CA1090803A - 2-piperazinyl-6,7-dimethoxyquinazolines - Google Patents
2-piperazinyl-6,7-dimethoxyquinazolinesInfo
- Publication number
- CA1090803A CA1090803A CA270,098A CA270098A CA1090803A CA 1090803 A CA1090803 A CA 1090803A CA 270098 A CA270098 A CA 270098A CA 1090803 A CA1090803 A CA 1090803A
- Authority
- CA
- Canada
- Prior art keywords
- amino
- dimethoxyquinazoline
- piperazinyl
- acceptable salt
- pharmaceutically acceptable
- 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.)
- Expired
Links
- GARLHAZGMDAWFE-UHFFFAOYSA-N 6,7-dimethoxy-2-piperazin-1-ylquinazoline Chemical class N1=C2C=C(OC)C(OC)=CC2=CN=C1N1CCNCC1 GARLHAZGMDAWFE-UHFFFAOYSA-N 0.000 title description 3
- -1 4-hydrazino-2-(substituted piperazinyl)-6,7-dimethoxyquinazolines Chemical class 0.000 claims abstract description 35
- BAENWMYNKDCUTC-UHFFFAOYSA-N [4-(4-amino-6,7-dimethoxyquinazolin-2-yl)piperazin-1-yl]-cyclopentylmethanone Chemical compound N=1C(N)=C2C=C(OC)C(OC)=CC2=NC=1N(CC1)CCN1C(=O)C1CCCC1 BAENWMYNKDCUTC-UHFFFAOYSA-N 0.000 claims abstract description 13
- 238000000034 method Methods 0.000 claims description 54
- 150000003839 salts Chemical class 0.000 claims description 44
- 230000008569 process Effects 0.000 claims description 34
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 22
- 238000006243 chemical reaction Methods 0.000 claims description 22
- 150000001875 compounds Chemical class 0.000 claims description 17
- 238000002360 preparation method Methods 0.000 claims description 17
- HWIIAAVGRHKSOJ-UHFFFAOYSA-N 2-chloro-6,7-dimethoxyquinazolin-4-amine Chemical compound ClC1=NC(N)=C2C=C(OC)C(OC)=CC2=N1 HWIIAAVGRHKSOJ-UHFFFAOYSA-N 0.000 claims description 14
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 14
- 125000004432 carbon atom Chemical group C* 0.000 claims description 13
- 239000002253 acid Substances 0.000 claims description 11
- 229910052736 halogen Inorganic materials 0.000 claims description 11
- 150000002367 halogens Chemical class 0.000 claims description 11
- 150000003246 quinazolines Chemical class 0.000 claims description 8
- 229910021529 ammonia Inorganic materials 0.000 claims description 7
- 239000000376 reactant Substances 0.000 claims description 7
- 125000001424 substituent group Chemical group 0.000 claims description 7
- 239000003960 organic solvent Substances 0.000 claims description 6
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 5
- CJQGSTFFFNJNMC-UHFFFAOYSA-N cyclopentyl(piperazin-1-yl)methanone Chemical compound C1CNCCN1C(=O)C1CCCC1 CJQGSTFFFNJNMC-UHFFFAOYSA-N 0.000 claims description 5
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 4
- 125000004193 piperazinyl group Chemical group 0.000 claims description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 4
- 239000000126 substance Substances 0.000 claims description 4
- HLCPWBZNUKCSBN-UHFFFAOYSA-N 2-aminobenzonitrile Chemical compound NC1=CC=CC=C1C#N HLCPWBZNUKCSBN-UHFFFAOYSA-N 0.000 claims description 3
- ZKPIXNBQUNALFD-UHFFFAOYSA-N [4-(4-amino-6,7-dimethoxyquinazolin-2-yl)piperazin-1-yl]-(cyclopenten-1-yl)methanone Chemical compound N=1C(N)=C2C=C(OC)C(OC)=CC2=NC=1N(CC1)CCN1C(=O)C1=CCCC1 ZKPIXNBQUNALFD-UHFFFAOYSA-N 0.000 claims description 3
- 125000004414 alkyl thio group Chemical group 0.000 claims description 3
- PXXJHWLDUBFPOL-UHFFFAOYSA-N benzamidine Chemical compound NC(=N)C1=CC=CC=C1 PXXJHWLDUBFPOL-UHFFFAOYSA-N 0.000 claims description 3
- 125000000717 hydrazino group Chemical group [H]N([*])N([H])[H] 0.000 claims description 3
- 150000002825 nitriles Chemical class 0.000 claims description 3
- UQCQRAUAAVOIHO-UHFFFAOYSA-N (2-chloro-6,7-dimethoxyquinazolin-4-yl)hydrazine Chemical compound ClC1=NC(NN)=C2C=C(OC)C(OC)=CC2=N1 UQCQRAUAAVOIHO-UHFFFAOYSA-N 0.000 claims description 2
- BJAYMNUBIULRMF-UHFFFAOYSA-N 2-amino-4,5-dimethoxybenzonitrile Chemical compound COC1=CC(N)=C(C#N)C=C1OC BJAYMNUBIULRMF-UHFFFAOYSA-N 0.000 claims description 2
- GXLPMEUYBFWKLS-UHFFFAOYSA-N 6,7-dimethoxy-2-methylsulfanylquinazolin-4-amine Chemical compound CSC1=NC(N)=C2C=C(OC)C(OC)=CC2=N1 GXLPMEUYBFWKLS-UHFFFAOYSA-N 0.000 claims description 2
- APKHJGDGWQDBGM-UHFFFAOYSA-N 6,7-dimethoxy-2-piperazin-1-ylquinazolin-4-amine Chemical compound N=1C(N)=C2C=C(OC)C(OC)=CC2=NC=1N1CCNCC1 APKHJGDGWQDBGM-UHFFFAOYSA-N 0.000 claims description 2
- RMIBQGNVCCOQQO-UHFFFAOYSA-N cycloheptyl(piperazin-1-yl)methanone Chemical compound C1CNCCN1C(=O)C1CCCCCC1 RMIBQGNVCCOQQO-UHFFFAOYSA-N 0.000 claims description 2
- WKLPKXATXOPSKH-UHFFFAOYSA-N cyclohex-3-en-1-yl(piperazin-1-yl)methanone Chemical compound C1CNCCN1C(=O)C1CCC=CC1 WKLPKXATXOPSKH-UHFFFAOYSA-N 0.000 claims description 2
- BQKUNHBVCSMMBB-UHFFFAOYSA-N cyclopent-3-en-1-yl(piperazin-1-yl)methanone Chemical compound C1CNCCN1C(=O)C1CC=CC1 BQKUNHBVCSMMBB-UHFFFAOYSA-N 0.000 claims description 2
- WEPUZBYKXNKSDH-UHFFFAOYSA-N cyclopentanecarbonyl chloride Chemical compound ClC(=O)C1CCCC1 WEPUZBYKXNKSDH-UHFFFAOYSA-N 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- JPQXXHIUGNWHSS-UHFFFAOYSA-N [4-(4-amino-6,7-dimethoxyquinazolin-2-yl)piperazin-1-yl]-cyclobutylmethanone Chemical compound N=1C(N)=C2C=C(OC)C(OC)=CC2=NC=1N(CC1)CCN1C(=O)C1CCC1 JPQXXHIUGNWHSS-UHFFFAOYSA-N 0.000 claims 2
- ZLKMLAMGZRYIGI-UHFFFAOYSA-N [4-(4-amino-6,7-dimethoxyquinazolin-2-yl)piperazin-1-yl]-cycloheptylmethanone Chemical compound N=1C(N)=C2C=C(OC)C(OC)=CC2=NC=1N(CC1)CCN1C(=O)C1CCCCCC1 ZLKMLAMGZRYIGI-UHFFFAOYSA-N 0.000 claims 2
- NGTFTEDHFMMCKI-UHFFFAOYSA-N [4-(4-amino-6,7-dimethoxyquinazolin-2-yl)piperazin-1-yl]-cyclohex-3-en-1-ylmethanone Chemical compound N=1C(N)=C2C=C(OC)C(OC)=CC2=NC=1N(CC1)CCN1C(=O)C1CCC=CC1 NGTFTEDHFMMCKI-UHFFFAOYSA-N 0.000 claims 2
- IKQVBHDWLBYMGG-UHFFFAOYSA-N [4-(4-amino-6,7-dimethoxyquinazolin-2-yl)piperazin-1-yl]-cyclohexylmethanone Chemical compound N=1C(N)=C2C=C(OC)C(OC)=CC2=NC=1N(CC1)CCN1C(=O)C1CCCCC1 IKQVBHDWLBYMGG-UHFFFAOYSA-N 0.000 claims 2
- YALCSACRZWNWRC-UHFFFAOYSA-N [4-(4-amino-6,7-dimethoxyquinazolin-2-yl)piperazin-1-yl]-cyclopent-3-en-1-ylmethanone Chemical compound N=1C(N)=C2C=C(OC)C(OC)=CC2=NC=1N(CC1)CCN1C(=O)C1CC=CC1 YALCSACRZWNWRC-UHFFFAOYSA-N 0.000 claims 2
- PQAOBJDQAFJTBT-UHFFFAOYSA-N [4-(4-amino-6,7-dimethoxyquinazolin-2-yl)piperazin-1-yl]-cyclopropylmethanone Chemical compound N=1C(N)=C2C=C(OC)C(OC)=CC2=NC=1N(CC1)CCN1C(=O)C1CC1 PQAOBJDQAFJTBT-UHFFFAOYSA-N 0.000 claims 2
- CEYAXPZJNTXRGA-UHFFFAOYSA-N cyclopentyl-[4-(4-hydrazinyl-6,7-dimethoxyquinazolin-2-yl)piperazin-1-yl]methanone Chemical compound N=1C(NN)=C2C=C(OC)C(OC)=CC2=NC=1N(CC1)CCN1C(=O)C1CCCC1 CEYAXPZJNTXRGA-UHFFFAOYSA-N 0.000 claims 2
- FKHMNODTEFBVPC-UHFFFAOYSA-N cyclobutyl(piperazin-1-yl)methanone Chemical compound C1CNCCN1C(=O)C1CCC1 FKHMNODTEFBVPC-UHFFFAOYSA-N 0.000 claims 1
- ZSZROXCAFYZNHE-UHFFFAOYSA-N cyclohexyl(piperazin-1-yl)methanone Chemical compound C1CNCCN1C(=O)C1CCCCC1 ZSZROXCAFYZNHE-UHFFFAOYSA-N 0.000 claims 1
- OQCVPEIHYUPZCC-UHFFFAOYSA-N cyclopenten-1-yl(piperazin-1-yl)methanone Chemical compound C=1CCCC=1C(=O)N1CCNCC1 OQCVPEIHYUPZCC-UHFFFAOYSA-N 0.000 claims 1
- KIALFUYSJAAJSU-UHFFFAOYSA-N cyclopropyl(piperazin-1-yl)methanone Chemical compound C1CNCCN1C(=O)C1CC1 KIALFUYSJAAJSU-UHFFFAOYSA-N 0.000 claims 1
- 230000003276 anti-hypertensive effect Effects 0.000 abstract description 11
- 102000004861 Phosphoric Diester Hydrolases Human genes 0.000 abstract 1
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- 230000002401 inhibitory effect Effects 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 27
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 15
- IENZQIKPVFGBNW-UHFFFAOYSA-N prazosin Chemical compound N=1C(N)=C2C=C(OC)C(OC)=CC2=NC=1N(CC1)CCN1C(=O)C1=CC=CO1 IENZQIKPVFGBNW-UHFFFAOYSA-N 0.000 description 10
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- 206010031127 Orthostatic hypotension Diseases 0.000 description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
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- 239000000460 chlorine Substances 0.000 description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
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Classifications
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US05/659,059 US4060615A (en) | 1976-02-18 | 1976-02-18 | 2-Piperazinyl-6,7-dimethoxyquinazolines |
| US659,059 | 1976-02-18 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1090803A true CA1090803A (en) | 1980-12-02 |
Family
ID=24643862
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA270,098A Expired CA1090803A (en) | 1976-02-18 | 1977-01-20 | 2-piperazinyl-6,7-dimethoxyquinazolines |
Country Status (22)
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| US9409886B2 (en) | 2007-07-05 | 2016-08-09 | Array Biopharma Inc. | Pyrimidyl cyclopentanes as AKT protein kinase inhibitors |
| ES2533557T3 (es) * | 2007-07-05 | 2015-04-13 | Array Biopharma, Inc. | Pirimidil ciclopentanos como inhibidores de proteína cinasa AKT |
| NZ586346A (en) * | 2008-01-09 | 2012-02-24 | Array Biopharma Inc | Hydroxylated pyrimidyl cyclopentanes as akt protein kinase inhibitors |
| RU2520735C2 (ru) * | 2008-01-09 | 2014-06-27 | Эррэй Биофарма Инк. | Гидроксилированный пиримидил циклопентан в качестве ингибитора протеинкиназы (акт) |
| EP2268279A1 (en) * | 2008-03-24 | 2011-01-05 | Celgene Corporation | Treatment of psoriasis or psoriatic arthritis using cyclopropyl-n-{2-{(1s)-1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl¨-3-oxoisoindoline-4-yl}carboxamide |
| JP6143739B2 (ja) | 2011-04-01 | 2017-06-07 | ジェネンテック， インコーポレイテッド | Ａｋｔ阻害剤化合物及びベムラフェニブの組み合わせ、及び使用方法 |
| BR112013025397A2 (pt) | 2011-04-01 | 2019-09-24 | Deepak Sampath | combinação de um composto, composto de fórmula i ou um sal farmaceuticamente aceitável do mesmo, uso, kit, produto, método para tratamento de um distúrbio hiperproliferativo e método para tratamento de uma doença ou afecção modulada por quinase akt em um mamífero |
| JP6687550B2 (ja) | 2014-06-23 | 2020-04-22 | セルジーン コーポレイション | 肝疾患又は肝機能異常を治療するためのアプレミラスト |
| EP3648766A4 (en) * | 2017-07-06 | 2021-07-07 | Case Western Reserve University | PEPTIDIC AND SMALL MOLECULE AGONISTS OF WPHA AND THEIR USES |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3511836A (en) * | 1967-12-13 | 1970-05-12 | Pfizer & Co C | 2,4,6,7-tetra substituted quinazolines |
| US3669968A (en) * | 1970-05-21 | 1972-06-13 | Pfizer | Trialkoxy quinazolines |
| JPS536156B2 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) * | 1972-10-30 | 1978-03-04 | ||
| US3935213A (en) * | 1973-12-05 | 1976-01-27 | Pfizer Inc. | Process for hypotensive 4-amino-2-(piperazin-1-yl) quinazoline derivatives |
-
1976
- 1976-02-18 US US05/659,059 patent/US4060615A/en not_active Expired - Lifetime
-
1977
- 1977-01-20 CA CA270,098A patent/CA1090803A/en not_active Expired
- 1977-02-02 ZA ZA770587A patent/ZA77587B/xx unknown
- 1977-02-03 AU AU21897/77A patent/AU505080B2/en not_active Expired
- 1977-02-15 NL NL7701584A patent/NL7701584A/xx not_active Application Discontinuation
- 1977-02-15 DK DK65077A patent/DK144010C/da not_active IP Right Cessation
- 1977-02-15 BE BE174951A patent/BE851447A/xx not_active IP Right Cessation
- 1977-02-15 FI FI770486A patent/FI64586C/fi not_active IP Right Cessation
- 1977-02-16 LU LU76779A patent/LU76779A1/xx unknown
- 1977-02-16 FR FR7704348A patent/FR2341576A1/fr active Granted
- 1977-02-16 JP JP1511077A patent/JPS52100479A/ja active Pending
- 1977-02-16 SE SE7701731A patent/SE431753B/xx unknown
- 1977-02-17 CY CY1155A patent/CY1155A/xx unknown
- 1977-02-17 YU YU00425/77A patent/YU42577A/xx unknown
- 1977-02-17 CH CH199377A patent/CH620925A5/fr not_active IP Right Cessation
- 1977-02-17 GB GB6703/77A patent/GB1545697A/en not_active Expired
- 1977-02-17 IE IE337/77A patent/IE44613B1/en unknown
- 1977-02-18 DE DE19772707068 patent/DE2707068A1/de not_active Withdrawn
-
1980
- 1980-02-04 CH CH88580A patent/CH623051A5/fr not_active IP Right Cessation
-
1982
- 1982-07-06 SG SG308/82A patent/SG30882G/en unknown
- 1982-07-07 KE KE3221A patent/KE3221A/xx unknown
- 1982-07-15 HK HK326/82A patent/HK32682A/xx unknown
- 1982-07-28 YU YU01654/82A patent/YU165482A/xx unknown
- 1982-07-28 YU YU1653/82A patent/YU40622B/xx unknown
- 1982-07-28 YU YU01652/82A patent/YU165282A/xx unknown
-
1983
- 1983-12-30 MY MY172/83A patent/MY8300172A/xx unknown
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