3745-79-7Relevant articles and documents
Synthesis of N-trifluoromethyl amides from carboxylic acids
Flavell, Robert R.,Liu, Jianbo,Parker, Matthew F. L.,Toste, F. Dean,Wang, Sinan,Wilson, David M.
supporting information, p. 2245 - 2255 (2021/08/12)
Found in biomolecules, pharmaceuticals, and agrochemicals, amide-containing molecules are ubiquitous in nature, and their derivatization represents a significant methodological goal in fluorine chemistry. Trifluoromethyl amides have emerged as important functional groups frequently found in pharmaceutical compounds. To date, there is no strategy for synthesizing N-trifluoromethyl amides from abundant organic carboxylic acid derivatives, which are ideal starting materials in amide synthesis. Here, we report the synthesis of N-trifluoromethyl amides from carboxylic acid halides and esters under mild conditions via isothiocyanates in the presence of silver fluoride at room temperature. Through this strategy, isothiocyanates are desulfurized with AgF, and then the formed derivative is acylated to afford N-trifluoromethyl amides, including previously inaccessible structures. This method shows broad scope, provides a platform for rapidly generating N-trifluoromethyl amides by virtue of the diversity and availability of both reaction partners, and should find application in the modification of advanced intermediates.
Thiazole carboxamide compound and synthesis and application thereof
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Paragraph 0121-0124, (2019/04/26)
The invention relates to a novel thiazole carboxamide compound. R1, R2, Z, X1, X2, X3, n and m have meanings defined in right claims. The compound has a main inhibiting effect on alpha-glucosidase inhibitor, and can be used for preventing or treating dise
Identification of Phenylpyrazolone Dimers as a New Class of Anti-Trypanosoma cruzi Agents
Sijm, Maarten,Siciliano de Araújo, Julianna,Ramos Llorca, Alba,Orrling, Kristina,Stiny, Lydia,Matheeussen, An,Maes, Louis,de Esch, Iwan J. P.,de Nazaré Correia Soeiro, Maria,Sterk, Geert Jan,Leurs, Rob
supporting information, p. 1662 - 1668 (2019/08/30)
Chagas disease is becoming a worldwide problem; it is currently estimated that over six million people are infected. The two drugs in current use, benznidazole and nifurtimox, require long treatment regimens, show limited efficacy in the chronic phase of infection, and are known to cause adverse effects. Phenotypic screening of an in-house library led to the identification of 2,2′-methylenebis(5-(4-bromophenyl)-4,4-dimethyl-2,4-dihydro-3H-pyrazol-3-one), a phenyldihydropyrazolone dimer, which shows an in vitro pIC50 value of 5.4 against Trypanosoma cruzi. Initial optimization was done by varying substituents of the phenyl ring, after which attempts were made to replace the phenyl ring. Finally, the linker between the dimer units was varied, ultimately leading to 2,2′-methylenebis(5-(3-bromo-4-methoxyphenyl)-4,4-dimethyl-2,4-dihydro-3H-pyrazol-3-one (NPD-0228) as the most potent analogue. NPD-0228 has an in vitro pIC50 value of 6.4 against intracellular amastigotes of T. cruzi and no apparent toxicity against the human MRC-5 cell line and murine cardiac cells.
Urea Derivatives of 2-Aryl-benzothiazol-5-amines: A New Class of Potential Drugs for Human African Trypanosomiasis
Patrick, Donald A.,Gillespie, J. Robert,McQueen, Joshua,Hulverson, Matthew A.,Ranade, Ranae M.,Creason, Sharon A.,Herbst, Zackary M.,Gelb, Michael H.,Buckner, Frederick S.,Tidwell, Richard R.
supporting information, p. 957 - 971 (2017/02/19)
A previous publication from this lab (Patrick, et al. Bioorg. Med. Chem. 2016, 24, 2451-2465) explored the antitrypanosomal activities of novel derivatives of 2-(2-benzamido)ethyl-4-phenylthiazole (1), which had been identified as a hit against Trypanosoma brucei, the causative agent of human African trypanosomiasis. While a number of these compounds, particularly the urea analogues, were quite potent, these molecules as a whole exhibited poor metabolic stability. The present work describes the synthesis of 65 new analogues arising from medicinal chemistry optimization at different sites on the molecule. The most promising compounds were the urea derivatives of 2-aryl-benzothiazol-5-amines. One such analogue, (S)-2-(3,4-difluorophenyl)-5-(3-fluoro-N-pyrrolidylamido)benzothiazole (57) was chosen for in vivo efficacy studies based upon in vitro activity, metabolic stability, and brain penetration. This compound attained 5/5 cures in murine models of both early and late stage human African trypanosomiasis, representing a new lead for the development of drugs to combat this neglected disease.
BIFLUORODIOXALANE-AMINO-BENZIMIDAZOLE KINASE INHIBITORS FOR THE TREATMENT OF CANCER, AUTOIMMUNEINFLAMMATION AND CNS DISORDERS
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Page/Page column 51; 76, (2014/01/17)
The invention relates to a compound of the general formula (I) or a physiologically functional derivative, solvate or salt thereof, (I) wherein A is a bond, alkyl or alkoxy optionally substituted with one or more R" as defined herein, *-N(R"')CO-, *-CON(R"')-, *-N(R'")CON(R"')-, -S-, -SO-, *-N(R'")-, *-N(R'")CO-, *-CON(R'")-, -CO-, *-COO-, *-OOC-, *-S02N(R"')-, -S02, or *-N(R"')-SO2-, wherein R"' is as defined herein and * specifies the point of attachment to X; X is aryl, cycloalkyl, aralkyl, heterocyclyl or heteroaryl, which may be substituted with one or more Rx further described herein; L is a bond or *-N(RN)CO-, *-CON(RN)-, *-N(RN)-, *-C=N(RN)-, *-N(RN)-alkyI-, *-alkyl-N(RN)-, *-N(RN)CON(RN)-, *-CO-, *-S02-, alkyl, *-alkyl-0-alkyl-, *-NCO-CH=CH-, *-CH=CH-CONH-, * -S02N(RN)-, *-N(RN)S02-, or heterocyclyl, wherein * specifies the point of attachment to X; Y is H, alkyl, aryl, aralkyl, cycloalkyl, heterocyclyl or heteroaryl, which may be substituted with one or more RY further described herein; and R and RN are further described herein; as well as their use as a medicament, a pharmaceutical composition comprising them, a method of treatment or prevention of a medical condition entailing the administration thereof, and the use thereof in the manufacture of a medicament for the treatment or prevention of a medical condition, particularly autoimmune inflammatory disorders, CNS disorders, sleeping disorders, or proliferative diseases including cancer. The invention further relates to a specific process for the preparation of said compounds.
INHIBITORS OF CYTOMEGALOVIRUS
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Page/Page column 17; 18, (2014/05/24)
Compounds of Formula (I) wherein n, R1, R1A, R2, R4 and Z are defined herein, are useful for the treatment of cytomegalovirus disease and/or infection.
INHIBITORS OF CYTOMEGALOVIRUS
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Page/Page column 17, (2015/03/06)
Compounds of Formula (I) wherein n, R1, R1A, R2, R3, Y and Z are defined herein, are useful for the treatment of cytomegalovirus disease and/or infection.
Novel tetrahydropyrido[1,2-a]isoindolone derivatives (valmerins): Potent cyclin-dependent kinase/glycogen synthase kinase 3 inhibitors with antiproliferative activities and antitumor effects in human tumor xenografts
Boulahjar, Rajaa,Ouach, Aziz,Matteo, Chiurato,Bourg, Stephane,Ravache, Myriam,Guével, Rémy Le,Marionneau, Séverine,Oullier, Thibauld,Lozach, Olivier,Meijer, Laurent,Guguen-Guillouzo, Christiane,Lazar, Sa?d,Akssira, Mohamed,Troin, Yves,Guillaumet, Gérald,Routier, Sylvain
, p. 9589 - 9606 (2013/01/16)
The development of CDK and GSK3 inhibitors has been regarded as a potential therapeutic approach, and a substantial number of diverse structures have been reported to inhibit CDKs and GSK-3β in recent years. Only a few molecules have gone through or are currently undergoing clinical trials as CDK and GSK inhibitors. In this paper, we prepared valmerins, a new family containing the tetrahydropyrido[1,2-a]isoindone core. The fused heterocycle was prepared with a straightforward synthesis that was functionalized by a (het)arylurea. Twelve valmerins inhibited the CDK5 and GSK3 with an IC50 100 nM. A semiquantitative kinase scoring was realized, and a cellular screening was done. At the end of our study, we investigated the in vivo potency of one valmerin. Mice exhibited good tolerance to our lead, which proved its efficacy and clearly blocked tumor growth. Valmerins appear also as good candidates for further development as anticancer agents.
Design and synthesis of 2-arylbenzimidazoles and evaluation of their inhibitory effect against Chlamydia pneumoniae
Keurulainen, Leena,Salin, Olli,Siiskonen, Antti,Kern, Jan Marco,Alvesalo, Joni,Kiuru, Paula,Maass, Matthias,Yli-Kauhaluoma, Jari,Vuorela, Pia
supporting information; experimental part, p. 7664 - 7674 (2011/03/17)
Chlamydia pneumoniae is an intracellular bacterium that responds poorly to antibiotic treatment. Insufficient antibiotic usage leads to chronic infection, which is linked to disease processes of asthma, atherosclerosis, and Alzheimer's disease. The Chlamydia research lacks genetic tools exploited by other antimicrobial research, and thus other approaches to drug discovery must be applied. A set of 2-arylbenzimidazoles was designed based on our earlier findings, and 33 derivatives were synthesized. Derivatives were assayed against C. pneumoniae strain CWL-029 in an acute infection model using TR-FIA method at a concentration of 10 μM, and the effects of the derivatives on the host cell viability were evaluated at the same concentration. Fourteen compounds showed at least 80% inhibition, with only minor changes in host cell viability. Nine most potential compounds were evaluated using immunofluorescence microscopy on two different strains of C. pneumoniae CWL-029 and CV-6. The N-[3-(1H-benzimidazol-2-yl)phenyl]-3-methylbenzamide (42) had minimal inhibitory concentration (MIC) of 10 μM against CWL-029 and 6.3 μM against the clinical strain CV-6. This study shows the high antichlamydial potential of 2-arylbenzimidazoles, which also seem to have good characteristics for lead compounds.
TETRAHYDRO-1H-PYRROLO FUSED PYRIDONES
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Page/Page column 50, (2009/10/21)
The present invention relates to tetrahydro-1H-pyrrolo fused pyridone compounds useful as HIF prolyl hydroxylase inhibitors to treat anemia and like conditions.
