3601-66-9Relevant academic research and scientific papers
Discovery of M3Antagonist-PDE4 Inhibitor Dual Pharmacology Molecules for the Treatment of Chronic Obstructive Pulmonary Disease
Armani, Elisabetta,Rizzi, Andrea,Capaldi, Carmelida,De Fanti, Renato,Delcanale, Maurizio,Villetti, Gino,Marchini, Gessica,Pisano, Anna Rita,Pitozzi, Vanessa,Pittelli, Maria Gloria,Trevisani, Marcello,Salvadori, Michela,Cenacchi, Valentina,Puccini, Paola,Amadei, Francesco,Pappani, Alice,Civelli, Maurizio,Patacchini, Riccardo,Baker-Glenn, Charles A.G.,Van De Po?l, Hervé,Blackaby, Wesley P.,Nash, Kevin,Amari, Gabriele
supporting information, p. 9100 - 9119 (2021/07/19)
In this paper, we report the discovery of dual M3 antagonist-PDE4 inhibitor (MAPI) compounds for the inhaled treatment of pulmonary diseases. The identification of dual compounds was enabled by the intuition that the fusion of a PDE4 scaffold derived from our CHF-6001 series with a muscarinic scaffold through a common linking ring could generate compounds active versus both the transmembrane M3 receptor and the intracellular PDE4 enzyme. Two chemical series characterized by two different muscarinic scaffolds were investigated. SAR optimization was aimed at obtaining M3 nanomolar affinity coupled with nanomolar PDE4 inhibition, which translated into anti-bronchospastic efficacy ex vivo (inhibition of rat trachea contraction) and into anti-inflammatory efficacy in vitro (inhibition of TNFα release). Among the best compounds, compound 92a achieved the goal of demonstrating in vivo efficacy and duration of action in both the bronchoconstriction and inflammation assays in rat after intratracheal administration.
Synthesis ofN-Boc-α-amino Acids from Carbon Dioxide by Electrochemical Carboxylation ofN-Boc-α-aminosulfones
Senboku, Hisanori,Minemura, Yoshihito,Suzuki, Yuto,Matsuno, Hidetoshi,Takakuwa, Mayu
, p. 16077 - 16083 (2021/10/12)
Electrochemical reduction ofN-Boc-α-aminosulfones in DMF using an undivided cell equipped with a Pt plate cathode and an Mg rod anode under atmospheric pressure of bubbling carbon dioxide through the solution under constant current conditions resulted in a reductive C-S bond cleavage with elimination of benzenesulfinate ion generating the corresponding anion species followed by fixation of carbon dioxide to give the correspondingN-Boc-α-amino acids in moderate to good yields.
ALLOSTERIC EGFR INHIBITORS AND METHODS OF USE THEREOF
-
Page/Page column 62-63; 90, (2021/01/22)
The disclosure relates to compounds that act as an allosteric inhibitors of epidermal growth factor receptor (EGFR); pharmaceutical compositions comprising the compounds; and methods of treating or preventing kinase-mediated disorders, including cancer and other proliferation diseases.
Mechanism of Oxidative Amidation of Nitroalkanes with Oxygen and Amine Nucleophiles by Using Electrophilic Iodine
Li, Jing,Lear, Martin J.,Kwon, Eunsang,Hayashi, Yujiro
, p. 5538 - 5542 (2016/04/20)
Recently, we developed a direct method to oxidatively convert primary nitroalkanes into amides that entailed mixing an iodonium source with an amine, base, and oxygen. Herein, we systematically investigated the mechanism and likely intermediates of such methods. We conclude that an amine-iodonium complex first forms through N-halogen bonding. This complex reacts with aci-nitronates to give both α-iodo- and α,α-diiodonitroalkanes, which can act as alternative sources of electrophilic iodine and also generate an extra equimolar amount of I+ under O2. In particular, evidence supports α,α-diiodonitroalkane intermediates reacting with molecular oxygen to form a peroxy adduct; alternatively, these tetrahedral intermediates rearrange anaerobically to form a cleavable nitrite ester. In either case, activated esters are proposed to form that eventually reacts with nucleophilic amines in a traditional fashion.
HETEROARYL DERIVATIVES
-
Paragraph 0502; 0503; 0504, (2015/06/17)
Compounds of formula (I) described herein are both phosphodiesterase 4 (PDE4) enzyme inhibitors and muscarinic M3 receptor antagonists and are useful for the prevention and/or treatment of diseases of the respiratory tract characterized by airway obstruction.
HETEROARYL DERIVATIVES FOR THE TREATMENT OF RESPIRATORY DISEASES
-
Page/Page column 116; 117, (2015/06/18)
The invention relates to novel compounds of formula (I) which are both phosphodiesterase 4 (PDE4) enzyme inhibitors and muscarinic M3 receptor antagonists, methods of preparing such compounds, compositions containing them and therapeutic use thereof.
Dual Catalytic Decarboxylative Allylations of α-Amino Acids and Their Divergent Mechanisms
Lang, Simon B.,O'Nele, Kathryn M.,Douglas, Justin T.,Tunge, Jon A.
supporting information, p. 18589 - 18593 (2016/01/25)
The room temperature radical decarboxylative allylation of N-protected α-amino acids and esters has been accomplished via a combination of palladium and photoredox catalysis to provide homoallylic amines. Mechanistic investigations revealed that the stability of the α-amino radical, which is formed by decarboxylation, dictates the predominant reaction pathway between competing mechanisms.
Oxidative Amidation of Nitroalkanes with Amine Nucleophiles using Molecular Oxygen and Iodine
Li, Jing,Lear, Martin J.,Kawamoto, Yuya,Umemiya, Shigenobu,Wong, Alice R.,Kwon, Eunsang,Sato, Itaru,Hayashi, Yujiro
, p. 12986 - 12990 (2015/11/02)
The formation of amides and peptides often necessitates powerful yet mild reagent systems. The reagents used, however, are often expensive and highly elaborate. New atom-economical and practical methods that achieve such goals are highly desirable. Ideally, the methods should start with substrates that are readily available in both chiral and non-chiral forms and utilize cheap reagents that are compatible with a wide variety of functional groups, steric encumberance, and epimerizable stereocenters. A direct oxidative method was developed to form amide and peptide bonds between amines and primary nitroalkanes simply by using I2 and K2CO3 under O2. Contrary to expectations, a 1:1 halogen-bonded complex forms between the iodonium source and the amine, which reacts with nitronates to form α-iodo nitroalkanes as precursors to the amides.
ANTI-PCSK9 COMPOUNDS AND METHODS FOR THE TREATMENT AND/OR PREVENTION OF CARDIOVASCULAR DISEASES
-
Page/Page column 32, (2014/10/04)
Disclosed are compounds that modulate the physiological action of the proprotein convertase subtilisin kexin type 9 (PCSK9), and methods of using these modulators to reduce LDL-cholesterol levels and/or for the treatment and/or prevention of cardiovascular disease (CVD), including treatment of hypercholesterolemia.
One-step synthesis of racemic α-amino acids from aldehydes, amine components, and gaseous CO2 by the aid of a bismetal reagent
Mita, Tsuyoshi,Higuchi, Yuki,Sato, Yoshihiro
, p. 1123 - 1128 (2013/02/23)
α-Amino acids are essential resources for human life and are highly useful as building blocks for organic synthesis. The core framework of an α-amino acid can be divided into three basic components: an aldehyde, an amine, and carbon dioxide (CO2). We report herein that a one-step synthesis of α-amino acids has been successfully achieved from these three basic and inexpensive chemicals with a single operation, in which the mixture of an aldehyde, a sulfonamide, and gaseous CO2 was heated at 100 °C in the presence of Bu3Sn-SnBu3 and CsF. In this one-pot sequential protocol, two important intermediates (imine and α-amino stannane) are involved and the stannyl anion generated in situ plays a crucial role, particularly for the efficient stannylation of the imine in the presence of proton sources and for promoting retrostannylation of the undesired α-alkoxy stannane owing to its high stability and tolerance of the presence of proton sources. This methodology enabled the synthesis of a wide range of racemic arylglycine derivatives in high yields. Go retro! α-Amino acids are essential resources for human life and are highly useful as building blocks for organic synthesis. The core framework of an α-amino acid is retrosynthesized to an aldehyde, an amine, and carbon dioxide. A one-step synthesis of α-amin Copyright
