Tag: 100-200

Discovery of (S)-1-(1-(4-Chloro-3-fluorophenyl)-2-hydroxyethyl)-4-(2-((1-methyl-1H-pyrazol-5-yl)amino)pyrimidin-4-yl)pyridin-2(1H)-one (GDC-0994), an Extracellular Signal-Regulated Kinase 1/2 (ERK1/2) Inhibitor in Early Clinical Development was written by Blake, James F.;Burkard, Michael;Chan, Jocelyn;Chen, Huifen;Chou, Kang-Jye;Diaz, Dolores;Dudley, Danette A.;Gaudino, John J.;Gould, Stephen E.;Grina, Jonas;Hunsaker, Thomas;Liu, Lichuan;Martinson, Matthew;Moreno, David;Mueller, Lars;Orr, Christine;Pacheco, Patricia;Qin, Ann;Rasor, Kevin;Ren, Li;Robarge, Kirk;Shahidi-Latham, Sheerin;Stults, Jeffrey;Sullivan, Francis;Wang, Weiru;Yin, Jianping;Zhou, Aihe;Belvin, Marcia;Merchant, Mark;Moffat, John;Schwarz, Jacob B.. And the article was included in Journal of Medicinal Chemistry in 2016.Electric Literature of C5H9N3 This article mentions the following:

The extracellular signal-regulated kinases ERK1/2 represent an essential node within the RAS/RAF/MEK/ERK signaling cascade that is commonly activated by oncogenic mutations in BRAF or RAS or by upstream oncogenic signaling. While targeting upstream nodes with RAF and MEK inhibitors has proven effective clin., resistance frequently develops through reactivation of the pathway. Simultaneous targeting of multiple nodes in the pathway, such as MEK and ERK, offers the prospect of enhanced efficacy as well as reduced potential for acquired resistance. Described herein is the discovery and characterization of GDC-0994 (22), an orally bioavailable small mol. inhibitor selective for ERK kinase activity. In the experiment, the researchers used many compounds, for example, 1-Ethyl-1H-pyrazol-5-amine (cas: 3528-58-3Electric Literature of C5H9N3).

1-Ethyl-1H-pyrazol-5-amine (cas: 3528-58-3) belongs to pyrazole derivatives. Pyrazoles, a five-membered heterocycle containing two adjacent nitrogen atoms, are the core structures found in a number of molecules that possess a wide range of pharmaceutical and agricultural activities. Pyrazoles are commonly used scaffold molecules in drug discovery projects. The use of pyrazole derivatives is based on their analgesic, anti-inflammatory, antipyretic, antiarrhythmic, sedative, muscle relaxant, neuroleptic, anticonvulsant, monoamine oxidase inhibitory, antidiabetic and antibacterial activities.Electric Literature of C5H9N3

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

Molecular-orbital and structural descriptors in theoretical investigation of electroreduction of nitrodiazoles was written by Kolaric, Branko;Juranic, Ivan;Dumanovic, Dragica. And the article was included in Journal of the Serbian Chemical Society in 2005.Computed Properties of C4H5N3O2 This article mentions the following:

It is shown how a simple theor. approach can be used for the investigation of electro-organic reactions. Mononitroimidazoles and mononitropyrazoles were studied by the semiempirical MNDO-PM3 MO method. The electrochem. reduction potentials of diazoles have been correlated with the energy of the LUMO. It was found that an admirable correlation could be obtained by the introduction of simple structural descriptors as a correction to the energy of the LUMO. The interaction of a mol. with its surrounding depends on electrostatic potential and on steric hindrance. Most of these steric effects are taken into account using two parameters having a very limited set of integer values. The first (灏? is the position of a ring substituent regarding ring nitrogens, which accounts for the different orientations of dipole moments and for the different shape of the electrostatic potential. The second (structural) parameter (锜? is the type of the ring, which accounts mostly for different modes of electrode approach, and for different charge polarization patterns in two diazole rings. The extended correlation with E_LUMO, 灏?and 锜? is very good, having a regression coefficient r = 0.991. The intrinsic importance of 灏?and 锜?is exemplified by their high statistical weight In the experiment, the researchers used many compounds, for example, 1-Methyl-3-nitro-1H-pyrazole (cas: 54210-32-1Computed Properties of C4H5N3O2).

1-Methyl-3-nitro-1H-pyrazole (cas: 54210-32-1) belongs to pyrazole derivatives. Pyrazole and its derivatives are considered a pharmacologically important active scaffold that possesses almost all types of pharmacological activities. Pyrazole the presence of this nucleus in pharmacological agents of diverse therapeutic categories such as celecoxib, a potent anti-inflammatory, the antidepressant agent fezolamide have proved the pharmacological potential of the pyrazole moiety. Computed Properties of C4H5N3O2

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

Thiophene isosteres: synthesis and pharmacological study of 3-(azol-1-yl)thienoisothiazole 1,1-dioxides was written by Vega, Salvador;Madronero, Ramon;Diaz, J. Antonio;Junquera, Francisco;Alonso, Javier;Darias, Victoriano;Bravo, Luis;Abdalah, Suzanne. And the article was included in European Journal of Medicinal Chemistry in 1988.Product Details of 15953-73-8 This article mentions the following:

Three series of new 3-(azol-1-yl)thienoisothiazole 1,1-dioxides, e.g., I (X = S, X¹ = CH; X = CH, CPh, X¹ = S: R, R¹, R² = H, Cl, Me) were synthesized and tested for antiinflammatory, analgesic and antipyretic activity as well as for acute toxicity. Acetylsalicylic acid was used as the reference standard In the experiment, the researchers used many compounds, for example, 4-Chloro-3,5-dimethyl-1H-pyrazole (cas: 15953-73-8Product Details of 15953-73-8).

4-Chloro-3,5-dimethyl-1H-pyrazole (cas: 15953-73-8) belongs to pyrazole derivatives. As is the case with imidazoles, the pyrazole ring offers many opportunities to create new multiring systems that incorporate this heterocycle. Pyrazoles can be selectively lithiated at different carbons and subsequently react with electrophiles depending on the substitution patterns.Product Details of 15953-73-8

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

Nitro azines. 20. Simple syntheses of pyrazolo-condensed nitropyridines from aliphatic nitro synthons and aminopyrazoles was written by Rusinov, V. L.;Petrova, A. Yu.;Chupakhin, O. N.. And the article was included in Khimiya Geterotsiklicheskikh Soedinenii in 1992.Recommanded Product: 55361-49-4 This article mentions the following:

Treating aminopyrazoles I (R, R¹ = H, Me, Ph) with the Na salt of O₂NCH(CHO)₂ in water gave 65-75% pyrazolopyridines II (R = H, R¹ = Ph, Me, H; R = Me, R¹ = Me, H; R = Ph, R¹ = H); and in AcOH 70-90% II (R = H, Me, Ph, R¹ = Ph; R = H, Me, R¹ = Me) were obtained. Addnl. obtained were pyrazolopyridines III (R = H, Me, R¹ = Ph). In the experiment, the researchers used many compounds, for example, 1-Ethyl-1H-pyrazol-3-amine (cas: 55361-49-4Recommanded Product: 55361-49-4).

1-Ethyl-1H-pyrazol-3-amine (cas: 55361-49-4) belongs to pyrazole derivatives. Pyrazole is a weak base, with pKb 11.5 (pKa of the conjugated acid 2.49 at 25 鎺矯).Pyrazole used as a ligand to prepare organometallic compounds. Pyrazole rings have been used as core components of several leading non-steroidal anti-inflammatory drugs (NSAIDs) and antihypertensive drugs. It has also been found to be useful as a bifunctional ligand for metal catalysis.Recommanded Product: 55361-49-4

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

Transition metal azolates from metallocenes. Part 3: polymeric manganese(II) and nickel(II) pyrazolates; synthesis, characterization, and magnetochemistry was written by Storr, Alan;Summers, David A.;Thompson, Robert C.. And the article was included in Canadian Journal of Chemistry in 1998.Recommanded Product: 15953-73-8 This article mentions the following:

Direct reactions of nickelocene and manganocene with molten pyrazoles in an inert atm. or under vacuum gave the following metal pyrazolate compounds: [Ni(4-Xpz)₂]_x (X = H, Cl and pz = pyrazolate); [M(4-Xdmpz)₂]_x (X = Cl, Br and pzH = pyrazole). On the bases of indirect evidence all compounds are considered to have extended chain structures with metal ions linked in chains by double bridging pyrazolates. The two [Ni(4-Xpz)₂]_x compounds are diamagnetic compounds while all others are paramagnetic and reveal antiferromagnetic coupling between neighboring metal ions. Analyses of the magnetic data (Hamiltonian H = -2J 鍗?S_i-S_j) yields values of the exchange coupling compounds and -0.41 cm^-1 for the [Mn(4-Xpz)₂(4-XpzH)]_x compounds In the experiment, the researchers used many compounds, for example, 4-Chloro-3,5-dimethyl-1H-pyrazole (cas: 15953-73-8Recommanded Product: 15953-73-8).

4-Chloro-3,5-dimethyl-1H-pyrazole (cas: 15953-73-8) belongs to pyrazole derivatives. The 1H-pyrazole provides an excellent means by which to provide the requisite hydrogen bond acceptor閳ユ徆onor motifs, whether as a monocyclic ring or as a fused indazole ring. The presence of both electronegative nitrogen atoms in the pyrazole ring reduces the electron density of the C3- and C5-positions leaving electron density of C4-position unaltered. Thus the C4-position is vulnerable to electrophilic attack. The C3 electrophilic-position may undergo deprotonation in the presence of a strong base leading to ring opening.Recommanded Product: 15953-73-8

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

The substituent effects on the chemical shifts of aromatic protons in heterocyclic compounds was written by Liang, Desheng;Lai, Zhugen;Xu, Guanzhi;Jiang, Mingqian. And the article was included in Huaxue Xuebao in 1982.Category: pyrazoles-derivatives This article mentions the following:

The substituent effect on the chem. shifts in ³H NMR of aromatic heterocycles (e.g., furan, thiophene) depended on the electronic effect and the position of the substituents. An empirical formula was derived and the chem. shifts of >700 aromatic protons were calculated to show a deviation of ±0.2-0.3 ppm. In the experiment, the researchers used many compounds, for example, 3-Methyl-4-nitro-1H-pyrazole (cas: 5334-39-4Category: pyrazoles-derivatives).

3-Methyl-4-nitro-1H-pyrazole (cas: 5334-39-4) belongs to pyrazole derivatives. Pyrazoles, a five-membered heterocycle containing two adjacent nitrogen atoms, are the core structures found in a number of molecules that possess a wide range of pharmaceutical and agricultural activities. Pyrazoles and pyrimidines have diverse biological and pharmacological activities. There are a number of antimicrobial compounds containing pyrazole moiety as the core unit. Pyrazofurin is important antimicrobial drug and 2-methylpyrimidine-4-ylamine derivatives I and II were found to be effective inhibitors of Escherichia coli PDHc-E1 with antibacterial and antifungal activity.Category: pyrazoles-derivatives

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

Pyrazolo-pyrimidines: A novel heterocyclic scaffold for potent and selective p38α inhibitors was written by Das, Jagabandhu;Moquin, Robert V.;Pitt, Sidney;Zhang, Rosemary;Shen, Ding Ren;McIntyre, Kim W.;Gillooly, Kathleen;Doweyko, Arthur M.;Sack, John S.;Zhang, Hongjian;Kiefer, Susan E.;Kish, Kevin;McKinnon, Murray;Barrish, Joel C.;Dodd, John H.;Schieven, Gary L.;Leftheris, Katerina. And the article was included in Bioorganic & Medicinal Chemistry Letters in 2008.Recommanded Product: 1-Ethyl-1H-pyrazol-3-amine This article mentions the following:

The synthesis and structure-activity relationships (SAR) of p38α MAP kinase inhibitors based on a pyrazolo-pyrimidine scaffold are described. These studies led to the identification of compound I as a potent and selective inhibitor of p38α MAP kinase with excellent cellular potency toward the inhibition of TNFα production I was highly efficacious in vivo in inhibiting TNFα production in an acute murine model of TNFα production X-ray co-crystallog. of a pyrazolopyrimidine analog bound to unphosphorylated p38α is also disclosed. In the experiment, the researchers used many compounds, for example, 1-Ethyl-1H-pyrazol-3-amine (cas: 55361-49-4Recommanded Product: 1-Ethyl-1H-pyrazol-3-amine).

1-Ethyl-1H-pyrazol-3-amine (cas: 55361-49-4) belongs to pyrazole derivatives. The strategies for the synthesis of pyrazoles generally can be applied for the construction of indazoles. The presence of both electronegative nitrogen atoms in the pyrazole ring reduces the electron density of the C3- and C5-positions leaving electron density of C4-position unaltered. Thus the C4-position is vulnerable to electrophilic attack. The C3 electrophilic-position may undergo deprotonation in the presence of a strong base leading to ring opening.Recommanded Product: 1-Ethyl-1H-pyrazol-3-amine

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

CO₂ Hydrogenation and Formic Acid Dehydrogenation Using Ir Catalysts with Amide-Based Ligands was written by Kanega, Ryoichi;Ertem, Mehmed Z.;Onishi, Naoya;Szalda, David J.;Fujita, Etsuko;Himeda, Yuichiro. And the article was included in Organometallics in 2020.Formula: C6H9N3O This article mentions the following:

A series of Ir catalysts [Cp*Ir(H₂O)(QCXNHR)][SO₄] (1–16; Q = 2-pyridyl, 4-hydroxy-2-pyridyl, 6-hydroxy-2-pyridyl, 2-imidazolyl, 1-pyrazolyl; X = O, S, NH; R = H, Me, Ph, 4-hydroxyphenyl) bearing amide-based ligands were isolated or generated in situ by a deprotonated amide moiety with the hypotheses that strong electron-donating ability of the coordinated anionic nitrogen atom and the proton-responsive OH group near the metal center will improve the catalytic activity for CO₂ hydrogenation and formic acid (FA) dehydrogenation. The effects of the modifications of the ligand architecture on the catalytic activity were investigated for CO₂ hydrogenation at ambient conditions (25° with 0.1 MPa H₂/CO₂ (volume/volume = 1/1)) and under slightly harsher conditions (50° with 1.0 MPa H₂/CO₂) in basic aqueous solutions together with deuterium kinetic isotope effects (KIEs) with selected catalysts. Complex [Cp*Ir(L12)(H₂O)][HSO₄] (12, L12 = 6-hydroxy-N-phenylpicolinamidate) that has an anionic coordinating N atom and an OH group in the second coordination sphere, exhibits a TOF of 198 h^-1 based on the initial 1 h of reaction. This TOF which, to the best of our knowledge, is the highest value ever reported under ambient conditions in basic aqueous solutions However, complex [Cp*Ir(L10)(H₂O)][HSO₄] (L10 = 4-hydroxy-N-methylpicolinamidate) performs better in long-term CO₂ hydrogenation (up to a TON of 14700 with [Ir] = 10μM after 348 h and the final formate concentration of 0.643 M with [Ir] = 250μM.) at ambient conditions. Further, the catalytic activity for FA dehydrogenation was examined under three different conditions (pH 1.6, 2.3 and 3.5). The complex 12 in any of these conditions is less active compared to the picolinamidate catalysts without ortho-OH, owing to its instability. Theor. calculations were performed to examine the catalytic mechanism, and a step-by-step mechanism has been proposed for both CO₂ hydrogenation and FA dehydrogenation reactions. D. functional theory calculations of [Cp*Ir(L3)(H₂O)][HSO₄] (L3 = picolinamidate) and the X-ray structure of the [Cp*Ir(L7)(H)]•H₂O (L7 = N-methylpicolinamidate) complex imply a pH-dependent conformational change from N,N coordination to N,O coordination upon lowering the pH of the aqueous solution In the experiment, the researchers used many compounds, for example, 3,5-Dimethyl-1H-pyrazole-1-carboxamide (cas: 934-48-5Formula: C6H9N3O).

3,5-Dimethyl-1H-pyrazole-1-carboxamide (cas: 934-48-5) belongs to pyrazole derivatives. An alternative way to synthesize multisubstituted pyrazoles is the Csingle bondH arylation of simple pyrazoles. Protonation of pyrazole in strong acid leads to pyrazolium cations, which undergo electrophilic substitution preferentially at C3 rather than C4. The pyrazole anion is not reactive toward nucleophiles but is mostly reactive to electrophiles.Formula: C6H9N3O

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

Oxidation of pyrazolinones was written by Bischoff, Christian;Ramm, Matthias;Schroeder, Edith;Jancke, Harald. And the article was included in Journal fuer Praktische Chemie/Chemiker-Zeitung in 1994.Computed Properties of C4H5BrN2O This article mentions the following:

Oxidation of pyrazolinones I (R = H, Ph, CONH₂) with H₂O₂/HCOOH gave dimer II which underwent cleavage on treatment with either phenylhydrazine or Br₂ to pyrazolinones III (Q = :NNHPh, Br, resp.). In the experiment, the researchers used many compounds, for example, 4-Bromo-3-methyl-1H-pyrazol-5(4H)-one (cas: 51395-52-9Computed Properties of C4H5BrN2O).

4-Bromo-3-methyl-1H-pyrazol-5(4H)-one (cas: 51395-52-9) belongs to pyrazole derivatives. An alternative way to synthesize multisubstituted pyrazoles is the Csingle bondH arylation of simple pyrazoles. The pyrazole ring is resistant to oxidation and reduction but the groups, such as alkyl and formyl attached to the ring, are oxidized to respective acids. Only electrolytic oxidation, ozonolysis, and a strong base cause ring opening.Computed Properties of C4H5BrN2O

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

Novel η³-Allylpalladium-Pyridinylpyrazole Complex: Synthesis, Reactivity, and Catalytic Activity for Cyclopropanation of Ketene Silyl Acetal with Allylic Acetates was written by Satake, Akiharu;Nakata, Tadashi. And the article was included in Journal of the American Chemical Society in 1998.Application of 19959-77-4 This article mentions the following:

Novel cationic η³-allylpalladium-pyridinylpyrazole complexes I (R = Me, Bu^t) were synthesized from 3-alkyl-5-(2-pyridinyl)pyrazole and η³-allylpalladium chloride dimer in the presence of AgBF₄. Cationic complexes I were converted into neutral complexes II under basic conditions. These complexes were characterized by ¹H, ¹³C, and ¹⁵N NMR studies. Neutral complexes II have high catalytic activity for cyclopropanation of ketene silyl acetals with allylic acetates. Comparison of the cationic and neutral complexes and the reaction mechanism of cyclopropanation were discussed. In the experiment, the researchers used many compounds, for example, 2-(5-Methyl-1H-pyrazol-3-yl)pyridine (cas: 19959-77-4Application of 19959-77-4).

2-(5-Methyl-1H-pyrazol-3-yl)pyridine (cas: 19959-77-4) belongs to pyrazole derivatives. Pyrazole has two ring nitrogen atoms in which N1 is pyrrolic and N2 is pyridine-like. The N1 nitrogen is not reactive but is deprotonated in the presence of a base-forming anion. The pyrazole ring is resistant to oxidation and reduction but the groups, such as alkyl and formyl attached to the ring, are oxidized to respective acids. Only electrolytic oxidation, ozonolysis, and a strong base cause ring opening.Application of 19959-77-4

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