190655-55-1

Upstream product

• 131137-03-6 methyl 4‐[(benzylideneamino)methyl]benzoate 
• 18469-52-8 methyl 4-(aminomethyl)benzoate 
• 100-52-7 benzaldehyde 
• 100-46-9 benzylamine 
• 1571-08-0 methyl 4-formylbenzoate 
• 7377-26-6 4-Methoxycarbonylbenzoyl chloride 
• 619-65-8 4-cyanobenzoic Acid 
• 349491-81-2 N-benzyl-terephthalamic acid methyl ester 
• 6232-11-7 methyl 4-(aminomethyl)benzoate hydrochloride 
• 1003314-87-1 4-[(E)-benzylimino-methyl]-benzoic acid methyl ester 
• 193821-09-9 N-benzyl-(4-methoxycarbonylphenyl)methanimine 

Downstream Products

• 199982-18-8 methyl 4-((benzyl(tert-butoxycarbonyl)amino)methyl)benzoate 
• 1059147-16-8 4-(((tert-butoxycarbonyl)benzylamino)methyl)benzoic acid 
• 1059144-23-8 4-((benzylamino)methyl)-N'-phenylbenzohydrazide 
• 1059145-17-3 N-benzyl-4-((benzylamino)methyl)-N'-phenylbenzohydrazide 
• 1059145-20-8 4-(((3-aminopropyl)(benzyl)amino)methyl)-N'-phenylbenzohydrazide 
• 1059145-23-1 4-((benzyl(3-(pyrimidin-2-ylamino)propyl)amino)methyl)-N'-phenylbenzohydrazide 
• 1191066-05-3 4-({benzyl[(4-chlorophenyl)sulfonyl]amin}lmethyl)-N-(3-chlorobenzyl)benzamide 
• 1191066-11-1 4-({benzyl[(4-chlorophenyl)sulfonyl]amino}methyl)-N-(2-thienylmethyl)benzamide 
• 721416-48-4 4-{[benzyl(4-chlorobenzenesulfonyl)amino]methyl}benzoic acid 
• 869775-77-9 4-{[benzyl(4-chlorobenzenesulfonyl)amino]methyl}benzoic acid methyl ester 
• 1191069-64-3 methyl 4-{[benzyl(4-methoxysulfonyl)amino]methyl}benzoate 

Relevant academic research and scientific papers

Design of Hydrazide-Bearing HDACIs Based on Panobinostat and Their p53 and FLT3-ITD Dependency in Antileukemia Activity

Here, we present a new series of hydrazide-bearing class I selective HDAC inhibitors designed based on panobinostat. The cap, linker, and zinc-binding group were derivatized to improve HDAC affinity and antileukemia efficacy. Lead inhibitor 13a shows picomolar or low nanomolar IC50 values against HDAC1 and HDAC3 and exhibits differential toxicity profiles toward multiple cancer cells with different FLT3 and p53 statuses. 13a indirectly inhibits the FLT3 signaling pathway and down-regulates master antiapoptotic proteins, resulting in the activation of pro-caspase3 in wt-p53 FLT3-ITD MV4-11 cells. While in the wt-FLT3 and p53-null cells, 13a is incapable of causing apoptosis at a therapeutic concentration. The MDM2 antagonist and the proteasome inhibitor promote 13a-triggered apoptosis by preventing p53 degradation. Furthermore, we demonstrate that apoptosis rather than autophagy is the key contributing factor for 13a-triggered cell death. When compared to panobinostat, 13a is not mutagenic and displays superior in vivo bioavailability and a higher AUC0-inf value.

Nidufexor (LMB763), a Novel FXR Modulator for the Treatment of Nonalcoholic Steatohepatitis

Farnesoid X receptor (FXR) agonists are emerging as important potential therapeutics for the treatment of nonalcoholic steatohepatitis (NASH) patients, as they exert positive effects on multiple aspects of the disease. FXR agonists reduce lipid accumulation in the liver, hepatocellular inflammation, hepatic injury, and fibrosis. While there are currently no approved therapies for NASH, the bile acid-derived FXR agonist obeticholic acid (OCA; 6-ethyl chenodeoxycholic acid) has shown promise in clinical studies. Previously, we described the discovery of tropifexor (LJN452), the most potent non-bile acid FXR agonist currently in clinical investigation. Here, we report the discovery of a novel chemical series of non-bile acid FXR agonists based on a tricyclic dihydrochromenopyrazole core from which emerged nidufexor (LMB763), a compound with partial FXR agonistic activity in vitro and FXR-dependent gene modulation in vivo. Nidufexor has advanced to Phase 2 human clinical trials in patients with NASH and diabetic nephropathy.

Expanding the Boundaries of Water-Tolerant Frustrated Lewis Pair Hydrogenation: Enhanced Back Strain in the Lewis Acid Enables the Reductive Amination of Carbonyls

The development of a boron/nitrogen-centered frustrated Lewis pair (FLP) with remarkably high water tolerance is presented. As systematic steric tuning of the boron-based Lewis acid (LA) component revealed, the enhanced back-strain makes water binding increasingly reversible in the presence of relatively strong base. This advance allows the limits of FLP's hydrogenation to be expanded, as demonstrated by the FLP reductive amination of carbonyls. This metal-free catalytic variant displays a notably broad chemoselectivity and generality.

1,3,4-OXADIAZOLE DERIVATIVE COMPOUNDS AS HISTONE DEACETYLASE 6 INHIBITOR, AND THE PHARMACEUTICAL COMPOSITION COMPRISING THE SAME

The present invention relates to novel compounds having histone deacetylase 6 (HDAC6) in-hibitory activity, stereoisomers thereof or pharmaceutically acceptable salts thereof, the use thereof for the preparation of therapeutic medicaments, pharmaceutical compositions containing the same, a method for treating diseases using the composition, and methods for preparing the novel compounds. The novel compounds, stereoisomers thereof or pharmaceutically acceptable salts thereof according to the present invention have histone deacetylase (HDAC) inhibitory activity and are effective for the prevention or treatment of HDAC6-mediated diseases, including infectious diseases; neoplasms; endocrine, nutritional and metabolic diseases; mental and be-havioral disorders; neurological diseases; diseases of the eye and adnexa; cardiovascular diseases; respiratory diseases; digestive diseases; diseases of the skin and subcutaneous tissue; diseases of the musculoskeletal system and connective tissue; or congenital malformations, de? formations and chromosomal abnormalities.

Expanding Water/Base Tolerant Frustrated Lewis Pair Chemistry to Alkylamines Enables Broad Scope Reductive Aminations

Lower Lewis acidity boranes demonstrate greater tolerance to combinations of water/strong Br?nsted bases than B(C6F5)3, this enables Si?H bond activation by a frustrated Lewis pair (FLP) mechanism to proceed in the presence of H2O/alkylamines. Specifically, BPh3has improved water tolerance in the presence of alkylamines as the Br?nsted acidic adduct H2O–BPh3does not undergo irreversible deprotonation with aliphatic amines in contrast to H2O–B(C6F5)3. Therefore BPh3is a catalyst for the reductive amination of aldehydes and ketones with alkylamines using silanes as reductants. A range of amines inaccessible using B(C6F5)3as catalyst, were accessible by reductive amination catalysed by BPh3via an operationally simple methodology requiring no purification of BPh3or reagents/solvent. BPh3has a complementary reductive amination scope to B(C6F5)3with the former not an effective catalyst for the reductive amination of arylamines, while the latter is not an effective catalyst for the reductive amination of alkylamines. This disparity is due to the different pKavalues of the water–borane adducts and the greater susceptibility of BPh3species towards protodeboronation. An understanding of the deactivation processes occurring using B(C6F5)3and BPh3as reductive amination catalysts led to the identification of a third triarylborane, B(3,5-Cl2C6H3)3, that has a broader substrate scope being able to catalyse the reductive amination of both aryl and alkyl amines with carbonyls.

A General and Selective Rhodium-Catalyzed Reduction of Amides, N-Acyl Amino Esters, and Dipeptides Using Phenylsilane

This article describes a selective reduction of functionalized amides, including N-acyl amino esters and dipeptides, to the corresponding amines using simple [Rh(acac)(cod)]. The catalyst shows excellent chemoselectivity in the presence of different sensitive functional moieties. A selective reduction of functionalized amides, including N-acyl amino esters and dipeptides, to the corresponding amines using simple [Rh(acac)(cod)] is described (see scheme). The catalyst shows excellent chemoselectivity in the presence of different sensitive functional moieties. Even the selective reduction of a secondary amide bond in the presence of a ketone is possible.

COMPOSITIONS AND METHODS FOR MODULATING FARNESOID X RECEPTORS

The present invention relates to compounds of Formula I, a stereoisomer, enantiomer, a pharmaceutically acceptable salt or an amino acid conjugate thereof; wherein variables are as defined herein; and their pharmaceutical compositions, which are useful as modulators of the activity of Farnesoid X receptors (FXR).

A general and selective copper-catalyzed reduction of secondary amides

In situ-generated cationic copper/pybox catalyst systems allow for the selective reduction of secondary amides into the corresponding amines under mild conditions. This novel protocol has a wide substrate scope and shows good functional group tolerance. The Royal Society of Chemistry 2012.

Zinc-catalyzed chemoselective reduction of tertiary and secondary amides to amines

General and convenient procedures for the catalytic hydrosilylation of secondary and tertiary amides under mild conditions have been developed. In the presence of inexpensive zinc catalysts, tertiary amides are easily reduced by applying monosilanes. Key to success for the reduction of the secondary amides is the use of zinc triflate and disilanes with dual Si-H moieties. The presented hydrosilylations proceed with excellent chemoselectivity in the presence of sensitive ester, nitro, azo, nitrile, olefins, and other functional groups, thus making the method attractive for organic synthesis.

SULFONAMIDES

The invention relates to compounds of formula (I) wherein R1, R2, R4, Ra, Rb, Rc, Re, A*, W1, W2 and W3 are as defined in claim 1, for the treatment of CXCR3 related diseases.