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AssigneeTanabe Seiyaku Co., Ltd.
InventorsIla Sircar, Kristjan S. Gudmundsson, Richard Martin
Estimating the term…
The present invention relates to a pharmaceutical composition comprising as an active ingredient a compound of formula (I), wherein Ring A is an aromatic or a heterocyclic ring; Q is a bond, carbonyl, lower alkylene, lower alkenylene, —O— -(lower alkylene)-, etc.; n is 0, 1 or 2; Z is oxygen or sulfur; W is oxygen, sulfur, —CH═CH—, —NH— or —N═CH—; R1, R2 and R3 are the same or different and are hydrogen, halogen, hydroxyl, a substituted or unsubstituted lower alkyl gorup, a substituted or unsubstituted lower alkoxy group, a substituted or unsubstituted amino group, etc.; R4 is tetrazolyl, carboxyl group, amide or ester; R5 is hydrogen, nitro, amino, hydroxyl, lower alkanoyl, lower alkyl, etc.; R6 is selected from (a) a substituted or unsubstituted phenyl group, (b) a substituted or unsubstituted pyridyl group, (c) a substituted or unsubstituted thienyl group, (d) a substituted or unsubstituted benzofuranyl group, etc.; or a pharmaceutically acceptable salt thereof.
A compound of formula [III]:
4-(2,6-dimethoxyphenyl)-L-phenylalanine, or a lower alkyl ester thereof, or a salt thereof.
Dependencies are inferred from the claim text.
From the US filing history. Foreign family members aren’t listed.
Backward citations are indexed for grants only.
Having no double bonds between ring members or between ring members and non-ring members: with hydrocarbon radicals, substituted by hetero atoms,…
Drugs for disorders of the alimentary tract or the digestive system
For glucose homeostasis: for hyperglycaemia, e.g. antidiabetics
Drugs for disorders of the respiratory system: antiasthmatics
Term end not estimated
1. Field of the Invention
The present invention relates to pharmaceutical compositions comprising molecules that are inhibitors of α4 mediated (including (α4β7) adhesion and which could be useful in treating conditions such as asthma, diabetes, rheumatoid arthritis, inflammatory bowel disease and other diseases involving leukocyte infiltration of the gastrointestinal tract or other epithelial lined tissues; such as, skin, urinary tract, respiratory airway and joint synovium.
The inhibitors of the present invention could also be useful in treating conditions involving leukocyte infiltration of other tissues including lung, blood vessels, heart and nervous system as well as transplanted organs such as kidney, liver, pancreas and heart.
N-(2,6-Dichlorobenzoyl)-4-(2-methoxyphenyl)-L-phenylalanine methyl ester (1A) and N-(2,6-Dichlorobenzoyl)-4-(2-methoxyphenyl)-L-phenylalanine (1B).
1) Pyridine (3.58 mL) was added to a solution of N-(tert-butoxycarbonyl)-L-tyrosine methyl ester (4.36 g) in anhydrous CH2Cl2 (100 mL) under N2. The solution was cooled to 0° C. and triflic anhydride (3 mL) was added dropwise with stirring. After the addition was over the ice-bath was removed and the mixture was stirred for 3 h at room temperature. The mixture was sequentially washed with water, 1 N HCl and water. The resulting CH2Cl2 solution was finally washed with NaHCO3, followed by water, dried (MgSO4) and evaporated. The residue was purified by flash column chromatography (silica gel; eluent: toluene/EtOAc 9:1) to yield N-(tert-butoxycarbonyl)-O-(trifluoromethanesulfonyl)-L-tyrosine methyl ester (6.2 g). ESMS: m/z 500 (MH+).
2) To a mixture of 2-methoxybenzene boronic acid (0.446 g) and anhydrous K2CO3 (0.84 g) in toluene/DMF (25 mL/2.5 mL) under N2 was added a solution of the product obtained above (1.0 g) in 5 mL of toluene. Pd(PPh3)4 (0.48 g) was added and the mixture was heated at 80° C. for 24 h. The mixture was cooled, filtered through Celite and evaporated. The residue was taken up in EtOAc and washed with water. The organic layer was dried (MgSO4), evaporated, and the crude material was purified by flash column chromatography (silica gel; eluent: EtOAc/hexane 1/3) to yield N-(tert-butoxycarbonyl)-4-(2-methoxyphenyl)-L-phenylalanine methyl ester (0.64 g). ESMS: m/z 386 (MH+).