EA019110B1 - Замещенные хиназолиновые соединения - Google Patents
Замещенные хиназолиновые соединения Download PDFInfo
- Publication number
- EA019110B1 EA019110B1 EA201101012A EA201101012A EA019110B1 EA 019110 B1 EA019110 B1 EA 019110B1 EA 201101012 A EA201101012 A EA 201101012A EA 201101012 A EA201101012 A EA 201101012A EA 019110 B1 EA019110 B1 EA 019110B1
- Authority
- EA
- Eurasian Patent Office
- Prior art keywords
- phenyl
- ylamino
- chloro
- compound according
- quinazolin
- Prior art date
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- 125000002294 quinazolinyl group Chemical class N1=C(N=CC2=CC=CC=C12)* 0.000 title abstract 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 164
- -1 2,6-dimethylphenyl Chemical group 0.000 claims description 35
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 18
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 15
- 125000001072 heteroaryl group Chemical group 0.000 claims description 14
- 125000003118 aryl group Chemical group 0.000 claims description 13
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 12
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 12
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 11
- 239000001257 hydrogen Substances 0.000 claims description 11
- 229910052739 hydrogen Inorganic materials 0.000 claims description 11
- 150000003839 salts Chemical class 0.000 claims description 11
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 claims description 10
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 9
- 150000002431 hydrogen Chemical class 0.000 claims description 9
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 8
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 8
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 8
- 239000012634 fragment Substances 0.000 claims description 8
- 125000000217 alkyl group Chemical group 0.000 claims description 7
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 6
- 125000004575 3-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 5
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 claims description 5
- 125000002618 bicyclic heterocycle group Chemical group 0.000 claims description 5
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 5
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- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 4
- 125000004432 carbon atom Chemical group C* 0.000 claims description 4
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- 125000005842 heteroatom Chemical group 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- 229910052757 nitrogen Inorganic materials 0.000 claims description 4
- 239000001301 oxygen Chemical group 0.000 claims description 4
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- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 4
- 239000011593 sulfur Chemical group 0.000 claims description 4
- 229910052717 sulfur Chemical group 0.000 claims description 4
- TYRDPAITJGOXCX-UHFFFAOYSA-N 1-[4-[[6-(2,6-dimethylphenyl)quinazolin-2-yl]amino]phenyl]-3-(2-pyrrolidin-1-ylethyl)imidazolidin-2-one Chemical compound CC1=CC=CC(C)=C1C1=CC=C(N=C(NC=2C=CC(=CC=2)N2C(N(CCN3CCCC3)CC2)=O)N=C2)C2=C1 TYRDPAITJGOXCX-UHFFFAOYSA-N 0.000 claims description 3
- PWAQGFBFYOSQKM-UHFFFAOYSA-N 1-[4-[[6-(2-chloro-5-hydroxyphenyl)quinazolin-2-yl]amino]phenyl]-3-(2-pyrrolidin-1-ylethyl)imidazolidin-2-one Chemical compound OC1=CC=C(Cl)C(C=2C=C3C=NC(NC=4C=CC(=CC=4)N4C(N(CCN5CCCC5)CC4)=O)=NC3=CC=2)=C1 PWAQGFBFYOSQKM-UHFFFAOYSA-N 0.000 claims description 3
- LPMCVZGZXTUCIL-UHFFFAOYSA-N 4-chloro-3-[2-[4-(2-pyrrolidin-1-ylethoxy)anilino]quinazolin-6-yl]phenol Chemical compound OC1=CC=C(Cl)C(C=2C=C3C=NC(NC=4C=CC(OCCN5CCCC5)=CC=4)=NC3=CC=2)=C1 LPMCVZGZXTUCIL-UHFFFAOYSA-N 0.000 claims description 3
- DPMRCMKQVYZSIO-UHFFFAOYSA-N [4-[4-[[6-(2,6-dimethylphenyl)quinazolin-2-yl]amino]phenyl]piperazin-1-yl]-pyridin-4-ylmethanone Chemical compound CC1=CC=CC(C)=C1C1=CC=C(N=C(NC=2C=CC(=CC=2)N2CCN(CC2)C(=O)C=2C=CN=CC=2)N=C2)C2=C1 DPMRCMKQVYZSIO-UHFFFAOYSA-N 0.000 claims description 3
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- DCUDFYSDQVJVAX-UHFFFAOYSA-N 1-[4-[4-[[6-(2,6-dimethylphenyl)quinazolin-2-yl]amino]phenyl]piperazin-1-yl]ethanone Chemical compound C1CN(C(=O)C)CCN1C(C=C1)=CC=C1NC1=NC=C(C=C(C=C2)C=3C(=CC=CC=3C)C)C2=N1 DCUDFYSDQVJVAX-UHFFFAOYSA-N 0.000 claims description 2
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- MCWXXILNYUKEIR-UHFFFAOYSA-N 1-[4-[[6-(2-chloro-5-hydroxyphenyl)-8-methylquinazolin-2-yl]amino]phenyl]-3-(2-pyrrolidin-1-ylethyl)imidazolidin-2-one Chemical compound N1=C2C(C)=CC(C=3C(=CC=C(O)C=3)Cl)=CC2=CN=C1NC(C=C1)=CC=C1N(C1=O)CCN1CCN1CCCC1 MCWXXILNYUKEIR-UHFFFAOYSA-N 0.000 claims description 2
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- MPNPFEPBTPBOAQ-UHFFFAOYSA-N [4-[4-[[6-(2-chloro-5-hydroxyphenyl)-8-methylquinazolin-2-yl]amino]phenyl]piperazin-1-yl]-pyridin-2-ylmethanone Chemical compound N1=C2C(C)=CC(C=3C(=CC=C(O)C=3)Cl)=CC2=CN=C1NC(C=C1)=CC=C1N(CC1)CCN1C(=O)C1=CC=CC=N1 MPNPFEPBTPBOAQ-UHFFFAOYSA-N 0.000 claims description 2
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Classifications
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- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic 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
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/517—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
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- A61P9/00—Drugs for disorders of the cardiovascular system
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/10—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing aromatic rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
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- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Ophthalmology & Optometry (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP08360043 | 2008-12-29 | ||
| PCT/EP2009/067494 WO2010076238A1 (en) | 2008-12-29 | 2009-12-18 | Substituted quinazoline compounds |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| EA201101012A1 EA201101012A1 (ru) | 2012-01-30 |
| EA019110B1 true EA019110B1 (ru) | 2014-01-30 |
Family
ID=41735344
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EA201101012A EA019110B1 (ru) | 2008-12-29 | 2009-12-18 | Замещенные хиназолиновые соединения |
Country Status (23)
| Country | Link |
|---|---|
| US (1) | US8389530B2 (https=) |
| EP (1) | EP2381943A1 (https=) |
| JP (1) | JP2012514020A (https=) |
| KR (1) | KR20110120878A (https=) |
| CN (1) | CN102333533A (https=) |
| AU (1) | AU2009334869A1 (https=) |
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Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AR081960A1 (es) | 2010-06-22 | 2012-10-31 | Fovea Pharmaceuticals Sa | Compuestos heterociclicos, su preparacion y su aplicacion terapeutica |
| SMT202100451T1 (it) | 2012-07-11 | 2021-09-14 | Blueprint Medicines Corp | Inibitori del recettore di crescita dei fibroblasti |
| CA2928042C (en) | 2013-10-25 | 2022-05-10 | Blueprint Medicines Corporation | Inhibitors of the fibroblast growth factor receptor |
| WO2015108992A1 (en) | 2014-01-15 | 2015-07-23 | Blueprint Medicines Corporation | Heterobicyclic compounds and their use as fgfr4 receptor inhibitors |
| KR101715448B1 (ko) * | 2014-07-16 | 2017-03-20 | 주식회사 큐리언트 | 염증성 질환 치료용 화합물 |
| TWI699355B (zh) | 2014-12-24 | 2020-07-21 | 美商基利科學股份有限公司 | 喹唑啉化合物 |
| BR112017013440A2 (pt) | 2014-12-24 | 2018-01-09 | Gilead Sciences, Inc. | compostos de isoquinolina para o tratamento de hiv |
| ES2735087T3 (es) | 2014-12-24 | 2019-12-16 | Gilead Sciences Inc | Compuestos de pirimidina fusionados para el tratamiento de VIH |
| CN112239459B (zh) * | 2019-07-19 | 2021-11-26 | 中国科学院上海药物研究所 | 稠环嘧啶氨基化合物、其制备方法、药物组合物及应用 |
| CN115916759B (zh) * | 2020-06-19 | 2025-07-15 | 泰州红云制药有限公司 | 取代喹唑啉类化合物、其制备方法、药物组合及应用 |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001038315A1 (en) * | 1999-11-22 | 2001-05-31 | Warner-Lambert Company | Quinazolines and their use for inhibiting cyclin-dependent kinase enzymes |
| WO2006039718A2 (en) * | 2004-10-01 | 2006-04-13 | Amgen Inc | Aryl nitrogen-containing bicyclic compounds and their use as kinase inhibitors |
| EP1878727A1 (en) * | 2005-04-28 | 2008-01-16 | Kyowa Hakko Kogyo Co., Ltd. | 2-aminoquinazoline derivatives |
| WO2008079988A2 (en) * | 2006-12-22 | 2008-07-03 | Novartis Ag | Quinazolines for pdk1 inhibition |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1590341B1 (en) | 2003-01-17 | 2009-06-17 | Warner-Lambert Company LLC | 2-aminopyridine substituted heterocycles as inhibitors of cellular proliferation |
| CN1882345A (zh) | 2003-10-16 | 2006-12-20 | 希龙公司 | 作为raf激酶抑制剂以治疗癌症的2,6－二取代的喹唑啉、喹喔啉、喹啉和异喹啉 |
| KR20070011458A (ko) | 2004-04-08 | 2007-01-24 | 탈자진 인코포레이티드 | 키나제의 벤조트리아진 억제제 |
| PL382308A1 (pl) | 2004-08-25 | 2007-08-20 | Targegen, Inc. | Związki heterocykliczne i sposoby stosowania |
| US20060247250A1 (en) | 2005-03-16 | 2006-11-02 | Targegen, Inc. | Pyrimidine inhibitors of kinases |
| NZ563984A (en) | 2005-06-08 | 2011-11-25 | Targegen Inc | Methods and compositions for the treatment of ocular disorders |
| TW200808739A (en) * | 2006-04-06 | 2008-02-16 | Novartis Vaccines & Diagnostic | Quinazolines for PDK1 inhibition |
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2009
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- 2009-12-18 CN CN2009801575427A patent/CN102333533A/zh active Pending
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- 2009-12-18 PE PE2011001296A patent/PE20120424A1/es not_active Application Discontinuation
- 2009-12-18 WO PCT/EP2009/067494 patent/WO2010076238A1/en not_active Ceased
- 2009-12-18 JP JP2011544017A patent/JP2012514020A/ja active Pending
- 2009-12-18 EP EP09799340A patent/EP2381943A1/en not_active Withdrawn
- 2009-12-18 SG SG2011047339A patent/SG172415A1/en unknown
- 2009-12-18 BR BRPI0924067A patent/BRPI0924067A2/pt not_active IP Right Cessation
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- 2009-12-18 MX MX2011007064A patent/MX2011007064A/es active IP Right Grant
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- 2009-12-18 US US13/142,333 patent/US8389530B2/en not_active Expired - Fee Related
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2011
- 2011-06-23 IL IL213742A patent/IL213742A0/en unknown
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- 2011-06-27 CR CR20110368A patent/CR20110368A/es not_active Application Discontinuation
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- 2011-06-29 CO CO11081323A patent/CO6390105A2/es not_active Application Discontinuation
- 2011-07-14 EC EC2011011204A patent/ECSP11011204A/es unknown
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001038315A1 (en) * | 1999-11-22 | 2001-05-31 | Warner-Lambert Company | Quinazolines and their use for inhibiting cyclin-dependent kinase enzymes |
| WO2006039718A2 (en) * | 2004-10-01 | 2006-04-13 | Amgen Inc | Aryl nitrogen-containing bicyclic compounds and their use as kinase inhibitors |
| EP1878727A1 (en) * | 2005-04-28 | 2008-01-16 | Kyowa Hakko Kogyo Co., Ltd. | 2-aminoquinazoline derivatives |
| WO2008079988A2 (en) * | 2006-12-22 | 2008-07-03 | Novartis Ag | Quinazolines for pdk1 inhibition |
Non-Patent Citations (1)
| Title |
|---|
| S. T. HENRIKSEN ET AL.: "2-Chloroquinazoline, Synthesis and reactivity of a versatile heterocyclic building block", TETRAHEDRON LETTERS, vol. 47, no. 47, 21 September 2006 (2006-09-21), pages 8251-8254, XP002572206, See compound lib, table 2, page 8253. * |
Also Published As
| Publication number | Publication date |
|---|---|
| NZ593949A (en) | 2013-08-30 |
| TN2011000319A1 (en) | 2012-12-17 |
| ZA201104777B (en) | 2012-03-28 |
| US20120004210A1 (en) | 2012-01-05 |
| BRPI0924067A2 (pt) | 2016-01-26 |
| CA2748319A1 (en) | 2010-07-08 |
| AU2009334869A2 (en) | 2011-09-29 |
| IL213742A0 (en) | 2011-07-31 |
| SG172415A1 (en) | 2011-07-28 |
| CO6390105A2 (es) | 2012-02-29 |
| WO2010076238A1 (en) | 2010-07-08 |
| JP2012514020A (ja) | 2012-06-21 |
| MX2011007064A (es) | 2012-01-20 |
| CR20110368A (es) | 2011-12-02 |
| AU2009334869A1 (en) | 2011-07-14 |
| PE20120424A1 (es) | 2012-05-04 |
| ECSP11011204A (es) | 2011-10-31 |
| EA201101012A1 (ru) | 2012-01-30 |
| US8389530B2 (en) | 2013-03-05 |
| MA32968B1 (fr) | 2012-01-02 |
| DOP2011000209A (es) | 2011-09-30 |
| KR20110120878A (ko) | 2011-11-04 |
| CN102333533A (zh) | 2012-01-25 |
| NI201100134A (es) | 2012-03-06 |
| EP2381943A1 (en) | 2011-11-02 |
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| MM4A | Lapse of a eurasian patent due to non-payment of renewal fees within the time limit in the following designated state(s) |
Designated state(s): AM AZ BY KZ KG MD TJ TM RU |