Day: October 26, 2022

On July 1, 2021, Pinkerton, Anthony; Sergienko, Eduard; Kiyotsuka, Yohei; Kagechika, Katsuji; Kurosaki, Yasunobu; Arai, Yoshikazu; Nagamochi, Masatoshi; Ishibashi, Koutaro published a patent.Safety of 1-Methyl-1H-pyrazolo[4,3-d]pyrimidin-7-ol The title of the patent was Preparation of bicyclic heteroaryls, especially thienopyrimidines, as ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) modulators. And the patent contained the following:

The invention is related to the preparation of bicyclic heteroaryl-based small mol. modulators of ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1), e.g., of formula I [B = aryl or a 5 or 6-membered heteroaryl; n = 0-3; X = (CH2)1-2; p = 0-3; Y1 = NR4, O; L1 = Y2L2, Y2L2L3; Y2 = a bond, CO; L2 = a bond, (un)substituted alk(en/yn)ylene, heteroalkylene, C2-C6 cycloalkylene; R1 = H, halo, CN, OH, etc.; R2 = H, COOH and derivatives, fluoroalkoxy, etc.; R3 = H, halo, SH and derivatives, NH2 and derivatives, etc.; R5 = independently at each occurrence H, NO2, CN, SO2NH2 and derivatives, etc.; R6 = independently at each occurrence halo, alk(en/yn)yl, etc.; ], their pharmaceutically acceptable salts and solvates , compositions containing them, and methods of using the compounds and compositions comprising the compounds for treating disorders associated with ENPP1, such as pseudogout. Thus, II was prepared by cyclization of Me 3-amino-4-methylthiophene-2-carboxylate with formamide, chlorination of 7-methylthieno[3,2-d]pyrimidin-4-ol with POCl3, amination of 4-chloro-7-methylthieno[3,2-d]pyrimidine with tert-Bu (piperidin-4-yl)carbamate, cleavage of tert-butoxycarbonyl group and benzylation of 1-(7-methylthieno[3,2-d]pyrimidin-4-yl)piperidin-4-amine with benzyl chloride. II inhibited ENPP1 in a TR-FRET assay (IC50 in the range of 0.1μM – 1.0μM). The experimental process involved the reaction of 1-Methyl-1H-pyrazolo[4,3-d]pyrimidin-7-ol(cas: 314021-93-7).Safety of 1-Methyl-1H-pyrazolo[4,3-d]pyrimidin-7-ol

The Article related to bicyclic heteroaryl preparation ectonucleotide pyrophosphatase phosphodiesterase 1 enpp1 inhibitor, thienopyrimidine pyrazolopyrimidine pyrazolopyridine thienopyridine preparation enpp1 inhibitor pseudogout antiarthritic, triazolopyrimidine isoxazolopyrimidine pyrazolopyridazine isothiazolopyrimidine preparation enpp1 inhibitor and other aspects.Safety of 1-Methyl-1H-pyrazolo[4,3-d]pyrimidin-7-ol

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

On March 31, 2016, Ashok, Dongamanti; Rangu, Kavitha; Hanumantha Rao, Velagapuri; Gundu, Srinivas; Srilata, Ballu; Vijjulatha, Manga published an article.COA of Formula: C20H14N2O The title of the article was Microwave-assisted synthesis, molecular docking and antimicrobial activity of novel 2-(3-aryl-1-phenyl-1H-pyrazol-4-yl)-8H-pyrano[2,3-f]chromen-4-ones. And the article contained the following:

A series of pyrano[2,3-f]chromenones I [Ar = C6H5, 4-BrC6H4, 3,4-(MeO)2C6H3, 2-naphthyl, etc.] was synthesized via microwave-assisted cyclization of chalcones II in the presence of iodine in DMSO. Precursor chalcones II were prepared by Claisen-Schmidt condensation of 1-(5-hydroxy-2H-chromen-6-yl)ethanone and substituted pyrazole aldehydes using KOH under microwave irradiation This approach for the preparation of pyrano[2,3-f]chromenones I offers the advantages of short reaction time (3-5 min), mild reaction conditions and high yields of products. The newly synthesized compounds I and II were tested in vitro for their antibacterial and antifungal activities. Among the tested compounds, compounds I [Ar = 4-ClC6H4, 4-HOC6H4, 3,4-(MeO)2C6H3] and II [Ar = 3-EtOC6H4] were found to be potent against tested bacterial strains whereas compounds I [Ar = 4-ClC6H4, 3,4-(MeO)2C6H3] and II [Ar = 4-EtOC6H4] were found to be potent against tested fungal strains. Furthermore, the synthesized compounds were subjected to mol. docking studies for the inhibition of enzyme DNA gyrase and compounds I [Ar = 4-HOC6H4, 4-EtOC6H4] showed promising dock score values. The in silico mol. docking results of compounds I and II were in accordance with the in vitro antimicrobial studies and they may be considered as good inhibitor of DNA gyrase. The experimental process involved the reaction of 3-(Naphthalen-2-yl)-1-phenyl-1H-pyrazole-4-carbaldehyde(cas: 36640-53-6).COA of Formula: C20H14N2O

The Article related to pyranochromenone pyrazolyl preparation antibacterial antifungal mol docking, hydroxychromenyl pyrazolyl propenone preparation oxidative cyclization microwave irradiation, pyrazole aldehyde hydroxychromenyl ethanone claisen schmidt condensation microwave irradiation, pyrazolyl hydroxychromenyl propenone antibacterial antifungal mol docking and other aspects.COA of Formula: C20H14N2O

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

On October 4, 2012, Vankayalapati, Hariprasad; Appalaneni, Rajendra P.; Reddy, Y. Venkata Krishna published a patent.COA of Formula: C7H8N4 The title of the patent was Preparation of substituted 5-(pyrazin-2-yl)-1H-pyrazolo[3,4-b]pyridine and pyrazolo[3,4-b]pyridine derivatives as protein kinase inhibitors. And the patent contained the following:

This invention relates to the title compounds I-III [X = N, CH; L1 = a bond, (un)substituted 6-membered aryl, heteroaryl, etc.; R1-R3 = H, halo, CN, etc.; Q = NH, O, S, etc.; L2 = IV (wherein X1 = N, CH; X2 = N, CH; X3 = N, CH; R10 = H, halo, CN, etc.)] which are inhibitors of constitutively activated Tyrosine Kinase-Like (TKL), CMGC protein kinases family members and can be useful in the treatment of Parkinson’s disease, Alzheimer’s disease, Down’s syndrome, Huntington’s disease, other neurodegenerative and central nervous system disorders, cancer, metabolic disorders and inflammatory diseases, and to methods for making them. Seventy title compounds were prepared and formulated. For example, a multi-step synthesis of V, starting from mucobromic acid, was described. Exemplified title compounds were tested in the LRRK2 kinase assay (data given). Also disclosed are pharmaceutical compositions including the title compounds and methods of inhibiting wild type and/or mutated protein kinase activities of these families and the treatment of disorders associated therewith using title compounds and pharmaceutical compositions including the title compounds The experimental process involved the reaction of 3-Methyl-1H-pyrazolo[3,4-b]pyridin-5-amine(cas: 1186608-73-0).COA of Formula: C7H8N4

The Article related to pyrazinylpyrazolopyridine pyrazolopyridine preparation protein kinase inhibitor antitumor antiinflammatory antiparkinsonian, parkinson’s alzheimer’s disease down’s syndrome treatment pyrazinylpyrazolopyridine pyrazolopyridine preparation, huntington’s disease neurodegenerative cns disorder treatment pyrazinylpyrazolopyridine pyrazolopyridine preparation and other aspects.COA of Formula: C7H8N4

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

On July 30, 2020, Tang, Guozhi; Li, Dongbo; Li, Liugen; Zha, Xianchan; Chen, Wenming; Wang, Shaomeng; Yang, Chao-Yie published a patent.Formula: C9H12N2O3 The title of the patent was Preparation of macrocyclic fused pyrazoles as Mcl-1 inhibitors. And the patent contained the following:

The title compounds represented by formula I [R = H or C1-6 alkyl; X = O, S, S(O), S(O)2, or (un)substituted NH; ring A = each (un)substituted 1,3-phenylene or 1,3-naphthalenylene; ring B = arylenyl and heteroarylenyl; ring C = each (un)substituted 1H-pyrazol-3,4-diyl or 1H-pyrazol-4,5-diyl; L1 = [C(R14a)(R14b)]s; L2 = [C(R14c)(R14d)]t; L3 = [C(R14c)(R14f)]v; R14a, R14b, R14d, R14f = each independently H or C1-4 alkyl; s = 2,3,4,5, or 6; t, v = each independently 1,2,3, or 4] or pharmaceutically acceptable salts or solvates thereof are prepared The compounds I are useful for treating a condition or disorder responsive to Mcl-1 inhibition such as cancer, a chronic autoimmune disorder, an inflammatory condition, a proliferative disorder, sepsis, or a viral infection. Thus, Et 7-[2-(bromomethyl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]-6-chloro-3-[3-[[3-[(4-methoxybenzyl)thio]naphthalen-1-yl]oxy]propyl]-1-methyl-1H-indole-2-carboxylate underwent thioetherification with S-[[5-[[(tert-butyldimethylsilyl)oxy]methyl]-1-methyl-1H-pyrazol-3-yl]methyl] ethanethioate in the presence of K2CO3 in methanol/THF at room for 1 h to give 27% Et 7-[2-[[[[5-[[(tert-butyldimethylsilyl)oxy]methyl]-1-methyl-1H-pyrazol-3-yl]methyl]thio]methyl]-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]-6-chloro-3-[3-[[3-[(4-methoxybenzyl)thio]naphthalen-1-yl]oxy]propyl]-1-methyl-1H-indole-2-carboxylate (II; Ra = 4-methoxybenzyl, Rb = tert-butyldimethylsilyloxy) which was treated with Bu4NF·3H2O in dry THF at room temperature for 2 h to give II (Ra = 4-methoxybenzyl, Rb = HO). Bromination of II (Ra = 4-methoxybenzyl, Rb = HO) with CBr4 and PPh3 in CH2Cl2 at room temperature for 3 h gave II (Ra = 4-methoxybenzyl, Rb = Br) as a brown oil which underwent debenzylation by treatment with triethylsilane and CF3CO2H in CH2Cl2 at room temperature overnight to give II (Ra = H, Rb = Br). Cyclization of II (Ra = H, Rb = Br) by treatment with K2CO3 in acetonitrile at room temperature for 3 h gave macrocyclic 7-(pyrrolo[1,2-b]pyrazol-3-yl)indole-2-carboxylic acid Et ester (III; Rc = Et) which was saponified with a mixture of 2 N aqueous NaOH solution, THF, and MeOH at room temperature for 5 h followed by acidification with 1 N aqueous HCl solution to give III (Rc = H) in 3% over 6 steps. III (Rc = H) showed IC50 of 15 nM against the competitive binding of a fluorescein labeled 21-residue Bid BH3 peptide (residues 79-99) [Swiss-Prot: P55957] to Mcl-1 protein. It showed IC50 of 437 and 123 nM against OPM2 and H929 cell, resp., in a cell viability assay. The experimental process involved the reaction of Ethyl 6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carboxylate(cas: 153597-59-2).Formula: C9H12N2O3

The Article related to indolyl fused pyrazole macrocyclic compound preparation mcl 1 inhibitor, macrocyclic fused pyrazole preparation mcl 1 inhibitor, cancer chronic autoimmune disorder treatment macrocyclic fused pyrazole preparation, inflammatory condition proliferative disorder macrocyclic fused pyrazole preparation, sepsis viral infection macrocyclic fused pyrazole preparation and other aspects.Formula: C9H12N2O3

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

On September 30, 2021, Ameriks, Michael K.; Laforteza, Brian Ngo; Ravula, Suchitra; Schiffer, Jamie M.; Stenne, Brice M. published a patent.Electric Literature of 143803-93-4 The title of the patent was Preparation of fused and bridged compounds as monoacylglycerol lipase modulators. And the patent contained the following:

This invention relates to the title compounds I [R1a = alkyl; R1b = H; or R1a and R1b taken together form (CH2)2-3; R2 = (un)substituted Ph, pyridyl, bicyclic heteroaryl; R3 = 1H-alkyl-pyrazolyl, 1H-haloalkyl-pyrazolyl, 1H-pyridyl-pyrazolyl, etc.; with the proviso], and pharmaceutically acceptable salts, isotopes, N-oxides, solvates, and stereoisomers thereof, to pharmaceutical compositions containing them, to methods of making them, and to methods of using them including methods for treating disease states, disorders, and conditions associated with MGL modulation, such as those associated with pain, psychiatric disorders, neurol. disorders (including, but not limited to major depressive disorder, treatment resistant depression, anxious depression, autism spectrum disorders, Asperger syndrome, bipolar disorder), cancers and eye conditions. E.g., a multi-step synthesis of (S)-II, starting from Et L-alaninate hydrochloride and Et 4-bromobutanoate, was described. Exemplified compounds I were tested for their in vitro activity of MGL (data given for representative compounds I). The experimental process involved the reaction of 4-Methylpyrazolo[1,5-a]pyridine-3-carboxylic acid(cas: 143803-93-4).Electric Literature of 143803-93-4

The Article related to analgesics, antidepressants, antitumor agents, anxiety disorders (anxious depression), anxiolytics, asperger syndrome, bipolar disorder, depression (treatment-resistant), eye disease and other aspects.Electric Literature of 143803-93-4

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