Category: 637336-53-9

Li, Minglei published the artcileN-Benzylpiperidinol derivatives as novel USP7 inhibitors: structure-activity relationships and X-ray crystallographic studies, Formula: C6H9N3O2, the main research area is piperidinol pyrazolopyrimidinone preparation SAR USP7 inhibitor human; Crystallographic study; Deubiquitinase; Piperidine; Structure-activity relationship; USP7.

Piperidinol derivatives I (R1 = 4-FC6H4; R2 = PhCH2, 2-pyridyl, 2-thiazolyl, etc.) and II (R3 = Br, 4-H2NCH2C6H4, 4-AcNHCH2C6H4CH2, 4-BocNHCH2C6H4; R4 = 2-Cl-4-MeO2CC6H3CH2) were designed, synthesized and biol. evaluated, and the compound II [R3 = 4-H2NCH2C6H4; R4 = 2-Cl-4-MeO2CC6H3CH2; (III)] was identified as a highly selective and potent USP7 inhibitor (IC50 = 40.8 nM, KD = 78.3 nM). X-Ray crystallog. studies revealed that the compound III bound to USP7 with a new pose that was very different than the previously reported inhibitors. The results of cellular assays showed that the compound III had strong antitumor activity against LNCaP (IC50 = 29.6 nM) and RS4; 11 (IC50 = 41.6 nM) cells, probably through inducing cell death and restricting G0/G1 and S phases. Moreover, III dose-dependently reduced the protein levels of MDM2 and DNMT1 and increased the protein levels of p53 and p21.

European Journal of Medicinal Chemistry published new progress about Antitumor agents. 637336-53-9 belongs to class pyrazoles-derivatives, name is Methyl 4-amino-1-methyl-1H-pyrazole-3-carboxylate, and the molecular formula is C6H9N3O2, Formula: C6H9N3O2.

Referemce:
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

La Rosa, Salvatore published the artcileFused 3-Hydroxy-3-trifluoromethylpyrazoles Inhibit Mutant Huntingtin Toxicity, Quality Control of 637336-53-9, the main research area is hydroxytrifluoromethylpyrazole preparation SAR Huntingtons disease; 3-hydroxy-3-trifluoromethylpyrazoles; ADME; Huntington’s disease; R6/2 mouse model; mutant Htt toxicity; phenotypic screening.

Here, we describe the selection and optimization of a chem. series active in both a full-length and a fragment-based Huntington’s disease (HD) assay. Twenty-four thousand small mols. were screened in a phenotypic HD assay, identifying a series of compounds bearing a 3-hydroxy-3-trifluoromethylpyrazole moiety as able to revert the toxicity induced by full-length mutant Htt by up to 50%. A chem. exploration around the series led to the identification of compound (I), which demonstrated to be active in a Htt171-82Q rat primary striatal neuron assay and a PC12-Exon-1 based assay. This compound was selected for testing in R6/2 mice, in which it was well-tolerated and showed a pos. effect on body weight and a pos. trend in preventing ventricular volume enlargement. These studies provide strong rationale for further testing the potential benefits of 3-hydroxy-3-trifluoromethylpyrazoles in treating HD.

ACS Medicinal Chemistry Letters published new progress about Huntington disease. 637336-53-9 belongs to class pyrazoles-derivatives, name is Methyl 4-amino-1-methyl-1H-pyrazole-3-carboxylate, and the molecular formula is C6H9N3O2, Quality Control of 637336-53-9.

Referemce:
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Mugnaini, Claudia published the artcileDesign, Synthesis, and Physicochemical and Pharmacological Profiling of 7-Hydroxy-5-oxopyrazolo[4,3-b]pyridine-6-carboxamide Derivatives with Antiosteoarthritic Activity In Vivo, Quality Control of 637336-53-9, the main research area is hydroxy oxopyrazolopyridine carboxamide preparation antiosteoarthritic osteoarthritis cannabinoid type receptor.

The hallmark of joint diseases, such as osteoarthritis (OA), is pain, originating from both inflammatory and neuropathic components, and compounds able to modulate the signal transduction pathways of the cannabinoid type-2 receptor (CB2R) can represent a helpful option in the treatment of OA. In this perspective, a set of 18 cannabinoid type-2 receptor (CB2R) ligands was developed based on an unprecedented structure. With the aim of improving the physicochem. properties of previously reported 4-hydroxy-2-quinolone-3-carboxamides, a structural optimization program led to the discovery of isosteric 7-hydroxy-5-oxopyrazolo[4,3-b]pyridine-6-carboxamide derivatives These new compounds are endowed with high affinity for the CB2R and moderate to good selectivity over the cannabinoid type-1 receptor (CB1R), associated with good physicochem. characteristics. As to the functional activity at the CB2R, compounds able to act either as agonists or as inverse agonists/antagonists were discovered. Among them, compound I emerged as a potent CB2R agonist able to reduce pain in rats carrying OA induced by injection of monoiodoacetic acid (MIA).

Journal of Medicinal Chemistry published new progress about Anti-inflammatory agents. 637336-53-9 belongs to class pyrazoles-derivatives, name is Methyl 4-amino-1-methyl-1H-pyrazole-3-carboxylate, and the molecular formula is C6H9N3O2, Quality Control of 637336-53-9.

Referemce:
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Mugnaini, Claudia published the artcileSynthesis of novel 2-(1-adamantanylcarboxamido)thiophene derivatives. Selective cannabinoid type 2 (CB2) receptor agonists as potential agents for the treatment of skin inflammatory disease, HPLC of Formula: 637336-53-9, the main research area is adamantanylcarboxamidothiophene preparation cannabinoid 2 receptor agonist skin inflammation; CB2R agonists; CBR ligands; Chemokine release; Skin inflammation.

A set of CB2R ligands, based on the thiophene scaffold, was synthesized and evaluated in in vitro assays. Compounds bearing the 3-carboxylate and 2-(adamantan-1-yl)carboxamido groups together with apolar alkyl/aryl substituents at 5-position or at 4- and 5-positions of the thiophene ring possess high CB2R affinity at low nanomolar concentration, good receptor selectivity, and agonistic functional activity. The full agonist Me 2-[((adamantan-1-yl)carbonyl)amino]-4-ethyl-5-methylthiophene-3-carboxylate , showing the best balance between receptor affinity and selectivity, was tested in vitro in an exptl. model of allergic contact dermatitis and is able to block the release of MCP-2 in HaCaT cells at 10 μM concentration

European Journal of Medicinal Chemistry published new progress about Allergic contact dermatitis. 637336-53-9 belongs to class pyrazoles-derivatives, name is Methyl 4-amino-1-methyl-1H-pyrazole-3-carboxylate, and the molecular formula is C6H9N3O2, HPLC of Formula: 637336-53-9.

Referemce:
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Squarcialupi, Lucia published the artcileStructural refinement of pyrazolo[4,3-d]pyrimidine derivatives to obtain highly potent and selective antagonists for the human A3 adenosine receptor, Safety of Methyl 4-amino-1-methyl-1H-pyrazole-3-carboxylate, the main research area is pyrazolopyrimidine derivative preparation A3 adenosine receptor antagonist structure activity; Adenosine receptor antagonists; G-protein-coupled receptors; Ligand-receptor modeling studies; Pyrazolopyrimidines.

In previous research, the authors identified some 7-oxo- and 7-acylamino-substituted pyrazolo[4,3-d]pyrimidine derivatives as potent and selective human (h) A3 adenosine receptor (AR) antagonists. Herein the authors report on the structural refinement of this class of antagonists aimed at achieving improved receptor-ligand recognition. Hence, substituents with different steric bulk, flexibility and lipophilicity (Me, Ar, heteroaryl, CH2Ph) were introduced at the 5- and 2-positions of the bicyclic scaffold of both the 7-oxo and 7-amino derivatives, and acyl residues were appended on the 7-amino group of the latter. All the 2-phenylpyrazolo[4,3-d]pyrimidin-7-amines and 7-acylamines bearing a 4-methoxyphenyl- or a 2-thienyl group at the 5-position showed high hA3 affinity and selectivity. In particular, the 2-phenyl-5-(2-thienyl)-pyrazolo[4,3-d]pyrimidin-7-(4-methoxybenzoyl)amine 25 (Ki = 0.027 nM) is one of the most potent and selective hA3 antagonists reported so far. By using an in silico receptor-driven approach the obtained binding data were rationalized and the mol. bases of the observed hA3 AR affinities were critically described.

European Journal of Medicinal Chemistry published new progress about Adenosine A3 receptor antagonists. 637336-53-9 belongs to class pyrazoles-derivatives, name is Methyl 4-amino-1-methyl-1H-pyrazole-3-carboxylate, and the molecular formula is C6H9N3O2, Safety of Methyl 4-amino-1-methyl-1H-pyrazole-3-carboxylate.

Referemce:
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Reference of 637336-53-9,Some common heterocyclic compound, 637336-53-9, name is Methyl 4-amino-1-methyl-1H-pyrazole-3-carboxylate, molecular formula is C6H9N3O2, 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.

Synthesis of Compound 32.6 [0287] To a solution of 32.5 (250 mg, 0.5 mmol, 1.0 eq) in DMF (5 mL) were added methyl 4-amino-l-methyl-lH-pyrazole-3-carboxylate (155 mg, 1.0 mmol, 2.0 eq), HBTU (190 mg, 0.5 mmol, 1.0 eq) and DIPEA (130 mg, 1.1 mmol, 2.0 eq). The reaction was stirred at room temperature for 2 h, diluted with EA (100 mL). The mixture was washed with water (30 mL x 3), brine (50 mL), dried over sodium sulfate and concentrated under reduced pressure. The residue was purified by prep-TLC (PE : EA = 1 : 1) to give 32.6 (100 mg, yield: 31%) as a red oil. 1H NMR (400 MHz, DMSO- 6) D delta: 10.29 (s, 1H), 9.07 (s, 1H), 8.61 (d, J = 5.2 Hz, 1H), 8.43 (s, 1H), 8.32 (s, 1H), 7.65 (d, J = 4.8 Hz, 1H), 6.73 (t, J = 5.6 Hz, 1H), 3.96 (s, 3H), 3.93-3.89 (m, 5H), 2.87 (q, J = 6.4 Hz, 2H), 1.60-1.57 (m, 2H), 1.52 (s, 9H), 1.38 (s, 9H), 1.26-1.23 (m, 6H); ESI-MS (M+H) +: 642.0.

The synthetic route of 637336-53-9 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; BIOGEN IDEC MA INC.; JENKINS, Tracy; VESSELS, Jeffery; WO2014/143672; (2014); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Related Products of 637336-53-9, Each compound has different characteristics, and only by selecting the characteristics of the compound suitable for a specific situation can the compound be applied on a large scale. 637336-53-9, name is Methyl 4-amino-1-methyl-1H-pyrazole-3-carboxylate, This compound has unique chemical properties. The synthetic route is as follows.

A mixture of 6-chloro-N-cyclopropyl-8-((4-methoxybenzyl)(methyl) amino)imidazo [1 ,2-bjpyridazine-3 -carboxamide (id) (125 mg, 0.324 mmol), methyl 4- amino-1-methyl-1H-pyrazole-3-carboxylate (101 mg, 0.648 mmol) [Free based (sodium bicarbonate solutionlEtOAc) from HC1 salt purchased from Art-Chem-BBj, Pd2(dba)3 (29.7 mg, 0.032 mmol), XANTPHOS (37.5 mg, 0.065 mmol) and C52CO3 (422 mg, 1.296mmol) in DMA (2 mL) was degassed by bubbling N2 through the mixture for 5 minutes. The reaction vessel was sealed and heated to 125 C for 8 hr. After cooling to rt, the reaction mixture was partitioned between EtOAc (30 ml) and water (20 ml). The organic layer was extracted with iN NaOH (10 ml) and the combined aqueous layers were washed with EtOAc (20 ml). The aqueous layer was acidified to pH 1 with iN HC1 andthe mixture was transfered to a separatory funnel and the aqueous layer was extracted with EtOAc (3 x 25 ml). The combined organic layers were washed with 10%LiC1 solution (2 x 50 ml) and brine (50 ml). After drying (Na2SO4) and filtration the organic layer was concentrated to afford 4-((3 -(cyclopropylcarbamoyl)-8-((4-methoxybenzyl)- (methyl)amino)imidazo [1 ,2-bj pyridazin-6-yl)amino)- 1-methyl- 1H-pyrazole-3 -carboxylicacid (le) (126 mg, 0.257 mmol, 79 % yield) as a tan solid. LC retention time 2.60 mm [Cj. MS (E+) m/z: 491 (MF-T)

The chemical industry reduces the impact on the environment during synthesis Methyl 4-amino-1-methyl-1H-pyrazole-3-carboxylate. I believe this compound will play a more active role in future production and life.

Reference:
Patent; BRISTOL-MYERS SQUIBB COMPANY; SPERGEL, Steven, H.; MERTZMAN, Michael, E.; (132 pag.)WO2018/67432; (2018); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Reference of 637336-53-9, In the chemical reaction process, reaction time, type of solvent, can easily affect the result of the reaction, thereby determining the yield and properties of the reaction product. An updated downstream synthesis route of 637336-53-9 as follows.

Isoamyl nitrite (1 .3 ml_, 9.67mmol) was added drop-wise to a suspension of methyl 4- amino-1 -methyl-1 H-pyrazole-3-carboxylate (p70, 1 g, 6.45 mmol), CuBr2 (1 .44 g, 6.45 mmol) and CuBr (924 mg, 6.45 mmol) in MeCN (25 ml_). The resulting mixture was stirred at 80 C for 2 hrs. After cooling to RT the volatiles were evaporated under vacuum and the residue was purified by FC on S1O2 column (eluting from cHex to 40% EtOAc) to afford methyl 4-bromo- 1 -methyl- 1 H-pyrazole-3-carboxylate (p71 , 500 mg, y= 35 %) as brown solid. MS (mlz): 220.9 [MH]+

According to the analysis of related databases, 637336-53-9, the application of this compound in the production field has become more and more popular.

Reference:
Patent; CHRONOS THERAPEUTICS LIMITED; MICHELI, Fabrizio; CREMONESI, Susanna; SEMERARO, Teresa; TARSI, Luca; GIBSON, Karl Richard; (116 pag.)WO2019/81939; (2019); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

Some common heterocyclic compound, 637336-53-9, name is Methyl 4-amino-1-methyl-1H-pyrazole-3-carboxylate, molecular formula is C6H9N3O2, 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. Quality Control of Methyl 4-amino-1-methyl-1H-pyrazole-3-carboxylate

Synthesis of compound 3d: 4-(3-{3-[5-(tert-Butoxycarbonylamino-methyl)-pyridin-3-yl]-6-oxo-6H-pyridazin-1-ylmethyl}-benzoylamino)-1-methyl-1H-pyrazole-3-carboxylic acid methyl ester A mixture of 3-{3-[5-(tert-Butoxycarbonylamino-methyl)-pyridin-3-yl]-6-oxo-6H-pyridazin-1-ylmethyl}-benzoic acid lithium salt (240.0 mg; 0.54 mmol; 1.0 eq.), (benzotriazol-1-yloxy)tris(dimethylamino)-phosphonium hexafluorophosphate (321.5 mg; 0.71 mmol; 1.3 eq.) and ethyldiisopropylamine (0.14 ml; 0.81 mmol; 1.5 eq.) in DMF (3 ml) was stirred at rt for 4 h. The reaction mixture was poured into water and extracted with ethyl acetate, washed with brine and concentrated to yield the crude title compound as off-white solid (310.0 mg; yield: 100%), which was used for next step without further purification. LC-MS (M+H)+: 574.

These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 637336-53-9, its application will become more common.

Reference:
Patent; Merck Patent GmbH; CHEN, Xiaoling; LAN, Ruoxi; JORAND-LEBRUN, Catherine; YU, Henry; GOUTOPOULOS, Andreas; (34 pag.)US2016/229871; (2016); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics

These common heterocyclic compound, 637336-53-9, name is Methyl 4-amino-1-methyl-1H-pyrazole-3-carboxylate, its 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. category: pyrazoles-derivatives

A solution of compound from step a (775 mg, 5 mmol), 1-chloro-2-(2-chloroethoxy)ethane (1420 mg, 10 mmol), KI (1660 mg, 10 mmol) and K2CO3 (2070 mg,15 mmol) in DMF (60 mL) was stirred for 3 hours at 120 oC. The solvent was removed and it was purified by reverse phase C18 column chromatography (MeCN/H2O) to give desired compound as a light yellow solid. (450 mg, 40%). ESI-MS m/z: 226.0 [M+H]+.

The synthetic route of Methyl 4-amino-1-methyl-1H-pyrazole-3-carboxylate has been constantly updated, and we look forward to future research findings.

Reference:
Patent; ENANTA PHARMACEUTICALS, INC.; SHOOK, Brian, C.; KIM, In, Jong; BLAISDELL, Thomas, P.; YU, Jianming; PANARESE, Joseph; LIN, Kai; RHODIN, Michael, H.J.; McALLISTER, Nicole, V.; OR, Yat, Sun; (447 pag.)WO2019/67864; (2019); A1;,
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics