On October 31, 2013, Ueno, Hirokazu; Yamamoto, Takashi; Takashita, Ryuta; Yokoyama, Ryohei; Sugiura, Toshihiko; Kageyama, Shunsuke; Ando, Ayatoshi; Eda, Hiroyuki; Eviryanti, Agung; Miyazawa, Tomoko; Kirihara, Aya; Tanabe, Itsuya; Nakamura, Tarou; Noguchi, Misato; Shuto, Manami; Sugiki, Masayuki; Dohi, Mizuki published a patent.Application In Synthesis of 4-Bromo-2-isopropylpyridine The title of the patent was Preparation of N-(4-sulfonamidobenzoyl)-L-phenylalanine and N-(4-sulfonamidobenzoyl)-3-(pyridin-2-yl)-L-alanine derivatives as α4-integrin inhibitors. And the patent contained the following:
There are provided L-phenylalanine and 3-(pyridin-2-yl)-L-alanine derivatives having terminal sulfonamide groups and heterocyclic groups [I; A = Q, Q1, Q2; Arm = cycloalkane or aromatic ring containing 0-4 heteroatoms selected from O, S, and N; R1, R2, R3, R11, R12, R13, R14, R21, R22, R23, R24, R25 = group A, H, lower alkylamino, lower alkylamino-lower alkyl; group A = halo, HO, each hydroxy- or halo-(un)substituted lower alkyl, alkenyl, alkynyl, or alkylthio, NO2, NH2, CO2H, lower alkyloxycarbonyl, CONH2, lower alkanoyl, aroyl, lower alkylsulfonyl, SO2NH2, ammonium group; B = (un)substituted lower alkoxy, HO, hydroxyamino; R41 = H, lower alkyl; a, b, c, d = CR31, CR32, CR33, CR34; e, f, g, h = CR35, CR36, CR37, CR38; R31-R38 = H, halo, lower alkyl, lower alkoxy, NO2; wherein one or two of a, b, c, and d = N atom; one or two of e, f, g, and h = N atom; at least one of R31-R34 = halo or lower alkyl; D = each (un)substituted Ph or heterocyclyl; E = group A, lower alkylaminoalkylene, (un)substituted 5- or 6-membered heterocyclyl, or substituted CONH2; or lower alkylcarbonyl and lower alkyloxycarbonyl in E group are linked to Ph of D group to form a ring] or pharmaceutically acceptable salts thereof. These compounds have excellent α4-integrin-inhibiting activity with high selectivity for α4β7-integrin over α4β1-integrin. They are useful for the treatment or prevention of inflammatory diseases related to α4β7 integrin-dependent adhesion process. Thus, 100 mg Me 4-(1-methyl-2,4-dioxo-1,4-dihydropyrido[3,4-d]pyrimidin-3(2H)-yl)-L-phenylalaninate and 89.0 mg 2,6-difluoro-4-[[[5-(1H-1,2,4-triazol-1-yl)pyridin-2-yl]sulfonyl]amino]benzoic acid were suspended in 2.0 mL CH2Cl2, treated with 133 mg HATU and 0.160 mL diisopropylethylamine, stirred at room temperature for 2 h, and concentrated under reduced pressure to give, after purification using reversed phase HPLC, Me N-[2,6-difluoro-4-([[5-(1H-1,2,4-triazol-1-yl)pyridin-2-yl]sulfonyl]amino)benzoyl]-4-(1-methyl-2,4-dioxo-1,4-dihydropyrido[3,4-d]pyrimidin-3(2H)-yl)-L-phenylalaninate (II; R = Me) tris(trifluoroacetate). II.3CF3CO2H (R = Me) (25.0 mg) was treated with 2.0 mL 4 N HCl/dioxane solution and 2.0 mL H2O, stirred at 80° for 1 h, and concentrated to give, after purification using reversed phase HPLC, II.3CF3CO2H (R = H). II (R = H) (free base) inhibited the binding of MAdCAM to human RPMI-8866 cells expressing α4β7 integrin and that of MAdCAM to human RPMI-8866 cells expressing α4β1 integrin with IC50 of 0.060 and nM, resp., and 220-fold inhibition selectivity for α4β7 integrin. The experimental process involved the reaction of 4-Bromo-2-isopropylpyridine(cas: 908267-63-0).Application In Synthesis of 4-Bromo-2-isopropylpyridine
The Article related to sulfonamidobenzoylhenylalanine preparation selective alpha 4 beta 7 integrin inhibitor, inflammatory disease treatment prevention sulfonamidobenzoylhenylalanine preparation, sulfonamidobenzoylpyridinylalanine preparation selective alpha 4 beta 7 integrin inhibitor and other aspects.Application In Synthesis of 4-Bromo-2-isopropylpyridine