- HPK1 INHIBITORS, PREPARATION METHOD AND APPLICATION THEREOF
-
Disclosed are HPK-1 inhibitors having a structure represented by Formula (X), pharmaceutical compositions comprising the HPK-1 inhibitors, methods of using the HPK-1 inhibitors, such as treating cancers, methods of preparing the HPK-1 inhibitors, and the synthetic intermediates.
- -
-
Page/Page column 130-131
(2019/11/12)
-
- Synthesis and biological evaluation of 2,4,5-trisubstituted thiazoles as antituberculosis agents effective against drug-resistant tuberculosis
-
The dormant and resistant form of Mycobacterium tuberculosis presents a challenge in developing new anti-tubercular drugs. Herein, we report the synthesis and evaluation of trisubstituted thiazoles as antituberculosis agents. The SAR study has identified a requirement of hydrophobic substituent at C2, ester functionality at C4, and various groups with hydrogen bond acceptor character at C5 of thiazole scaffold. This has led to the identification of 13h and 13p as lead compounds. These compounds inhibited the dormant Mycobacterium tuberculosis H37Ra strain and M. tuberculosis H37Rv selectively. Importantly, 13h and 13p were non-toxic to CHO cells. The 13p showed activity against multidrug-resistant tuberculosis isolates.
- Karale, Uttam B.,Krishna, Vagolu Siva,Krishna, E. Vamshi,Choudhari, Amit S.,Shukla, Manjulika,Gaikwad, Vikas R.,Mahizhaveni,Chopra, Sidharth,Misra, Sunil,Sarkar, Dhiman,Sriram, Dharmarajan,Dusthackeer, V.N. Azger,Rode, Haridas B.
-
p. 315 - 328
(2019/06/14)
-
- Agonists for the adenosine A1 receptor with tunable residence time. a case for nonribose 4-amino-6-aryl-5-cyano-2-thiopyrimidines
-
We report the synthesis and evaluation of previously unreported 4-amino-6-aryl-5-cyano-2-thiopyrimidines as selective human adenosine A 1 receptor (hA1AR) agonists with tunable binding kinetics, this without affecting their nanomolar affinity for the target receptor. They show a very diverse range of kinetic profiles (from 1 min (compound 52) to 1 h (compound 43)), and their structure-affinity relationships (SAR) and structure-kinetics relationships (SKR) were established. When put in perspective with the increasing importance of binding kinetics in drug discovery, these results bring new evidence of the consequences of affinity-only driven selection of drug candidates, that is, the potential elimination of slightly less active compounds that may display preferable binding kinetics.
- Louvel, Julien,Guo, Dong,Agliardi, Marta,Mocking, Tamara A. M.,Kars, Roland,Pham, Tan Phát,Xia, Lizi,De Vries, Henk,Brussee, Johannes,Heitman, Laura H.,Ijzerman, Adriaan P.
-
supporting information
p. 3213 - 3222
(2014/05/20)
-
- HETEROCYCLE-SUBSTITUED TETRACYCLIC COMPOUNDS AND METHODS OF USE THEREOF FOR TREATMENT OF VIRAL DISEASES
-
The present invention relates to novel Heterocycle-Substituted Tetracyclic Compounds of Formula (I): (I) and pharmaceutically acceptable salts thereof, wherein A, A', R 2 R 3, R 4 and R are as defined herein. The present i
- -
-
Page/Page column 144
(2014/08/06)
-
- Microwave-assisted synthesis of potent PDE7 inhibitors containing a thienopyrimidin-4-amine scaffold
-
A series of novel thienopyrimidin-4-amines have been synthesized and evaluated as phosphodiesterase (PDE) inhibitors. A rationale for the observed selectivity against PDE7 has been obtained from molecular modelling studies on the most active compounds. This journal is the Partner Organisations 2014.
- Sanchez, Ana I.,Meneses, Ricardo,Minguez, Jose M.,Nunez, Araceli,Castillo, Rafael R.,Filace, Fabiana,Burgos, Carolina,Vaquero, Juan J.,Alvarez-Builla, Julio,Cortes-Cabrera, Alvaro,Gago, Federico,Terricabras, Emma,Segarra, Victor
-
p. 4233 - 4242
(2014/06/10)
-
- Single-step microwave-mediated synthesis of oxazoles and thiazoles from 3-oxetanone: A synthetic and computational study
-
The direct microwave-mediated condensation between 3-oxetanone and primary amides and thioamides has delivered moderate to good yields of (hydroxymethyl)oxazoles and (hydroxymethyl)thiazoles. The reactions use a sustainable solvent and only require short reaction times. These are highly competitive methods for the construction of two classes of valuable heteroarenes, which bear a useful locus for further elaboration. Electronic structure calculations have shown that the order of events involves chalcogen atom attack at sp3 carbon and alkyl-oxygen cleavage. The critical role of acid catalysis was shown clearly, and the importance of acid strength was demonstrated. The calculated barriers were also fully consistent with the observed order of thioamide and amide reactivity. Spontaneous ring opening involves a modest degree of C-O cleavage, moderating the extent of strain relief. On the acid-catalysed pathway, C-O cleavage is less extensive still, but proton transfer to the nucleofuge is well advanced with the carboxylic acid catalysts, and essentially complete with methanesulfonic acid. Open sesame: The direct microwave-mediated condensation between 3-oxetanone and primary amides and thioamides has delivered moderate to good yields of oxazoles and thiazoles. The reactions use a sustainable solvent, require only short reaction times and represent a highly competitive method for the construction of two classes of valuable heteroarenes. Electronic structure calculations have been used to probe a range of potential reaction mechanisms (see figure). Copyright
- Orr, David,Tolfrey, Alexandra,Percy, Jonathan M.,Frieman, Joanna,Harrison, Zo? A.,Campbell-Crawford, Matthew,Patel, Vipulkumar K.
-
supporting information
p. 9655 - 9662
(2013/07/26)
-
- Pim kinase inhibitors and methods of their use
-
The present invention relates to new compounds of Formulas I and II, their tautomers, stereoisomers and polymorphs, and pharmaceutically acceptable salts, esters, metabolites or prodrugs thereof, compositions of the new compounds together with pharmaceutically acceptable carriers, and uses of the new compounds, either alone or in combination with at least one additional therapeutic agent, in the inhibition of Pim kinase activity and/or the prophylaxis or treatment of cancer.
- -
-
Page/Page column 44
(2010/09/05)
-
- Efficient and green protocol for the synthesis of thioamides in C 6 (mim)2Cl2 as a dicationic ionic liquid
-
A simple, efficient, facile and eco-friendly process for the synthesis of thioamides from nitriles using 1,6-bis(3methylimidazolium-1-yl)hexane chloride [C6(mim)2Cl2] as a dicationic ionic liquid (DIL) was developed. The ionic liquid was easily separated from the reaction mixture and was recycled at least four times without any loss of its activity.
- Khosropour,Noei,Mirjafari
-
experimental part
p. 752 - 758
(2010/11/04)
-
- PIM KINASE INHIBITORS AND METHODS OF THEIR USE
-
The present invention relates to new compounds of Formulas (I) and (II), their tautomers, stereoisomers and polymorphs, and pharmaceutically acceptable salts, esters, metabolites or prodrugs thereof, compositions of the new compounds together with pharmac
- -
-
Page/Page column 103
(2009/10/22)
-
- Phenyl-1,2,4-Oxadiazolone Derivatives, Processes For Their Preparation and Methods For Their Use as Pharmaceuticals
-
The inventive compounds of the present invention are comprised of phenyl and pyridinyl-1,2,4-oxadiazolone derivatives and their physiologically acceptable salts and functional derivatives that are shown to provide peroxisome proliferator activator recepto
- -
-
Page/Page column 53
(2008/12/04)
-
- MACROCYCLIC INHIBITORS OF HEPATITIS C VIRUS
-
Inhibitors of HCV replication of formula (I) and the N-oxides, salts, and stereoisomers, wherein each dashed line represents an optional double bond; X is N, CH and where X bears a double bond it is C; R1 is -OR7, -NH-SO2R8; R2 is hydrogen, and where X is C or CH, R2 may also be C1-6alkyl; R3 is hydrogen, C1-6alkyl, C1-6alkoxyC1-6alkyl, C3-7cycloalkyl; R4 is aryl or Het; n is 3, 4, 5, or 6; R5 is halo, C1-6alkyl, hydroxy, C1-6alkoxy, phenyl, or Het; R6 is C1-6alkoxy, or dimethylamino; R7 is hydrogen; aryl; Het; C3-7cycloalkyl optionally substituted with C1-6alkyl; or C1-6alkyl optionally substituted with C3-7cycloalkyl, aryl or with Het; R8 is aryl; Het; C3-7cycloalkyl optionally substituted with C1-6alkyl; or C1-6alkyl optionally substituted with C3-7cycloalkyl, aryl or with Het; aryl is phenyl optionally substituted with one, two or three substituents; Het is a 5 or 6 membered saturated, partially unsaturated or completely unsaturated heterocyclic ring containing 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, and being optionally substituted with one, two or three substituents ; pharmaceutical compositions containing compounds (I) and processes for preparing compounds (I). Bioavailable combinations of the inhibitors of HCV of formula (I) with ritonavir are also provided.
- -
-
Page/Page column 113
(2008/06/13)
-
- Phosphorus pentasulfide: A mild and versatile reagent for the preparation of thioamides from nitriles
-
A simple, efficient, and new method has been developed for the synthesis of thioamides from nitriles. The reaction of a variety of aromatic and aliphatic nitriles in the presence of phosphorus pentasulfide afforded the corresponding thioamides in high yields. This method is easy, rapid, and high-yielding for the synthesis of thioamides from nitriles. Georg Thieme Verlag Stuttgart.
- Kaboudin, Babak,Elhamifar, Dawood
-
p. 224 - 226
(2007/10/03)
-
- Ramoplanin derivatives possessing antibacterial activity
-
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.
- -
-
Page/Page column 77
(2010/11/23)
-
- Simple microwave-assisted method for the synthesis of primary thioamides from nitriles
-
Primary thioamides are prepared in excellent yield from the corresponding nitrile by treatment with ammonium sulfide in methanol, at room temperature for electron-deficient aromatic nitriles or under microwave irradiation at 80 °C or 130 °C in 15-30 minutes for other aromatic and aliphatic nitriles. This procedure avoids the use of gaseous H2S under high pressure, proceeds in the absence of base and provides thioamides usually without the need for chromatographic purification.
- Bagley, Mark C.,Chapaneri, Krishna,Glover, Christian,Merritt, Eleanor A.
-
p. 2615 - 2617
(2007/10/03)
-