HK1207381A1 - 作為 阻斷劑的吡咯並吡啶酮衍生物 - Google Patents

作為 阻斷劑的吡咯並吡啶酮衍生物

Info

Publication number
HK1207381A1
HK1207381A1 HK15108099.6A HK15108099A HK1207381A1 HK 1207381 A1 HK1207381 A1 HK 1207381A1 HK 15108099 A HK15108099 A HK 15108099A HK 1207381 A1 HK1207381 A1 HK 1207381A1
Authority
HK
Hong Kong
Prior art keywords
ttx
blockers
pyrrolopyridinone derivatives
pyrrolopyridinone
derivatives
Prior art date
Application number
HK15108099.6A
Other languages
English (en)
Inventor
Kiyoshi Kawamura
Mikio Morita
Tatsuya Yamagishi
Original Assignee
Raqualia Pharma Inc
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 Raqualia Pharma Inc filed Critical Raqualia Pharma Inc
Publication of HK1207381A1 publication Critical patent/HK1207381A1/zh

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D471/00Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04Ortho-condensed systems
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/4353Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/437Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/444Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445Non condensed piperidines, e.g. piperocaine
    • A61K31/4523Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
    • A61K31/4545Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/4965Non-condensed pyrazines
    • A61K31/497Non-condensed pyrazines containing further heterocyclic rings
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/50Pyridazines; Hydrogenated pyridazines
    • A61K31/501Pyridazines; Hydrogenated pyridazines not condensed and containing further heterocyclic rings
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/535Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/5355Non-condensed oxazines and containing further heterocyclic rings
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/535Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/53751,4-Oxazines, e.g. morpholine
    • A61K31/53771,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00Drugs for disorders of the urinary system
    • A61P13/10Drugs for disorders of the urinary system of the bladder
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00Drugs for skeletal disorders
    • A61P19/02Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/02Drugs for disorders of the nervous system for peripheral neuropathies
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/04Centrally acting analgesics, e.g. opioids
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/06Antimigraine agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/08Antiepileptics; Anticonvulsants
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/22Anxiolytics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/24Antidepressants
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/28Drugs 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A61P29/02Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] without antiinflammatory effect
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00Drugs for disorders of the endocrine system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • A61P9/06Antiarrhythmics

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • Organic Chemistry (AREA)
  • Epidemiology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Neurosurgery (AREA)
  • Neurology (AREA)
  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
  • Psychiatry (AREA)
  • Cardiology (AREA)
  • Endocrinology (AREA)
  • Hospice & Palliative Care (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Immunology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Urology & Nephrology (AREA)
  • Diabetes (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
HK15108099.6A 2012-04-25 2015-08-20 作為 阻斷劑的吡咯並吡啶酮衍生物 HK1207381A1 (zh)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201261638085P 2012-04-25 2012-04-25
JP2012260231 2012-11-28
PCT/JP2013/002825 WO2013161312A1 (en) 2012-04-25 2013-04-25 Pyrrolopyridinone derivatives as ttx-s blockers

Publications (1)

Publication Number Publication Date
HK1207381A1 true HK1207381A1 (zh) 2016-01-29

Family

ID=49482654

Family Applications (2)

Application Number Title Priority Date Filing Date
HK15104385.8A HK1203940A1 (zh) 2012-04-25 2015-05-08 作為 阻斷劑的吡咯並吡啶酮衍生物
HK15108099.6A HK1207381A1 (zh) 2012-04-25 2015-08-20 作為 阻斷劑的吡咯並吡啶酮衍生物

Family Applications Before (1)

Application Number Title Priority Date Filing Date
HK15104385.8A HK1203940A1 (zh) 2012-04-25 2015-05-08 作為 阻斷劑的吡咯並吡啶酮衍生物

Country Status (14)

Country Link
US (1) US9187475B2 (zh)
EP (1) EP2841435B1 (zh)
JP (1) JP6175672B2 (zh)
KR (1) KR102090944B1 (zh)
CN (1) CN104520296B (zh)
BR (1) BR112014026283B1 (zh)
CA (1) CA2871229C (zh)
ES (1) ES2645984T3 (zh)
HK (2) HK1203940A1 (zh)
IN (1) IN2014MN02056A (zh)
MX (1) MX360323B (zh)
RU (1) RU2646754C2 (zh)
TW (1) TWI577677B (zh)
WO (1) WO2013161312A1 (zh)

Families Citing this family (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP6173364B2 (ja) * 2014-01-29 2017-08-02 大正製薬株式会社 部分的に飽和された含窒素複素環化合物を有効成分として含有する医薬
CA2959531C (en) * 2014-08-29 2023-01-10 Chdi Foundation, Inc. Probes for imaging huntingtin protein
US10202365B2 (en) 2015-02-06 2019-02-12 Blueprint Medicines Corporation 2-(pyridin-3-yl)-pyrimidine derivatives as RET inhibitors
JP6807385B2 (ja) 2015-11-02 2021-01-06 ブループリント メディシンズ コーポレイション Retの阻害剤
WO2018112843A1 (en) 2016-12-22 2018-06-28 Merck Sharp & Dohme Corp. Heteroaryl piperidine ether allosteric modulators of the m4 muscarinic acetylcholine receptor
AU2018238138A1 (en) * 2017-03-21 2019-10-17 Arbutus Biopharma Corporation Substituted dihydroindene-4-carboxamides and analogs thereof, and methods using same
EP3619196B1 (de) 2017-05-04 2022-03-30 Bayer CropScience Aktiengesellschaft 2-{[2-(phenyloxymethyl)pyridin-5-yl]oxy}-ethanamin-derivate und verwandte verbindungen als schädlingsbekämpfungsmittel z.b. für den pflanzenschutz
CA3096043A1 (en) 2018-04-03 2019-10-10 Blueprint Medicines Corporation Ret inhibitor for use in treating cancer having a ret alteration
CA3120268A1 (en) * 2018-12-26 2020-07-02 Raqualia Pharma Inc. Heterocyclic derivatives as nav1.7 and nav1.8 blockers
EP3936192A4 (en) 2019-03-06 2022-11-16 Daiichi Sankyo Company, Limited PYRROLOPYRAZOL DERIVATIVES

Family Cites Families (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002081446A1 (en) * 2001-04-06 2002-10-17 Daewoong Co., Ltd. 3-cyclopentyloxy-4-methoxyphenyl-isoindolinone derivatives and the use thereof
AU2003250482A1 (en) * 2002-08-13 2004-02-25 Warner-Lambert Company Llc Phthalimide derivatives as matrix metalloproteinase inhibitors
AR053713A1 (es) * 2005-04-20 2007-05-16 Xenon Pharmaceuticals Inc Compuestos heterociclicos y sus usos como agentes terapeuticos
NL2000284C2 (nl) * 2005-11-04 2007-09-28 Pfizer Ltd Pyrazine-derivaten.
JP2009523842A (ja) * 2006-01-23 2009-06-25 ファイザー・リミテッド ナトリウムチャネルモジュレーターとしてのピリジン誘導体
DE102006025318A1 (de) * 2006-05-31 2007-12-06 Bayer Healthcare Ag Dihydro-pyrrolopyridin-, Dihydro-pyrrolopyridazin- und Dihydro-pyrrolopyrimidin-Derivate und ihre Verwendung
CN101522685A (zh) 2006-10-12 2009-09-02 泽农医药公司 三环螺-吲哚酮衍生物及其作为治疗剂的用途
RU2513636C2 (ru) * 2008-01-04 2014-04-20 Интелликайн ЭлЭлСи Некоторые химические структуры, композиции и способы
ES2842399T3 (es) * 2009-12-22 2021-07-14 Vertex Pharma Inhibidores isoindolinona de fosfatidilinositol 3-quinasa
WO2011083316A1 (en) 2010-01-08 2011-07-14 Takeda Pharmaceutical Company Limited Benzazepine derivatives for the treatment of central nervous system disorders
US8999974B2 (en) * 2010-08-09 2015-04-07 Raqualia Pharma Inc. Acyl piperazine derivatives as TTX-S blockers
JP2013543480A (ja) 2010-10-18 2013-12-05 ラクオリア創薬株式会社 Ttx−s遮断薬としてのアリールアミド誘導体
EP2632461A4 (en) * 2010-10-29 2014-04-02 Merck Sharp & Dohme ISOINDOLINONE COMPOUNDS USEFUL AS PDE INHIBITORS 10
US9938269B2 (en) * 2011-06-30 2018-04-10 Abbvie Inc. Inhibitor compounds of phosphodiesterase type 10A

Also Published As

Publication number Publication date
US20150094306A1 (en) 2015-04-02
EP2841435B1 (en) 2017-09-06
JP6175672B2 (ja) 2017-08-09
ES2645984T3 (es) 2017-12-11
MX360323B (es) 2018-10-29
RU2646754C2 (ru) 2018-03-07
EP2841435A1 (en) 2015-03-04
MX2014012915A (es) 2014-11-25
BR112014026283B1 (pt) 2022-08-02
EP2841435A4 (en) 2015-11-11
CA2871229C (en) 2020-10-27
JP2015514679A (ja) 2015-05-21
CA2871229A1 (en) 2013-10-31
TW201350480A (zh) 2013-12-16
CN104520296A (zh) 2015-04-15
BR112014026283A2 (pt) 2017-06-27
CN104520296B (zh) 2016-11-16
KR20150006001A (ko) 2015-01-15
WO2013161312A1 (en) 2013-10-31
US9187475B2 (en) 2015-11-17
HK1203940A1 (zh) 2015-11-06
RU2014147243A (ru) 2016-06-10
KR102090944B1 (ko) 2020-03-19
IN2014MN02056A (zh) 2015-08-21
TWI577677B (zh) 2017-04-11

Similar Documents

Publication Publication Date Title
HUS2200040I1 (hu) Benzimidazol-prolin származékok
HK1205740A1 (zh) 吡咯並三嗪酮衍生物
HK1207380A1 (zh) 作為 阻斷劑的酰胺衍生物
HK1207381A1 (zh) 作為 阻斷劑的吡咯並吡啶酮衍生物
ZA201502175B (en) Oxazolidin-2-one-pyrimidine derivatives
HK1212697A1 (zh) 作為 阻斷劑的吡唑並吡啶衍生物
HK1207376A1 (zh) 芳基乙炔基衍生物
HK1202544A1 (zh) 芳基乙炔基衍生物
SG11201404325VA (en) Pyrimidooxazocine derivatives as mtor - inhibitors