62124-77-0Relevant academic research and scientific papers
Optimization of pyrrolamide topoisomerase II inhibitors toward identification of an antibacterial clinical candidate (AZD5099)
Basarab, Gregory S.,Hill, Pamela J.,Garner, C. Edwin,Hull, Ken,Green, Oluyinka,Sherer, Brian A.,Dangel, P. Brian,Manchester, John I.,Bist, Shanta,Hauck, Sheila,Zhou, Fei,Uria-Nickelsen, Maria,Illingworth, Ruth,Alm, Richard,Rooney, Mike,Eakin, Ann E.
supporting information, p. 6060 - 6082 (2014/08/18)
AZD5099 (compound 63) is an antibacterial agent that entered phase 1 clinical trials targeting infections caused by Gram-positive and fastidious Gram-negative bacteria. It was derived from previously reported pyrrolamide antibacterials and a fragment-based approach targeting the ATP binding site of bacterial type II topoisomerases. The program described herein varied a 3-piperidine substituent and incorporated 4-thiazole substituents that form a seven-membered ring intramolecular hydrogen bond with a 5-position carboxylic acid. Improved antibacterial activity and lower in vivo clearances were achieved. The lower clearances were attributed, in part, to reduced recognition by the multidrug resistant transporter Mrp2. Compound 63 showed notable efficacy in a mouse neutropenic Staphylococcus aureus infection model. Resistance frequency versus the drug was low, and reports of clinical resistance due to alteration of the target are few. Hence, 63 could offer a novel treatment for serious issues of resistance to currently used antibacterials.
Simple, fast and efficient synthesis of β-keto esters from the esters of heteroaryl compounds, its antimicrobial study and cytotoxicity towards various cancer cell lines
Venkat Ragavan,Vijayakumar,Rajesh,Palakshi Reddy,Karthikeyan,Suchetha Kumari
supporting information; experimental part, p. 4193 - 4197 (2012/07/14)
A series of β-keto esters were synthesized from heteroaryl esters and ethyl acetate using LiHMDS as base at -50 to -30 °C. The increase in yields of cross condensed product were observed and the percentage of self condensed product was reduced drastically by applying the suitable base (LiHMDS), solvent and the minimum amount of ethyl acetate. All these β-keto esters were characterized using 1H NMR, 13C NMR and mass spectral data. A plausible mechanism is also depicted to prove the formation of trans-esterified products. All the synthesized compounds were subjected to test for their cytotoxicity towards various cancer cell lines and also tested for their antimicrobial activity towards various bacterial and fungal strains and some of them were found to have promising activity.
2- (PIPERIDIN-1-YL) -4-HETEROCYCLYL-THIAZOLE-5-CARBOXYLIC ACID DERIVATIVES AGAINST BACTERIAL INFECTIONS
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Page/Page column 166, (2010/07/02)
Compounds of formula (I) and their pharmaceutically acceptable salts are described. Processes for their preparation, pharmaceutical compositions containing them, their use as medicaments and their use in the treatment of bacterial infections are also described. Ring A is selected from formula (a), (b) or (b'):
PIPERDINE COMPOUNDS AND USES THEREOF-911
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Page/Page column 75, (2009/01/24)
Compounds of formula (I) and their pharmaceutically acceptable salts are described. Processes for their preparation, pharmaceutical compositions containing them, their use as medicaments and their use in the treatment of bacterial infections are also described.
Pyrazolo [1,5-A] pyrimidine adenosine A2a receptor antagonists
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Page/Page column 24, (2008/06/13)
Compounds having the structural formula I are disclosed, wherein A is alkylene, or optionally substituted arylene, cycloalkylene or heteroaryldiyl; X is —C(O)— or —S(O)2—; R1 is alkyl or cycloalkyl; R2 is hydrogen, halo or —CN; R3 is hydrogen or alkyl; R4 is hydrogen, alkyl, alkoxy, hydroxyalkyl, aminoalkyl-, cycloalkyl, heterocycloalkyl, heterocycloalkyl substituted by alkyl, optionally substituted arylalkyl or optionally substituted heteroarylalkyl; or R3 and R4, form an optionally substituted 5-7 membered ring, said ring optionally comprising an additional heteroatom ring member; R7 is alkyl, optionally substituted phenyl, optionally substituted heteroaryl, cycloalkyl, halo, morpholinyl, optionally substituted piperazinyl, or optionally substituted azacycloalkyl. Also disclosed is the use of the compounds in the treatment of Parkinson's disease, alone or in combination with other agents for treating Parkinson's disease, pharmaceutical compositions comprising them and kits comprising the components of the combinations.
2-pyrazolin-5-ones
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Page/Page column 122, (2010/11/08)
Chemical compounds having structural formula I and physiologically acceptable salts thereof, are inhibitors of serine/threonine and tyrosine kinase activity. Several of the tyrosine kinases, whose activity is inhibited by these chemical compounds, are involved in angiogenic processes. Thus, these chemical compounds can ameliorate disease states where angiogenesis or endothelial cell hyperproliferation is a factor. These compounds can be used to treat cancer and hyperproliferative disorders.
TACHYKININ RECEPTOR ANTAGONISTS
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Page 52, (2010/02/10)
The present invention relates to selective NK-1 receptor antagonists of Formula (I) or a pharmaceutically acceptable salt thereof, for the treatment of disorders associated with an excess of tachykinins.
IMMUNO INHIBITORY PYRAZOLONE COMPOUNDS
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Page/Page column 17-18, (2010/02/11)
Compounds of formula (IA) or (IB) are inhibitors of CD80 and useful in immunomodulation therapy: wherein Ar represents an optionally substituted monocyclic or bicyclic aromatic or heteroaromatic group having from 5 to 10 ring atoms; R1 and R2 independently represent H, or Cl-C6 alkyl; R3 represents H; F; CI; Br; -NO2; - CN; C1-C6 alkyl optionally substituted by F or CI; or C1-C6 alkoxy optionally substituted by F; R4 represents a carboxylic acid group (-COOH) or an ester thereof, or -C(=O)NR6R7, -NR7C(=O)R6, -NR7C(=O)OR6, -NHC(=O)NR7R6 or -NHC(=S)NR7R6 wherein R6 represents H, or a radical of formula -(Alk)m-Q wherein m is 0 or 1, Alk is an optionally substituted divalent straight or branched C1-C12 alkylene, or C2-C12 alkenylene, or C2-C12 alkynylene radical or a divalent C3-C12 carbocyclic radical, any of which radicals may be interrupted by one or more -0-, -S- or -N(R8)- radicals wherein R8 represents H or C1-C4 alkyl, C3-C4 alkenyl, C3-C4 alkynyl, or C3-C6 cycloalkyl, and Q represents H; -CF3;-OH; -SH; -NR8R8wherein each R8 may be the same or different, or form a ring when taken together with the nitrogen to which they are attached; an ester group; or an optionally substituted aryl, aryloxy, cycloalkyl, cycloalkenyl or heterocyclic group; and R7 represents H or C1-C6 alkyl; or when taken together with the atom or atoms to which they are attached R6 and R7 form a monocyclic heterocyclic ring having 5, 6 or 7 ring atoms; and X represents a bond or a divalent radical of formula -(Z)n-(Alk)- or -(Alk)-(Z)n- wherein Z represents -0-, -S- or -NH-, Alk is as defined in relation to R6 and n is 0 or 1.
PYRAZOLOPYRIMIDINES AS CYCLIN-DEPENDENT KINASE INHIBITORS
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Page 55, (2008/06/13)
In its many embodiments, the present invention provides a novel class of pyrazolo[1,5-a]pyrimidine compounds as inhibitors of cyclin dependent kinases, methods of preparing such compounds, pharmaceutical compositions containing one or more such compounds, methods of preparing pharmaceutical formulations comprising one or more such compounds, and methods of treatment, prevention, inhibition, or amelioration of one or more diseases associated with the CDKs using such compounds or pharmaceutical compositions.
Beta-ketoester compounds
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Page column 10, (2010/11/30)
The beta-ketoesters of formula I are useful as precursors for organoleptic compounds, especially for flavors, fragrances and masking agents and antimicrobial compounds.
