- Development and Molecular Understanding of a Pd-Catalyzed Cyanation of Aryl Boronic Acids Enabled by High-Throughput Experimentation and Data Analysis
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A synthetic method for the palladium-catalyzed cyanation of aryl boronic acids using bench stable and non-toxic N-cyanosuccinimide has been developed. High-throughput experimentation facilitated the screen of 90 different ligands and the resultant statistical data analysis identified that ligand σ-donation, π-acidity and sterics are key drivers that govern yield. Categorization into three ligand groups – monophosphines, bisphosphines and miscellaneous – was performed before the analysis. For the monophosphines, the yield of the reaction increases for strong σ-donating, weak π-accepting ligands, with flexible pendant substituents. For the bisphosphines, the yield predominantly correlates with ligand lability. The applicability of the designed reaction to a wider substrate scope was investigated, showing good functional group tolerance in particular with boronic acids bearing electron-withdrawing substituents. This work outlines the development of a novel reaction, coupled with a fast and efficient workflow to gain understanding of the optimal ligand properties for the design of improved palladium cross-coupling catalysts.
- De Jesus Silva, Jordan,Bartalucci, Niccolò,Jelier, Benson,Grosslight, Samantha,Gensch, Tobias,Schünemann, Claas,Müller, Bernd,Kamer, Paul C. J.,Copéret, Christophe,Sigman, Matthew S.,Togni, Antonio
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- Late-stage Pd-catalyzed Cyanations of Aryl/Heteroaryl Halides in Aqueous Micellar Media
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New technology is described that enables late stage ppm Pd-catalyzed cyanations of highly complex molecules, as well as a wide variety of aryl and heteroaryl halides possessing sensitive functional groups. These reactions are efficient in water containing nanomicelles, formed from a commercially available and inexpensive surfactant. The implications for advancing drug synthesis and discovery are apparent.
- Thakore, Ruchita R.,Takale, Balaram S.,Singhania, Vani,Gallou, Fabrice,Lipshutz, Bruce H.
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p. 212 - 216
(2020/12/01)
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- SUBSTITUTED 4-ARYL-1,4-DIHYDRO-1,6-NAPHTHYRIDINAMIDES AND USE THEREOF
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1,6-Naphthyridine or 8-azaquinazoline derivatives (I) are new. 1,6-Naphthyridine or 8-azaquinazoline derivatives of formula (I) are new. D : N or CR 4>; R 4> : H, F, CF 3 or 1-4C alkyl; Ar : 5-R 5>-6-R 6>-2-methyl-4-oxo-4H-1-benzopyran-8-yl; 3-R 6>-4-R 8>-1-naphthyl optionally substituted with 1-3 of R 7>; 7-R 6>-8-R 8>-5-quinolinyl optionally substituted with 1-2 of R 7>; or 2-R 9>-3-R 10>-4-R 8>-5-R 6>-phenyl; R 5> : H, F, Cl, CN, NO 2, CF 3 or 1-4C alkyl; R 6> : H or F; R 7> : halo, 1-4C alkyl, CF 3, 1-4C alkoxy or OCF 3; R 8> : CN or NO 2; R 9> : H or halo; optionally fluorinated 1-4C alkyl, 1-4C alkoxy, 1-4C alkylthio of di(1-4C alkyl)amino; or phenyl optionally substituted with halo, 1-4C alkyl or CF 3; R 10> : H, halo or 1-4C alkyl; R 1> : optionally fluorinated 1-4C alkyl; R 2> : 1-6C alkyl optionally substituted with 3-7C cycloalkyl or F; or SO 2R 11>; R 11> : 1-6C alkyl, CF 3 or 3-7C cycloalkyl; or phenyl or heteroaryl optionally substituted with 1-2 of halo, CN, 1-4C alkyl, CF 3, 1-4C alkoxy and/or OCF 3; R 3> : H, F, CF 3 or 1-4C alkyl. An independent claim is also included for a process for preparing (I). [Image] ACTIVITY : Hypotensive; Cardiant; Hepatotropic; Nephrotropic; Cerebroprotective. MECHANISM OF ACTION : Mineralocorticoid receptor (MR) antagonist. 4-(4-cyano-2-methoxyphenyl)-5-ethoxy-2-methyl-1,4-dihydro-1,6-naphthyridine-3-carboxamide had an IC 50 of 35 nM when tested on cells expressing a GAL4-MR chimera.
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Paragraph 0349-0351
(2016/10/17)
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- NOVEL AROMATIC COMPOUND AND USE THEREOF
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Provided is a compound showing a bone formation promoting action (and/or bone resorption suppressive action). A compound of the formula (I) or a pharmacologically acceptable salt: [wherein each substituent is as defined in the DESCRIPTION], has low toxicity, shows good pharmacokinetics, has an action to promote bone formation, and is useful for the prophylaxis or To treatment of metabolic bone diseases (osteoporosis, fibrous osteitis (hyperparathyroidism), osteomalacia, Paget's disease that influences the systemic bone metabolism parameter etc.) associated with a decrease in the bone formation ability as compared to the bone resorption capacity.
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Paragraph 0916-0918
(2016/08/17)
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- BICYCLOHETEROARYL-HETEROARYL-BENZOIC ACID COMPOUNDS AS RETINOIC ACID RECEPTOR BETA (RARβ) AGONISTS
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The present invention pertains generally to the field of therapeutic compounds, and more specifically to certain bicycloheteroaryl-heteroaryl-benzoic acid compounds of the following formula (for convenience, collectively referred to herein as "BHBA compou
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Page/Page column 71; 72
(2016/07/05)
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- AMIDE DERIVATIVES AS LYSOPHOSPHATIDIC ACID RECEPTOR ANTAGONISTS
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The present invention provides compounds of formula (I) and pharmaceutically acceptable salts thereof, formula (I) wherein R1. X, m. R2, Y, R3, Z, n, R4. A and B are as defined in the specification, processes for their preparation, pharmaceutical compositions containing them and their use in therapy.
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Page/Page column 81-82
(2015/03/13)
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- NOVEL COMPOUNDS
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The present invention provides compounds of formula (I) and pharmaceutically acceptable salts thereof, wherein R1, X, m, R2, Y, R3, Z, n, R4, A and B are as defined in the specification, processes for their prep
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Paragraph 0551
(2015/03/04)
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- AMIDE DERIVATIVE
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Provided are a compound having an excellent hypoglycemic action, or a pharmaceutically acceptable salt thereof, and a pharmaceutical composition having an excellent therapeutic effect and/or prophylactic effect on type 1 diabetes, type 2 diabetes, and the like, which cause an increase in the blood sugar level due to abnormal sugar metabolism. A compound represented by general formula (I), or a pharmaceutically acceptable salt thereof, is disclosed.
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Page/Page column 9
(2012/06/01)
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- NOVEL N-SUBSTITUTED-PYRROLIDINES AS INHIBITORS OF MDM2-P-53 INTERACTIONS
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There are provided compounds of the formula wherein X, Y, R1, R2, R3, R3, R4, and R5 are as described herein and enantiomers and pharmaceutically acceptable salts and esters thereof which are useful as anticancer agents.
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Page/Page column 44
(2011/04/25)
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- SUBSTITUTED 4-ARYL-1,4-DIHYDRO-1,6-NAPHTHYRIDINES AND USE THEREOF
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The present application relates to novel substituted 4-aryl-1,4-dihydro-1,6-naphthyridines, a process for their preparation, their use for the treatment and/or prophylaxis of diseases, and their use for the manufacture of medicaments for the treatment and/or prophylaxis of diseases, especially cardiovascular disorders.
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Page/Page column 23
(2010/12/29)
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- SUBSTITUTED-4-ARYL-1,4-DIHYDRO-1,6-NAPHTHYRIDINAMIDES AND USE THEREOF
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The present application relates to novel substituted 4-aryl-1,4-dihydro-1,6-naphthyridine-3-carboxamides, a process for their preparation, their use for the treatment and/or prophylaxis of diseases, and their use for the manufacture of medicaments for the treatment and/or prophylaxis of diseases, especially cardiovascular disorders.
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- IMIDAZOLE CARBOXAMIDES
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The present invention provides certain imidazole carboxamide derivatives, pharmaceutical compositions thereof, methods of using the same and processes for preparing the same.
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Page/Page column 14
(2010/02/17)
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- OXADIAZOLE DERIVATIVES
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The invention relates to compounds of formula (I); wherein R1, R2, Ra, Rb, W, Q and S have the meanings given in claim 1. The compounds are useful e.g. in the treatment of autoimmune disorders, such as multiple
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Page/Page column 75
(2010/11/03)
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- SULFONAMIDES
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The invention relates to compounds of formula (I) wherein R1, R2, R4, Ra, Rb, Rc, Re, A*, W1, W2 and W3 are as defined in claim 1, for the treatment of CXCR3 related diseases.
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Page/Page column 141
(2009/11/29)
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- TROPANE COMPOUNDS
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A compound according to Formula I or II: (I) or (II) wherein R1, R1b, R2, L1, and L2 and L2b are as defined in the specification, pharmaceutical compositions thereof, and methods of use thereof.
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Page/Page column 448
(2009/05/30)
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- TRIAZOLE OXADIAZOLES DERIVATIVES
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The invention relates to compounds of formula (I), wherein R1, R2, Ra, Rb, X have the meanings given in claim 1. The compounds are useful e.g. in the treatment of autoimmune disorders, such as multiple sclerosis.
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Page/Page column 96
(2009/07/25)
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- OXADIAZOLE DERIVATIVES
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The invention relates to compounds of formula (I): wherein R1, R2, Ra, Rb, W, Q and S have the meanings given in claim 1. The compounds are useful e.g. in the treatment of autoimmune disorders, such as multiple sclerosis.
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Page/Page column 111
(2009/05/29)
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- SUBSTITUTED 1H-BENZIMIDAZOLE-4-CARBOXAMIDES ARE POTENT PARP INHIBITORS
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Compounds of Formula (I) inhibit the PARP enzyme and are useful for treating a disease or a disorder associated with PARP. Also disclosed are pharmaceutical compositions comprising compounds of Formula (I), methods of treatment comprising compounds of For
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Page/Page column 15-16
(2008/06/13)
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- GPCR AGONISTS
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Compounds of formula (I): or pharmaceutically acceptable salts thereof, are GPCR agonists and are useful as for the treatment of obesity and diabetes.
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Page/Page column 28
(2010/11/25)
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- SUBSTITUTED 1H-BENZIMIDAZOLE-4-CARBOXAMIDES ARE POTENT PARP INHIBITORS
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The present invention relates to 1H-benzimidazole-4-carboxamides of formula (I), their preparation, and their use as inhibitors of the enzyme poly(ADP-ribose)polymerase for the preparation of drugs.
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Page/Page column 13
(2008/06/13)
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- HETEROCYCLIC GPCR AGONISTS
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Compounds of formula (I) or pharmaceutically acceptable salts thereof, are agonists of GPR119 and are useful as regulators of satiety, e.g. for the treatment of obesity, and for the treatment of diabetes.
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Page/Page column 23
(2008/06/13)
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