256453-94-8

Upstream product

• 614-69-7 2-tolyl isothiocyanate 

Downstream Products

• 422279-96-7 [1-{4-[2-[2-o-tolylamino-benzoxazol-6-yl]-acetylamino]-phenyl}-cyclopentyl]-acetic acid tert-butyl ester 
• 422280-01-1 (2-(4-(2-(2-o-tolylamino-benzoxazol-6-yl)-acetylamino)-phenyl)-indan-2-yl)-acetic acid ethyl ester 
• 358974-09-1 (5-[2-{2-o-Tolylamino-benzoxazol-6-yl}-acetylamino]-indan-2-yl)-acetic acid 
• 358974-08-0 ethyl 3-{7-[2-(2-o-tolylamino-benzoxazol-6-yl)-acetylamino]-indan-4-yl}-butanoate 
• 288580-39-2 3(R)-{4-[2-(2-o-tolylaminobenzoxazol-6-yl)acetylamino]phenyl}butanoic acid 
• 306767-88-4 [R] 3-(Acetyl-methyl-amino)-3-(4-{methyl-[(2-o-tolylamino-benzoxazol-6-yl)-acetyl]-amino}:-phenyl)-propionic Acid 
• 306767-90-8 (R) 3-[(5-methyl-isoxazole-3-carbonyl)-amino]-3-{4-[2-(2-o-tolylamino-benzoxazol-6-yl)-acetylamino]-phenyl}-propionic acid 
• 441713-54-8 methyl 4-(4,4-difluoro-1-(2-(2-methylphenylamino)-6-benzoxazolylacetyl)-(2S)-pyrrolidinylmethoxy)benzoate 
• 441714-08-5 methyl 5-((2S,4S)-4-fluoro-1-(2-(2-methylphenylamino)-6-benzoxazolylacetyl)-2-pyrrolidinylmethoxy)pentanoate 
• 441769-13-7 methyl 4-(1-(2-(2-methylphenylamino)-6-benzoxazolylacetyl)-(2S)-pyrrolidinylmethoxy)cyclohexanecarboxylate 
• 441713-67-3 methyl 4-((2S,4S)-4-acetoxy-1-(2-(2-methylphenylamino)-6-benzoxazolylacetyl)-2-pyrrolidinylmethoxy)benzoate 
• 441713-99-1 methyl 4-[(4S)-fluoro-1-[2-(2-methylphenylamino)-6-benzoxazolylacetyl]-(2S)-pyrrolidinylmethoxy]butanoate 
• 441769-12-6 C₂₉H₃₄FN₃O₅ 
• 441769-12-6 C₂₉H₃₄FN₃O₅ 

Relevant academic research and scientific papers

A novel and potent VLA-4 antagonist based on trans-4-substituted cyclohexanecarboxylic acid

During the course of our study, it was revealed that the poor pharmacokinetic properties of a series of benzoic acid derivatives such as 1 should be attributed to the diphenylurea moiety. Thus, we replaced the diphenylurea moiety in 1 with a 2-(2-methylphenylamino)benzoxazole moiety which mimics the diphenylurea structure. However, this modification resulted in a significant decrease (3, IC50 = 19 nM) in VLA-4 inhibitory activity compared to 1 (IC50 = 1.6 nM). To address this discrepancy, we worked on optimization of the carboxylic acid moiety in compound 3. As a result, our efforts have led to the discovery of trans-4-substituted cyclohexanecarboxylic acid derivative 11b (IC50 = 2.8 nM) as a novel and potent VLA-4 antagonist. In addition, compound 11b exhibited favorable pharmacokinetic properties (CL = 3.3 ml/min/kg, F = 51%) in rats.

Substituted alkanoic acids

The invention is directed to physiologically active compounds of general formula (I): wherein:- represents (i) a saturated 3 to 6 membered carbocycle, optionally substituted by one or more alkyl groups, (ii) indanyl or (iii) a saturated 4 to 6 membered heterocyclic ring; R1 represents R3Z1-Het- or R4N(R5)—C(═O)—NH—Ar1—; L1 represents an —R6—R7— linkage; R2 represents hydrogen, halogen, lower alkyl or lower alkoxy; L2 represents an alkylene linkage; Y is carboxy or an acid bioisostere; and their corresponding N-oxides or prodrugs, and pharmaceutically acceptable salts and solvates of such compounds and their corresponding N-oxides or prodrugs. Such compounds have valuable pharmaceutical properties, in particular the ability to regulate the interaction of VCAM-1 and fibronectin with the integrin VLA-4 (α4β1).

VLA-4 INHIBITORS

The present invention relates to a compound represented by the following formula (I): (wherein, W represents WA-A1 -WB - (in which, WA is substituted or unsubstituted aryl, etc., A1 is -NR1-, single bond, -C(O)-, etc., and WB is substituted or unsubstituted arylene, etc.), R is single bond, -NH-, -OCH2-, alkenylene, etc., X is -C(O) -CH2-, etc., and M is, for example, the following formula: (in which, R11, R12 and R13 each independently represents hydrogen, hydroxyl, amino, halogen, etc., R14 is hydrogen or lower alkyl, Y represents -CH2-O-, etc., Z is substituted or unsubstituted arylene, etc., A2 is single bond, etc, and R10 is hydroxyl or lower alkoxy)), or salt thereof; and a medicament containing the same. This compound or salt thereof selectively inhibits binding of cell adhesion molecules to VAL-4 and exhibits high bioavailability so that it is useful as a preventive and/or remedy for inflammatory diseases, autoimmune diseases, metastasis, bronchial asthma, rhinostenosis, diabetes, and the like.