400652-49-5

Upstream product

• 211568-63-7 (S)-tert-butyl 1-azido-3-methylbutan-2-ylcarbamate 
• 228557-24-2 benzyl N-[1-(azidomethyl)-3-methylbutyl]carbamate 
• 228557-26-4 benzyl N-[1-(aminomethyl)-3-methyl-butyl]carbamate 
• 142554-61-8 (S)-(-)-1,1-dimethylethyl <1-(azidomethyl)-3-methylbutyl>carbamate 
• 72-18-4 L-valine 
• 24424-99-5 di-tert-butyl dicarbonate 
• 2026-48-4 (S)-valinol 
• 216319-90-3 (S)-tert-butyl 1-cyano-2-methylpropylcarbamate 
• 864943-54-4 [(1S)-1-[(1,3-dihydro-1,3-dioxo-2H-isoindol-2-yl)methyl]-2-methylpropyl]carbamic acid 1,1-dimethylethyl ester 
• 35150-08-4 Boc-Val-NH₂ 
• 110694-59-2 N-tertbutyloxycarbonyl-S-valine methyl ester 
• 126301-18-6 [(2S)-2-(tert-butoxycarbonylamino)-3-methyl-butyl] methanesulfonate 
• 79069-14-0 (S)-2-<(tert-butoxycarbonyl)amino>-3-methylbutan-1-ol 
• 75-52-5 nitromethane 

Downstream Products

• 1027192-04-6 {(S)-1-[3-(2,6-Diisopropyl-phenyl)-ureidomethyl]-2-methyl-propyl}-carbamic acid tert-butyl ester 
• 1132809-54-1 C₁₆H₂₆N₂O₄S 
• 662143-01-3 [(1S)-2-methyl-1-[[[(4-methylphenyl)sulfonyl]amino]methyl]propyl]carbamic acid 1,1-dimethylethyl ester 
• 871235-33-5 N¹-[4-(2,4-dichloro-benzyloxy)-pyrimidin-2-yl]-3-methyl-butane-1,2-diamine 
• 871235-27-7 (1-{[4-(2,4-dichloro-benzyloxy)-pyrimidin-2-ylamino]-methyl}-2-methyl-propyl)-carbamic acid tert-butyl ester 

Relevant academic research and scientific papers

Phase-transfer-catalyzed asymmetric aza-Henry reaction using N-carbamoyl imines generated in situ from α-amido sulfones

(Chemical Equation Presented) A general approach to the catalytic asymmetric aza-Henry reaction has been developed. The combination of a commercially available phase-transfer catalyst (PTC) with a base is able to promote the in situ formation of N-carbamo

Development of Chiral Organosuperbase Catalysts Consisting of Two Different Organobase Functionalities

In the field of chiral Br?nsted base catalysis, a new generation of chiral catalysts has been highly anticipated to overcome the intrinsic limitation of pronucleophiles that are applicable to the enantioselective reactions. Herein, we reveal conceptually new chiral Br?nsted base catalysts consisting of two different organobase functionalities, one of which functions as an organosuperbase and the other as the substrate recognition site. Their prominent activity, which stems from the distinctive cooperative function by the two organobases in a single catalyst molecule, was demonstrated in the unprecedented enantioselective direct Mannich-type reaction of α-phenylthioacetate as a less acidic pronucleophile. The present achievement would provide a new guiding principle for the design and development of chiral Br?nsted base catalysts and significantly broaden the utility of Br?nsted base catalysis in asymmetric organic synthesis.

NOVEL NICOTINAMIDE DERIVATIVES OR SALTS THEREOF

An object of the present invention is to provide to a compound and a pharmaceutical composition, which have excellent Syk-inhibitory activity. Th e present invention provides a nicotinamide derivative represented by the follo wing formula (I) (wherein R 1 represents a halogen atom; R 2 represents a C 1-12 alkyl group, a C 2-12 alkenyl group, a C 2-12 alkynyl group, a C 3-8 cycloalkyl g roup, an aryl group, an ar-C 1-6 alkyl group or a heterocyclic group, each opti onally having at least one substituent; R 3 represents an aryl group or a hetero cyclic group each optionally having at least one substituent; and R 4 and R 5 e ach independently represent a hydrogen atom; and R 2 and R 4 may form a cyc lic amino group optionally having at least one substituent together with the ni trogen atom to which they bind) or a salt thereof, and a pharmaceutical comp osition for use in the treatment of a Syk-related disease which comprises the nicotinamide derivative or a salt thereof.

TREATMENT OF RB-NEGATIVE TUMORS USING TOPOISOMERASE INHIBITORS IN COMBINATION WITH CYCLIN DEPENDENT KINASE 4/6 INHIBITORS

This invention is in the area of improved therapeutic combinations for and methods of treating selected retinoblastoma (Rb)-negative cancers and Rb-negative abnormal cellular proliferative disorders using particular topoisomerase inhibitors and specific c

COMBINATIONS AND DOSING REGIMES TO TREAT RB-POSITIVE TUMORS

This invention directed to methods for treating select RB-positive cancers and other Rb- positive abnormal cellular proliferative disorders using CDK4/6 inhibitors in specific dosing and combination or alternation regimes. In one aspect, treatments of select RB-positive cancers are disclosed using specific CDK4/6 inhibitors in combination or alternation with another chemotherapeutic, for example, an additional kinase inhibitor, PD-1 inhibitor, or BCL-2 inhibitor, or combination thereof.

TRANSIENT PROTECTION OF NORMAL CELLS DURING CHEMOTHERAPY

This invention is in the area of improved compounds, compositions and methods of transiently protecting healthy cells, and in particular hematopoietic stem and progenitor cells (HSPC) as well as renal cells, from damage associated with DNA damaging chemotherapeutic agents. In one aspect, improved protection of healthy cells is disclosed using disclosed compounds that act as highly selective and short, transiently-acting cyclin-dependent kinase 4/6 (CDK 4/6) inhibitors when administered to subjects undergoing DNA damaging chemotherapeutic regimens for the treatment of proliferative disorders.

CDK INHIBITORS

Compounds of formulae I, II or III, and pharmaceutically acceptable salts thereof, are useful as CDK inhibitors.

Synthesis of imidacloprid derivatives with a chiral alkylated imidazolidine ring and evaluation of their insecticidal activity and affinity to the nicotinic acetylcholine receptor

A series of imidacloprid (IMI) derivatives with an alkylated imidazolidine ring were asymmetrically synthesized to evaluate their insecticidal activity against adult female housefly, Musca domestica, and affinity to the nicotinic acetylcholine receptor of the flies. The bulkier the alkyl group, the lower was the receptor affinity, but the derivatives methylated and ethylated at the R-5-position of the imidazolidine ring were equipotent to the unsubstituted compound. Quantitative structure-activity relationship (QSAR) analysis of the receptor affinity demonstrated that the introduction of a substituent into the imidazolidine ring was fundamentally disadvantageous, but the introduction of a substituent at the R-5-position was permissible in the case of its small size. The binding model of the synthesized derivatives with the receptor supported the QSAR analysis, indicating the existence of space for a short alkyl group around the R-5-position in the ligand-binding site. In addition, positive correlation was observed between the insecticidal activity and receptor affinity, suggesting that the receptor affinity was the primary factor in influencing the insecticidal activity even if the imidazolidine ring was modified.

Discovery of a novel chemotype of potent human ENaC blockers using a bioisostere approach. Part 2: α-Branched quaternary amines

We report the synthesis and biological evaluation of a series of novel α-branched pyrazinoyl quaternary amines for their ability to block ion transport via the epithelial sodium channel (ENaC) in human bronchial epithelial cells (HBECs). Compound 12g has an IC50 of 30 nM and is highly efficacious in the Guinea-pig tracheal potential difference (TPD) model of ENaC blockade with an ED50 of 1 μg kg-1 at 1 h. In addition the SAR results demonstrate for the first time the chiral nature of the binding site of human ENaC. As such, pyrazinoyl quaternary amines represent a promising new class of ENaC blockers for the treatment of cystic fibrosis that are structurally distinct from the pyrazinoyl guanidine chemotype found in prototypical ENaC blockers such as amiloride.

Isoselenocyanates derived from Boc/Z-amino acids: Synthesis, isolation, characterization, and application to the efficient synthesis of unsymmetrical selenoureas and selenoureidopeptidomimetics

Isoselenocyanates derived from Boc/Z-amino acids are prepared by the reaction of the corresponding isonitriles with selenium powder in presence of triethylamine at reflux. The utility of these new classes of isoselenocyanates in the preparation of selenoureidodipeptidomimetics possessing both amino as well as carboxy termini has been accomplished. The 1H NMR analysis confirmed that the protocol involving the conversion of isonitriles to isoselenocyanates and their use as coupling agents in assembling selenoureido derivatives is free from racemization.