- An alternate route to 2-amino-3-nitro-5-bromo-4-picoline: Regioselective pyridine synthesis via 2-nitramino-picoline intermediate
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The 2-nitramino functionality in 2-nitramino-4-picoline was successfully exploited not only as a protecting group but also as a directional handle to afford an efficient, atom-economic, and regioselective synthesis of 2-amino-5-bromo-3-nitro-4-picoline (4), a precursor for a drug candidate in development.
- Bhattacharya, Apurba,Purohit, Vikram C.,Deshpande, Prashant,Pullockaran, Annie,Grosso, John A.,DiMarco, John D.,Gougoutas, Jack Z.
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Read Online
- Scalable synthesis and properties of 7-methyl-4-azaindole
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An approach to the synthesis of 7-methyl-4-azaindole, which is a valuable building block for drug discovery programs, is described. The method relies on using a bromine atom as a 'place holding group' for one of the carbon atoms of the pyridine ring throughout the reaction sequence, and it is removed only upon the final reductive cyclization leading to the azaindole ring. Exhaustive hydrogenation of the target product proceeds in a diastereoselective manner and leads to a bicyclic conformationally restricted diamine derivative.
- Subota, Andrii I.,Volochnyuk, Dmitriy M.,Gorlova, Alina O.,Grygorenko, Oleksandr O.
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Read Online
- QUINOXALINE DERIVATIVES AS MODULATORS OF THE GLUCOCORTICOID RECEPTOR
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The present invention relates to compounds according to general formula (I) which act as modulators of the glucocorticoid receptor and can be used in the treatment and/or prophylaxis of disorders which are at least partially mediated by the glucocorticoid receptor.
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Page/Page column 33-34
(2021/07/24)
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- Compound with BRD4 inhibitory activity, preparation method and application thereof
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The invention discloses a compound with BRD4 inhibitory activity, a preparation method and application thereof. The structure of the compound with the BRD4 inhibitory activity is shown as a formula I, and definitions of substituent groups are shown in the specification and claims. The compound provided by the invention has very high bromodomain protein inhibition activity, especially BRD4 targeted inhibition activity, and can be used for treating or/and preventing related diseases mediated by bromodomain protein.
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Paragraph 0252-0257
(2021/04/10)
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- Preparation of the HIV Attachment Inhibitor BMS-663068. Part 1. Evolution of Enabling Strategies
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The development of two enabling routes that led to the production of >1000 kg of BMS-663068 (3) is described. The route identified for the initial 100 kg delivery to support development activities and initial clinical trials involved the conversion of 2-amino-4-picoline to the parent active pharmaceutical ingredient (API), followed by pro-drug installation and deprotection. To eliminate the problematic isolation of the parent API and synthesis of di-t-butyl(chloromethyl)phosphate, a second-generation pro-drug installation route was developed which involved the conversion of a late-stage common intermediate to an N(1)-thioether derivative followed by chloromethylation, displacement with di-t-butylpotassium phosphate, and deprotection. This second strategy resulted in the multikilogram scale preparation of the API in 14 linear steps and ~7% overall yield.
- Fox, Richard J.,Tripp, Jonathan C.,Schultz, Mitchell J.,Payack, Joseph F.,Fanfair, Dayne D.,Mudryk, Boguslaw M.,Murugesan, Saravanababu,Chen, Chung-Pin H.,La Cruz, Thomas E.,Ivy, Sabrina E.,Broxer, Sévrine,Cullen, Ryan,Erdemir, Deniz,Geng, Peng,Xu, Zhongmin,Fritz, Alan,Doubleday, Wendel W.,Conlon, David A.
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p. 1095 - 1109
(2017/08/23)
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- ARYLOAZOL-2-YL CYANOETHYLAMINO COMPOUNDS, METHOD OF MAKING AND METHOD OF USING THEREOF
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The present invention relates to novel aryloazol-2-yl-cyanoethylamino derivatives of formula (I): wherein R3, R4, R5, R6, R7, P, Q, V, W, X, Y, Z and a are as defined in the description, compositions thereof, processes for their preparation and their uses as pesticides.
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Paragraph 0533; 0747
(2014/04/03)
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- SUBSTITUTED 1H-PYRROLOPYRIDINONE DERIVATIVES AS KINASE INHIBITORS
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The present invention provides novel substituted 1H-Pyrrolopyridinone derivatives of formula (1) as protein kinase inhibitors, in which R1, R2, R3, R4, R5, R6 and 'p' have the meanings given in the specification, and pharmaceutically acceptable salts thereof that are useful in the treatment and prevention in diseases or disorder, in particular their use in diseases or disorder where there is an advantage in inhibiting kinase enzyme, more particularly BTK enzyme. The present invention also provides methods for synthesizing and administering the kinase inhibitor compounds. The present invention also provides pharmaceutical formulations comprising at least one of the kinase inhibitor compounds together with a pharmaceutically acceptable carrier, diluent or excipient therefor.
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Page/Page column 38
(2014/09/03)
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- METHODS OF MAKING HIV ATTACHMENT INHIBITOR PRODRUG COMPOUND AND INTERMEDIATES
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A method for making the compound of Formula ( I ) is set forth using alkylation, amidation, chlorination and phosphate installation procedures.
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- IMIDAZOPYRIDIN-2-ONE DERIVATIVES
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A compound represented by formula (I) having mTOR inhibitory activity or a pharmacologically acceptable salt thereof.
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Page/Page column 21
(2011/04/24)
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- Synthesis of a 6-methyl-7-deaza analogue of adenosine that potently inhibits replication of polio and dengue viruses
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Bioisosteric deaza analogues of 6-methyl-9-β-d-ribofuranosylpurine, a hydrophobic analogue of adenosine, were synthesized and evaluated for antiviral activity. Whereas the 1-deaza and 3-deaza analogues were essentially inactive in plaque assays of infectivity, a novel 7-deaza-6-methyl-9-β-d- ribofuranosylpurine analogue, structurally related to the natural product tubercidin, potently inhibited replication of poliovirus (PV) in HeLa cells (IC50 = 11 nM) and dengue virus (DENV) in Vero cells (IC50 = 62 nM). Selectivity against PV over cytotoxic effects to HeLa cells was >100-fold after incubation for 7 h. Mechanistic studies of the 5′-triphosphate of 7-deaza-6-methyl-9-β-d-ribofuranosylpurine revealed that this compound is an efficient substrate of PV RNA-dependent RNA polymerase (RdRP) and is incorporated into RNA mimicking both ATP and GTP.
- Wu, Runzhi,Smidansky, Eric D.,Oh, Hyung Suk,Takhampunya, Ratree,Padmanabhan, Radhakrishnan,Cameron, Craig E.,Peterson, Blake R.
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experimental part
p. 7958 - 7966
(2011/03/19)
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- ENANTIOMERICALLY ENRICHED ARYLOAZOL-2-YL CYANOETHYLAMINO COMPOUNDS, METHOD OF MAKING AND METHOD OF USING THEREOF
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The present invention relates to novel aryloazol-2-yl-cyanoethylamino derivatives substantially enriched in an enantiomer of formula (I): and compounds of formula (IH) wherein R3, R4, R5, R6, R7, R13a, R13b, R14a, R14b, P, Q, V, W, X, Y, Z and a are as defined in the description, compositions thereof, processes for their preparation and their uses as pesticides.
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Page/Page column 84
(2010/06/13)
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- ARYLOAZOL-2-YL CYANOETHYLAMINO COMPOUNDS, METHOD OF MAKING AND METHOD OF USING THEREOF
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The present invention relates to novel aryloazol-2-yl-cyanoethylamino derivatives of formula (I):wherein R3, R4, R5, R6, R7, P, Q, V, W, X, Y, Z and a are as defined in the description, compositions thereof, processes for their preparation and their uses as pesticides.
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Page/Page column 106
(2009/01/20)
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- Method of preparation of nitroaminopyridine compounds
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A method of preparing an intermediate which is useful for the preparation of azaindole derivatives.
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Page/Page column 4
(2008/06/13)
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- Method of preparation of azaindole derivatives
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A method of preparing azaindole compounds for antiviral use having the formula
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Page/Page column 8-9; 10
(2008/06/13)
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- Process for preparing triazole substituted azaindoleoxoacetic piperazine derivatives and novel salt forms produced therein
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A process is provided for preparing triazole substituted azaindoleoxoacetic piperazine derivative. Novel intermediates produced in the above process, and novel N-1 and amorphous forms of a 1,2,3-triazole substituted azaindoloxoacetic piperazine derivatives and processes for producing such novel forms are also provided.
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Page/Page column 28-29
(2008/06/13)
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- Method of producing 2-acyl amino 5-halogenopyridine compounds
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A 2-amino-3-nitro-5-halogenopyridine is formed from a 2-acylaminopyridine by way of a 2-acylamino-5-halogenopyridine. The 2-acetamido-5-bromopyridine may be formed from the 2-acylaminopyridine by way of a 2-acylaminopyridinium-HBr3 salt.
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- Method of producing 2-amino-3-nitro-5-halogenopyridine
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A 2-amino-3-nitro-5-halogenopyridine is formed from a 2-acylaminopyridine by way of a 2-acylamino-5-halogenopyridine. The 2-acetamido-5-bromopyridine may be formed from the 2-acylaminopyridine by way of a 2-acylaminopyridinium-HBr3 salt.
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