JP2013531074A5 - - Google Patents
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- Publication number
- JP2013531074A5 JP2013531074A5 JP2013520865A JP2013520865A JP2013531074A5 JP 2013531074 A5 JP2013531074 A5 JP 2013531074A5 JP 2013520865 A JP2013520865 A JP 2013520865A JP 2013520865 A JP2013520865 A JP 2013520865A JP 2013531074 A5 JP2013531074 A5 JP 2013531074A5
- Authority
- JP
- Japan
- Prior art keywords
- fluoro
- tetrazol
- pyrimidine
- alkyl
- cyclopropyl
- 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.)
- Granted
Links
- 229910052739 hydrogen Inorganic materials 0.000 claims 19
- 239000001257 hydrogen Substances 0.000 claims 19
- 150000001875 compounds Chemical class 0.000 claims 18
- 125000000217 alkyl group Chemical group 0.000 claims 17
- 229910052736 halogen Inorganic materials 0.000 claims 11
- 150000002367 halogens Chemical class 0.000 claims 11
- 150000002431 hydrogen Chemical class 0.000 claims 11
- 125000000753 cycloalkyl group Chemical group 0.000 claims 9
- 125000002252 acyl group Chemical group 0.000 claims 7
- 125000000266 alpha-aminoacyl group Chemical group 0.000 claims 6
- 125000004093 cyano group Chemical group *C#N 0.000 claims 6
- 125000005346 substituted cycloalkyl group Chemical group 0.000 claims 6
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims 5
- 125000000547 substituted alkyl group Chemical group 0.000 claims 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 4
- 150000003839 salts Chemical class 0.000 claims 4
- -1 4-Cyclopropyl-2-fluoro-5- (5- (fluoromethyl) -1H-tetrazol-1-yl) phenyl Chemical group 0.000 claims 3
- 125000001188 haloalkyl group Chemical group 0.000 claims 3
- NLEYISANNHYRCL-UHFFFAOYSA-N 2-n-[4-cyclopropyl-2-fluoro-5-(tetrazol-1-yl)phenyl]-5-fluoro-4-n-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1C(C)(C)NC(C)(C)CC1NC1=NC(NC=2C(=CC(=C(C=2)N2N=NN=C2)C2CC2)F)=NC=C1F NLEYISANNHYRCL-UHFFFAOYSA-N 0.000 claims 2
- 102000003923 Protein Kinase C Human genes 0.000 claims 2
- 108090000315 Protein Kinase C Proteins 0.000 claims 2
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 2
- BGCSFEUZFIJMEM-UHFFFAOYSA-N 2-[2-fluoro-4-propan-2-yl-5-(tetrazol-1-yl)anilino]-4-[(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyrimidine-5-carbonitrile Chemical compound C1=C(N2N=NN=C2)C(C(C)C)=CC(F)=C1NC(N=1)=NC=C(C#N)C=1NC1CC(C)(C)NC(C)(C)C1 BGCSFEUZFIJMEM-UHFFFAOYSA-N 0.000 claims 1
- OTAGZYATKQXAPD-UHFFFAOYSA-N 2-[3-cyclopropyl-4-fluoro-5-(tetrazol-1-yl)anilino]-4-[(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyrimidine-5-carbonitrile Chemical compound C1C(C)(C)NC(C)(C)CC1NC1=NC(NC=2C=C(C(F)=C(C3CC3)C=2)N2N=NN=C2)=NC=C1C#N OTAGZYATKQXAPD-UHFFFAOYSA-N 0.000 claims 1
- WQEZWROZVMAYJW-UHFFFAOYSA-N 2-[4-cyclopropyl-2-fluoro-5-(tetrazol-1-yl)anilino]-4-[(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyrimidine-5-carbonitrile Chemical compound C1C(C)(C)NC(C)(C)CC1NC1=NC(NC=2C(=CC(=C(C=2)N2N=NN=C2)C2CC2)F)=NC=C1C#N WQEZWROZVMAYJW-UHFFFAOYSA-N 0.000 claims 1
- KFCUUWLZKICCEH-UHFFFAOYSA-N 2-[4-cyclopropyl-2-fluoro-5-(tetrazol-1-yl)anilino]-4-[(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyrimidine-5-carboxamide Chemical compound C1C(C)(C)NC(C)(C)CC1NC1=NC(NC=2C(=CC(=C(C=2)N2N=NN=C2)C2CC2)F)=NC=C1C(N)=O KFCUUWLZKICCEH-UHFFFAOYSA-N 0.000 claims 1
- BGQQESNPKUILBZ-UHFFFAOYSA-N 2-[4-cyclopropyl-3-fluoro-5-(tetrazol-1-yl)anilino]-4-[(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyrimidine-5-carbonitrile Chemical compound C1C(C)(C)NC(C)(C)CC1NC1=NC(NC=2C=C(C(C3CC3)=C(F)C=2)N2N=NN=C2)=NC=C1C#N BGQQESNPKUILBZ-UHFFFAOYSA-N 0.000 claims 1
- YMILVTXUQRUHQG-UHFFFAOYSA-N 2-[4-propan-2-yl-3-(tetrazol-1-yl)anilino]-4-[(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyrimidine-5-carbonitrile Chemical compound C1=C(N2N=NN=C2)C(C(C)C)=CC=C1NC(N=1)=NC=C(C#N)C=1NC1CC(C)(C)NC(C)(C)C1 YMILVTXUQRUHQG-UHFFFAOYSA-N 0.000 claims 1
- CJPZZAWHCBYQNI-UHFFFAOYSA-N 2-[4-propan-2-yl-3-(tetrazol-1-yl)anilino]-4-[(2,2,6,6-tetramethylpiperidin-4-yl)amino]pyrimidine-5-carboxylic acid Chemical compound CC(C)c1ccc(Nc2ncc(C(O)=O)c(NC3CC(C)(C)NC(C)(C)C3)n2)cc1-n1cnnn1 CJPZZAWHCBYQNI-UHFFFAOYSA-N 0.000 claims 1
- IJMPAUUHSKHQFO-UHFFFAOYSA-N 2-n-[3-cyclopropyl-4-fluoro-5-(tetrazol-1-yl)phenyl]-5-fluoro-4-n-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1C(C)(C)NC(C)(C)CC1NC1=NC(NC=2C=C(C(F)=C(C3CC3)C=2)N2N=NN=C2)=NC=C1F IJMPAUUHSKHQFO-UHFFFAOYSA-N 0.000 claims 1
- KAFUQEJULKKDLE-UHFFFAOYSA-N 2-n-[4-cyclopropyl-2-fluoro-5-(5-methyltetrazol-1-yl)phenyl]-5-fluoro-4-n-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound CC1=NN=NN1C1=CC(NC=2N=C(NC3CC(C)(C)NC(C)(C)C3)C(F)=CN=2)=C(F)C=C1C1CC1 KAFUQEJULKKDLE-UHFFFAOYSA-N 0.000 claims 1
- IJFJLIHZXMHOKH-UHFFFAOYSA-N 2-n-[4-cyclopropyl-2-fluoro-5-(5-propan-2-yltetrazol-1-yl)phenyl]-5-fluoro-4-n-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound CC(C)C1=NN=NN1C1=CC(NC=2N=C(NC3CC(C)(C)NC(C)(C)C3)C(F)=CN=2)=C(F)C=C1C1CC1 IJFJLIHZXMHOKH-UHFFFAOYSA-N 0.000 claims 1
- OYXBPAGAOJQYJT-UHFFFAOYSA-N 2-n-[4-cyclopropyl-2-fluoro-5-[5-(trifluoromethyl)tetrazol-1-yl]phenyl]-5-fluoro-4-n-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1C(C)(C)NC(C)(C)CC1NC1=NC(NC=2C(=CC(=C(C=2)N2C(=NN=N2)C(F)(F)F)C2CC2)F)=NC=C1F OYXBPAGAOJQYJT-UHFFFAOYSA-N 0.000 claims 1
- SPIFVSSDMFAXEU-UHFFFAOYSA-N 2-n-[4-cyclopropyl-3-[5-(trifluoromethyl)tetrazol-1-yl]phenyl]-5-fluoro-4-n-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1C(C)(C)NC(C)(C)CC1NC1=NC(NC=2C=C(C(C3CC3)=CC=2)N2C(=NN=N2)C(F)(F)F)=NC=C1F SPIFVSSDMFAXEU-UHFFFAOYSA-N 0.000 claims 1
- KLVSZGNKCOMWCP-UHFFFAOYSA-N 2-n-[4-cyclopropyl-3-fluoro-5-(tetrazol-1-yl)phenyl]-5-fluoro-4-n-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1C(C)(C)NC(C)(C)CC1NC1=NC(NC=2C=C(C(C3CC3)=C(F)C=2)N2N=NN=C2)=NC=C1F KLVSZGNKCOMWCP-UHFFFAOYSA-N 0.000 claims 1
- UAZALSQBZVWHKH-UHFFFAOYSA-N 2-n-[4-cyclopropyl-5-(5-cyclopropyltetrazol-1-yl)-2-fluorophenyl]-5-fluoro-4-n-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1C(C)(C)NC(C)(C)CC1NC1=NC(NC=2C(=CC(=C(C=2)N2C(=NN=N2)C2CC2)C2CC2)F)=NC=C1F UAZALSQBZVWHKH-UHFFFAOYSA-N 0.000 claims 1
- FJNLCHNQVJVCPY-UHFFFAOYSA-N 2-n-methoxy-2-n-methyl-4-n,6-n-dipropyl-1,3,5-triazine-2,4,6-triamine Chemical compound CCCNC1=NC(NCCC)=NC(N(C)OC)=N1 FJNLCHNQVJVCPY-UHFFFAOYSA-N 0.000 claims 1
- JZVKSOLBEXLNQM-DZGCQCFKSA-N 5-fluoro-2-n-[2-fluoro-5-(tetrazol-1-yl)-4-[(1r,2r)-2-(trifluoromethyl)cyclopropyl]phenyl]-4-n-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1C(C)(C)NC(C)(C)CC1NC1=NC(NC=2C(=CC(=C(C=2)N2N=NN=C2)[C@H]2[C@@H](C2)C(F)(F)F)F)=NC=C1F JZVKSOLBEXLNQM-DZGCQCFKSA-N 0.000 claims 1
- XLKVLDGUVMCYIN-UHFFFAOYSA-N 5-fluoro-2-n-[2-fluoro-5-(tetrazol-1-yl)phenyl]-4-n-(1,2,2,6,6-pentamethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1C(C)(C)N(C)C(C)(C)CC1NC1=NC(NC=2C(=CC=C(C=2)N2N=NN=C2)F)=NC=C1F XLKVLDGUVMCYIN-UHFFFAOYSA-N 0.000 claims 1
- LAJVCOAQJHECDY-UHFFFAOYSA-N 5-fluoro-2-n-[2-fluoro-5-(tetrazol-1-yl)phenyl]-4-n-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1C(C)(C)NC(C)(C)CC1NC1=NC(NC=2C(=CC=C(C=2)N2N=NN=C2)F)=NC=C1F LAJVCOAQJHECDY-UHFFFAOYSA-N 0.000 claims 1
- CCHXGPNWZDBDFH-UHFFFAOYSA-N 5-fluoro-2-n-[4-propan-2-yl-3-(tetrazol-1-yl)phenyl]-4-n-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidine-2,4-diamine Chemical compound C1=C(N2N=NN=C2)C(C(C)C)=CC=C1NC(N=1)=NC=C(F)C=1NC1CC(C)(C)NC(C)(C)C1 CCHXGPNWZDBDFH-UHFFFAOYSA-N 0.000 claims 1
- BDAGIHXWWSANSR-UHFFFAOYSA-N Formic acid Chemical group OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims 1
- 125000003545 alkoxy group Chemical group 0.000 claims 1
- 150000001408 amides Chemical class 0.000 claims 1
- 201000010099 disease Diseases 0.000 claims 1
- 208000035475 disorder Diseases 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 230000000694 effects Effects 0.000 claims 1
- 125000001153 fluoro group Chemical group F* 0.000 claims 1
- 230000001404 mediated effect Effects 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 239000000651 prodrug Substances 0.000 claims 1
- 229940002612 prodrug Drugs 0.000 claims 1
- YAAWASYJIRZXSZ-UHFFFAOYSA-N pyrimidine-2,4-diamine Chemical compound NC1=CC=NC(N)=N1 YAAWASYJIRZXSZ-UHFFFAOYSA-N 0.000 claims 1
- 239000012453 solvate Substances 0.000 claims 1
- 125000005415 substituted alkoxy group Chemical group 0.000 claims 1
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US36646410P | 2010-07-21 | 2010-07-21 | |
| US61/366,464 | 2010-07-21 | ||
| PCT/US2011/044824 WO2012012619A1 (en) | 2010-07-21 | 2011-07-21 | Protein kinase c inhibitors and uses thereof |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2013531074A JP2013531074A (ja) | 2013-08-01 |
| JP2013531074A5 true JP2013531074A5 (enExample) | 2014-09-04 |
| JP6035238B2 JP6035238B2 (ja) | 2016-11-30 |
Family
ID=44533110
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2013520865A Expired - Fee Related JP6035238B2 (ja) | 2010-07-21 | 2011-07-21 | プロテインキナーゼｃ阻害剤およびその使用 |
Country Status (5)
| Country | Link |
|---|---|
| US (2) | US8710223B2 (enExample) |
| EP (1) | EP2595982B1 (enExample) |
| JP (1) | JP6035238B2 (enExample) |
| CA (1) | CA2801781C (enExample) |
| WO (1) | WO2012012619A1 (enExample) |
Families Citing this family (23)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0645071B2 (ja) | 1986-07-18 | 1994-06-15 | 住友特殊金属株式会社 | バイメタル板の製造方法 |
| JPH0645072B2 (ja) | 1986-07-21 | 1994-06-15 | 住友特殊金属株式会社 | 耐食性バイメタル板の製造方法 |
| JPH0645073B2 (ja) | 1986-07-21 | 1994-06-15 | 住友特殊金属株式会社 | 耐食性バイメタル板の製造方法 |
| JPH0647177B2 (ja) | 1986-07-21 | 1994-06-22 | 住友特殊金属株式会社 | 耐食性バイメタル板の製造方法 |
| US7722620B2 (en) | 2004-12-06 | 2010-05-25 | Dfine, Inc. | Bone treatment systems and methods |
| US8377924B2 (en) * | 2009-01-21 | 2013-02-19 | Rigel Pharmaceuticals Inc. | Protein kinase C inhibitors and uses thereof |
| CN111471021B (zh) | 2011-04-22 | 2024-04-02 | 西格诺药品有限公司 | 取代的二氨基甲酰胺和二氨基甲腈嘧啶，其组合物，和用其治疗的方法 |
| US9547017B2 (en) | 2012-03-15 | 2017-01-17 | Montana Molecular Llc | Genetically encoded fluorescent sensors for detecting intracellular signalling through diacylglycerol pathways |
| US9321763B2 (en) | 2012-04-04 | 2016-04-26 | Rigel Pharmaceuticals, Inc. | Protein kinase C inhibitors and uses thereof |
| CA2892677A1 (en) | 2012-12-04 | 2014-06-12 | Rigel Pharmaceuticals, Inc. | Protein kinase c inhibitors and uses thereof |
| CA2904610A1 (en) | 2013-03-14 | 2014-09-25 | Rigel Pharmaceuticals, Inc. | Protein kinase c inhibitors and uses thereof |
| US11366114B2 (en) | 2013-11-04 | 2022-06-21 | Montana Molecular Llc | Genetically encoded fluorescent sensors for detecting ligand bias and intracellular signaling through cAMP pathways |
| NZ715903A (en) | 2014-01-30 | 2017-06-30 | Signal Pharm Llc | Solid forms of 2-(tert-butylamino)-4-((1r,3r,4r)-3-hydroxy-4-methylcyclohexylamino)-pyrimidine-5-carboxamide, compositions thereof and methods of their use |
| EP3312164B1 (en) | 2014-03-28 | 2020-12-09 | Calitor Sciences, LLC | Substituted heteroaryl compounds and methods of use |
| JP6649540B2 (ja) | 2014-10-14 | 2020-02-19 | ノース・アンド・サウス・ブラザー・ファーマシー・インベストメント・カンパニー・リミテッド | 置換されたヘテロアリール化合物および使用方法 |
| EP3233808B1 (en) | 2014-12-16 | 2021-07-14 | Signal Pharmaceuticals, LLC | Medical uses comprising methods for measurement of inhibition of c-jun n-terminal kinase in skin |
| ES2972295T3 (es) | 2014-12-16 | 2024-06-12 | Signal Pharm Llc | Sales de 2-(tert-butilamino)-4-((1R,3R,4R)-3-hidroxi-4-metilciclohexilamino)-pirimidin-5-carboxamida |
| CA2975260C (en) | 2015-01-29 | 2024-05-21 | Signal Pharmaceuticals Llc | Isotopologues of 2-(tert-butylamino)-4-((1r,3r,4r)-3-hydroxy-4-methylcyclohexylamino)-pyrimidine-5-carboxamide |
| MX385379B (es) | 2015-07-24 | 2025-03-18 | Celgene Corp | Metodos de sintesis de clorhidrato de (1r,2r,5r)-5-amino-2-metilciclohexanol e intermedios utiles en este. |
| WO2017044434A1 (en) | 2015-09-11 | 2017-03-16 | Sunshine Lake Pharma Co., Ltd. | Substituted heteroaryl compounds and methods of use |
| EP3284739A1 (de) | 2017-07-19 | 2018-02-21 | Bayer CropScience Aktiengesellschaft | Substituierte (het)arylverbindungen als schädlingsbekämpfungsmittel |
| JP7254076B2 (ja) | 2017-11-19 | 2023-04-07 | サンシャイン・レイク・ファーマ・カンパニー・リミテッド | 置換ヘテロアリール化合物及び使用方法 |
| TW202045008A (zh) | 2019-02-01 | 2020-12-16 | 印度商皮埃企業有限公司 | 4-取代的異噁唑/異噁唑啉(雜)芳基脒化合物、及其製備與用途 |
Family Cites Families (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9523675D0 (en) | 1995-11-20 | 1996-01-24 | Celltech Therapeutics Ltd | Chemical compounds |
| TWI329105B (en) | 2002-02-01 | 2010-08-21 | Rigel Pharmaceuticals Inc | 2,4-pyrimidinediamine compounds and their uses |
| IL166241A0 (en) | 2002-07-29 | 2006-01-15 | Rigel Pharmaceuticals Inc | Method of treating or preventing autoimmune diseases with 2,4-pyrimidinedinediamine compounds |
| EP1565218A2 (en) | 2002-11-08 | 2005-08-24 | Tolerrx Inc. | Molecules preferentially associated with effector t cells and methods of their use |
| US8178671B2 (en) * | 2003-07-30 | 2012-05-15 | Rigel Pharmaceuticals, Inc. | Methods of treating or preventing autoimmune diseases with 2, 4-pyrimidinediamine compounds |
| SI1663242T1 (sl) * | 2003-08-07 | 2011-09-30 | Rigel Pharmaceuticals Inc | 2,4-pirimidindiaminske spojine in uporabe kot antiproliferativna sredstva |
| CA2545722A1 (en) | 2003-12-24 | 2005-07-14 | Wyeth | Methods of treating asthma |
| CN105348203B (zh) * | 2005-06-08 | 2018-09-18 | 里格尔药品股份有限公司 | 抑制jak途径的组合物和方法 |
| NZ541934A (en) | 2005-08-19 | 2008-05-30 | Splintiz Invest Ltd | Carbonated milk product comprising a combination of agents that control the foaming of the product while retaining an effective effervescence in the carbonated milk-based beverage |
| BRPI0814432A2 (pt) | 2007-07-17 | 2017-05-09 | Rigel Pharmaceuticals Inc | pirimidinadiaminas substituídas por amina cíclica como inibidores de pkc |
| WO2009145856A1 (en) * | 2008-04-16 | 2009-12-03 | Portola Pharmaceuticals, Inc. | 2, 6-diamino-pyrimidin- 5-yl-carboxamides as syk or jak kinases inhibitors |
| TW201016676A (en) * | 2008-10-03 | 2010-05-01 | Astrazeneca Ab | Heterocyclic derivatives and methods of use thereof |
| JP5781942B2 (ja) * | 2009-01-14 | 2015-09-24 | ライジェル ファーマシューティカルズ， インコーポレイテッド | ２，４−ピリミジンジアミン化合物を用いた炎症性障害の治療法 |
| US8394951B2 (en) | 2009-01-15 | 2013-03-12 | Rigel Pharmaceuticals Inc. | Protein kinase C inhibitors and uses thereof |
| US8377924B2 (en) * | 2009-01-21 | 2013-02-19 | Rigel Pharmaceuticals Inc. | Protein kinase C inhibitors and uses thereof |
| JP5802677B2 (ja) | 2009-12-01 | 2015-10-28 | ライジェル ファーマシューティカルズ， インコーポレイテッド | プロテインキナーゼｃ阻害剤およびその使用 |
-
2011
- 2011-07-21 JP JP2013520865A patent/JP6035238B2/ja not_active Expired - Fee Related
- 2011-07-21 CA CA2801781A patent/CA2801781C/en active Active
- 2011-07-21 WO PCT/US2011/044824 patent/WO2012012619A1/en not_active Ceased
- 2011-07-21 US US13/188,222 patent/US8710223B2/en active Active
- 2011-07-21 EP EP11741505.9A patent/EP2595982B1/en not_active Not-in-force
-
2014
- 2014-03-07 US US14/200,951 patent/US9181222B2/en active Active