42900-98-1

Upstream product

• 1687-64-5 2-ethyl-6-methylphenol 
• 64-19-7 acetic acid 
• 100-97-0 hexamethylenetetramine 
• 74-90-8 hydrogen cyanide 

Downstream Products

• 1011476-72-4 C₁₃H₁₆O₂ 
• 944327-07-5 4-benzyloxy-3-ethyl-5-methylbenzaldehyde 
• 1011264-26-8 3-ethyl-4-hydroxy-5-methylbenzoic acid 
• 2219-79-6 2-ethyl-4,6-dimethyl-phenol 
• 910814-18-5 3-(3-ethyl-4-hydroxy-5-methylphenyl)-1-((1aS,5aR)-1,1,2-trimethyl-1,1a,5,5a-tetrahydro-3-thia-cyclopropa[a]pentalen-4-yl)-propenone 
• 1187029-86-2 {3-[5-(4-benzyloxy-3-ethyl-5-methyl-phenyl)-[1,3,4]oxadiazol-2-yl]-5-methyl-benzyl}-ethyl-methyl-amine 
• 1187029-85-1 2-ethyl-4-(5-{3-[(ethyl-methyl-amino)-methyl]-5-methyl-phenyl}-[1,3,4]oxadiazol-2-yl)-6-methyl-phenol 
• 1160956-60-4 4-benzyloxy-3-ethyl-5-methyl-benzoic acid tert-butyl ester 
• 1160956-61-5 3-ethyl-4-hydroxy-5-methyl-benzoic acid tert-butyl ester 
• 1014691-18-9 4-benzyloxy-3-ethyl-5-methyl-benzoic acid N'-(4-isopropoxy-3-methyl-benzoyl)hydrazide 
• 1014691-19-0 2-(4-benzyloxy-3-ethyl-5-methyl-phenyl)-5-(4-isopropoxy-3-methyl-phenyl)-[1,3,4]oxadiazole 
• 1011263-86-7 3-ethyl-5-methyl-4-trifluoromethanesulfonyloxy-benzoic acid benzyl ester 
• 1011263-87-8 4-(2-tert-butoxycarbonyl-vinyl)-3-ethyl-5-methyl-benzoic acid benzyl ester 
• 1011263-84-5 3-[2-ethyl-4-(N-hydroxycarbamimidoyl)-6-methyl-phenyl]-propionic acid tert-butyl ester 

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

Novel S1P1 receptor agonists - Part 1: From pyrazoles to thiophenes

From a high-throughput screening campaign aiming at the identification of novel S1P1 receptor agonists, the pyrazole derivative 2 emerged as a hit structure. Medicinal chemistry efforts focused not only on improving the potency of the compound but in particular also on resolving its inherent instability issue. This led to the discovery of novel bicyclo[3.1.0]hexane fused thiophene derivatives. Compounds with high affinity and selectivity for S1P1 efficiently reducing the blood lymphocyte count in the rat were identified. For instance, compound 85 showed EC50 values of 7 and 2880 nM on S1P1 and S1P3, respectively, had favorable pharmacokinetic properties in rat and dog, distributed well into brain tissue, and efficiently and dose dependently reduced the blood lymphocyte count in the rat. After oral administration to spontaneously hypertensive rats, the S1P 1 selective compound 85 showed no effect on mean arterial blood pressure and affected the heart rate during the wake phase of the animals only.

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.

NOVEL THIOPHENE DERIVATIVES AS SPHINGOSINE-1-PHOSPHATE-1 RECEPTOR AGONISTS

The invention relates to novel thiophene derivatives, their preparation and their use as pharmaceutically active compounds. Said compounds particularly act as immunosuppressive agents.

Pyridin-4-yl derivatives as immunomodulating agents

The invention relates to pyridine derivatives of Formula (I) wherein A, R1, R2, R3, R4, R5, and R6 are as described in the description, their preparation and their use as pharmaceutically active compounds. Said compounds particularly act as immunomodulating agents.

AMINO-PYRIDINE DERIVATIVES AS S1P1 /EDG1 RECEPTOR AGONISTS

The invention relates to novel amino-pyridine derivatives, their preparation and their use as pharmaceutically active compounds. Said compounds particularly act as immunomodulating agents.

Pyridin-3-yl derivatives as immunomodulating agents

The invention relates to pyridin-3-yl derivatives of Formula (I) wherein R1, R2, R3, R4, R5; R6 and A are as described in the description, their preparation and their use as pharmaceuticall

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).

Thiophene derivatives as S1P1/EDGE1 receptor agonists

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