazol-2-carbonsäureamid derivate als raf- kinase-inhibitoren
BRPI0618552B8 (pt) compostos derivados de pirimidina ligados ao oxigênio,composição farmacêutica que inclui os ditos compostos,método de síntese dos compostos e usos terapêuticos dos mesmos
NO20076425L (no) Fremgangsmater for behandling av drug-resistent cancer
BRPI0414514A (pt) uso de um composto, composto, e, composições farmacêuticas
BRPI0409198A (pt) derivados quinolin-2-ona para o tratamento de doenças de vias aéreas
BRPI0512974A (pt) novos derivados de hidantoìna para o tratamento de doenças obstrutivas das vias aéreas
BRPI0718803B8 (pt) composto para inibir a progressão mitótica, composição farmacêutica e método in vitro para inibir a atividade de aurora cinase em uma célula
EA200601846A1 (ru) Содержащие бензоксазины лекарственные комбинации для лечения заболеваний дыхательных путей
ES2340502T3 (es) Compuestos de 1,4,8-triazaespiro(4,5)decan-2-ona sustituidos para el tratamiento de la obesidad.
BRPI0408353A (pt) composto, composição farmacêutica, métodos para o tratamento de neoplasias suscetìveis e para o tratamento de infecções virais, e, uso de um composto
CY1109569T1 (el) Υποκατεστημενα παραγωγα κυκλοεξανο-1,4-διαμινης
BR0313377A (pt) Bifenilcarnboxamidas substituìdas por n-aril piperidina como inibidores de secreção de apolipoproteìna b
CO6210702A2 (es) Derivado de pirazolopirimidina
UY30356A1 (es) Derivados de 3-halo-n-(2.(4-fluorofenil)-4-oxobutil)-n-metil-5-(trifluorometil)benzamida y composiciones de los mismos.
EA200870223A1 (ru) Производные бензоизоиндола для лечения боли
AU2005238141A8 (en) Pentenoic acid derivatives, processes for the preparation thereof, pharmaceutical compositions comprising them, and therapeutic applications thereof

Legal Events

Date Code Title Description
B11A Dismissal acc. art.33 of ipl - examination not requested within 36 months of filing
B11Y Definitive dismissal acc. article 33 of ipl - extension of time limit for request of examination expired