4909-95-9

Upstream product

• 42900-98-1 3-ethyl-4-hydroxy-5-methylbenzaldehyde 
• 70598-49-1 4-bromo-2-ethyl-6-methylphenylamine 
• 1150644-73-7 4-amino-3-ethyl-5-methylbenzonitrile 
• 1687-64-5 2-ethyl-6-methylphenol 
• 24549-06-2 6-ethyl-o-toluidine 

Downstream Products

• 1150644-92-0 4-benzyloxy-3-ethyl-5-methyl-benzonitrile 
• 1160956-55-7 3-ethyl-5-methyl-4-oxiranylmethoxy-benzonitrile 
• 1062669-89-9 4-(5-(2-(diethylamino)-6-methylpyridin-4-yl)-1,2,4-oxadiazol-3-yl)-2-ethyl-6-methylphenol 
• 1062670-10-3 (S)-N,N-diethyl-4-(3-(3-ethyl-5-methyl-4-(oxiran-2-ylmethoxy)phenyl)-1,2,4-oxadiazol-5-yl)-6-methylpyridin-2-amine 
• 1062670-13-6 (S)-N-(3-(4-(5-(2-(diethylamino)-6-methylpyridin-4-yl)-1,2,4-oxadiazol-3-yl)-2-ethyl-6-methylphenoxy)-2-hydroxypropyl)-2-hydroxyacetamide 
• 1062670-07-8 (S)-1-amino-3-(4-(5-(2-(diethylamino)-6-methylpyridin-4-yl)-1,2,4-oxadiazol-3-yl)-2-ethyl-6-methylphenoxy)propan-2-ol 
• 910635-33-5 3-ethyl-N,4-dihydroxy-5-methylbenzimidamide 
• 1150644-85-1 (R)-4-((2,2-dimethyl-1,3-dioxolan-4-yl)methoxy)-3-ethyl-N-hydroxy-5-methylbenzylhydrazine 
• 1150644-94-2 4-(2,2-dimethyl-[1,3]dioxan-5-ylmethoxy)-3-ethyl-N-hydroxy-5-methyl-benzamidine 

Relevant academic research and scientific papers

Novel S1P1 receptor agonists - Part 3: From thiophenes to pyridines

In preceding communications we summarized our medicinal chemistry efforts leading to the identification of potent, selective, and orally active S1P 1 agonists such as the thiophene derivative 1. As a continuation of these efforts, we replaced the thiophene in 1 by a 2-, 3-, or 4-pyridine and obtained less lipophilic, potent, and selective S1P1 agonists (e.g., 2) efficiently reducing blood lymphocyte count in the rat. Structural features influencing the compounds' receptor affinity profile and pharmacokinetics are discussed. In addition, the ability to penetrate brain tissue has been studied for several compounds. As a typical example for these pyridine based S1P 1 agonists, compound 53 showed EC50 values of 0.6 and 352 nM for the S1P1 and S1P3 receptor, respectively, displayed favorable PK properties, and penetrated well into brain tissue. In the rat, compound 53 maximally reduced the blood lymphocyte count for at least 24 h after oral dosing of 3 mg/kg.

PYRIDIN-4-YL DERIVATIVES

The invention relates to compounds of the Formula (I), Formula (I) wherein R1 and R2 are as described in the description, their preparation and their use as pharmaceutically active compounds. Said compounds particularly act as immuno

Mechanistic insight into the formal [1,3]-migration in the thermal claisen rearrangement

The thermal formal [1,3]-sigmatropic shift of allyl aryl ethers has been studied in depth experimentally with the aid of the density functional theory (DFT) calculations of the B3LYP function. Three mechanistic possibilities, referred to as the radical, ionic, and concerted mechanisms, have previously been put forth to explain the thermal [1,3]-rearrangement process. However, the intercrossing and radical trapping experiments indicate the rearrangement is an intramolecular process. The computational studies reveal that the concerted C[1,3]-sigmatropic shift suffered from a higher energetic barrier to allow the rearrangement to proceed under the conditions used. However, a tandem O[1,3]-sigmatropic shift with a configuration inversion of the oxygen atom and [3,3]-sigmatropic shift (the Claisen rearrangement) is the most likely pathway for the formal [1,3] rearrangement. Furthermore, the rearrangement experiments with a designed optically active substrate and O[1,3]-sigmatropic shift examples verify the new cascade rearrangement. In addition, computational and experimental studies indicate that water molecule assists the proton shift during the isomerization. The combined methods provide the new insight into the mechanism of the thermal formal [1,3]-migration in the Claisen rearrangement and the novel O[1,3]-sigmatropic shift as well.

Practical and scalable synthesis of S1P1 receptor agonist ACT-209905

A practical and scalable route for the fast delivery of 12 kg of S1P 1 agonist (ACT-209905) has been developed. ACT-209905 is composed of an amino pyridine group, an oxadiazole spacer, a 2-ethyl-5-methylphenol moiety and a chiral 1-amino-2-propanol side chain. The convergent synthesis consists of 16 steps with 9 isolated intermediates and is chromatography-free. Key building blocks are accessed from low-cost starting materials, such as acetone, diethyl oxalate, cyanoacetamide, and 2-ethyl-5-methyl aniline. A Negishi coupling that was troubled by the use of metal reagents and concomitant metal waste streams has been replaced by a less expensive Guareschi-Thorpe reaction to build up an amino isonicotinic acid. The chiral 1-amino-2-propanol moiety was secured by selective ring-opening of an epoxide with lithium hexamethyldisilazide as an ammonia surrogate, thus omitting the notorious double alkylated byproduct.

PYRAZOLE DERIVATIVES AS S1P1 AGONISTS

The present invention relates to a compound of formula (I), to the process for preparing such compounds and to their use in the treatment of a pathological condition or disease susceptible to amelioration by sphingosine-1-phosphate receptors (S1P1) agonists.

New pyrazole derivatives

The present invention relates to a compound of formula (I), to the process for preparing such compounds and to their use in the treatment of a pathological condition or disease susceptible to amelioration by sphingosine-1-phosphate receptors (S1P1) agonists.

THIOPHENE DERIVATIVES AS AGONISTS OF S1P1/EDG1

The invention relates to novel thiophene derivatives (1), their preparation and their use as pharmaceutically active compounds.Said compounds particularly act as immunomodulating agents. Formula (I).