Category: 401567-00-8

Hua, Zihao; Huang, Xin; Bregman, Howard; Chakka, Nagasree; DiMauro, Erin F.; Doherty, Elizabeth M.; Goldstein, Jon; Gunaydin, Hakan; Huang, Hongbing; Mercede, Stephanie; Newcomb, John; Patel, Vinod F.; Turci, Susan M.; Yan, Jie; Wilson, Cindy; Martin, Matthew W. published the artcile< 2-(Phenylamino)-6-cyano-1H-benzimidazole-based isoform selective casein kinase 1 gamma (CK1γ) inhibitors>, HPLC of Formula: 401567-00-8, the main research area is phenylamino cyano benzimidazole preparation casein kinase inhibitor treatment cancer.

Screening of the amgen compound library led to the identification of 2-(phenylamino)-6-cyano-1H-benzimidazole, I, as a potential CK1 gamma inhibitor (CK1γ) with excellent kinase selectivity and unprecedented CK1 isoform selectivity. Further structure-based optimization of this series resulted in the discovery of II, which possessed good enzymic and cellular potency, excellent CK1 isoform and kinase selectivity, and acceptable pharmacokinetic properties.

Bioorganic & Medicinal Chemistry Letters published new progress about Antitumor agents. 401567-00-8 belongs to class imidazoles-derivatives, and the molecular formula is C8H4ClN3, HPLC of Formula: 401567-00-8.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Ogino, Yoshio; Ohtake, Norikazu; Nagae, Yoshikazu; Matsuda, Kenji; Moriya, Minoru; Suga, Takuya; Ishikawa, Makoto; Kanesaka, Maki; Mitobe, Yuko; Ito, Junko; Kanno, Tetsuya; Ishihara, Akane; Iwaasa, Hisashi; Ohe, Tomoyuki; Kanatani, Akio; Fukami, Takehiro published the artcile< Design, syntheses, and structure-activity relationships of novel NPY Y5 receptor antagonists: 2-{3-Oxospiro[isobenzofuran-1(3H),4'-piperidin]-1'-yl}benzimidazole derivatives>, HPLC of Formula: 401567-00-8, the main research area is isobenzofuran piperidinyl benzimidazole preparation neuropeptide Y Y5 receptor antagonist; NPY Y Y5 receptor antagonist sar isobenzofuran piperidinyl benzimidazole.

Design, syntheses, and structure-activity relationships of a novel class of 2-{3-oxospiro[isobenzofuran-1(3H),4′-piperidin]-1′-yl}benzimidazole NPY Y5 receptor antagonists are described. The benzimidazole structures were newly designed based on the urea linkage of our prototype Y5 receptor antagonists. By optimizing substituents on the benzimidazole core part of the lead compound I (R = H), a potent, orally available, and brain-penetrable Y5 selective antagonist I (R = CF3) was developed.

Bioorganic & Medicinal Chemistry Letters published new progress about Drug design. 401567-00-8 belongs to class imidazoles-derivatives, and the molecular formula is C8H4ClN3, HPLC of Formula: 401567-00-8.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Garbaccio, Robert M.; Brnardic, Edward J.; Fraley, Mark E.; Hartman, George D.; Hutson, Pete H.; O’Brien, Julie A.; Magliaro, Brian C.; Uslaner, Jason M.; Huszar, Sarah L.; Fillgrove, Kerry L.; Small, James H.; Tang, Cuyue; Kuo, Yuhsin; Jacobson, Marlene A. published the artcile< Discovery of Oxazolobenzimidazoles as Positive Allosteric Modulators for the mGluR2 Receptor>, Product Details of C8H4ClN3, the main research area is oxazolo benzimidazole derivative preparation allosteric modulator mGluR2 receptor antipsychotic; GPCR; Oxazolobenzimidazoles; allosteric modulators; hyperlocomotion model; metabotropic glutamate 2 receptor; schizophrenia.

Novel oxazolobenzimidazoles are described as potent and selective pos. allosteric modulators of the metabotropic glutamate receptor 2. The discovery of this class and optimization of its phys. and pharmacokinetic properties led to the identification of potent and orally bioavailable compounds (20 and 21) as advanced leads. Compound 20 (TBPCOB) was shown to have robust activity in a PCP-induced hyperlocomotion model in rat, an assay responsive to clin. antipsychotic treatments for schizophrenia.

ACS Medicinal Chemistry Letters published new progress about Antipsychotics. 401567-00-8 belongs to class imidazoles-derivatives, and the molecular formula is C8H4ClN3, Product Details of C8H4ClN3.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Garbaccio, Robert M.; Brnardic, Edward J.; Fraley, Mark E.; Hartman, George D.; Hutson, Pete H.; O’Brien, Julie A.; Magliaro, Brian C.; Uslaner, Jason M.; Huszar, Sarah L.; Fillgrove, Kerry L.; Small, James H.; Tang, Cuyue; Kuo, Yuhsin; Jacobson, Marlene A. published the artcile< Discovery of Oxazolobenzimidazoles as Positive Allosteric Modulators for the mGluR2 Receptor>, Product Details of C8H4ClN3, the main research area is oxazolo benzimidazole derivative preparation allosteric modulator mGluR2 receptor antipsychotic; GPCR; Oxazolobenzimidazoles; allosteric modulators; hyperlocomotion model; metabotropic glutamate 2 receptor; schizophrenia.

Novel oxazolobenzimidazoles are described as potent and selective pos. allosteric modulators of the metabotropic glutamate receptor 2. The discovery of this class and optimization of its phys. and pharmacokinetic properties led to the identification of potent and orally bioavailable compounds (20 and 21) as advanced leads. Compound 20 (TBPCOB) was shown to have robust activity in a PCP-induced hyperlocomotion model in rat, an assay responsive to clin. antipsychotic treatments for schizophrenia.

ACS Medicinal Chemistry Letters published new progress about Antipsychotics. 401567-00-8 belongs to class imidazoles-derivatives, and the molecular formula is C8H4ClN3, Product Details of C8H4ClN3.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Ognyanov, Vassil I.; Balan, Chenera; Bannon, Anthony W.; Bo, Yunxin; Dominguez, Celia; Fotsch, Christopher; Gore, Vijay K.; Klionsky, Lana; Ma, Vu V.; Qian, Yi-Xin; Tamir, Rami; Wang, Xianghong; Xi, Ning; Xu, Shimin; Zhu, Dawn; Gavva, Narender R.; Treanor, James J. S.; Norman, Mark H. published the artcile< Design of potent, orally available antagonists of the transient receptor potential vanilloid 1. Structure-activity relationships of 2-piperazin-1-yl-1H-benzimidazoles>, Recommanded Product: 2-Chloro-1H-benzo[d]imidazole-5-carbonitrile, the main research area is benzimidazole piperazinyl preparation transient receptor potential vanilloid antagonist antihyperalgesic.

The vanilloid receptor-1 (VR1 or TRPV1) is a membrane-bound, nonselective cation channel that is predominantly expressed by peripheral neurons sensing painful stimuli. TRPV1 antagonists produce antihyperalgesic effects in animal models of inflammatory and neuropathic pain. The synthesis and the structure-activity relationships of a series of 2-(4-pyridin-2-ylpiperazin-1-yl)-1H-benzo[d]imidazoles I [R1 = H, Me3SiCH2CH2OCH2, PhCH2; R2 = F, Cl, Br, F3C, Me, CN, Me3C, MeO2C, etc.; R3 = H, 4-(2-thiazolyl), 4-(4-pyridyl), 5-(4-F3CC6H4), etc.; R4 = H, Me; R5 = H, H2N, MeCHOH, H2C:CH, etc.; R6 = H, Cl, F3C, etc.] and analogs as novel TRPV1 antagonists have been described. I [R1 = H; R2 = F3C; R3 = 4-(3,4,5-F3C6H2); R4 = (R)-Me; R5 = HOCH2CHOH; R6 = Cl; (II)] was among the most potent analogs in this series. This compound was orally bioavailable in rats and was efficacious in blocking capsaicin-induced flinch in rats in a dose-dependent manner. II also reversed thermal hyperalgesia in a model of inflammatory pain, which was induced by complete Freund’s adjuvant (CFA).

Journal of Medicinal Chemistry published new progress about Analgesics. 401567-00-8 belongs to class imidazoles-derivatives, and the molecular formula is C8H4ClN3, Recommanded Product: 2-Chloro-1H-benzo[d]imidazole-5-carbonitrile.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Okazaki, Shogo; Noguchi-Yachide, Tomomi; Sakai, Taki; Ishikawa, Minoru; Makishima, Makoto; Hashimoto, Yuichi; Yamaguchi, Takao published the artcile< Discovery of N-(1-(3-(4-phenoxyphenyl)-1,2,4-oxadiazol-5-yl)ethyl)acetamides as novel acetyl-CoA carboxylase 2 (ACC2) inhibitors with peroxisome proliferator-activated receptor α/δ (PPARα/δ) dual agonistic activity>, Reference of 401567-00-8, the main research area is phenoxyphenyloxadiazolylethylacetamide acetyl CoA carboxylase ACC2 inhibitor PPAR agonist; Acetyl-CoA carboxylase; Multi-target drug; Peroxisome proliferator-activated receptor.

Acetyl-Co-A carboxylases (ACCs) catalyze a critical step in de novo lipogenesis, and are considered as promising targets for treatment of obesity, dyslipidemia and type 2 diabetes mellitus. On the other hand, peroxisome proliferator-activated receptors (PPARs) are well-established therapeutic targets for these metabolic syndrome-related diseases. Therefore, the authors considered that dual modulators of ACC and PPARs would be promising candidates as therapeutic agents. Here, the authors designed a series of acetamides based on the mol. similarity between ACC inhibitors and PPAR agonists. Screening of the synthesized compounds identified N-(1-(3-(4-phenoxyphenyl)-1,2,4-oxadiazol-5-yl)ethyl)acetamides as novel ACC2 inhibitors with PPARα/PPARδ dual agonistic activity. Structure-activity relationship studies and further structural elaboration afforded compounds with distinct activity profiles. The findings should be helpful for the discovery of candidate agents with an appropriate balance of ACC-inhibitory and PPAR-activating activities for therapeutic lipid control.

Bioorganic & Medicinal Chemistry published new progress about Homo sapiens. 401567-00-8 belongs to class imidazoles-derivatives, and the molecular formula is C8H4ClN3, Reference of 401567-00-8.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Yoshida, Tomohiro; Akahoshi, Fumihiko; Sakashita, Hiroshi; Sonda, Shuji; Takeuchi, Masahiro; Tanaka, Yoshihito; Nabeno, Mika; Kishida, Hiroyuki; Miyaguchi, Ikuko; Hayashi, Yoshiharu published the artcile< Fused bicyclic heteroarylpiperazine-substituted L-prolylthiazolidines as highly potent DPP-4 inhibitors lacking the electrophilic nitrile group>, Synthetic Route of 401567-00-8, the main research area is antidiabetic DPP4 inhibitor heteroarylpiperazine prolylthiazolidine preparation structure activity.

Hypoglycemic agents with a mechanism of dipeptidyl peptidase IV (DPP-4) inhibition are suitable for once daily oral dosing. It is difficult to strike a balance between inhibitory activity and duration of action in plasma for inhibitors bearing an electrophilic nitrile group. We explored fused bicyclic heteroarylpiperazine substituted at the γ-position of the proline structure in the investigation of L-prolylthiazolidines lacking the electrophilic nitrile. Among them, 2-trifluoroquinolyl compound 8g is the most potent, long-lasting DPP-4 inhibitor (IC50 = 0.37 nmol/L) with high selectivity against other related peptidases. X-ray crystal structure determination of 8g indicates that CH-π interactions generated between the quinolyl ring and the guanidinyl group of Arg358 enhances the DPP-4 inhibitory activity and selectivity.

Bioorganic & Medicinal Chemistry published new progress about Antidiabetic agents. 401567-00-8 belongs to class imidazoles-derivatives, and the molecular formula is C8H4ClN3, Synthetic Route of 401567-00-8.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Application of 401567-00-8,Some common heterocyclic compound, 401567-00-8, name is 2-Chloro-1H-benzo[d]imidazole-5-carbonitrile, molecular formula is C8H4ClN3, traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route.

A mixture of 2-chloro-1H-benzimidazole~5-carbonitrile (3.0 g, 17 mmol, 1.0 eq), (2S)-2-[(4-tert-0 butylphenoxy)methyl]oxirane (1-2) (3.5 g, 19 mmol, 1.1 eq) and cesium carbonate (0.10 g, 0,31 mmol, 0.020 eq) were heated under microwave irradiation at 130 C for 45 minutes. Ethyl acetate was added (200 ml) and the organic layer was washed with water (50 ml) and dried over sodium sulfate. The residue was purified by silica gel chromatography (0-100% ethyl acetate/hexanes) followed by purification by super critical fluid chromatography (ChiraiPak AS-5 H, 21x250mm, 90/10 CO2/Methanol, 70 ml/min) to separate regioisomers and yield (2S)-2- ( { [tert-butyl(dimethyl )si Iy I ]oxy } methy l)-2 , 3 -dihydro [1,3] oxazolo [3 ,2 -a] benzi midazole-7 – carbonitrile (1-3) as a yellow oil. 1H NMR (400 MHz, CDCl3) delta 7.80 (s, 1H), 7.42 (d, 1H, J = 8.2 Hz), 7.19 (d, 1H, J = 8.2 Hz), 5.51-5.44 (m, 1H), 4.35-4.26 (m, 2H), 4.10 (dd, 1H, J – 1 1.8, 3.8 Hz), 3.95 (d, 1H, J – 3.1 Hz), 0.76 (s, 9 H), 0.00 (s, 6 H). LRMS m/z (M+H) 330.0 found,0 330.2 required. The alternative regioisomer (1-4) was also isolated and characterized.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 2-Chloro-1H-benzo[d]imidazole-5-carbonitrile, its application will become more common.

Reference:
Patent; MERCK & CO., INC.; WO2009/140163; (2009); A1;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Adding a certain compound to certain chemical reactions, such as: 401567-00-8, name is 2-Chloro-1H-benzo[d]imidazole-5-carbonitrile, belongs to imidazoles-derivatives compound, can increase the reaction rate and produce products with better performance than those obtained under traditional synthetic methods. Here is a downstream synthesis route of the compound 401567-00-8, Recommanded Product: 401567-00-8

General procedure: A mixture of 10 (345 mg, 0.853 mmol), 2,5-dichlorobenzimidazole (11a) (191 mg, 1.02 mmol) and N,N-diisopropylethylamine (0.18 mL, 1.0 mmol) in N-methyl-2-pyrrolidone (6 mL) was stirred at 100 C overnight. The reaction mixture was poured into water and extracted with ethyl acetate. The extract was washed with brine, dried and concentrated under reduced pressure. The residue was purified by high performance liquid chromatography to give 3-{(2S,4S)-1-benzyloxycarbonyl-4-[4-(5-chlorobenzimidazol-2-yl)piperazin-1-yl]pyrrolidin-2-ylcarbonyl}thiazolidine (122 mg, 26%) as a pale-yellow powder.A mixture of the above compound (110 mg, 0.198 mmol) and 30% hydrogen bromide-acetic acid solution (10 mL) was stirred at room temperature for 6 h. Diethyl ether was added to the reaction mixture, and the precipitate was collected by filtration and recrystallized with ethanol to give the title compound (56 mg, 40%) as a white powder.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 2-Chloro-1H-benzo[d]imidazole-5-carbonitrile, and friends who are interested can also refer to it.

Reference:
Article; Yoshida, Tomohiro; Akahoshi, Fumihiko; Sakashita, Hiroshi; Sonda, Shuji; Takeuchi, Masahiro; Tanaka, Yoshihito; Nabeno, Mika; Kishida, Hiroyuki; Miyaguchi, Ikuko; Hayashi, Yoshiharu; Bioorganic and Medicinal Chemistry; vol. 20; 16; (2012); p. 5033 – 5041;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Reference of 401567-00-8, As we all know, there are many different methods for the synthesis of a compound, and people can choose the synthesis method that suits their own laboratory according to the actual situation. 401567-00-8 name is 2-Chloro-1H-benzo[d]imidazole-5-carbonitrile, This compound is widely used in many fields, so it is necessary to find a new synthetic route. The downstream synthesis method of this compound is introduced below.

General procedure: 4.1.6. General procedure E: removal of SEM group To a solution of SEM-protected compound (1.0 equiv) in THFwas added TBAF (3.0 equiv, 1 M in THF). The mixture was reuxedfor 11-20 h, then cooled to room temperature, and concentratedunder reduced pressure. The residue was puried by silica gel col-umn chromatography or PTLC to afford the product.

At the same time, in my other blogs, there are other synthetic methods of this type of compound, 2-Chloro-1H-benzo[d]imidazole-5-carbonitrile, and friends who are interested can also refer to it.

Reference:
Article; Okazaki, Shogo; Noguchi-Yachide, Tomomi; Sakai, Taki; Ishikawa, Minoru; Makishima, Makoto; Hashimoto, Yuichi; Yamaguchi, Takao; Bioorganic and Medicinal Chemistry; vol. 24; 21; (2016); p. 5258 – 5269;,
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem