Tag: M.W=250-300

Kamenecka, Ted published the artcileStructure-Activity Relationships and X-ray Structures Describing the Selectivity of Aminopyrazole Inhibitors for c-Jun N-terminal Kinase 3 (JNK3) over p38, Category: chlorides-buliding-blocks, the main research area is structure activity aminopyrazole indazole preparation crystal structure JNK3 p38.

C-Jun N-terminal kinase 3α1 (JNK3α1) is a mitogen-activated protein kinase family member expressed primarily in the brain that phosphorylates protein transcription factors, including c-Jun and activating transcription factor-2 (ATF-2) upon activation by a variety of stress-based stimuli. In this study, we set out to design JNK3-selective inhibitors that had >1000-fold selectivity over p38, another closely related mitogen-activated protein kinase family member. To do this we employed traditional medicinal chem. principles coupled with structure-based drug design. Inhibitors from the aminopyrazole class, such as SR-3576, were found to be very potent JNK3 inhibitors (IC50 = 7 nM) with >2800-fold selectivity over p38 (p38 IC50 > 20 μM) and had cell-based potency of ∼1 μM. In contrast, indazole-based inhibitors exemplified by SR-3737 were potent inhibitors of both JNK3 (IC50 = 12 nM) and p38 (IC50 = 3 nM). These selectivity differences between the indazole class and the aminopyrazole class came despite nearly identical binding (root mean square deviation = 0.33 Å) of these two compound classes to JNK3. The structural features within the compounds giving rise to the selectivity in the aminopyrazole class include the highly planar nature of the pyrazole, N-linked Ph structures, which better occupied the smaller active site of JNK3 compared with the larger active site of p38.

Journal of Biological Chemistry published new progress about Crystal structure. 1095274-55-7 belongs to class chlorides-buliding-blocks, name is Ethyl 3-bromo-5-chlorobenzoate, and the molecular formula is C9H8BrClO2, Category: chlorides-buliding-blocks.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Yamada, Ken published the artcileDiscovery of a Novel Piperidine-Based Inhibitor of Cholesteryl Ester Transfer Protein (CETP) That Retains Activity in Hypertriglyceridemic Plasma, Formula: C8H5BrClF3, the main research area is CETP inhibition piperidine analog hypertriglyceridemic plasma activity; piperidine analog preparation hypertriglyceridemic plasma activity.

Herein we describe the discovery and characterization of a novel, piperidine-based inhibitor of cholesteryl ester transfer protein (CETP) with a core structure distinct from other reported CETP inhibitors. A versatile synthesis starting from 4-methoxypyridine enabled an efficient exploration of the SAR, giving a lead mol. with potent CETP inhibition in human plasma. The subsequent optimization focused on improvement of pharmacokinetics and mitigation of off-target liabilities, such as CYP inhibition, whose improvement correlated with increased lipophilic efficiency. The effort led to the identification of an achiral, carboxylic acid-bearing compound I (TAP311) with excellent pharmacokinetics in rats and robust efficacy in hamsters. Compared to anacetrapib, the compound showed substantially reduced lipophilicity, had only modest distribution into adipose tissue, and retained potency in hypertriglyceridemic plasma in vitro and in vivo. Furthermore, in contrast to torcetrapib, the compound did not increase aldosterone secretion in human adrenocortical carcinoma cells nor in chronically cannulated rats. On the basis of its preclin. efficacy and safety profile, the compound was advanced into clin. trials.

Journal of Medicinal Chemistry published new progress about Antitumor agents. 886496-91-9 belongs to class chlorides-buliding-blocks, name is 1-(Bromomethyl)-3-chloro-5-(trifluoromethyl)benzene, and the molecular formula is C8H5BrClF3, Formula: C8H5BrClF3.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Deng, Guanghui published the artcileNovel complex crystal structure of prolyl hydroxylase domain-containing protein 2 (PHD2): 2,8-Diazaspiro[4.5]decan-1-ones as potent, orally bioavailable PHD2 inhibitors, Related Products of chlorides-buliding-blocks, the main research area is crystal structure prolyl hydroxylase domain protein diazaspirodecanone; 2,8-Diazaspiro[4.5]decan-1-one; Hypoxia inducible factor (HIF); PHD inhibitors; PHD2 crystal structure; Prolyl hydroxylase domain-containing protein 2 (PHD2); SAR study.

We have discovered a novel complex crystal structure of the PHD2 enzyme with its inhibitor, the 2,8-diazaspiro[4.5]decan-1-one analog 4b. The widely reported salt bridge between Arg383 of the enzyme and its inhibitors in all complex structures published thus far was not observed in our case. In our complex structure compound 4b forms several novel interactions with the enzyme, which include a hydrogen bond with Arg322, a π-cation interaction with Arg322, a π-π stacking with Trp389, and a π-π stacking with His313. Guided by the structural information, SAR studies were performed on the 2,8-diazaspiro[4.5]decan-1-one series leading to the discovery of compound 9p with high potency and good oral pharmacokinetic profile in mice.

Bioorganic & Medicinal Chemistry published new progress about Drug bioavailability. 6797-79-1 belongs to class chlorides-buliding-blocks, name is 4-Chloro-2-fluoroiodobenzene, and the molecular formula is C6H3ClFI, Related Products of chlorides-buliding-blocks.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Rombouts, Frederik J. R. published the artcilePyrido[4,3-e][1,2,4]triazolo[4,3-a]pyrazines as Selective, Brain Penetrant Phosphodiesterase 2 (PDE2) Inhibitors, Category: chlorides-buliding-blocks, the main research area is pyrido triazolo pyrazine brain phosphodiesterase inhibitor; PDE2 inhibitor; Pyrido[4,3-e][1,2,4]triazolo[4,3-a]pyrazine; phosphodiesterase 2 inhibitor; selective; tricycle.

A novel series of pyrido[4,3-e][1,2,4]triazolo[4,3-a]pyrazines is reported as potent PDE2/PDE10 inhibitors with drug-like properties. Selectivity for PDE2 was obtained by introducing a linear, lipophilic moiety on the meta-position of the Ph ring pending from the triazole. The SAR and protein flexibility were explored with free energy perturbation calculations Rat pharmacokinetic data and in vivo receptor occupancy data are given for two representative compounds 6 and 12.

ACS Medicinal Chemistry Letters published new progress about Drug bioavailability. 468075-00-5 belongs to class chlorides-buliding-blocks, name is 2-Bromo-1-chloro-4-(trifluoromethoxy)benzene, and the molecular formula is C7H3BrClF3O, Category: chlorides-buliding-blocks.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Cox, Jason M. published the artcileDesign, Synthesis, and Evaluation of Novel and Selective G-protein Coupled Receptor 120 (GPR120) Spirocyclic Agonists, Recommanded Product: 2-Bromo-1-chloro-4-(trifluoromethoxy)benzene, the main research area is preparation GPR120 spirocyclic agonist diabetes; FFAR4; GPR120; insulin sensitization; spirocyclic; type 2 diabetes.

Type 2 diabetes mellitus (T2DM) is an ever increasing worldwide epidemic, and the identification of safe and effective insulin sensitizers, absent of weight gain, has been a long-standing goal of diabetes research. G-protein coupled receptor 120 (GPR120) has recently emerged as a potential therapeutic target for treating T2DM. Natural occurring, and more recently, synthetic agonists have been associated with insulin sensitizing, anti-inflammatory, and fat metabolism effects. Herein we describe the design, synthesis, and evaluation of a novel spirocyclic GPR120 agonist series, which culminated in the discovery of potent and selective agonist 14. Furthermore, compound 14 was evaluated in vivo and demonstrated acute glucose lowering in an oral glucose tolerance test (oGTT), as well as improvements in homeostatic measurement assessment of insulin resistance (HOMA-IR; a surrogate marker for insulin sensitization) and an increase in glucose infusion rate (GIR) during a hyperinsulinemic euglycemic clamp in diet-induced obese (DIO) mice.

ACS Medicinal Chemistry Letters published new progress about Antidiabetic agents. 468075-00-5 belongs to class chlorides-buliding-blocks, name is 2-Bromo-1-chloro-4-(trifluoromethoxy)benzene, and the molecular formula is C7H3BrClF3O, Recommanded Product: 2-Bromo-1-chloro-4-(trifluoromethoxy)benzene.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Zhou, Xian-yan published the artcileDT-GC-MS analysis on environmental risk of poplar engineering biocomposites, HPLC of Formula: 18585-06-3, the main research area is Populus engineering biocomposite thermodesorber gas chromatog mass spectrometer.

Poplar engineering biocomposites are new engineering material. In order to evaluate its potential environmental risk to human, the volatile organic compounds of poplar engineering biocomposites were adsorbed and determined by TD-GC-MS. The result were: (1) The main constituents of volatiles at 40°C were bicyclo[2.2.1]heptan-2-one, 1,7,7- trimethyl-, (1r)-(31.55%), 1,2-benzenedicarboxylic acid, mono(2-ethylhexyl) ester(14.94%), 2,6,10,14,18,22-tetracosahexaene, 2,6,10,15,19,23-hexamethyl-(7.34%), [1,1′:3′,1″”-terphenyl]-2′-ol(5.97%), cedrol (5.29%), caryophyllene(5.26%), 3-[(1z)-1,3-butadienyl]-4-vinylcyc lopentene(3.92%), etc. (2) The main constituents of volatiles at 60°C were 1,2-benzenedicarboxylic acid, mono(2-ethylhexyl) ester(17.13%), [1,1′:3′,1″”-terphenyl]-2′-ol(9.11%), camphor(8.6%), 4-imidazolidinone, 5-(phenylmethyl)-2-thioxo- (7.6%), cedrol(7.26%), 2,5-cyclohexadiene-1,4-dione, 2,5-diphenyl-(4.58%), 1h-indole, 5-methyl- 2-phenyl-(3.94%), 2,6,10,14,18,22-tetracosahexaene, 2,6,10,15,19,23-hexamethyl- (3.63%), phenol,2,4-bis(1,1-dimethylethyl) (3.56%), etc. So the poplar engineering biocomposites was safe under 40-60°C.

Advanced Materials Research (Zuerich, Switzerland) published new progress about Gas chromatography. 18585-06-3 belongs to class chlorides-buliding-blocks, name is Ethyl (4-chloro-3-(trifluoromethyl)phenyl)carbamate, and the molecular formula is C10H9ClF3NO2, HPLC of Formula: 18585-06-3.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Pytlarczyk, Marta published the artcileNematic stability of 2,2′,4-trifluoro-4”-alkyl-[1,1′:4′,1”]terphenyls and its deuterated isotopologue, Safety of 4-Chloro-2-fluoroiodobenzene, the main research area is alkylphenyl boronic acid chlorotrifluoro biphenyl palladium SPhos catalyst coupling; trifluoro alkyl terphenyl preparation.

In this work, three synthetic methodologies of 2,2′,4-trifluoro-4”-alkyl-[1,1′:4′,1”]terphenyls were presented. The most convenient synthetic method was used for homologous series of 2,2′,4-trifluoro-4”-alkyl-[1,1′:4′,1”]terphenyls (alkyl chain from Me to hexyl). The results showed that fluorination in the inner-core position (at 2 and 2′ position of terphenyl core) promoted only a nematic phase. The results was discussed with other chloro- and fluoro- substituted 4”-alkyl-[1,1′:4′,1”]terphenyls and one perdeuterated terphenyl analog. The synthesis and purity of synthesized compounds were monitored by gas chromatog. GC-MS, GC-FID and by thin layer chromatog. (TLC). The phase situation and the phase transition temperatures were determined by polarized optical microscopy (POM). The temperatures and enthalpies of the phase transitions were measured by using differential scanning calorimetry (DSC).

Journal of Molecular Liquids published new progress about Bond angle, torsional. 6797-79-1 belongs to class chlorides-buliding-blocks, name is 4-Chloro-2-fluoroiodobenzene, and the molecular formula is C6H3ClFI, Safety of 4-Chloro-2-fluoroiodobenzene.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Katircioglu, Hikmet published the artcileSynthesis of 2,4-dihalogenofluorobenzenes and their antimicrobial and antifungal activity studies, Recommanded Product: 4-Chloro-2-fluoroiodobenzene, the main research area is trihalobenzene preparation antibacterial antifungal; dihaloaniline Schiemann reaction.

Six 2,4-dihalofluorobenzene derivatives were synthesized from their dihaloaniline derivatives The in vitro antibacterial and antifungal activities of the trihalobenzenes were studied against the bacteria Staphylococcus aureus ATCC 25923 G(+), Bacillus cereus ATCC 6633 G(+), Micrococcus flavus (clin. isolate) Gram(+), Morgenella morganii (clin. isolate) Gram(-), Escherichia coli ATCC 27853 G(-) and fungus Candida albicans (clin. isolate), obtained from the biol. departments of the Pamukkale and Gazi Universities. The antibacterial and antifungal activities were measured by min. inhibition concentration (MIC) method and the disk-diffusion method used to measure zone diameter against Gram-pos. and Gram-neg. bacteria and fungi. All these bacteria and fungi were studied against antibiotics to compare the zone diameters with the results from our treatments.

Medicinal Chemistry Research published new progress about Antibacterial agents. 6797-79-1 belongs to class chlorides-buliding-blocks, name is 4-Chloro-2-fluoroiodobenzene, and the molecular formula is C6H3ClFI, Recommanded Product: 4-Chloro-2-fluoroiodobenzene.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Kumar, Navneet published the artcileSynthesis and antibacterial evaluation of some new Schiff bases, Related Products of chlorides-buliding-blocks, the main research area is Schiff base stereoselective preparation antibacterial.

Various Schiff bases such as 2-(3-hydroxy-4-methoxybenzylideneamino)benzoic acid, (E)-2-(2-carboxybenzylideneamino)benzoic acid, (E)-2-(pyridin-2-ylmethyleneamino)benzoic acid, (E)-2-((2,5-dihydrothiazol-2-ylimino)-methyl)benzoic acid, (E)-2-(3-hydroxy-4-methylbenzyl ideneamino)benzoic acid, etc. were prepared via reaction of various aldehydes with 2-aminobenzoic acid. The antibacterial activity was evaluated against pathogenic strain E. coli. Compounds exhibited significant activity against all the tested microorganisms.

International Journal of Pharmaceutical Sciences Review and Research published new progress about Antibacterial agents. 1184936-21-7 belongs to class chlorides-buliding-blocks, name is 4-Chloro-2-(trifluoroacetyl)aniline Hydrochloride Hydrate, and the molecular formula is C8H8Cl2F3NO2, Related Products of chlorides-buliding-blocks.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Lachance, Nicolas published the artcileDiscovery of potent and liver-targeted stearoyl-CoA desaturase (SCD) inhibitors in a bispyrrolidine series, COA of Formula: C7H3BrClF3O, the main research area is arylheterocyclyl thiazolyltetrazoleacetic thiadiazolyltetrazoleacetic acid preparation stearoyl CoA desaturase inhibitor; arylpyrrolopyrrole isoxazolyltetrazoleacetic acid preparation stearoyl CoA desaturase inhibitor; structure arylheterocyclyl thiazolyltetrazoleacetic thiadiazolyltetrazoleacetic acid inhibition stearoyl CoA desaturase; liver selectivity pharmacokinetics thiazolyltetrazoleacetic thiadiazolyltetrazoleacetic acid stearoyl desaturase inhibitor; tissue distribution stearoyl CoA desaturase inhibitor oral administration.

Arylheterocyclyl-substituted thiazolyltetrazoleacetic acids such as I and an isoxazolyltetrazoleacetic acid and a thiadiazolyltetrazoleacetic acid are prepared as inhibitors of stearoyl-CoA desaturase (SCD) with selectivity for the liver over other organs such as the skin and eyes in which SCD inhibitors cause undesired side effects. Coupling of a mono-Boc-protected perhydropyrrolopyrrole with 2-bromo-1-chloro-4-trifluoromethoxybenzene followed by Boc deprotection yielded a salt of the arylperhydropyrrolopyrrole II (either a chloride or trifluoroacetate); amidation of Et 2-bromo-5-thiazolecarboxylate, dehydration to the nitrile, and reaction with sodium azide yielded the bromothiazolyltetrazole III. Regioselective alkylation of III with a bromoacetate ester, coupling to II, and cleavage of the ester yielded I. The inhibition of stearoyl-CoA desaturase and its inhibition in rat hepatic cells and rat cells possessing active transporters by arylheterocyclyl-substituted thiazolyltetrazoleacetic acids and thiadiazolyltetrazoleacetic acids was determined; for I and two related compounds, their tissue distributions and in vivo stearoyl-CoA desaturase inhibitions on oral administration to mice were determined

Bioorganic & Medicinal Chemistry Letters published new progress about Active biological transport. 468075-00-5 belongs to class chlorides-buliding-blocks, name is 2-Bromo-1-chloro-4-(trifluoromethoxy)benzene, and the molecular formula is C7H3BrClF3O, COA of Formula: C7H3BrClF3O.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics