- A 2 - methyl -7 - aza indole synthesis method (by machine translation)
-
The invention discloses a 2 - methyl - 7 - aza indole synthesis method, comprises the following steps: the 2 - amino - 3 - chloro pyridine added in DMF, heating to 150 - 220 °C, adding Cp2 ZrCl2 And catalyst, under stirring conditions, adding methylacetylene, reflux reaction 4 - 6 h, after the reaction, filtration, the filtrate is distilled under reduced pressure to remove the DMF, ethyl acetate extraction, recrystallization, extraction, drying, to obtain 2 - methyl - 7 - azaindole. The application of the synthesis method adopts the one-pot synthesis, the operation is simple, without intermediate purification step, high conversion rate of raw materials, and has high economic benefits. (by machine translation)
- -
-
Paragraph 0018-0052
(2019/10/29)
-
- PREPARATION OF 2-[2-METHYL-1-[[4-METHYLSULFONYL-2-(TRIFLUORO METHYL)PHENYL]METHYL] PYRROLO[2,3-B]PYRIDIN-3-YL]ACETIC ACID
-
The present invention relates to a novel compound of Formula IV and use of said compound for the preparation of 2-[2-methyl-1-[[4-methylsulfonyl-2-(trifluoromethyl)phenyl] methyl]pyrrolo[2,3-b]pyridine-3-yl]acetic acid [fevipiprant], Formula IV wherein A is SO2Me, halogen or a leaving group. The present invention further relates to a process of preparation of pharmaceutical acceptable salts of fevipiprant and composition thereof.
- -
-
Page/Page column 23
(2019/07/17)
-
- Depsipeptides Featuring a Neutral P1 Are Potent Inhibitors of Kallikrein-Related Peptidase 6 with On-Target Cellular Activity
-
Kallikrein-related peptidase 6 (KLK6) is a secreted serine protease that belongs to the family of tissue kallikreins (KLKs). Many KLKs are investigated as potential biomarkers for cancer as well as therapeutic drug targets for a number of pathologies. KLK6, in particular, has been implicated in neurodegenerative diseases and cancer, but target validation has been hampered by a lack of selective inhibitors. This work introduces a class of depsipeptidic KLK6 inhibitors, discovered via high-throughput screening, which were found to function as substrate mimics that transiently acylate the catalytic serine of KLK6. Detailed structure-activity relationship studies, aided by in silico modeling, uncovered strict structural requirements for potency, stability, and acyl-enzyme complex half-life. An optimized scaffold, DKFZ-251, demonstrated good selectivity for KLK6 compared to other KLKs, and on-target activity in a cellular assay. Moreover, DKFZ-633, an inhibitor-derived activity-based probe, could be used to pull down active endogenous KLK6.
- De Vita, Elena,Schüler, Peter,Lovell, Scott,Lohbeck, Jasmin,Kullmann, Sven,Rabinovich, Eitan,Sananes, Amiram,He?ling, Bernd,Hamon, Veronique,Papo, Niv,Hess, Jochen,Tate, Edward W.,Gunkel, Nikolas,Miller, Aubry K.
-
p. 8859 - 8874
(2018/10/09)
-
- Transition-metal-free access to 7-azaindoles
-
A novel method for transition-metal-free synthesis of 7-azaindoles is developed through a one-pot synthesis involving amination of pyridine N-oxides and intramolecular enamine formation. Remarkable features of the method include simple operation, mild reaction conditions, wide substrate scope, and easily accessible starting materials.
- Wang, Dong,Hu, Jianyong,Zhao, Junjie,Shen, Meng,Wang, Yuxi,Yu, Peng
-
supporting information
p. 4100 - 4110
(2018/06/25)
-
- Asymmetric Hydrogenation of Azaindoles: Chemo- and Enantioselective Reduction of Fused Aromatic Ring Systems Consisting of Two Heteroarenes
-
High enantioselectivity was achieved for the hydrogenation of azaindoles by using the chiral catalyst, which was prepared from [Ru(η3-methallyl)2(cod)] and a trans-chelating bis(phosphine) ligand (PhTRAP). The dearomative reaction exclusively occurred on the five-membered ring, thus giving the corresponding azaindolines with up to 97:3 enantiomer ratio.
- Makida, Yusuke,Saita, Masahiro,Kuramoto, Takahiro,Ishizuka, Kentaro,Kuwano, Ryoichi
-
supporting information
p. 11859 - 11862
(2016/11/16)
-
- Structure-activity relationships (SAR) and structure-kinetic relationships (SKR) of sulphone-based CRTh2 antagonists
-
Monocyclic and bicyclic ring systems were investigated as the "core" section of a series of diphenylsulphone-containing acetic acid CRTh2 receptor antagonists. A range of potencies were observed and single-digit nanomolar potencies were obtained in both the monocyclic and bicyclic cores. Residence times for the monocyclic compounds were very short. Some of the bicyclic cores displayed better residence times. A methyl group in the northern part of the core, between the head and tail was a necessary requirement for the beginnings of long residence times. Variations of the tail substitution maximised potencies and residence times.
- Buil, Maria Antonia,Calbet, Marta,Castillo, Marcos,Castro, Jordi,Esteve, Cristina,Ferrer, Manel,Forns, Pilar,González, Jacob,López, Sara,Roberts, Richard S.,Sevilla, Sara,Vidal, Bernat,Vidal, Laura,Vilaseca, Pere
-
p. 102 - 133
(2016/03/04)
-
- Synthesis of Indoles by Palladium-Catalyzed Reductive Cyclization of β-Nitrostyrenes with Carbon Monoxide as the Reductant
-
An efficient catalytic cyclization of β-nitrostyrenes to indoles was developed. The reaction was applied to the synthesis of 3-arylindoles and 2-alkylindoles. Given that in the latter case the starting β-nitrostyrenes can be easily obtained by a Henry reaction, the present method allows indoles to be obtained in a two-step sequence starting from cheap reactants.
- Ferretti, Francesco,El-Atawy, Mohamed A.,Muto, Stefania,Hagar, Mohamed,Gallo, Emma,Ragaini, Fabio
-
supporting information
p. 5712 - 5715
(2015/09/15)
-
- PROTEASOME ACTIVITY ENHANCING COMPOUNDS
-
The present invention is directed to compounds having the Formula (I), (II), (III), (IV), and (V), compositions thereof, the methods of synthesis of the compouds of interest, and to methods for the treatment of a condition associated with a dysfunction in proteostasis, such as cancer, inflammatory conditions, neurodegeneration, metabolic conditions, comprising administering an effective amount of a compound of the invention.
- -
-
-
- A convenient palladium-catalyzed azaindole synthesis
-
A one-pot protocol is described which allows direct access to azaindoles from amino-halopyridines and ketones.
- De Gasparo, Raoul,Lustenberger, Philipp,Mathes, Christian,Schlama, Thierry,Veitch, Gemma E.,Le Paih, Jacques J. M.
-
supporting information
p. 197 - 200
(2015/03/03)
-
- A convenient palladium-catalyzed azaindole synthesis
-
A one-pot protocol is described which allows direct access to azaindoles from amino-halopyridines and ketones.
- De Gasparo, Raoul,Lustenberger, Philipp,Mathes, Christian,Schlama, Thierry,Veitch, Gemma E.,Le Paih, Jacques J. M.
-
supporting information
(2015/01/08)
-
- Discovery and characterization of NVP-QAV680, a potent and selective CRTh2 receptor antagonist suitable for clinical testing in allergic diseases
-
Optimization of a 7-azaindole-3-acetic acid CRTh2 receptor antagonist chemotype derived from high throughput screening furnished a highly selective compound NVP-QAV680 with low nM functional potency for inhibition of CRTh2 driven human eosinophil and Th2 lymphocyte activation in vitro. The molecule exhibited good oral bioavailability in the rat, combined with efficacy in rodent CRTh2-dependent mechanistic and allergic disease models and was suitable for clinical development.
- Sandham, David A.,Arnold, Nicola,Aschauer, Heinrich,Bala, Kamlesh,Barker, Lucy,Brown, Lyndon,Brown, Zarin,Budd, David,Cox, Brian,Docx, Cerys,Dubois, Gerald,Duggan, Nicholas,England, Karen,Everatt, Brian,Furegati, Marcus,Hall, Edward,Kalthoff, Frank,King, Anna,Leblanc, Catherine J.,Manini, Jodie,Meingassner, Josef,Profit, Rachael,Schmidt, Alfred,Simmons, Jennifer,Sohal, Bindi,Stringer, Rowan,Thomas, Matthew,Turner, Katharine L.,Walker, Christoph,Watson, Simon J.,Westwick, John,Willis, Jennifer,Williams, Gareth,Wilson, Caroline
-
supporting information
p. 6582 - 6591
(2013/10/22)
-
- 7-Azaindole-3-acetic acid derivatives: Potent and selective CRTh2 receptor antagonists
-
High throughput screening identified a 7-azaindole-3-acetic acid scaffold as a novel CRTh2 receptor antagonist chemotype, which could be optimised to furnish a highly selective compound with good functional potency for inhibition of human eosinophil shape change in whole blood and oral bioavailability in the rat.
- Sandham, David A.,Adcock, Claire,Bala, Kamlesh,Barker, Lucy,Brown, Zarin,Dubois, Gerald,Budd, David,Cox, Brian,Fairhurst, Robin A.,Furegati, Markus,Leblanc, Catherine,Manini, Jodie,Profit, Rachael,Reilly, John,Stringer, Rowan,Schmidt, Alfred,Turner, Katharine L.,Watson, Simon J.,Willis, Jennifer,Williams, Gareth,Wilson, Caroline
-
scheme or table
p. 4794 - 4798
(2010/05/18)
-
- NEW IMIDAZOLONE DERIVATIVES, PREPARATION THEREOF AS DRUGS, PHARMACEUTICAL COMPOSITIONS, AND USE THEREOF AS PROTEIN KINASE INHIBITORS, IN PARTICULAR CDC7
-
The present invention relates to imidazolone derivatives of formula (I) to methods of preparing such derivatives, intermediates thereto, pharmaceutical compositions comprising such derivatives, and methods of inhibiting protein kinase, and methods of treatment comprising administration of such derivatives.
- -
-
Page/Page column 37
(2009/10/17)
-
- Highly functionalized 7-azaindoles as selective PPARγ modulators
-
A series of highly functionalized 3-aroyl and 3-phenoxy-2-methyl-7-azaindoles have been identified, which are potent selective PPARγ modulators (SPPARγMs). Addition of substituents at the 6-position of the 7-azaindoles improves in vitro potency and pharmacokinetics. 7-Azaindoles have significantly improved off-target profiles compared to the parent indole series.
- Debenham, Sheryl D.,Chan, Audrey,Lau, Fiona WaiYu,Liu, Weiguo,Wood, Harold B.,Lemme, Karen,Colwell, Lawrence,Habulihaz, Bahanu,Akiyama, Taro E.,Einstein, Monica,Doebber, Thomas W.,Sharma, Neelam,Wang, Chaunlin F.,Wu, Margaret,Berger, Joel P.,Meinke, Peter T.
-
supporting information; experimental part
p. 4798 - 4801
(2009/06/17)
-
- NOVEL HETEROARYL DERIVATIVE
-
A compound of the following formula (1), or its prodrug or pharmaceutically acceptable salt thereof, being useful as a diabetic medicine or preventive, or blood sugar regulator, or therapeutic agent for hyperlipemia, etc. wherein the ring Z is an optionally substituted heteroaryl, W4 is a single bond, lower alkylene, etc., Ar2 is an optionally substituted aryl, etc., W3 is a single bond, lower alkylene, etc., Ar1 is an optionally substituted arylene, etc., each of W1 and W2 is an optionally substituted lower alkylene, etc., and R1 is carboxyl, an alkoxycarbonyl.
- -
-
-
- NOVEL HETEROARYL DERIVATIVE
-
A compound of the following formula (1), or its prodrug or pharmaceutically acceptable salt thereof, being useful as a diabetic medicine or preventive, or blood sugar regulator, or therapeutic agent for hyperlipemia, etc. (1) wherein: the ring Z is an optionally substituted heteroaryl, W4 is a single bond, lower alkylene, etc., Ar2 is an optionally substituted aryl, etc., W3 is a single bond, lower alkylene, etc., Ar1 is an optionally substituted arylene, etc., each of W1 and W2 is an optionally substituted lower alkylene, etc., and R1 is carboxyl, an alkoxycarbonyl, etc.
- -
-
Page/Page column 70
(2008/06/13)
-
- Chemical synthesis of azaindoles
-
The present invention relates to a process for the preparation of azaindole derivatives of the formula STR1 wherein Q is hydrogen, C1-6 alkyl, C2-6 alkenyl, C1-6 alkoxy, hydroxy, aryl or arylC1-4 alkyl; one of X, Y and Z is --N= and the others are --CH=; R1 is hydrogen, C1-6 alkyl, C2-6 alkenyl or C1-6 alkyl substituted by a group selected from aryl or --NR2 R3 where R2 and R3 each independently represent C1-4 alkyl, or R2 and R3, together with the nitrogen atom to which they are attached, form a 4-7 membered saturated heterocyclic ring, optionally containing in the ring an oxygen or sulphur atom or a group NR4 where R4 is C1-4 alkyl, aryl or arylC1-4 alkyl; and R5 is a hydrogen atom or a group selected from C1-6 alkyl or aryl.
- -
-
-
- A convenient method for the preparation of 5-, 6- and 7-azaindoles and their derivatives
-
The directed ortho lithiation of 2-tert-butoxycarbonylamino-3-methylpyridine (6a) has provided a convenient method for the preparation of 1H-pyrrolo[2,3-b]pyridine (4a, 7-azaindole). This procedure has been used to prepare a range of 3-substituted 2-tert-butoxycarbonylaminopyridines 6, 2- and 3-substituted and 2,3-disubstituted 1H-pyrrolo[2,3-b]pyridines 4 and shown to be of value in the preparation of 1H-pyrrolo[3,2-c]pyridine (15, 5-azaindole) and 1H-pyrrolo[2,3-c]pyridine (18, 6-azaindole) and derivatives.
- Hands, David,Bishop, Brian,Cameron, Mark,Edwards, John S.,Cottrell, Ian F.,Wright, Stanley H. B.
-
p. 877 - 882
(2007/10/03)
-
- Metalation/SRN1 Coupling in Heterocyclic Synthesis. A Convenient Methodology for Ring Functionalization
-
Lithiation, iodination, and fluorine substitution on 2-fluoropyridine gave 2-substituted 3-iodopyridines, which were further subjected to iodine SRN1 substitution by carbon, sulfur, and phosphorus nucleophiles.Iodine substitution by enolates on 2-amino-3-iodopyridines afforded ketones, which were further cyclized to various 1,2-disubstituted pyrrolopyridines. 2-Amino-3-iodo-, 3-amino-4-iodo, and 4-amino-3-iodopyridines were prepared by directed metalation of 2-, 3-, and 4-(pivaloylamino)pyridines.Substitution of iodine by enolates under SRN1 conditions and acidic cyclization led to various 2-substituted pyrrolo, --, and -pyridines in high yields.
- Estel, L.,Marsais, F.,Queguiner, G.
-
p. 2740 - 2744
(2007/10/02)
-