- Synthesis method of 1, 3-dimethyl-1H-pyrazole-4-carboxylic acid
-
The invention relates to a synthesis method of 1, 3-dimethyl-1H-pyrazole-4-carboxylic acid, and the method comprises the following steps: 1, carrying out condensation reaction on N, N-dimethylamino ethyl acrylate, triethylamine and acetyl chloride to generate ethyl 2-dimethylamino-3-oxobutyrate and triethylamine hydrochloride; 2, carrying out a cyclization reaction on 2-dimethylamino ethyl-3-oxobutyrate and methylhydrazine to generate 1, 3-dimethyl-1H-pyrazole ethyl-4-formate and a dimethylamine aqueous solution; 3, carrying out a reaction on formic acid, ethyl acetoacetate and dimethylamine generated in the step 2 cyclization reaction to generate 2-dimethylamino ethyl-3-oxobutyrate and water, wherein the ethyl 2-dimethylamino-3-oxobutyrate generated in the step 3 is recycled as a reactantin the step 2; 4, hydrolyzing the ethyl 1, 3-dimethyl-1H-pyrazole-4-formate to obtain the 1, 3-dimethyl-1H-pyrazole-4-carboxylic acid. The 1, 3-dimethyl-1H-pyrazole-4-carboxylic acid has the advantages of few synthesis steps, safe reaction process and no three-waste pollution, and is suitable for industrial batch large-scale preparation.
- -
-
Paragraph 0025; 0032; 0037
(2021/03/13)
-
- INDAZOLES AND AZAINDAZOLES AS LRRK2 INHIBITORS
-
The present invention is directed to indazole and azaindazole compounds which are inhibitors of LRRK2 and are useful in the treatment of CNS disorders.
- -
-
Page/Page column 347
(2021/01/29)
-
- Deconstructing Noncovalent Kelch-like ECH-Associated Protein 1 (Keap1) Inhibitors into Fragments to Reconstruct New Potent Compounds
-
Targeting the protein-protein interaction (PPI) between nuclear factor erythroid 2-related factor 2 (Nrf2) and Kelch-like ECH-associated protein 1 (Keap1) is a potential therapeutic strategy to control diseases involving oxidative stress. Here, six classes of known small-molecule Keap1-Nrf2 PPI inhibitors were dissected into 77 fragments in a fragment-based deconstruction reconstruction (FBDR) study and tested in four orthogonal assays. This gave 17 fragment hits of which six were shown by X-ray crystallography to bind in the Keap1 Kelch binding pocket. Two hits were merged into compound 8 with a 220-380-fold stronger affinity (Ki = 16 μM) relative to the parent fragments. Systematic optimization resulted in several novel analogues with Ki values of 0.04-0.5 μM, binding modes determined by X-ray crystallography, and enhanced microsomal stability. This demonstrates how FBDR can be used to find new fragment hits, elucidate important ligand-protein interactions, and identify new potent inhibitors of the Keap1-Nrf2 PPI.
- Pallesen, Jakob S.,Narayanan, Dilip,Tran, Kim T.,Solbak, Sara M. ?.,Marseglia, Giuseppe,S?rensen, Louis M. E.,H?j, Lars J.,Munafò, Federico,Carmona, Rosa M. C.,Garcia, Anthony D.,Desu, Haritha L.,Brambilla, Roberta,Johansen, Tommy N.,Popowicz, Grzegorz M.,Sattler, Michael,Gajhede, Michael,Bach, Anders
-
p. 4623 - 4661
(2021/05/07)
-
- Design, Synthesis, In Silico Docking Studies, and Antibacterial Activity of Some Thiadiazines and 1,2,4-Triazole-3-Thiones Bearing Pyrazole Moiety
-
Abstract: In view of developing new bioactive compounds, a series of 6-(substituted-phenyl)-3-(5-methyl-1-phenyl-1H-pyrazol-4-yl)-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazines and 4-[(substituted-benzylidene)amino]-5-(5-methyl-1-phenyl-1H-pyrazol-4-yl)-2,4-dihydro-3H-1,2,4-triazole-3-thiones were synthesized in good yields. The compounds were confirmed by elemental analyses, mass spectrometry, FT-IR, 1H, and 13CNMR spectroscopy. To study the binding interactions of the derivatives with the receptor, they were docked with the prostaglandin D2 synthase (PGDS). The docking pose and non-covalent interactions gave insights into their plausible inhibitory action. They showed good antibacterial activity against Staphylococcus aureus, Enterococcus faecalis, Escherichia coli, and Pseudomonas aeruginosa. Particularly, chloro, fluoro, dimethoxy, and dihydroxy substituted derivatives displayed good activity over other derivatives.
- Nayak, Soukhyarani Gopal,Poojary, Boja
-
-
- Fused tetracyclic compounds and application thereof in medicines
-
The invention relates to fused tetracyclic compounds and an application thereof in medicines, and in particular, relates to the application of the fused tetracyclic compounds as medicines for treatingand/or preventing hepatitis B. Specifically, the invention relates to the compounds represented by a general formula (I) or stereoisomers, tautomers, nitrogen oxides, solvates, metabolites, pharmaceutically acceptable salts or prodrugs thereof, wherein the variables are defined in the specification. The invention further relates to the application of the compounds represented by the general formula (I) or the stereoisomers, the tautomers, the nitric oxides, the solvates, the metabolites, the pharmaceutically acceptable salts or the prodrugs thereof as medicines, and in particular, relates tothe application of the compounds as the medicines for treating and/or preventing hepatitis B.
- -
-
Paragraph 0512; 0530-0532
(2020/04/17)
-
- Preparation method of (by machine translation)
-
The invention relates to a novel process for preparing flutamipide by using a pharmaceutical active pharmaceutical ingredient, wherein ethyl acetoacetate is taken as a raw material and mixed with hydroxylamine hydrochloride to obtain fluticide. The process not only can better control the content of 3 - methyl isomers and 4 - trifluoromethylaniline in the baflunomide product, and is higher in yield and more concise. The industrial wastewater generated by the process is less in waste gas, environmentally friendly, capable of effectively reducing production cost and corrosion to equipment. (by machine translation)
- -
-
Paragraph 0025; 0027; 0029; 0031; 0033; 0035; 0037
(2020/06/24)
-
- Novel N-thioamide analogues of pyrazolylpyrimidine based piperazine: Design, synthesis, characterization, in-silico molecular docking study and biological evaluation
-
Utilizing molecular hybridization approach, a progression of novel pyrazolylpyrimidine based N-thioamide derivatives of piperazine were identified in an effort to develop newer antibacterial and antitubercular agents against the cumulative bacterial resistance. Spectral analysis using Mass, 1H NMR and 13C NMR spectral techniques have been studied in order to affirm the structure of synthesized end molecules. Biological evaluation of all synthesized molecules were studied in-vitro for their antibacterial, antituberculosis and antimalarial efficacy against various bacterial and fungal strains, H37Rv and Plasmodium falciparum respectively. Molecular docking and ADME properties prediction study were also carried out for better insights of responsible proteins with the synthesized molecules. Interestingly, some of the pyrazolylpyrimidine based piperazine N-thioamide derivatives exhibited potential antibacterial, antifungal and antimalarial potency.
- Vekariya, Mayur K.,Patel, Dhaval B.,Pandya, Pranav A.,Vekariya, Rajesh H.,Shah, Prapti U.,Rajani, Dhanji P.,Shah, Nisha K.
-
p. 551 - 565
(2018/09/18)
-
- Polysubstituted thieno[2,3-b]pyridine derivatives, and preparation method and application thereof
-
The invention discloses polysubstituted thieno[2,3-b]pyridine derivatives, and a preparation method and an application thereof. The structural formula of the derivatives are represented by formula I shown in the description. A compound for inhibiting a urea transporter is screened by using an erythrocyte model. Experimental results show that the compounds (represented by formula I-1) can inhibit the permeation of a urea transporter UT-B mediated erythrocyte membrane to urea, and the effect of the compounds has a dose-dependent relationship; the compounds represented by the formula I-1 have nocytotoxic effect on MDCK cells within an effective dose range, so the effect of the compounds represented by the formula I-1 on inhibiting cell permeation urea is irrelevant to the cytotoxicity of thecompounds; the inhibition effect of the compounds represented by the formula I-1 on the urea transporter UT-B is gradually enhanced; the inhibiting effect of the compounds represented by the formulaI-1 on the UT-B is reversible; and in-vivo test results show that the compounds represented by the formula I-1 can significantly increase the urination volume of rats, reduce the concentration of ureain rat urine and reduce the osmotic pressure, so that the compounds represented by the formula I-1 generate a urea selective diuresis effect in vivo.
- -
-
Paragraph 0117-0119
(2020/01/12)
-
- Pyrazole-4-Carboxamide (YW2065): A Therapeutic Candidate for Colorectal Cancer via Dual Activities of Wnt/β-Catenin Signaling Inhibition and AMP-Activated Protein Kinase (AMPK) Activation
-
Dysregulation of the Wnt/β-catenin signaling pathway has been widely recognized as a pathogenic mechanism for colorectal cancer (CRC). Although numerous Wnt inhibitors have been developed, they commonly suffer from toxicity and unintended effects. Moreover, concerns have been raised in targeting this pathway because of its critical roles in maintaining stem cells and regenerating tissues and organs. On the basis of the anthelmintic drug pyrvinium and previous lead FX1128, we have developed a compound YW2065 (1c) which demonstrated excellent anti-CRC effects in vitro and in vivo. YW2065 achieves its inhibitory activity for Wnt signaling by stabilizing Axin-1, a scaffolding protein that regulates proteasome degradation of β-catenin. Simultaneously, YW2065 also led to the activation of the tumor suppressor AMPK, providing an additional anticancer mechanism. In addition, YW2065 showed favorable pharmacokinetic properties without obvious toxicity. The anti-CRC effect of YW2065 was highlighted by its promising efficacy in a mice xenograft model.
- Yang, Wei,Li, Yingjun,Ai, Yong,Obianom, Obinna N.,Guo, Dong,Yang, Hong,Sakamuru, Srilatha,Xia, Menghang,Shu, Yan,Xue, Fengtian
-
p. 11151 - 11164
(2019/12/27)
-
- 1-(4-(ISOXAZOL-5-YL)-1H-PYRAZOL-1-YL)-2-METHYLPROPAN-2-OL DERIVATIVES AND RELATED COMPOUNDS AS IL-17 AND IFN-GAMMA INHIBITORS FOR TREATING AUTOIMMUNE DISEASES AND CHRONIC INFLAMMATION
-
The present invention relates to compounds of the general formula (I), and the pharmaceutically acceptable salts and solvates thereof, wherein Ar, Z and Y are as described herein and R1 is a group of the structure (formula (II)), wherein n is 0 or 1; R2 is H, deuterium or methyl; R3 is methyl, trilluoromethyl, ethyl, or taken with R2 together forms a cyclopropyl group, or R3 forms a methylene bridge to the carbon atom marked *, which are suitable for the treatment of autoimmune diseases and chronic inflammation.
- -
-
-
- Pyrimidine-based pyrazoles as cyclin-dependent kinase 2 inhibitors: Design, synthesis, and biological evaluation
-
A series of new pyrimidine-pyrazole hybrid molecules were designed as inhibitors of cyclin-dependent kinase 2. Designed compounds were docked using Glide and the compounds showing good score values and encouraging interactions with the residues were selected for synthesis. They were then evaluated using CDK2-CyclinA2 enzyme inhibition by a luminescent ADP detection assay. We show that of the 26 compounds synthesized and evaluated, at least 5 compounds were found to be highly potent (IC50??20?nm); which can be further optimized to have selectivity over other kinase isoforms.
- Vekariya, Mayur K.,Vekariya, Rajesh H.,Brahmkshatriya, Pathik S.,Shah, Nisha K.
-
p. 1683 - 1691
(2018/09/10)
-
- Synthesis, biological evaluation and docking studies of a new series of tris-heterocycles containing pyrazole, triazole and oxadiazole
-
A new series of 3-aryl/hetaryl-6-(5-methyl-l-phenyl-lH-pyrazol-4-yl)-[l,2,4]triazolo[3,4-b][l,3,4]oxadiazoles 7a-j have been synthesized, characterized by spectral means, and evaluated for their antimicrobial and antioxidant properties. Amongst the screened compounds 7a-j, the triazole moiety bearing electron-withdrawing group on the 4th position of phenyl viz. 4-chlorophenyl 7c, 4-nitrophenyl 7f and 2,4-difluorophenyl 7h exhibit excellent antibacterial activity towards all the tested bacteria viz. Staphylococcus aureus. Bacillus licheniformis, Pseudomonas aeruginosa and Escherichia coli. On the other hand, triazole moiety bearing electron-donating group on the 4th position of phenyl viz. 4-hydroxyphenyl 7d, 4-methoxy-phenyl 7e and 4-aminophenyl 7g show prominent antifungal activity towards the tested fungi viz. Candida albicans and Fusarium oxysporum. These results are supported by molecular docking studies and through binding interactions as well. Antioxidant studies reveal that the compounds in which the triazole moiety bearing phenyl 7a, 4-methoxyphenyl 7e, 2,4-difluorophenyl 7h and 3-pyridyl 7j is present on the 4th position, display significant antioxidant "' properties. In brief, most of the newly synthesized compounds have emerged as potential antimicrobial and antioxidant agents for further development.
- Kumar, Gaddam Rajesh,Shankar, Kurre,Reddy, Cherkupally Sanjeeva
-
p. 687 - 699
(2019/05/22)
-
- 3-Aryl-6-formamidopyrazolo[1,5-a]pyrimidine compounds and application thereof
-
The invention belongs to the technical field of medicines, and concretely relates to 3-aryl-6-formamidopyrazolo[1,5-a]pyrimidine compounds and an application thereof. The compounds are six 2,7-dimethyl-3-aryl-6-formamidopyrazolo[1,5-a]pyrimidine compounds prepared by preparing ethyl 2-dimethylaminomethylene-3-oxobutyrate (1) through a reaction of ethyl acetoacetate and N,N-dimethylformamide dimethyl acetal and carrying out cyclization, hydrolysis and amidation on the compound (1) and 3-methyl-4-(2,4-dichlorophenyl)-5-aminopyrazole, and the structure of the compounds is characterized by nuclear magnetic resonance hydrogen spectrum and infrared spectroscopy. A result of detection of the compounds by an MABA method shows that the synthesized compounds have an inhibition effect on Mycobacterium tuberculosis H37Rv. A pharmacological activity screening detection result shows that parts of the compounds have a very good inhibition effect on the Mycobacterium tuberculosis H37Rv and Mycobacterium phlei M. phlei1180, and has good anti-tuberculosis exploitation and application prospect.
- -
-
Paragraph 0017; 0018; 0019; 0020; 0021
(2017/07/20)
-
- Simple access toward 3-halo- and 3-nitro-pyrazolo[1,5-a] pyrimidines through a one-pot sequence
-
Herein, a regioselective, time-efficient and one-pot route for the synthesis of diversely substituted 3-halo- and 3-nitropyrazolo[1,5-a]pyrimidines in good to excellent yields through a microwave-assisted process is provided. The reaction features a sequential cyclocondensation reaction of β-enaminones with NH-5-aminopyrazoles, followed by a regioselective electrophilic substitution with easily available electrophilic reagents. This methodology is distinguished by its short reaction times, high-yield, operational simplicity, broad substrate scope and pot-economy. Furthermore, these 3-functionalized heterocycles have been successfully used in the synthesis of 3-alkynyl and 3-aminopyrazolo[1,5-a]pyrimidines in yields up to 92%.
- Castillo, Juan-Carlos,Rosero, Hernán-Alejandro,Portilla, Jaime
-
p. 28483 - 28488
(2017/07/07)
-
- cGAS ANTAGONIST COMPOUNDS
-
Disclosed are novel compounds of Formula (I) that are cGAS antagonists, methods of preparation of the compounds, pharmaceutical compositions comprising the compounds, and their use in medical therapy.
- -
-
Paragraph 0271
(2017/11/06)
-
- Design, synthesis, and pharmacological studies of some new Mannich bases and S-alkylated analogs of pyrazole integrated 1,3,4-oxadiazole
-
A facile and convenient synthesis of Mannich bases 5a-f and S-alkylated derivatives 6a-f and 7a-f has been carried out from the key intermediate 5-(5-methyl-1-phenyl-1H-pyrazol-4-yl)-1,3,4-oxadiazole-2(3H)-thione (4). Intermediate 4 was obtained from one-pot reaction of ethyl acetoacetate, phenylhydrazine, and N,N-dimethylformamide dimethyl acetal (DMF-DMA) followed by reaction with hydrazine hydrate and carbon disulfide. The structure of the newly synthesized compounds was established on the basis of elemental analysis, infrared (IR), 1H nuclear magnetic resonance (NMR), 13C NMR, and mass spectroscopic data. All synthesized compounds were screened for in vivo antiinflammatory, in vivo analgesic, and in vitro antimicrobial activity. From the activity studies, it was concluded that, among all the derivatives, compounds 5c, 5e, 5f, 6c, 7b, and 7c showed potent antiinflammatory activity, whereas 5b, 5c, 5e, 5f, 6c, 6f, 7b, 7c, and 7e exhibited good analgesic activity. Compounds 6a, 6c, 7b, 7c, and 7d showed maximum activity against the bacterial strains. Efforts were also made to establish structure-activity relationships among the tested compounds.
- Viveka, Shivapura,Dinesha,Shama, Prasanna,Nagaraja, Gundibasappa Karikannar,Deepa, Nagaraju,Sreenivasa, Marikunte Yanjarappa
-
p. 2597 - 2617
(2016/03/16)
-
- A facile, regioselective synthesis of pyrazolo[1, 5-a]pyrimidine analogs in the presence of KHSO4 in aqueous media assisted by ultrasound and their anti-inflammatory and anti-cancer activities
-
Abstract: An environmentally benign, simple, efficient, and convenient route is described for the synthesis of novel pyrazolo[1,5-a]pyrimidine derivatives under ultrasound irradiation assisted by KHSO4 in aqueous medium. 3-(4-Methoxyphenyl)-3-o
- Kaping, Shunan,Kalita, Utpalparna,Sunn, Melboureen,Singha, Laishram Indira,Vishwakarma, Jai Narain
-
p. 1257 - 1276
(2016/07/30)
-
- N -[6-(4-Butanoyl-5-methyl-1 H -pyrazol-1-yl)pyridazin-3-yl]-5-chloro-1-[2-(4-methylpiperazin-1-yl)-2-oxoethyl]-1 H -indole-3-carboxamide (SAR216471), a Novel Intravenous and Oral, Reversible, and Directly Acting P2Y12 Antagonist
-
In the search of a potential backup for clopidogrel, we have initiated a HTS campaign designed to identify novel reversible P2Y12 antagonists. Starting from a hit with low micromolar binding activity, we report here the main steps of the optimization process leading to the identification of the preclinical candidate SAR216471. It is a potent, highly selective, and reversible P2Y12 receptor antagonist and by far the most potent inhibitor of ADP-induced platelet aggregation among the P2Y12 antagonists described in the literature. SAR216471 displays potent in vivo antiplatelet and antithrombotic activities and has the potential to differentiate from other antiplatelet agents.
- Boldron, Christophe,Besse, Angélina,Bordes, Marie-Fran?oise,Tissandié, Stéphanie,Yvon, Xavier,Gau, Benjamin,Badorc, Alain,Rousseaux, Tristan,Barré, Guillaume,Meneyrol, Jér?me,Zech, Gernot,Nazare, Marc,Fossey, Valérie,Pflieger, Anne-Marie,Bonnet-Lignon, Sandrine,Millet, Laurence,Briot, Christophe,Dol, Frédérique,Hérault, Jean-Pascal,Savi, Pierre,Lassalle, Gilbert,Delesque, Nathalie,Herbert, Jean-Marc,Bono, Fran?oise
-
supporting information
p. 7293 - 7316
(2015/01/08)
-
- PROCESS FOR PREPARING COMPOUND HAVING HIV INTEGRASE INHIBITORY ACTIVITY
-
A process for preparing a compound represented by formula (Y1) or (Y2) [wherein Rx is an optionally substituted carbocyclyl lower alkyl, or the like] or a salt thereof, using a novel process for preparing a pyridone derivative represented by formula (X4) [wherein R1d is hydrogen, halogen, or the like; R2d is hydrogen, a lower alkyl optionally substituted with substituent E, or the like; R4d is a lower alkyl optionally substituted with substituent E, or the like; and R6d is a lower alkyl group optionally substituted with substituent group E, or the like].
- -
-
Paragraph 0141
(2013/06/27)
-
- Development of a Multi-Kilogram-Scale Synthesis of AZD1283: A Selective and Reversible Antagonist of the P2Y12 Receptor
-
Ethyl 6-chloro-5-cyano-2-methylnicotinate (4) was coupled with 4-piperidinecarboxylic acid (isonipecotic acid) in 81% yield to pyridine acid 10. An amide coupling between 10 and benzylsulfonamide (6) afforded AZD1283 (1) in 79% yield using CDI as coupling reagent. The synthesis has been developed and scaled up to 20 kg batches of 1, supporting preclinical and clinical studies. Development work towards 2-chloropyridine 4 and benzylsulfonamide (6) is included.
- Andersen, Soren M.,Aurell, Carl-Johan,Zetterberg, Fredrik,Bollmark, Martin,Ehrl, Robert,Schuisky, Peter,Witt, Anette
-
supporting information
p. 1543 - 1551
(2014/01/06)
-
- 4-Oxo-1,4-dihydropyridines as selective CB2 cannabinoid receptor ligands part 2: Discovery of new agonists endowed with protective effect against experimental colitis
-
Further on to our earlier work on the 4-oxo-1,4-dihydropyridine, we describe herein our strategy to get access to potent selective CB2 receptor agonists. Thus, we designed and synthesized 29 compounds, evaluated on both hCB1 and hCB
- El Bakali, Jamal,Gilleron, Pauline,Mansouri, Roxane,Barczyk, Amelie,Klupsch, Frederique,Andrzejak, Virginie,Chavatte, Philippe,Millet, Regis,Body-Malapel, Mathilde,Djouina, Madjid,Desreumaux, Pierre,Muccioli, Giulio G.,Lambert, Didier M.,Lipka, Emmanuelle,Furman, Christophe
-
supporting information
p. 8948 - 8952,5
(2020/09/16)
-
- METHOD OF PRODUCING PYRONE AND PYRIDONE DERIVATIVES
-
The present invention provides a pyrone derivative and a pyridone derivative, which are novel intermediates for synthesizing an anti-influenza drug, a method of producing the same, and a method of using the same.
- -
-
Page/Page column 27
(2012/02/03)
-
- Optimisation of pharmacokinetic properties in a neutral series of 11β-HSD1 inhibitors
-
11β-HSD1 is increasingly seen as an attractive target for the treatment of type II diabetes and other elements of the metabolic syndrome. In this program of work we describe how a series of neutral 2-thioalkyl-pyridine 11β-HSD1 inhibitors were optimized in terms of their pharmacokinetic properties to give compounds with excellent bioavailability in both rat and dog through a core change to pyrimidine. A potential reactive metabolite issue with 4-thioalkyl-pyrimidines was circumvented by a switch from sulfur to carbon substitution.
- Scott, James S.,Gill, Adrian L.,Godfrey, Linda,Groombridge, Sam D.,Rees, Amanda,Revill, John,Schofield, Paul,S?rme, Pernilla,Stocker, Andrew,Swales, John G.,Whittamore, Paul R.O.
-
p. 6756 - 6761
(2013/01/14)
-
- Development of a practical synthesis of a functionalized pyrrolo[2,1-f][1,2,4]triazine nucleus
-
Functionalized pyrrolotriazine 1b is a key heterocyclic building block in the synthesis of BMS-690514, a potent anticancer agent. Described herein are our development activities that led to the efficient preparation of 1b on a large scale. The key transformations include a selective C-alkylation of an oxalacetate salt with a hydrazonyl bromide to form a 2-hydrazonoethyl-3- oxosuccinate, followed by cyclodehydration to an aminopyrrole. Subsequent deprotection and condensation with formamidine afforded the pyrrolotriazine scaffold. Further elaboration of this core provided the desired pyrrolotriazinyl amine.
- Zheng, Bin,Conlon, David A.,Corbett, R. Michael,Chau, Melissa,Hsieh, Dau-Ming,Yeboah, Agnes,Hsieh, Daniel,Mueslehiddinoglu, Jale,Gallagher, William P.,Simon, Jeffrey N.,Burt, Justin
-
p. 1846 - 1853
(2013/01/15)
-
- Development of a practical synthesis of a p38 kinase inhibitor via a safe and robust amination
-
The development of a practical synthesis for a p38 kinase inhibitor is described. The key advances include an improved route to the key intermediate, a substituted pyrrole, and a subsequent animation utilizing O-(4-nitrobenzoyl)- hydroxylamine, which provides a safe, scalable, and robust amination method. The new protocol was successfully demonstrated to generate 1.6 kg of API in seven steps and 26% overall yield.
- Shi, Zhongping,Kiau, Susanne,Lobben, Paul,Hynes Jr., John,Wu, Hong,Parlanti, Luca,Discordia, Robert,Doubleday, Wendel W.,Leftheris, Katerina,Dyckman, Alaric J.,Wrobleski, Stephen T.,Dambalas, Konstantinos,Tummala, Srinivas,Leung, Simon,Lo, Ehrlic
-
p. 1618 - 1625
(2013/02/23)
-
- The 14C, 13C, and 15N syntheses of a potent VEGFR-2 kinase inhibitor, Brivanib, and its prodrug, Brivanib Alaninate
-
The interruption of tyrosine kinase vascular endothelial growth factor receptor-2 (VEGFR-2) signaling by the binding of a small molecule inhibitor, for example, Brivanib, to VEGFR-2 kinase domain has been shown as an effective method of slowing angiogenes
- Tran, Scott B.,Lago, Michael W.,Tian, Yuan,Gong, Sharon X.,Batra, Indu,Allentoff, Alban J.,Maxwell, Brad D.,Bonacorsi, Samuel J.,Ogan, Marc,Rinehart, J. Kent,Balasubramanian, Balu
-
scheme or table
p. 324 - 331
(2012/06/04)
-
- PYRAZOLE DERIVATIVES AS MODULATORS OF CALCIUM RELEASE -ACTIVATED CALCIUM CHANNEL
-
Disclosed are novel calcium release-activated calcium (CRAC) channel inhibitors, methods for preparing them, pharmaceutical compositions containing them, and methods of treatment using them. The present disclosure also relates to methods for treating non-small cell lung cancer (NSCLC) with CRAC inhibitors, and to methods for identifying therapeutics for treating and of diagnosing cancer.
- -
-
Page/Page column 69
(2011/04/26)
-
- 1,4 DIHYDROPYRIDINE DERIVATIVES AND THEIR USES
-
The present invention relates to 1,4-dihydropyridine derivatives of the formula (I) and their uses in the treatment and/or prevention of diseases and disorders directly or indirectly associated with the modification (increase or decrease) of the activity
- -
-
Page/Page column 27
(2010/12/18)
-
- 4-oxo-1,4-dihydropyridines as selective CB2 cannabinoid receptor ligands: Structural insights into the design of a novel inverse agonist series
-
Growing evidence shows that CB2 receptor is an attractive therapeutic target. Starting from a series of 4-oxo-1,4-dihydroquinoline-3- carboxamide as selective CB2 agonists, we describe here the medicinal chemistry approach leading to
- El Bakali, Jamal,Muccioli, Giulio G.,Renault, Nicolas,Pradal, Delphine,Body-Malapel, Mathilde,Djouina, Madjid,Hamtiaux, Laurie,Andrzejak, Virginie,Desreumaux, Pierre,Chavatte, Philippe,Lambert, Didier M.,Millet, Régis
-
scheme or table
p. 7918 - 7931
(2011/03/19)
-
- 2-AMINO-6-ALKYL SUBSTITUTED PYRIDINE DERIVATIVES USEFUL AS P2Y12 INHIBITORS 308
-
The present invention relates to certain new pyridin analogues of Formula ( I ) to processes for preparing such compounds, to their utility as P2Y12 inhibitors and as anti-trombotic agents etc, their use as medicaments in cardiovascular disease
- -
-
Page/Page column 77; 85
(2010/04/03)
-
- 5-HT7 RECEPTOR ANTAGONISTS
-
The present invention provides selective 5-HT7 receptor antagonist compounds of Formula I and their use in the treatment of migraine: where A is C(H)= or -N= and R1-7 are as defined herein.
- -
-
Page/Page column 13
(2009/05/28)
-
- Design and synthesis of 6-oxo-1,6-dihydropyridines as CDK5 inhibitors
-
Cyclin-dependent kinase 5 (CDK5) is a serine-threonine protein kinase that plays a significant role in neuronal development. In association with p25, CDK5 abnormally phosphorylates a number of cellular targets involved in neurodegenerative disorders. Usin
- Kaller, Matthew R.,Zhong, Wenge,Henley, Charles,Magal, Ella,Nguyen, Thomas,Powers, David,Rzasa, Robert M.,Wang, Weiya,Xiong, Xiaoling,Norman, Mark H.
-
scheme or table
p. 6591 - 6594
(2010/05/18)
-
- New Pyridine Analogues IV
-
The present invention relates to certain new pyridin analogues of Formula (I) to processes for preparing such compounds, to their utility as P2Y12 inhibitors and as anti-trombotic agents etc, their use as medicaments in cardiovascular diseases
- -
-
Page/Page column 18; 19
(2008/06/13)
-
- NEW PYRIDINE ANALOGUES
-
The present invention relates to certain new pyridin analogues of Formula ( I ) to processes for preparing such compounds, to their utility as P2Y12 inhibitors and as anti-trombotic agents etc, their use as medicaments in cardiovascular disease
- -
-
Page/Page column 59
(2008/06/13)
-
- NEW PYRIDINE ANALOGUES
-
The present invention relates to certain new pyridin analogues of Formula ( I ) to processes for preparing such compounds, to their utility as P2Y12 inhibitors and as anti-trombotic agents etc, their use as medicaments in cardiovascular disease
- -
-
Page/Page column 56
(2010/11/29)
-
- 2-[4-(PYRAZOL-4-YLALKYL)PIPERAZIN-1-YL]-3-PHENYL PYRAZINES AND PYRIDINES AND 3-[4-(PYRAZOL-4-YLALKYL)PIPERAZIN-1-YL]-2-PHENYL PYRIDINES AS 5-HT7 RECEPTOR ANTAGONISTS
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The present invention provides selective 5-HT7 receptor antagonist compounds of Formula I and their use in the treatment of migraine, persistent pain, and anxiety: where A and B are each independently C(H)= or N=, provided that at least one of A and B is -N=, n is 1-3, m is 0-3, and R14 are as defined herein.
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Page/Page column 59
(2009/01/20)
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- New Pyridine Analogues VII 543
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The present invention relates to certain new pyridin analogues of Formula (I) to processes for preparing such compounds, to their utility as P2Y12 inhibitors and as anti-trombotic agents etc, their use as medicaments in cardiovascular diseases
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Page/Page column 18
(2008/12/07)
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- NEW PYRIDINE ANALOGUES VIII 518
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The present invention relates to certain new pyridin analogues of Formula ( I ) to processes for preparing such compounds, to their utility as P2Y12 inhibitors and as anti-trombotic agents etc, their use as medicaments in cardiovascular diseases as well as pharmaceutical compositions containing them.
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Page/Page column 103
(2008/12/07)
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- NEW PYRIDINE ANALOGUES II
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The present invention relates to certain new pyridin analogues of Formula (I) to processes for preparing such compounds, to their utility in medicine in general and especially as P2Y12 inhibitors and as anti-thrombotic agents, etc, their use as medicaments in cardiovascular diseases as well as pharmaceutical compositions containing them.
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Page/Page column 38
(2008/06/13)
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- NEW PYRIDINE ANALOGUES
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The present invention relates to certain new pyridin analogues of Formula (I) Chemical formula should be inserted here. Please see paper copy Formula (I) to processes for preparing such compounds, to their utility as P2Y12 inhibitors and as anti-trombotic agents etc, their use as medicaments in cardiovascular diseases as well as pharmaceutical compositions containing them.
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Page/Page column 86
(2008/06/13)
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- NOVEL PYRIDINE COMPOUNDS
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The present invention relates to certain novel pyridin compounds of Formula ( I ) to processes for preparing such compounds, to their utility as P2Y12 inhibitors and as anti-trombotic agents etc, and processes for their preparation, their use as medicaments in cardiovascular diseases as well as pharmaceutical compositions containing them.
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Page/Page column 147
(2008/06/13)
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- Ramoplanin derivatives possessing antibacterial activity
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Novel ramoplanin derivatives are disclosed. These ramoplanin derivatives exhibit antibacterial activity. As the compounds of the subject invention exhibit potent activities against gram positive bacteria, they are useful antimicrobial agents. Methods of synthesis and of use of the compounds are also disclosed.
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Page/Page column 80-81
(2010/11/23)
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- NOVEL COMPOUNDS AS AGONIST FOR PPAR GAMMA AND PPAR ALPHA, METHOD FOR PREPARATION OF THE SAME, AND PHARMACEUTICAL COMPOSITION CONTAINING THE SAME
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The present invention relates to novel compounds accelerating the activity of Peroxisome proliferator-activated receptor gamma (PPARγ) and alpha (PPARα), processes of preparing the same, and pharmaceutical compositions containing the same as an active agent.
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Page/Page column 33
(2010/02/11)
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- Pyrazole-amides and sulfonamides as sodium channel modulators
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Compounds of the present invention modulate PN3 in mammals and are useful in treating pain in mammals.
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Page/Page column 14
(2010/02/10)
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- Pyrid-2-one derivatives and methods of use
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Selected compounds are effective for treatment of diseases, such as cell proliferation or apoptosis mediated diseases. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable derivatives thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving stroke, cancer and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.
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- Pyrazole-amides and sulfonamides as sodium channel modulators
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Compounds of the present invention modulate PN3 in mammals and are useful in treating pain in mammals.
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- JNK INHIBITOR
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The present invention relates to a c-Jun N-terminal kinase inhibitor containing an azole compound (I) substituted by a nitrogen-containing aromatic group having substituent(s)(except a compound represented by the formula: ) or a salt thereof or a prodrug thereof.
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Page/Page column 100
(2010/02/07)
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- A facile synthesis of 2,2-disubstituted 5-carbethoxy-2,3-dyhydro-4H-pyran-4-ones
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A facile synthesis of 5-carbethoxy-2,3-dihydropyran-4-ones is described via the condensation of ethyl 2-formyl-3-oxobutanoate with various ketones.
- Totah, Nancy I.,Chen, Deqi
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p. 213 - 216
(2007/10/03)
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- 2-Benzoyl-2-ethoxycarbonylvinyl-l and 2-Benzoylamino-2-methoxy-carbonylvinyl-1 as N-Protecting Groups in Peptide Synthesis. Their Application in the Synthesis of Dehydropeptide Derivatives Containing N-Terminal 3-Heteroarylamino-2,3-dehydroalanine
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Ethyl 2-benzoyl-3-dimethylaminopropenoate (6) and methyl 2-benzoylamino-3-dimethylaminopropenoate (46) were used as reagents for the protection of the amino group with 2-benzoyl-2-ethoxycarbonylvinyl-1 and 2-benzoylamino-2-methoxycarbonylvinyl groups in t
- Svete, Jurij,Aljaz-Rozic, Mateja,Stanovnik, Branko
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p. 177 - 193
(2007/10/03)
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- Herbicidal derivatives of 2-(1-aryl-4-cyano-5-pyrazolylmethyleneiminooxy)alkanoic acids
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Herbicidal compounds, compositions containing them, and a method for controlling weeds by application of the compositions are disclosed. The herbicidal compounds are 2-(1-aryl-4-cyano-5-pyrazolylmethyleneiminooxy)alkanoic acid derivatives of the structure
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