JP6913955B2 - PI3K/mTOR阻害剤としての溶融キノリン化合物 - Google Patents
PI3K/mTOR阻害剤としての溶融キノリン化合物 Download PDFInfo
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- JP6913955B2 JP6913955B2 JP2018500670A JP2018500670A JP6913955B2 JP 6913955 B2 JP6913955 B2 JP 6913955B2 JP 2018500670 A JP2018500670 A JP 2018500670A JP 2018500670 A JP2018500670 A JP 2018500670A JP 6913955 B2 JP6913955 B2 JP 6913955B2
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- Prior art keywords
- hexadeca
- pentaazatetracyclo
- heptane
- phenyl
- alkoxy
- Prior art date
- Legal status (The legal status 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 status listed.)
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- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 201000008968 osteosarcoma Diseases 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- AHHWIHXENZJRFG-UHFFFAOYSA-N oxetane Chemical compound C1COC1 AHHWIHXENZJRFG-UHFFFAOYSA-N 0.000 description 1
- 229960001592 paclitaxel Drugs 0.000 description 1
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 1
- 239000002540 palm oil Substances 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000009054 pathological process Effects 0.000 description 1
- WVUNYSQLFKLYNI-AATRIKPKSA-N pelitinib Chemical compound C=12C=C(NC(=O)\C=C\CN(C)C)C(OCC)=CC2=NC=C(C#N)C=1NC1=CC=C(F)C(Cl)=C1 WVUNYSQLFKLYNI-AATRIKPKSA-N 0.000 description 1
- 230000000149 penetrating effect Effects 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 description 1
- XUWHAWMETYGRKB-UHFFFAOYSA-N piperidin-2-one Chemical compound O=C1CCCCN1 XUWHAWMETYGRKB-UHFFFAOYSA-N 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 1
- OIGNJSKKLXVSLS-VWUMJDOOSA-N prednisolone Chemical compound O=C1C=C[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 OIGNJSKKLXVSLS-VWUMJDOOSA-N 0.000 description 1
- 229960005205 prednisolone Drugs 0.000 description 1
- XOFYZVNMUHMLCC-ZPOLXVRWSA-N prednisone Chemical compound O=C1C=C[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 XOFYZVNMUHMLCC-ZPOLXVRWSA-N 0.000 description 1
- 238000012746 preparative thin layer chromatography Methods 0.000 description 1
- CPTBDICYNRMXFX-UHFFFAOYSA-N procarbazine Chemical compound CNNCC1=CC=C(C(=O)NC(C)C)C=C1 CPTBDICYNRMXFX-UHFFFAOYSA-N 0.000 description 1
- 229960000624 procarbazine Drugs 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 230000004224 protection Effects 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- USPWKWBDZOARPV-UHFFFAOYSA-N pyrazolidine Chemical compound C1CNNC1 USPWKWBDZOARPV-UHFFFAOYSA-N 0.000 description 1
- ABMYEXAYWZJVOV-UHFFFAOYSA-N pyridin-3-ylboronic acid Chemical compound OB(O)C1=CC=CN=C1 ABMYEXAYWZJVOV-UHFFFAOYSA-N 0.000 description 1
- DWHCQRBWSBKHMI-UHFFFAOYSA-N quinolin-2-ylboronic acid Chemical compound C1=CC=CC2=NC(B(O)O)=CC=C21 DWHCQRBWSBKHMI-UHFFFAOYSA-N 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 108091008020 response regulators Proteins 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 239000002356 single layer Substances 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 208000000587 small cell lung carcinoma Diseases 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- 229910001467 sodium calcium phosphate Inorganic materials 0.000 description 1
- 229940001593 sodium carbonate Drugs 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 229960003787 sorafenib Drugs 0.000 description 1
- 235000011069 sorbitan monooleate Nutrition 0.000 description 1
- 239000001593 sorbitan monooleate Substances 0.000 description 1
- 229940035049 sorbitan monooleate Drugs 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 210000000278 spinal cord Anatomy 0.000 description 1
- 206010041823 squamous cell carcinoma Diseases 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 210000004500 stellate cell Anatomy 0.000 description 1
- 230000000707 stereoselective effect Effects 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 150000003456 sulfonamides Chemical class 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 229940126703 systemic medication Drugs 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 229960001603 tamoxifen Drugs 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 1
- WFWLQNSHRPWKFK-ZCFIWIBFSA-N tegafur Chemical compound O=C1NC(=O)C(F)=CN1[C@@H]1OCCC1 WFWLQNSHRPWKFK-ZCFIWIBFSA-N 0.000 description 1
- 229960001674 tegafur Drugs 0.000 description 1
- 229960003604 testosterone Drugs 0.000 description 1
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- 229960001196 thiotepa Drugs 0.000 description 1
- 229940044693 topoisomerase inhibitor Drugs 0.000 description 1
- UCFGDBYHRUNTLO-QHCPKHFHSA-N topotecan Chemical compound C1=C(O)C(CN(C)C)=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 UCFGDBYHRUNTLO-QHCPKHFHSA-N 0.000 description 1
- 229960000303 topotecan Drugs 0.000 description 1
- 230000014616 translation Effects 0.000 description 1
- DQJCHOQLCLEDLL-UHFFFAOYSA-N tricyclazole Chemical compound CC1=CC=CC2=C1N1C=NN=C1S2 DQJCHOQLCLEDLL-UHFFFAOYSA-N 0.000 description 1
- NOYPYLRCIDNJJB-UHFFFAOYSA-N trimetrexate Chemical compound COC1=C(OC)C(OC)=CC(NCC=2C(=C3C(N)=NC(N)=NC3=CC=2)C)=C1 NOYPYLRCIDNJJB-UHFFFAOYSA-N 0.000 description 1
- 229960001099 trimetrexate Drugs 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 210000003932 urinary bladder Anatomy 0.000 description 1
- 210000001215 vagina Anatomy 0.000 description 1
- 229960000241 vandetanib Drugs 0.000 description 1
- 239000002525 vasculotropin inhibitor Substances 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 239000000052 vinegar Substances 0.000 description 1
- 235000021419 vinegar Nutrition 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 229940033942 zoladex Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic 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
- C07D471/12—Heterocyclic 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 three hetero rings
- C07D471/14—Ortho-condensed systems
-
- 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
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms 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
- C07D215/18—Halogen atoms or nitro radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms 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
- C07D215/20—Oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms 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
- C07D215/38—Nitrogen atoms
- C07D215/42—Nitrogen atoms attached in position 4
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic 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
- C07D471/02—Heterocyclic 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
- C07D471/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic 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
- C07D471/22—Heterocyclic 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 systems contains four or more hetero rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Description
Zは、NまたはC−Rであり;
RおよびR1は、H、ハロゲン、ハロゲンC1−C6アルキル、−C1−C6アルキル、−OR7または−NR7R8から独立して選択され;
R2およびR3は、H、ハロゲン、−OH、−C1−C6アルキル、−C1−C6アルコキシル、−C1−C6アルケニル、または−C1−C6アルキニルから独立して選択され;R2は−CF3でなく;R4およびR5は、H、ハロゲン、ハロゲン−C1−C6アルキル、−C1−C6アルキル、−OH、−C1−C6アルコキシル、シクロアルキルから独立して選択され;
または、R4およびR5は、共に結合させて、脂肪族シクリルまたはヘテロシクリルとなり得る3〜8員飽和または不飽和環を形成することが可能であり;
R6は、H、−CH3または−CNから選択され;
R7およびR8は、H、ハロゲン、−C1−C6アルキル、−C1−C6アルキルOH、−C1−C6アルコキシル、−C1−C6アルキルNR4R5、−C(=O)C1−C6アルキル、−C(=O)C1−C6アルキル−R4R5、−C(=O)C1−C6アルキルOH、−C(=O)C1−C6アルコキシル、−C(=O)C1−C6アルキルNR4R5、−C(=O)OC1−C6アルキル、−C(=O)OC1−C6アルキルOH、−C(=O)OC1−C6アルコキシル、−C(=O)OC1−C6アルキルNR4R5、−C(=O)NR4C1−C6アルキル、−C(=O)NR4C1−C6アルキル−OH、−C(=O)−NR4C1−C6アルコキシル、−C(=O)NR4C1−C6アルキルNR4R5から選択される。
Q1およびQ2は、アリール、5〜6員ヘテロシクリル、または9〜11員二環ヘテロシクリルから独立して選択され;好ましくは、Q1は、ピリジニル、ピリミジニル、キノリニル、またはキナゾリニルから独立して選択され、Q2はフェニルであり;
Q1は、RおよびR1が示されない場合のハロゲンであり;好ましくはBrまたはIであり;
Zは、NまたはC−Rであり;好ましくはNであり;
RおよびR1は、H、ハロゲン、ハロゲンC1−C6アルキル、C1−C6アルキル、−OR7、または−NR7R8から独立して選択され;好ましくはHまたは−NR7R8であり;
R2およびR3は、H、−OH、C1−C6アルキル、−C1−C6アルコキシル、−C1−C6アルケニル、または−C1−C6アルキニルから独立して選択され;R2は−CF3でなく;好ましくは、H、ハロゲン、または−C1−C6アルキルから独立して選択され、R2は−CF3でなく;
R4およびR5は、H、ハロゲン、ハロゲンC1−C6アルキル、C1−C6アルキル、−OH、−C1−C6アルコキシル、シクロアルキルから独立して選択され;または、R4およびR5は、共に結合させて、脂肪族シクリルまたはヘテロシクリルとなり得る3〜8員飽和または不飽和環を形成することが可能であり;好ましくは、H、ハロゲンC1−C6アルキル、C1−C6アルキルであり、または、共に結合して飽和脂肪族シクリルまたはヘテロシクリル環を形成し;
R6は、H、−CH3、または−CNから選択され;好ましくは、−CH3または−CNであり;
R7及びR8は、H、ハロゲン、−C1−C6アルキル、−C1−C6アルキルOH、−C1−C6アルコキシル、−C1−C6アルキルNR4R5R、−C(=O)C1−C6アルキル、−C(=O)C1−C6アルキル−R4R5R、−C(=O)C1−C6アルキルOH、−C(=O)C1−C6アルコキシル、−C(=O)C1−C6アルキルNR4R5、−C(=O)OC1−C6アルキル、−C(=O)OC1−C6アルキルOH、−C(=O)OC1−C6アルコキシル、−C(=O)OC1−C6アルキルNR4R5、−C(=O)NR4C1−C6アルキル、−C(=O)NR4C1−C6アルキルOH、−C(=O)N−R4C1−C6アルコキシル、−C(=O)NR4C1−C6アルキルNR4R5から独立して選択され;好ましくは、H、−C(=O)C1−C6アルキル、−C1−C6アルキルNR4R5、または−C(=O)−C1−C6アルキルNR4R5から独立して選択される。
たとえば甘味料、調味料および色素等の追加の賦形剤が存在していてもよい。
−NH2、−NHCH3、−N(CH3)2、−NHCOCH3、−NHCO(CH2)nCH3、−NHCO(CH2)nNH2、−NHCO(CH2)nNHCH3、−NHCO(CH2)nN(CH3)2、−NHCO(CH2)n−ピロリジン、−NHCO(CH2)n−ピペラジン、−NHCO(CH2)n−モルホリン、−NH(CH2)nNHCH3、−NH(CH2)nN(CH3)2、−NH(CH2)n−ピロリジン、−NH(CH2)n−ピペラジン、−NH(CH2)n−モルホリン;
n=1、2、3または4であり、
R3は、H、またはC1−C6アルキルであり、
Q1は、ピリジン、ピリミジン、キノリンまたはキナゾリンから独立して選択される。
式II
Q1は、RおよびR1が示されない場合のハロゲンであり;好ましくはBrまたはIであり;
Zは、NまたはC−Rであり;好ましくはNであり;
RおよびR1は、H、ハロゲン、ハロゲンC1−C6アルキル、C1−C6アルキル、−OR7、または−NR7R8から独立して選択され;好ましくはHまたは−NR7R8であり;
R2およびR3は、H、−OH、C1−C6アルキル、−C1−C6アルコキシル、−C1−C6アルケニル、または−C1−C6アルキニルから独立して選択され;R2は−CF3でなく;好ましくは、H、ハロゲン、または−C1−C6アルキルから独立して選択され、R2は−CF3でなく;
R4およびR5は、H、ハロゲン−C1−C6アルキル、C1−C6アルキルから、独立して選択され、または、共に結合させて、飽和脂肪族シクリルまたはヘテロシクリル環を形成し;
R7およびR8は、H、ハロゲン、C1−C6アルキル、−C1−C6アルキルOH、−C1−C6アルコキシル、−C1−C6アルキルNR4R5、−C(=O)−C1−C6アルキル、−C(=O)−C1−C6アルキル−R4R5、−C(=O)C1−C6アルキルOH、−C(=O)C1−C6アルコキシル、−C(=O)−C1−C6アルキルNR4R5、−C(=O)OC1−C6アルキル、−C(=O)OC1−C6アルキルOH、−C(=O)OC1−C6アルコキシル、−C(=O)O−C1−C6アルキルNR4R5、−C(=O)NR4−C1−C6アルキル、−C(=O)NR4−C1−C6アルキルOH、−C(=O)NR4C1−C6アルコキシル、−C(=O)NR4−C1−C6アルキルNR4R5から独立して選択され;好ましくは、H、−C(=O)−C1−C6アルキル、−C1−C6アルキルNR4R5、または−C(=O)−C1−C6アルキルNR4R5から独立して選択される;
又は、これらの薬理学的に許容される塩である。
2−(4−{4−ブロモ−8,11,13,14,16−ペンタアザテトラシクロ−[8.6.0.02,7.011,15]ヘキサデカ−1(10)、2、4、6、8、12、14−ヘプタエヌ−16−イル}フェニル)−2−メチルプロパンニトリル;
16−(4−第三級ブチルフェニル)−4−(ブロモ−3−イル)−12−メチル−8,11,13,14,16−ペンタアザテトラシクロ−[8.6.0.02,7.011,15]ヘキサデカ−1(10)、2、4、6、8、12、14−ヘプタエン;
2−(4−{4−ブロモ−12−エチル−8,11,13,14,16−ペンタアザテトラシクロ−[8.6.0.02,7.011,15]ヘキサデカ1(10),2,4,6,8,12,14−ヘプタン − 16−イル}フェニル)−2−メチルプロパンニトリル;
16−(4−第三級ブチルフェニル)−4−(ブロモ−3−イル)−12−エチル−8,11,13,14,16−ペンタアザテトラシクロ−[8.6.0.02,7.011,15]ヘキサデカ−1(10)、2、4、6、8、12、14−ヘプタエン;
2−メチル−2−{4[4−(ピリジン−3−イル)−8,11,13,14,16−ペンタアザテトラシクロ[8.6.0.02,7.011,15]−ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタン − 16−イル]フェニル}プロパンニトリル;
2−メチル−2−{4−[12−メチル−4−(ピリジン−3−イル)−8,11,13,14,16−ペンタアザテトラシクロ−[8.6.0.02,7.011,15] − ヘキサデカ−1(10)、2、4、6、8、12、14−ヘプタン−16−イル]フェニル}プロパンニトリル;
1−{4−[4−(キノリン−3−イル)−8,11,13,14,16−ペンタアザテトラシクロ−[8.6.0.02,7.011,15]ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタン−16−イル]フェニル}シクロペンタン − 1−カルボニトリル;
1−{4−[12−メチル−4−(ピリジン−3−イル)−8,11,13,14,16−ペンタアザテトラシクロ[8.6.0.02,7.011,15]ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタン−16−イル]フェニル}シクロペンタン − 1−カルボニトリル;
1−{4−[12−メチル−4−(ピリジン−3−イル)−8,11,13,14,16−ペンタアザテトラシクロ[8.6.0.02,7.011,15]−ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタン−16−イル]フェニル}シクロプロパン−1−カルボニトリル;
2−メチル−2−{4−[12−メチル−4−(ピリジン−4−イル)−8,11,13,14,16−ペンタアザテトラシクロ[8.6.0.02,7.011,15]− ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタエヌ−16−イル]フェニル}プロパンニトリル;
4−(4−フルオロフェニル)−12−メチル−16−[4−(2−メチルブタ−3−イン−2−イル)フェニル]−8,11,13,14,16−ペンタアザテトラシクロ−[8.6.0.02,7.011,15]ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタエン;
4−(3−フルオロフェニル)−12−メチル−16−[4−(2−メチルブタ−3−イン−2−イル)フェニル]−8,11,13,14,16−ペンタアザテトラシクロ[8.6.0.02,7.011,15]ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタエン;
4−(3、4−ジフルオロフェニル)−12−メチル−16−[4−(2−メチルブタ−3−イン−2−イル)フェニル]−8,11,13,14,16−ペンタ−アザテトラシクロ[8.6.0.02,7.011,15]ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタエン;
4−(2−フルオロフェニル)−12−メチル−16−[4−(2−メチルブタ−3−イン−2−イル)フェニル]−8,11,13,14,16−ペンタアザテトラシクロ[8.6.0.02,7.011,15]ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタエン;
16−(4−第三級ブチルフェニル)−12−メチル−4−{1H−ピロロ[2、3−b]ピリジン−5−イル}−8,11,13,14,16−ペンタアザテトラシクロ[8.6.0.02,7.011,15]ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタエン;
N−{5−[16−(4−第三級ブチルフェニル)−12−メチル−8,11,13,14,16−ペンタアザテトラシクロ[8.6.0.02,7.011,15]−ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタン−4−イル]ピリジン−2−イル}アセトアミド;
16−(4−第三級ブチルフェニル)−4−(6−メトキシピリジン−3−イル)−12−メチル−8,11,13,14,16−ペンタアザテトラシクロ[8.6.0.02,7.011,15]ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタエン;
16−(4−第三級ブチルフェニル)−12−メチル−4−(ピリミジン−5−イル)−8,11,13,14,16−ペンタアザテトラシクロ−[8.6.0.02,7.011,15]ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタエン;
16−(4−第三級ブチルフェニル)−12−メチル−4−(ピリジン−3−イル)−8,11,13,14,16−ペンタアザテトラシクロ−[8.6.0.02,7.011,15]ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタエン;
2−{4−[4−(6−アミノピリジン−3−イル)−8,11,13,14,16−ペンタアザテトラシクロ[8.6.0.02,7.011,15]ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタン−16−イル]フェニル}−2−メチルプロパンニトリル;
2−メチル−2−{4−[4−(ピリミジン−5−イル)−8,11,13,14,16−ペンタアザテトラシクロ[8.6.0.02,7.011,15]ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタン−16−イル]フェニル}プロパンニトリル;
N−{5−[16−(4−第三級ブチルフェニル)−8,11,13,14,16−ペンタアザテトラシクロ[8.6.0.02,7.011,15]ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタン−4−イル]ピリジン−2−イル}アセトアミド;
16−(4−第三級ブチルフェニル)−4−{1H−ピロロ[2、3−b]ピリジン−5−イル}−8,11,13,14,16−ペンタアザテトラシクロ−[8.6.0.02,7.011,15]ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタエン;
5−[16−(4−第三級ブチルフェニル)−8,11,13,14,16−ペンタアザテトラシクロ[8.6.0.02,7.011,15]ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタン−4−イル]ピリジン−2−アミン;
5−[16−(4−第三級ブチルフェニル)−12−メチル−8,11,13,14,16−ペンタアザテトラシクロ[8.6.0.02,7.011,15]−ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタン−4−イル]ピリジン−2−アミン;
16−(4−第三級ブチルフェニル)−4−(6−メトキシピリジン−3−イル)−8,11,13,14,16−ペンタアザテトラシクロ−[8.6.0.02,7.011,15]ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタエン;
16−(4−第三級ブチルフェニル)−4−(ピリミジン−5−イル)−8,11,13,14,16−ペンタアザテトラシクロ[8.6.0.02,7.011,15]−ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタエン;
16−(4−第三級ブチルフェニル)−4−(ピリジン−3−イル)−8,11,13,14,16−ペンタアザテトラシクロ[8.6.0.02,7.011,15]−ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタエン;
2−[4−(12−エチル−4−{1H−ピロロ[2、3−b]ピリジン−5−イル}−8,11,13,14,16−ペンタアザテトラシクロ−[8.6.0.02,7.011,15]ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタン−16−イル)フェニル]−2−メチルプロパンニトリル;
N−(5{16−[4−(1−シアノ−1−メチルエチル)フェニル]−12−エチル−8,11,13,14,16−ペンタアザテトラシクロ−[8.6.0.02,7.011,15]ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタン−4−イル}ピリジン−2−イル)アセトアミド;
5−{12−エチル − 16−[4−(2−メチルブタ−3−イン−2−イル)フェニル]−8,11,13,14,16−ペンタアザテトラシクロ−[8.6.0.02,7.011,15]ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタン−4−イル}ピリジン−2−アミン;
2−{4−[12−エチル−4−(ピリミジン−5−イル)−8,11,13,14,16−ペンタアザテトラシクロ[8.6.0.02,7.011,15]−ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタン−16−イル]フェニル}−2−メチルプロパンニトリル;
12−エチル−4−(6−メトキシピリジン−3−イル)−16−[4−(2−メチルブタ−3−イン−2−イル)フェニル]−8,11,13,14,16−ペンタアザテトラシクロ[8.6.0.02,7.011,15]ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタエン;
2−メチル−2−[4−(4−{1H−ピロロ[2、3−b]ピリジン−4−イル}−8,11,13,14,16−ペンタアザテトラシクロ−[8.6.0.02,7.011,15]ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタン−16−イル)フェニル]プロパンニトリル;
N−(5−{16−[4−(1−シアノ−1−メチルエチル)フェニル]−12−メチル−8,11,13,14,16−ペンタアザテトラシクロ−[8.6.0.02,7.011,15]ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタン−4−イル}ピリジン−2−イル)アセトアミド;
N−(5−{16−[4−(1−シアノ−1−メチルエチル)フェニル]−8,11,13,14,16−ペンタアザテトラシクロ−[8.6.0.02,7.011,15]ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタン−4−イル}ピリジン−2−イル)アセトアミド;
2−メチル−2−{4−[12−メチル−4−(ピリミジン−5−イル)−8,11,13,14,16−ペンタアザテトラシクロ−[8.6.0.02,7.011,15]ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタン−16−イル]フェニル}プロパンニトリル;
4−(6−メトキシピリジン−3−イル)−12−メチル−16−[4−(2−メチルブタ−3−イン−2−イル)フェニル]8,11,13,14,16−ペンタアザテトラシクロ[8.6.0.02,7.011,15]ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタエン;
2メチル−2−[4−(12−メチル−4−{1H−ピロロ[2、3−b]ピリジン−5−イル}−8,11,13,14,16−ペンタアザテトラシクロ[8.6.0.02,7.011,15]ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタン−16−イル)フェニル]プロパンニトリル;
2−{4−[4−(6−アミノピリジン−3−イル)−12−メチル−8,11,13,14,16−ペンタアザテトラシクロ[8.6.0.02,7.011,15]−ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタン−16−イル]フェニル}−2−メチルプロパンニトリル;
5−[16−(4−第三級ブチルフェニル)−12−メチル−8,11,13,14,16−ペンタアザテトラシクロ[8.6.0.02,7.011,15]ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタン−4−イル]−4−(トリフロロメチル)ピリジン−2−アミン;
5−[16−(4−第三級ブチルフェニル)−8,11,13,14,16−ペンタアザテトラシクロ[8.6.0.02,7.011,15]ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタン−4−イル]−4−(トリフロロメチル)ピリジン−2−アミン;
16−(4−第三級ブチルフェニル)−12−エチル−4−(ピリジン−3−イル)−8,11,13,14,16−ペンタアザテトラシクロ−[8.6.0.02,7.011,15]ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタエン;
5−[16−(4−第三級ブチルフェニル)−12−エチル−8,11,13,14,16−ペンタアザテトラシクロ[8.6.0.02,7.011,15]ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタン−4−イル]ピリジン−2−アミン;
2−(4−{4−[6−アミノ−4−(トリフロロメチル)ピリジン−3−イル]−8,11,13,14,16−ペンタアザテトラシクロ−[8.6.0.02,7.011,15]ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタン−16−イル}フェニル)−2−メチルプロパンニトリル;
2−{4−[4−(6−アミノピリジン−3−イル)−8,11,13,14,16−ペンタアザテトラシクロ[8.6.0.02,7.011,15]ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタン−16−イル]フェニル}−2−メチルプロパンニトリル;
5−[16−(4−第三級ブチルフェニル)−8,11,13,14,16−ペンタアザテトラシクロ[8.6.0.02,7.011,15]ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタン−4−イル]ピリジン−2−アミン。
N−(5−{16−[4−(1−シアノ−1−メチルエチル)フェニル]−8,11,13,14,16−ペンタアザテトラシクロ[8.6.0.02,7.011,15]−ヘキサデカ1(10),2,4,6,8,12,14−ヘプタン−4−イル}ピリジン−2−イル)−2−(シクロヘキシルアミノ)アセトアミド;
N−(5{16−[4−(1−シアノ−1−メチルエチル)フェニル]−8,11,13,14,16−ペンタアザテトラシクロ[8.6.0.02,7.011,15]−ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタン−4−イル}ピリジン−2−イル)−2−(オキサン−4−イルアミノ)アセトアミド;
N−(5{16−[4−(1−シアノ−1−メチルエチル)フェニル]−8,11,13,14,16−ペンタアザテトラシクロ[8.6.0.02,7.011,15]−ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタン−4−イル}ピリジン−2−イル)−2−(チアン−4−イルアミノ)アセトアミド;
N−(5{16−[4−(1−シアノ−1−メチルエチル)フェニル]−8,11,13,14,16−ペンタアザテトラシクロ[8.6.0.02,7.011,15]−ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタン−4−イル}ピリジン−2−イル)−2−(ジメチルアミノ)アセトアミド;
N−(5{16−[4−(1−シアノ−1−メチルエチル)フェニル]−8,11,13,14,16−ペンタアザテトラシクロ[8.6.0.02,7.011,15]−ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタン−4−イル}ピリジン−2−イル)−2−(メチルアミノ)アセトアミド;
16−(4−第三級ブチルフェニル)−4キノリン−3−イル)−8,11,13,14,16−ペンタアザテトラシクロ[8.6.0.02,7.011,15]−ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタエン;
N−(5{16−[4−(1−シアノ−1−メチルエチル)フェニル]−8,11,13,14,16−ペンタアザテトラシクロ[8.6.0.02,7.011,15]−ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタン−4−イル}ピリジン−2−イル)−2−(4オキソピペリジン−1−イル)アセトアミド;
N−(5{16−[4−(1−シアノ−1−メチルエチル)フェニル]−8,11,13,14,16−ペンタアザテトラシクロ[8.6.0.02,7.011,15]−ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタン−4−イル}ピリジン−2−イル)−2−(4−ヒドロキシピペリジン−1−イル)アセトアミド;
N−(5{16−[4−(1−シアノ−1−メチルエチル)フェニル]−8,11,13,14,16−ペンタアザテトラシクロ[8.6.0.02,7.011,15]−ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタン−4−イル}ピリジン−2−イル)−2−(4−メチルピペラジン−1−イル)アセトアミド;
N−(5{16−[4−(1−シアノ−1−メチルエチル)フェニル]−8,11,13,14,16−ペンタアザテトラシクロ[8.6.0.02,7.011,15]−ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタン−4−イル}ピリジン−2−イル)−2−(モルホリン−4−イル)アセトアミド;
N−(5{16−[4−(1−シアノ−1−メチルエチル)フェニル]−8,11,13,14,16−ペンタアザテトラシクロ[8.6.0.02,7.011,15]−ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタン−4−イル}ピリジン−2−イル)−2−(ピロリジン−1−イル)アセトアミド;
N−{5[16−(4−第三級ブチルフェニル)−8,11,13,14,16−ペンタアザテトラシクロ[8.6.0.02,7.011,15]ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタン−4−イル]ピリジン−2−イル}−2−(ピロリジン−1−イル)アセトアミド;
N−{5−[16−(4−第三級−ブチルフェニル)−8,11,13,14,16−ペンタアザテトラシクロ[8.6.0.02,7.011,15]−ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタン−4−イル]ピリジン−2−イル}−2−(メチルアミノ)アセトアミド;
N−{5−[16−(4−第三級ブチルフェニル)−12−エチル−8,11,13,14,16−ペンタアザテトラシクロ[8.6.0.02,7.011,15]−ヘキサデカ1(10),2,4,6,8,12,14−ヘプタン−4−イル]ピリジン−2−イル}−2−(メチルアミノ)アセトアミド;
N−{5−[16−(4−第三級ブチルフェニル)−12−エチル−8,11,13,14,16−ペンタアザテトラシクロ[8.6.0.02,7.011,15]−ヘキサデカ1(10),2,4,6,8,12,14−ヘプタン−4−イル]ピリジン−2−イル}−2−(ピロリジン−1−イル)アセトアミド;
5−[16−(4−第三級ブチルフェニル)−12−エチル−8,11,13,14,16−ペンタアザテトラシクロ[8.6.0.02,7.011,15]ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタン−4−イル]−N−メチルピリジン−2−アミン;
5−[16−(4−第三級ブチルフェニル)− 12−エチル−8,11,13,14,16−ペンタアザテトラシクロ[8.6.0.02,7.011,15]ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタン−4−イル]−N−(2−メトキシエチル)ピリジン−2−アミン;
5−[16−(4−第三級ブチルフェニル)−12−エチル−8,11,13,14,16−ペンタアザテトラシクロ[8.6.0.02,7.011,15]ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタン−4−イル]−N−[2−(ピロリジン−1−イル)エチル]ピリジン−2−アミン;
5−[16−(4−第三級ブチルフェニル)−12−エチル−8,11,13,14,16−ペンタアザテトラシクロ[8.6.0.02,7.011,15]ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタン−4−イル]−N−[2−(モルホリン−4−イル)エチル]ピリジン−2−アミン;
N−{5−[16−(4−第三級ブチルフェニル)−12−エチル−8,11,13,14,16−ペンタアザテトラシクロ[8.6.0.02,7.011,15]−ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタン−4−イル]ピリジン−2−イル}−2−(モルホリン−4−イル)アセトアミド。
4−ブロモ−16−(4−第三級ブチルフェニル)−8,11,14,16−テトラアザテトラシクロ[8.6.0.02,7.011,15]ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタエン;
16−(4−第三級ブチルフェニル)−4−(ピリジン−3−イル)−8,11,14,16−テトラアザテトラシクロ[8.6.0.02,7.011,15]−ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタエン;
16−(4−第三級ブチルフェニル)−4−(キノリン−3−イル)−8,11,14,16−テトラアザテトラシクロ[8.6.0.02,7.011,15]−ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタエン;
16−(3−第三級ブチルフェニル)−4−(キノリン−3−イル)−8,11,14,16−テトラアザテトラシクロ[8.6.0.02,7.011,15]−ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタエン。
以下は配合の例であり、これらは全く例示的であり、制限的であるようになんら解釈されない。
それぞれのカプセルは、以下を含む:
上記の化合物からの1つの化合物:100.0mg
コーンスターチ:23.0mg
繊維素グリコール酸カルシウム:22.5mg
ヒドロキシプロピルメチルセルロース:3.0mg
ステアリン酸マグネシウム:1.5mg
合計:150.0mg
配合例2:
下記溶液は、以下を含む:
上記の化合物からの1つの化合物:1〜10g
酢酸または水酸化ナトリウム:0.5〜1g
エチルp−ヒドロキシベンゾアート:0.1 g
精製水:88.9〜98.4g
合計:100.0g
配合例3:
飼料に混合させる粉末は、以下を含む:
上記の化合物からの1つの化合物:1〜10g
コーンスターチ:98.5〜89.5g
軽質無水珪酸:0.5g
合計:100.0g
Claims (6)
- 式I(化1)の化合物又は薬理学的に許容されるその塩であって、
Q1およびQ2は、アリール、5〜6員ヘテロシクリル、または9〜11員二環ヘテロシクリルから独立して選択され;
Zは、NまたはC−Rであり;
RおよびR1は、H、ハロゲン、ハロゲンC1−C6アルキル、−C1−C6アルキル、−OR7または−NR7R8から独立して選択され;
R2およびR3は、H、ハロゲン、−OH、−C1−C6アルキル、−C1−C6アルコキシル、−C1−C6アルケニル、または−C1−C6アルキニルから独立して選択され;R2は−CF3でなく;
R4およびR5は、H、ハロゲン、ハロゲン−C1−C6アルキル、−C1−C6アルキル、−OH、−C1−C6アルコキシル、シクロアルキルから独立して選択され;または、R4およびR5は、共に結合させて、脂肪族シクリルまたはヘテロシクリルとなり得る3〜8員飽和または不飽和環を形成することが可能であり;
R6は、H、−CH3または−CNから選択され;
R7およびR8は、H、ハロゲン、−C1−C6アルキル、−C1−C6アルキルOH、−C1−C6アルコキシル、−C1−C6アルキルNR4R5、−C(=O)C1−C6アルキル、−C(=O)C1−C6アルキル−R4R5、−C(=O)C1−C6アルキルOH、−C(=O)C1−C6アルコキシル、−C(=O)C1−C6アルキルNR4R5、−C(=O)OC1−C6アルキル、−C(=O)OC1−C6アルキルOH、−C(=O)OC1−C6アルコキシル、−C(=O)OC1−C6アルキルNR4R5、−C(=O)NR4C1−C6アルキル、−C(=O)NR4C1−C6アルキル−OH、−C(=O)−NR4C1−C6アルコキシル、−C(=O)NR4C1−C6アルキルNR4R5から独立して選択される。 - 請求項1に記載の化合物又は薬理学的に許容されるその塩であって、
Q1およびQ2は、アリール、5〜6員ヘテロシクリル、または9〜11員二環ヘテロシクリルから独立して選択され;
Zは、NまたはC−Rであり;
RおよびR1は、H、ハロゲン、ハロゲンC1−C6アルキル、C1−C6アルキル、−OR7、または−NR7R8から独立して選択され;
R2およびR3は、H、−OH、C1−C6アルキル、−C1−C6アルコキシル、−C1−C6アルケニル、または−C1−C6アルキニルから独立して選択され;R2は−CF3でなく;
R4およびR5は、H、ハロゲン、ハロゲンC1−C6アルキル、C1−C6アルキル、−OH、−C1−C6アルコキシル、シクロアルキルから独立して選択され;または、R4およびR5は、共に結合させて、脂肪族シクリルまたはヘテロシクリルとなり得る3〜8員飽和または不飽和環を形成することが可能であり;
R6は、H、−CH3、または−CNから選択され;
R7及びR8は、H、ハロゲン、−C1−C6アルキル、−C1−C6アルキルOH、−C1−C6アルコキシル、−C1−C6アルキルNR4R5、−C(=O)C1−C6アルキル、−C(=O)C1−C6アルキル−R4R5、−C(=O)C1−C6アルキルOH、−C(=O)C1−C6アルコキシル、−C(=O)C1−C6アルキルNR4R5、−C(=O)OC1−C6アルキル、−C(=O)OC1−C6アルキルOH、−C(=O)OC1−C6アルコキシル、−C(=O)OC1−C6アルキルNR4R5、−C(=O)NR4C1−C6アルキル、−C(=O)NR4C1−C6アルキルOH、−C(=O)N−R4C1−C6アルコキシル、−C(=O)NR4−C1−C6アルキルNR4R5から独立して選択される。 - 式II(化2)に表される、請求項1に記載の化合物又は薬理学的に許容されるその塩であって、
Q1は、アリール、5〜6員ヘテロシクリルまたは9〜11員二環ヘテロシクリルから独立して選択され;
Zは、NまたはC−Rであり;
RおよびR1は、H、ハロゲン、ハロゲンC1−C6アルキル、C1−C6アルキル、−OR7、または−NR7R8から独立して選択され;
R2およびR3は、H、−OH、C1−C6アルキル、−C1−C6アルコキシル、−C1−C6アルケニル、または−C1−C6アルキニルから独立して選択され;R2は−CF3でなく;
R4およびR5は、H、ハロゲン−C1−C6アルキル、C1−C6アルキルから、独立して選択され、または、共に結合させて、飽和脂肪族シクリルまたはヘテロシクリル環を形成し;
R7およびR8は、H、ハロゲン、C1−C6アルキル、−C1−C6アルキルOH、−C1−C6アルコキシル、−C1−C6アルキルNR4R5、−C(=O)−C1−C6アルキル、−C(=O)−C1−C6アルキル−R4R5、−C(=O)C1−C6アルキルOH、−C(=O)C1−C6アルコキシル、−C(=O)−C1−C6アルキルNR4R5、−C(=O)OC1−C6アルキル、−C(=O)OC1−C6アルキルOH、−C(=O)OC1−C6アルコキシル、−C(=O)O−C1−C6アルキルNR4R5、−C(=O)NR4−C1−C6アルキル、−C(=O)NR4−C1−C6アルキルOH、−C(=O)NR4C1−C6アルコキシル、−C(=O)NR4−C1−C6アルキルNR4R5から独立して選択される。 - 以下からなる群より選択される、請求項1に記載の化合物又は薬理学的に許容されるその塩、
2−メチル−2−{4−[12−メチル−4−(キノリン−3−イル)−8,11,13,14,16−ペンタアザテトラシクロ[8.6.0.02,7.011,15] ― ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタン−16−イル]フェニル}プロパンニトリル;
2−メチル−2−{4−[4−(キノリン−3−イル)−8,11,13,14,16−ペンタアザテトラシクロ[8.6.0.02,7.011,15]−ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタン−16−イル]フェニル}プロパンニトリル;
2−{4−[12−エチル−4−(ピリジン−3−イル)−8,11,13,14,16−ペンタアザテトラシクロ[8.6.0.02,7.011,15]−ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタン−16−イル]フェニル}−2−メチルプロパンニトリル;
2−メチル−2−{4−[4−(ピリジン−3−イル)−8,11,13,14,16−ペンタアザテトラシクロ[8.6.0.02,7.011,15]−ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタン−16−イル]フェニル}プロパンニトリル;
2−メチル−2−{4−[12−メチル−4−(ピリジン−3−イル)−8,11,13,14,16−ペンタアザテトラシクロ[8.6.0.02,7.011,15]−ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタン−16−イル]フェニル}プロパンニトリル;
1−{4−[4−(キノリン−3−イル)−8,11,13,14,16−ペンタアザテトラシクロ−[8.6.0.02,7.011,15]ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタン−16−イル]フェニル}シクロペンタン−1−カルボニトリル;
1−{4−[12−メチル−4−(ピリジン−3−イル)−8,11,13,14,16−ペンタアザテトラシクロ[8.6.0.02,7.011,15]ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタン−16−イル]フェニル}シクロペンタン−1−カルボニトリル;
1−{4−[12−メチル−4−(ピリジン−3−イル)−8,11,13,14,16−ペンタアザテトラシクロ[8.6.0.02,7.011,15]−ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタン−16−イル]フェニル}シクロプロパン−1−カルボニトリル;
2−メチル−2−{4−[12−メチル−4−(ピリジン−4−イル)−8,11,13,14,16−ペンタアザテトラシクロ[8.6.0.02,7.011,15]−ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタン−16−イル]フェニル}プロパンニトリル;
4−(4−フルオロフェニル)−12−メチル−16−[4−(2−メチルブタ−3−イン−2−イル)フェニル]−8,11,13,14,16−ペンタアザテトラシクロ−[8.6.0.02,7.011,15]ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタエン;
4−(3−フルオロフェニル)−12−メチル−16−[4−(2−メチルブタ−3−イン−2−イル)フェニル]−8,11,13,14,16−ペンタアザテトラシクロ[8.6.0.02,7.011,15]ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタエン;
4−(3、4−ジフルオロフェニル)−12−メチル−16−[4−(2−メチルブタ−3−イン−2−イル)フェニル]−8,11,13,14,16−ペンタアザテトラシクロ[8.6.0.02,7.011,15]ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタエン;
4−(2−フルオロフェニル)−12−メチル−16−[4−(2−メチルブタ−3−イン−2−イル)フェニル]−8,11,13,14,16−ペンタアザテトラシクロ[8.6.0.02,7.011,15]ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタエン;
16−(4−第三級ブチルフェニル)−12−メチル−4−{1H−ピロロ[2、3−b]ピリジン−5−イル}−8,11,13,14,16−ペンタアザテトラシクロ[8.6.0.02,7.011,15]ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタエン;
N−{5−[16−(4−第三級ブチルフェニル)−12−メチル−8,11,13,14,16−ペンタアザテトラシクロ[8.6.0.02,7.011,15]−ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタン−4−イル]ピリジン−2−イル}アセトアミド;
16−(4−第三級ブチルフェニル)−4−(6−メトキシピリジン−3−イル)−12−メチル−8,11,13,14,16−ペンタアザテトラシクロ[8.6.0.02,7.011,15]ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタエン;
16−(4−第三級ブチルフェニル)−12−メチル−4−(ピリミジン−5−イル)−8,11,13,14,16−ペンタアザテトラシクロ−[8.6.0.02,7.011,15]ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタエン;
16−(4−第三級ブチルフェニル)−12−メチル−4−(ピリジン−3−イル)−8,11,13,14,16−ペンタアザテトラシクロ−[8.6.0.02,7.011,15]ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタエン;
2−{4−[4−(6−アミノピリジン−3−イル)−8,11,13,14,16−ペンタアザテトラシクロ[8.6.0.02,7.011,15]ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタン−16−イル]フェニル}−2−メチルプロパンニトリル;
2−メチル−2−{4−[4−(ピリミジン−5−イル)−8,11,13,14,16−ペンタアザテトラシクロ[8.6.0.02,7.011,15]ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタン−16−イル]フェニル}プロパンニトリル;
N−{5−[16−(4−第三級ブチルフェニル)−8,11,13,14,16−ペンタアザテトラシクロ[8.6.0.02,7.011,15]ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタン−4−イル]ピリジン−2−イル}アセトアミド;
16−(4−第三級−ブチルフェニル)−4−{1H−ピロロ[2、3−b]ピリジン−5−イル}−8,11,13,14,16−ペンタアザテトラシクロ−[8.6.0.02,7.011,15]ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタエン;
5−[16−(4−第三級ブチルフェニル)−8,11,13,14,16−ペンタアザテトラシクロ[8.6.0.02,7.011,15]ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタン−4−イル]ピリジン−2−アミン;
5−[16−(4−第三級ブチルフェニル)−12−メチル−8,11,13,14,16−ペンタアザテトラシクロ[8.6.0.02,7.011,15]−ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタン−4−イル]ピリジン−2−アミン;
16−(4−第三級ブチルフェニル)−4−(6−メトキシピリジン−3−イル)−8,11,13,14,16−ペンタアザテトラシクロ−[8.6.0.02,7.011,15]ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタエン;
16−(4−第三級ブチルフェニル)−4−(ピリミジン−5−イル)−8,11,13,14,16−ペンタアザテトラシクロ[8.6.0.02,7.011,15]−ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタエン;
16−(4−第三級ブチルフェニル)−4−(ピリジン−3−イル)−8,11,13,14,16−ペンタアザテトラシクロ[8.6.0.02,7.011,15]−ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタエン;
2−[4−(12−エチル−4−{1H−ピロロ[2、3−b]ピリジン−5−イル}−8,11,13,14,16−ペンタアザテトラシクロ−[8.6.0.02,7.011,15]ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタン−16−イル)フェニル]−2−メチルプロパンニトリル;
N−(5{16−[4−(1−シアノ−1−メチルエチル)フェニル]−12−エチル−8,11,13,14,16−ペンタアザテトラシクロ−[8.6.0.02,7.011,15]ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタン−4−イル}ピリジン−2−イル)アセトアミド;
5−{12−エチル−16−[4−(2−メチルブタ−3−イン−2−イル)フェニル]−8,11,13,14,16−ペンタアザテトラシクロ−[8.6.0.02,7.011,15]ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタン−4−イル}ピリジン−2−アミン;
2−{4−[12−エチル−4−(ピリミジン−5−イル)−8,11,13,14,16−ペンタアザテトラシクロ−[8.6.0.02,7.011,15]ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタン−16−イル]フェニル}−2−メチルプロパンニトリル;
12−エチル−4−(6−メトキシピリジン−3−イル)−16−[4−(2−メチルブタ−3−イン−2−イル)フェニル]−8,11,13,14,16−ペンタアザテトラシクロ[8.6.0.02,7.011,15]ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタエン;
2−メチル−2−[4−(4−{1H−ピロロ[2、3−b]ピリジン−4−イル}−8,11,13,14,16−ペンタアザテトラシクロ−[8.6.0.02,7.011,15]ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタン−16−イル)フェニル]プロパンニトリル;
N−(5−{16−[4−(1−シアノ−1−メチルエチル)フェニル]−12−メチル−8,11,13,14,16−ペンタアザテトラシクロ−[8.6.0.02,7.011,15]ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタン−4−イル}ピリジン−2−イル)アセトアミド;
N−(5{16−[4−(1−シアノ−1−メチルエチル)フェニル]−8,11,13,14,16−ペンタアザテトラシクロ−[8.6.0.02,7.011,15]−ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタン−4−イル}ピリジン−2−イル)アセトアミド;
2−メチル−2−{4−[12−メチル−4−(ピリミジン−5−イル)−8,11,13,14,16−ペンタアザテトラシクロ−[8.6.0.02,7.011,15]ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタン−16−イル]フェニル}プロパンニトリル;
4−(6−メトキシピリジン−3−イル)−12−メチル−16−[4−(2−メチルブタ−3−イン−2−イル)フェニル]8,11,13,14,16−ペンタアザテトラシクロ[8.6.0.02,7.011,15]ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタエン;
2−メチル−2−[4−(12−メチル−4−{1H−ピロロ[2、3−b]ピリジン−5−イル}−8,11,13,14,16−ペンタアザテトラシクロ[8.6.0.02,7.011,15]ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタン−16−イル)フェニル]プロパンニトリル;
2−{4−[4−(6−アミノピリジン−3−イル)−12−メチル−8,11,13,14,16−ペンタアザテトラシクロ[8.6.0.02,7.011,15]−ヘキサデカ1(10),2,4,6,8,12,14−ヘプタン−16−イル]フェニル}−2−メチルプロパンニトリル;
5−[16−(4−第三級ブチルフェニル)−12−メチル−8,11,13,14,16−ペンタアザテトラシクロ[8.6.0.02,7.011,15]ヘキサ−デカ−1(10),2,4,6,8,12,14−ヘプタン−4−イル]−4−(トリフロロメチル)ピリジン−2−アミン;
5−[16−(4−第三級ブチルフェニル)−8,11,13,14,16−ペンタアザテトラシクロ[8.6.0.02,7.011,15]ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタン−4−イル]−4−(トリフロロメチル)ピリジン−2−アミン;
16−(4−第三級ブチルフェニル)−12−エチル−4−(ピリジン−3−イル)−8,11,13,14,16−ペンタアザテトラシクロ−[8.6.0.02,7.011,15]ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタエン;
5−[16−(4−第三級ブチルフェニル)−12−エチル−8,11,13,14,16−ペンタアザテトラシクロ[8.6.0.02,7.011,15]ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタン−4−イル]ピリジン−2−アミン;
2−(4−{4−[6−アミノ−4−(トリフロロメチル)ピリジン−3−イル]−8,11,13,14,16−ペンタアザテトラシクロ−[8.6.0.02,7.011,15]ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタン−16−イル}フェニル)−2−メチルプロパンニトリル;
2−{4−[4−(6−アミノピリジン−3−イル)−8,11,13,14,16−ペンタアザテトラシクロ[8.6.0.02,7.011,15]ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタン−16−イル]フェニル}−2−メチルプロパンニトリル;
5−[16−(4−第三級ブチルフェニル)−8,11,13,14,16−ペンタアザテトラシクロ[8.6.0.02,7.011,15]ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタン−4−イル]ピリジン−2−アミン;
2−アミノ−N−(5 ― {16−[4−(1−シアノ−1−メチルエチル)フェニル]−8,11,13,14,16−ペンタアザテトラシクロ[8.6.0.02,7.011,15]ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタン−4−イル}ピリジン−2−イル)アセトアミド;
N−(5−{16−[4−(1−シアノ−1−メチルエチル)フェニル]−8,11,13,14,16−ペンタアザテトラシクロ[8.6.0.02,7.011,15]−ヘキサデカ1(10),2,4,6,8,12,14−ヘプタン−4−イル}ピリジン−2−イル)−2−(シクロペンチルアミノ)アセトアミド;
N−(5−{16−[4−(1−シアノ−1−メチルエチル)フェニル]−8,11,13,14,16−ペンタアザテトラシクロ[8.6.0.02,7.011,15]−ヘキサデカ1(10),2,4,6,8,12,14−ヘプタン−4−イル}ピリジン−2−イル)−2−(シクロヘキシルアミノ)アセトアミド;
N−(5{16−[4−(1−シアノ−1−メチルエチル)フェニル]−8,11,13,14,16−ペンタアザテトラシクロ[8.6.0.02,7.011,15]−ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタン−4−イル}ピリジン−2−イル)−2−(オキサン−4−イルアミノ)アセトアミド;
N−(5−{16−[4−(1−シアノ−1−メチルエチル)フェニル]−8,11,13,14,16−ペンタアザテトラシクロ[8.6.0.02,7.011,15]−ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタン−4−イル}ピリジン−2−イル)−2−(チアン−4−イルアミノ)アセトアミド;
N−(5−{16−[4−(1−シアノ−1−メチルエチル)フェニル]−8,11,13,14,16−ペンタアザテトラシクロ[8.6.0.02,7.011,15]−ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタン−4−イル}ピリジン−2−イル)−2−(ジメチルアミノ)アセトアミド;
N−(5−{16−[4−(1−シアノ−1−メチルエチル)フェニル]−8,11,13,14,16−ペンタアザテトラシクロ[8.6.0.02,7.011,15]−ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタン−4−イル}ピリジン−2−イル)−2−(メチルアミノ)アセトアミド;
16−(4−第三級ブチルフェニル)−4−(キノリン−3−イル)−8,11,13,14,16−ペンタアザテトラシクロ[8.6.0.02,7.011,15]−ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタエン;
N−(5−{16−[4−(1−シアノ−1−メチルエチル)フェニル]−8,11,13,14,16−ペンタアザテトラシクロ[8.6.0.02,7.011,15]−ヘキサデカ1(10),2,4,6,8,12,14−ヘプタン−4−イル}ピリジン−2−イル)−2−(4−オキソピペリジン−1−イル)アセトアミド;
N−(5−{16−[4−(1−シアノ−1−メチルエチル)フェニル]−8,11,13,14,16−ペンタアザテトラシクロ[8.6.0.02,7.011,15]−ヘキサデカ1(10),2,4,6,8,12,14−ヘプタン−4−イル}ピリジン−2−イル)−2−(4−ヒドロキシピペリジン−1−イル)アセトアミド;
N−(5−{16−[4−(1−シアノ−1−メチルエチル)フェニル]−8,11,13,14,16−ペンタアザテトラシクロ[8.6.0.02,7.011,15]−ヘキサデカ1(10),2,4,6,8,12,14−ヘプタン−4−イル}ピリジン−2−イル)−2−(4−メチルピペラジン−1−イル)アセトアミド;
N−(5−{16−[4−(1−シアノ−1−メチルエチル)フェニル]−8,11,13,14,16−ペンタアザテトラシクロ[8.6.0.02,7.011,15]−ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタン−4−イル}ピリジン−2−イル)−2−(モルホリン−4−イル)アセトアミド;
N−(5−{16−[4−(1−シアノ−1−メチルエチル)フェニル]−8,11,13,14,16−ペンタアザテトラシクロ[8.6.0.02,7.011,15]−ヘキサデカ1(10),2,4,6,8,12,14−ヘプタン−4−イル}ピリジン−2−イル)−2−(ピロリジン−1−イル)アセトアミド;
N−{5−[16−(4−第三級ブチルフェニル)−8,11,13,14,16−ペンタアザテトラシクロ[8.6.0.02,7.011,15]ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタン−4−イル]ピリジン−2−イル}−2−(ピロリジン−1−イル)アセトアミド;
N−{5−[16−(4−第三級ブチルフェニル)−8,11,13,14,16−ペンタアザテトラシクロ[8.6.0.02,7.011,15]−ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタン−4−イル]ピリジン−2−イル}−2−(メチルアミノ)アセトアミド;
N−{5−[16−(4−第三級ブチルフェニル)−12−エチル−8,11,13,14,16−ペンタアザテトラシクロ[8.6.0.02,7.011,15]−ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタン−4−イル]ピリジン−2−イル}−2−(メチルアミノ)アセトアミド;
N−{5−[16−(4−第三級ブチルフェニル)−12−エチル−8,11,13,14,16−ペンタアザテトラシクロ[8.6.0.02,7.011,15]−ヘキサデカ1(10),2,4,6,8,12,14−ヘプタン−4−イル]ピリジン−2−イル}−2−(ピロリジン−1−イル)アセトアミド;
5−[16−(4−第三級ブチルフェニル)−12−エチル−8,11,13,14,16−ペンタアザテトラシクロ[8.6.0.02,7.011,15]ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタン−4−イル]−N−メチルピリジン−2−アミン;
5−[16−(4−第三級ブチルフェニル)−12−エチル−8,11,13,14,16−ペンタアザテトラシクロ[8.6.0.02,7.011,15]ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタン−4−イル]−N−(2−メトキシエチル)ピリジン−2−アミン;
5−[16−(4−第三級ブチルフェニル)−12−エチル−8,11,13,14,16−ペンタアザテトラシクロ[8.6.0.02,7.011,15]ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタン−4−イル]−N−[2−(ピロリジン−1−イル)エチル]ピリジン−2−アミン;
5−[16−(4−第三級ブチルフェニル)−12−エチル−8,11,13,14,16−ペンタアザテトラシクロ[8.6.0.02,7.011,15]ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタン−4−イル]−N−[2−(モルホリン−4−イル)エチル]ピリジン−2−アミン;
N−{5−[16−(4−第三級ブチルフェニル)−12−エチル−8,11,13,14,16−ペンタアザテトラシクロ[8.6.0.02,7.011,15]−ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタン−4−イル]ピリジン−2−イル}−2−(モルホリン−4−イル)アセトアミド;
2−メチル−2−{4−[4−(ピリジン−3−イル)−8,11,14,16−テトラアザテトラシクロ[8.6.0.02,7.011,15]ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタン−16−イル]フェニル}プロパンニトリル;
16−(4−第三級ブチルフェニル)−4−(ピリジン−3−イル)−8,11,14,16−テトラアザテトラシクロ[8.6.0.02,7.011,15]−ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタエン;
16−(4−第三級ブチルフェニル)−4−(キノリン−3−イル)−8,11,14,16−テトラアザテトラシクロ[8.6.0.02,7.011,15]−ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタエン;
16−(3−第三級ブチルフェニル)−4−(キノリン−3−イル)−8,11,14,16−テトラアザテトラシクロ[8.6.0.02,7.011,15]−ヘキサデカ−1(10),2,4,6,8,12,14−ヘプタエン。 - 請求項1の式I(化1)を有する化合物を、生産する方法であって、
次の化学物質プロセスの使用を示す:
スキームII
−NH2、−NHCH3、−N(CH3)2、−NHCOCH3、−NHCO(CH2)nCH3、−NHCO(CH2)nNH2、−NHCO(CH2)nNHCH3、−NHCO(CH2)nN(CH3)2、−NHCO(CH2)n−ピロリジン、−NHCO(CH2)n−ピペラジン、−NHCO(CH2)n−モルホリン、−NH(CH2)nNHCH3、−NH(CH2)nN(CH3)2、−NH(CH2)n−ピロリジン、−NH(CH2)n−ピペラジン、−NH(CH2)n−モルホリン;
n=1、2、3または4であり、
R3は、H、またはC1−C6アルキルであり、
Q1は、ピリジン、ピリミジン、キノリンまたはキナゾリンから独立して選択される、方法。 - 腫瘍性疾患または増殖性疾患または刺激性疾患、または移植性疾患の治療で使用するための、請求項1〜4のいずれかに記載の化合物。
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EP3319602A4 (en) | 2019-01-09 |
CN114805352A (zh) | 2022-07-29 |
EP3319602A1 (en) | 2018-05-16 |
JP2018520167A (ja) | 2018-07-26 |
CN110078730B (zh) | 2021-09-07 |
CN110156782B (zh) | 2023-02-14 |
CN110128425B (zh) | 2021-09-07 |
ES2782113T3 (es) | 2020-09-10 |
CN114790207B (zh) | 2023-07-25 |
AU2016293841B2 (en) | 2020-10-08 |
CN110128425A (zh) | 2019-08-16 |
WO2017011363A1 (en) | 2017-01-19 |
CN110156783A (zh) | 2019-08-23 |
CN114805351B (zh) | 2023-05-09 |
US10730878B2 (en) | 2020-08-04 |
CN108601773A (zh) | 2018-09-28 |
EP3319602B1 (en) | 2020-02-05 |
US20180201613A1 (en) | 2018-07-19 |
CN110156783B (zh) | 2021-09-07 |
CN110078730A (zh) | 2019-08-02 |
CN114790207A (zh) | 2022-07-26 |
AU2016293841A1 (en) | 2018-03-01 |
CN114805351A (zh) | 2022-07-29 |
CN110156782A (zh) | 2019-08-23 |
CN114805352B (zh) | 2023-09-15 |
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