Tag: M.W=100-150

Jersovs, Glebs published the artcileSynthetic Approach toward Enantiopure Cyclic Sulfinamides, Recommanded Product: (S)-2-Methylpropane-2-sulfinamide, the main research area is sulfinamide haloalkenyl diastereoselective cyclization tert butyl cleavage; cyclic sulfinamide asym synthesis oxidation alkylation.

A synthetic approach toward densely substituted enantiopure cyclic sulfinamides possessing up to four consecutive stereogenic centers has been developed based on a completely diastereoselective SN2′ cyclization/tert-Bu cleavage sequence. Diastereospecific transformation of the obtained scaffold into chiral SVI derivatives such as sulfoximines and sulfonimidamides is demonstrated.

Organic Letters published new progress about Bond cleavage. 343338-28-3 belongs to class amides-buliding-blocks, name is (S)-2-Methylpropane-2-sulfinamide, and the molecular formula is C4H11NOS, Recommanded Product: (S)-2-Methylpropane-2-sulfinamide.

Referemce:
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

Okuma, Rika published the artcileA macrocyclic peptide library with a structurally constrained cyclopropane-containing building block leads to thiol-independent inhibitors of phosphoglycerate mutase, COA of Formula: C4H11NOS, the main research area is peptide cyclopropane macrocycle library thioether synthesis mRNA encoded; cyclopropane amino acid synthesis peptide cyclization anthelmintic agent filarial; anthelmintic drug target phosphoglycerate mutase enzyme inhibiting structure activity; DNA library sequence mutagenesis genetic code reprogramming SPR; cyclopropane; genetic code reprogramming; mRNA display; macrocyclic peptide.

Here we report the construction of an mRNA-encoded library of thioether-closed macrocyclic peptides by using an N-chloroacetyl-cyclopropane-containing exotic initiator whose structure is more constrained than the ordinary N-chloroacetyl-α-amino acid initiators. The use of such an initiator has led to a macrocycle library with significantly suppressed population of lariat-shaped species compared with the conventional libraries. We previously used a conventional library and identified a small lariat thioether-macrocycle with a tail peptide with a C-terminal free Cys whose side-chain plays an essential role in potent inhibitory activity against a parasitic model enzyme, phosphoglycerate mutase. On the other hand, the cyclopropane-containing macrocycle library has yielded a larger thioether-macrocycle lacking a free Cys residue, which exhibits potent inhibitory activity to the same enzyme with a different mode of action. This result indicates that such a cyclopropane-containing macrocycle library would allow us to access mechanistically distinct macrocycles.

Chemistry – An Asian Journal published new progress about Aminoacylation. 343338-28-3 belongs to class amides-buliding-blocks, name is (S)-2-Methylpropane-2-sulfinamide, and the molecular formula is C4H11NOS, COA of Formula: C4H11NOS.

Referemce:
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

Corte, James R. published the artcilePotent, Orally Bioavailable, and Efficacious Macrocyclic Inhibitors of Factor XIa. Discovery of Pyridine-Based Macrocycles Possessing Phenylazole Carboxamide P1 Groups, HPLC of Formula: 343338-28-3, the main research area is thrombosis FXIa inhibitors orally bioavailable blood coagulation enzymes.

Factor XIa (FXIa) inhibitors are promising novel anticoagulants, which show excellent efficacy in preclin. thrombosis models with minimal effects on hemostasis. The discovery of potent and selective FXIa inhibitors which are also orally bioavailable has been a challenge. Here, we describe optimization of the imidazole-based macrocyclic series and our initial progress toward meeting this challenge. A two-pronged strategy, which focused on replacement of the imidazole scaffold and the design of new P1 groups, led to the discovery of potent, orally bioavailable pyridine-based macrocyclic FXIa inhibitors. Moreover, pyridine-based macrocycle 19, possessing the phenylimidazole carboxamide P1, exhibited excellent selectivity against relevant blood coagulation enzymes and displayed antithrombotic efficacy in a rabbit thrombosis model.

Journal of Medicinal Chemistry published new progress about Anticoagulants. 343338-28-3 belongs to class amides-buliding-blocks, name is (S)-2-Methylpropane-2-sulfinamide, and the molecular formula is C4H11NOS, HPLC of Formula: 343338-28-3.

Referemce:
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

Fang, Tianan published the artcileOrally bioavailable amine-linked macrocyclic inhibitors of factor XIa, SDS of cas: 343338-28-3, the main research area is preparation oral amine linked macrocyclic factor XIa inhibitor anticoagulant; Activated partial thromboplastin time; FXIa; Factor Xia; Thrombosis; aPTT.

The discovery of orally bioavailable FXIa inhibitors has been a challenge. Herein, we describe our efforts to address this challenge by optimization of our imidazole-based macrocyclic series. Our optimization strategy focused on modifications to the P2 prime, macrocyclic amide linker, and the imidazole scaffold. Replacing the amide of the macrocyclic linker with amide isosteres led to the discovery of substituted amine linkers which not only maintained FXIa binding affinity but also improved oral exposure in rats. Combining the optimized macrocyclic amine linker with a pyridine scaffold afforded compounds 23 and 24 that were orally bioavailable, single-digit nanomolar FXIa inhibitors with excellent selectivity against relevant blood coagulation enzymes.

Bioorganic & Medicinal Chemistry Letters published new progress about Anticoagulants. 343338-28-3 belongs to class amides-buliding-blocks, name is (S)-2-Methylpropane-2-sulfinamide, and the molecular formula is C4H11NOS, SDS of cas: 343338-28-3.

Referemce:
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

Reichard, Holly A. published the artcileDiscovery of TAK-041: a Potent and Selective GPR139 Agonist Explored for the Treatment of Negative Symptoms Associated with Schizophrenia, COA of Formula: C4H11NOS, the main research area is amidomethyl benzotriazinone preparation antipsychotic structure activity relationship.

The chem. optimization that led to the discovery and validation of multiple potent and selective in vivo GPR139 agonist tool compounds, including our clin. candidate TAK-041, also known as NBI-1065846. The pharmacol. characterization of these GPR139 agonists in vivo demonstrated GPR139-agonist-dependent modulation of habenula cell activity and revealed consistent in vivo efficacy to rescue social interaction deficits in the BALB/c mouse strain. The clin. GPR139 agonist TAK-041 was being explored as a novel drug to treat neg. symptoms in SCZ.

Journal of Medicinal Chemistry published new progress about Antipsychotics. 343338-28-3 belongs to class amides-buliding-blocks, name is (S)-2-Methylpropane-2-sulfinamide, and the molecular formula is C4H11NOS, COA of Formula: C4H11NOS.

Referemce:
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

Prasad, Kavirayani R. published the artcileStereoselective addition of Grignard reagents to sulfinimines derived from tartrate diol (threitol): Generation of chiral building blocks for the collective total synthesis of lentiginosine, conhydrine and methyldihydropalustramate, Product Details of C4H11NOS, the main research area is stereoselective Grignard sulfinimine threitol sulfinimine; lentiginosine synthesis; conhydrine synthesis; methyl dihydropalustramate synthesis.

A systematic investigation of the addition of Grignard reagents to sulfinimines derived from tartaric acid diol was undertaken. It was observed that the chirality of the inherent tartrate moiety influences the diastereoselectivity of the resultant sulfinamides formed in the reaction. The formed products serve as excellent building blocks for the synthesis of natural products. This has been demonstrated in the collective total synthesis of lentiginosine, (+)-α-conhydrine and Me dihydropalustramate (I – III, resp.).

Tetrahedron published new progress about Chiral auxiliary. 343338-28-3 belongs to class amides-buliding-blocks, name is (S)-2-Methylpropane-2-sulfinamide, and the molecular formula is C4H11NOS, Product Details of C4H11NOS.

Referemce:
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

Zhu, Yijun published the artcileA novel and efficient asymmetric synthesis of anti-HIV drug maraviroc, Computed Properties of 343338-28-3, the main research area is maraviroc antiHIV drug preparation enantioselective.

A novel and efficient route to asym. synthesis of maraviroc by using (S)-tert-butanesulfinamide as chiral auxiliary is described. Two interesting impurities of the process are isolated and identified. The synthesis was concise, mild, and easy to operate. The overall yield and stereoselectivity were excellent.

Synthetic Communications published new progress about Chiral auxiliary. 343338-28-3 belongs to class amides-buliding-blocks, name is (S)-2-Methylpropane-2-sulfinamide, and the molecular formula is C4H11NOS, Computed Properties of 343338-28-3.

Referemce:
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

Yang, Wu published the artcileDiscovery of a High Affinity, Orally Bioavailable Macrocyclic FXIa Inhibitor with Antithrombotic Activity in Preclinical Species, Product Details of C4H11NOS, the main research area is FXIa inhibitors antithrombotic therapy SAR pharmacokinetics oral bioavailability hemostasis.

Oral factor XIa (FXIa) inhibitors may provide a promising new antithrombotic therapy with an improved benefit to bleeding risk profile over existing antithrombotic agents. Herein, we report application of a previously disclosed cyclic carbamate P1 linker which provided improved oral bioavailability in the imidazole-based 13-membered macrocycle to the 12-membered macrocycle. This resulted in identification of compound 4 with desired FXIa inhibitory potency and good oral bioavailability but high in vivo clearance. Further structure-activity relationship (SAR) studies of heterocyclic core modifications to replace the imidazole core as well as various linkers to the P1 group led to the discovery of compound 6f(I), a potent FXIa inhibitor with selectivity against most of the relevant serine proteases. Compound 6f also demonstrated excellent pharmacokinetics (PK) profile (high oral bioavailability and low clearance) in multiple preclin. species. Compound 6f achieved robust antithrombotic efficacy in a rabbit efficacy model at doses which preserved hemostasis.

Journal of Medicinal Chemistry published new progress about Antithrombotics. 343338-28-3 belongs to class amides-buliding-blocks, name is (S)-2-Methylpropane-2-sulfinamide, and the molecular formula is C4H11NOS, Product Details of C4H11NOS.

Referemce:
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

Karim, Rezaul Md published the artcileDiscovery of Dual TAF1-ATR Inhibitors and Ligand-Induced Structural Changes of the TAF1 Tandem Bromodomain, Application In Synthesis of 343338-28-3, the main research area is AZD6738 pyrrolopyridine synthesis anticancer SAR ATR kinase bromodomain TAF1.

Bromodomains regulate chromatin remodeling and gene transcription through recognition of acetylated lysines on histones and other proteins. Bromodomain-containing protein TAF1, a subunit of general transcription factor TFIID, initiates preinitiation complex formation and cellular transcription. TAF1 serves as a cofactor for certain oncogenic transcription factors and is implicated in regulating the p53 tumor suppressor. Therefore, TAF1 is a potential target to develop small mol. therapeutics for diseases arising from dysregulated transcription, such as cancer. Here, we report the ATR kinase inhibitor AZD6738 (Ceralasertib) and analogs thereof as bona fide inhibitors of TAF1. Crystallog. and small-angle X-ray scattering studies established that newly identified and previously reported inhibitors stabilize distinct structural states of the TAF1 tandem bromodomain through “”open-closed”” transitions and dimerization. Combined with functional studies on p53 signaling in cancer cell lines, the data provide new insights into the feasibility and challenges of TAF1 inhibitors as chem. probes and therapeutics.

Journal of Medicinal Chemistry published new progress about Antitumor agents. 343338-28-3 belongs to class amides-buliding-blocks, name is (S)-2-Methylpropane-2-sulfinamide, and the molecular formula is C4H11NOS, Application In Synthesis of 343338-28-3.

Referemce:
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics

Blaszczyk, Roman published the artcileDiscovery and Pharmacokinetics of Sulfamides and Guanidines as Potent Human Arginase 1 Inhibitors, Synthetic Route of 343338-28-3, the main research area is arginase inhibitor pharmacokinetics sulfamide guanidine cancer immunotherapy.

We designed and synthesized a series of arginase inhibitors as derivatives of the well-known 2-(S)-amino-6-boronohexanoic acid (ABH) with basic and neutral side chains in the α-position relative to the amino acid group. In an effort to improve the pharmacokinetic profile of literature examples and retain potent enzymic activity, sulfamido moieties were introduced to generate hydrogen bond interaction with the aspartic acid residue in the arginase active site. The compounds with basic guanidine-containing side chains were even more potent arginase inhibitors. Both groups of compounds, as designed, demonstrated low clearance in their pharmacokinetic profile. The most active inhibitor 15aa showed high nanomolar potency with IC50 = 32 nM toward human arginase 1 and demonstrated low clearance (4.2 mL/min/kg), long t1/2, and moderate volume of distribution in rat pharmacokinetic studies.

ACS Medicinal Chemistry Letters published new progress about Antitumor agents. 343338-28-3 belongs to class amides-buliding-blocks, name is (S)-2-Methylpropane-2-sulfinamide, and the molecular formula is C4H11NOS, Synthetic Route of 343338-28-3.

Referemce:
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics