Category: 153597-59-2

On August 31, 2017, Chappie, Thomas Allen; Patel, Nandini Chaturbhai; Verhoest, Patrick Robert; Helal, Christopher John; Sciabola, Simone; Lachapelle, Erik Alphie; Wager, Travis T.; Hayward, Matthew Merrill published a patent.Reference of Ethyl 6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carboxylate The title of the patent was 6,7-Dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carboxamide compounds as PDE4 inhibitors and their preparation. And the patent contained the following:

The invention is directed to PDE4B inhibitors of formula Ior a pharmaceutically acceptable salt thereof. The invention is also directed to pharmaceutical compositions comprising the compounds, methods of treatment using the compounds, and methods of preparing the compounds Compounds of formula I wherein R1 is (un)substituted C3-8 cycloalkyl, (un)substituted C6-10 aryl, (un)substituted 5- to 10-membered heteroaryl, etc.; R2 and R3 are independently H, (un)substituted C1-6 alkyl, (un)substituted C3-8 cycloalkyl, (un)substituted C6-10 aryl, etc.; n is 0, 1, 2 and 3; each R4 is independently halo, CN, OH, SF5, NO2, etc.; and pharmaceutically acceptable salts thereof, are claimed. Example compound II was prepared by cross-coupling of azetidin-1-yl(3-bromo-6,7-dihydro-5H-pyrazolo[5,1-b]oxazin-2-yl)methanol with 4-chloro-2-methylphenylboronic acid. The invention compounds were evaluated for their PDE4 inhibitory activity. From the assay, it was determined that compound II exhibited IC50 values of 211 nM, 241 nM and 653 nM towards PDE4B1, PDE4A3 and PDE4C1, resp. 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).Reference of Ethyl 6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carboxylate

The Article related to pyrazolooxazinecarboxamide preparation pde4 inhibitor, Heterocyclic Compounds (More Than One Hetero Atom): Oxazines (Including Morpholine) and other aspects.Reference of Ethyl 6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carboxylate

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 December 7, 2006, Mansour, Tarek Suhayl; Venkatesan, Aranapakam Mudumbai published a patent.HPLC of Formula: 153597-59-2 The title of the patent was Bicyclic 6-alkylidene-penems as class-D β-lactamase inhibitors. And the patent contained the following:

Penems, such as I [R = H, alkali metal, C1-6 alkyl, C5-6 cycloalkyl, or substituted ester; A, B = H, heteroaryl, fused bicycles, fused tricycles, etc.], were prepared for use in pharmaceutical compositions as inhibitors of β-lactamases which are class-D enzymes that hydrolyze β-lactam antibiotics, and as such serve as the primary cause of bacterial resistance. The compounds of the present invention when combined with β-lactam antibiotics will provide an effective treatment against life threatening bacterial infections. Thus, (5R,6Z)-6-(7-methyl-5,6,7,8-tetrahydroimidazo[1,2-a]pyrazin-2-ylmethylene)-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid sodium salt (II) was prepared via a coupling reaction of 7-methyl-5,6,7,8-tetrahydroimidazo[1,2-a]pyrazine-2-carboxaldehyde with (5R,6S)-6-bromo-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid 4-nitrobenzyl ester. The prepared penems were assayed for microbial susceptibility against E. coli GC 2883, a class-D producing organism. 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).HPLC of Formula: 153597-59-2

The Article related to alkylidene penem derivative preparation beta lactamase inhibitor, beta lactam antibiotic alkylidene penem derivative preparation, antibacterial agent alkylidene penem derivative preparation beta lactamase inhibitor, bacterial infection treatment alkylidene penem preparation beta lactamase inhibitor and other aspects.HPLC of Formula: 153597-59-2

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