153623-86-0

Upstream product

• 19947-75-2 5-amino-3,4-dimethylisoxazol 
• 2905-25-1 o-bromobenzenesulfonyl chloride 
• 7440-44-0 pyrographite 
• 4468-47-7 2-methyl-3-oxo-butyronitrile 

Downstream Products

• 153624-30-7 2-bromo-N-(3,4-dimethyl-5-isoxazolyl)-N-[(2-methoxyethoxy)methyl]benzenesulfonamide 
• 1393601-31-4 4'-[(2-butyl-6-methyl-1H-benzimidazol-1-yl)methyl]-N-(3,4-dimethyl-5-isoxazolyl)-[1,1'-biphenyl]-2-sulfonamide 
• 1393601-32-5 4'-[(2-butyl-6-methoxy-1H-benzimidazol-1-yl)methyl]-N-(3,4-dimethyl-5-isoxazolyl)-[1,1'-biphenyl]-2-sulfonamide 
• 1393601-33-6 4'-[(2-butyl-6-chloro-1H-benzimidazol-1-yl)methyl]-N-(3,4-dimethyl-5-isoxazolyl)-[1,1'-biphenyl]-2-sulfonamide 
• 1393601-34-7 4'-[(2-butyl-6-bromo-1H-benzimidazol-1-yl)methyl]-N-(3,4-dimethyl-5-isoxazolyl)-[1,1'-biphenyl]-2-sulfonamide 
• 1393601-35-8 4'-[(2-butyl-6-fluoro-1H-benzimidazol-1-yl)methyl]-N-(3,4-dimethyl-5-isoxazolyl)-[1,1'-biphenyl]-2-sulfonamide 
• 1393601-36-9 4'-[(2-butyl-6-trifluoromethyl-1H-benzimidazol-1-yl)methyl]-N-(3,4-dimethyl-5-isoxazolyl)-[1,1'-biphenyl]-2-sulfonamide 
• 1393601-37-0 4'-[(2-butyl-6-nitro-1H-benzimidazol-1-yl)methyl]-N-(3,4-dimethyl-5-isoxazolyl)-[1,1'-biphenyl]-2-sulfonamide 
• 1247725-75-2 4'-[(1H-benzimidazol-1-yl)-methyl]-N-(3,4-dimethyl-5-isoxazolyl)-N-((2-methoxyethoxy)methyl)-[1,1'-biphenyl]-2-sulfonamide 
• 1247725-78-5 C₃₀H₃₂N₄O₅S 
• 1247725-80-9 C₃₁H₃₄N₄O₅S 
• 1247725-81-0 C₃₂H₃₆N₄O₅S 
• 1247725-86-5 4'-[(2-methyl-1H-benzimidazol-1-yl)methyl]-N-(3,4-dimethyl-5-isoxazolyl)-[1,1'-biphenyl]-2-sulfonamide 
• 1247725-89-8 4'-[(2-ethyl-1H-benzimidazol-1-yl)methyl]-N-(3,4-dimethyl-5-isoxazolyl)-[1,1'-biphenyl]-2-sulfonamide 

Relevant academic research and scientific papers

Synthesis and biological evaluation of 4′-[(benzimidazole-1-yl) methyl]biphenyl-2-sulfonamide derivatives as dual angiotensin II/endothelin A receptor antagonists

A series of 4′-[(benzimidazole-1-yl)methyl]biphenyl-2-sulfonamide derivatives (Ia-Il) were synthesized and biologically evaluated. It was found that Ig, the most active compound, antagonized both Ang II AT1 and endothelin ETA receptors (AT1 IC50 = 8.5, ETA IC50 = 8.9 nM), and was more potent than losartan in RHRs with no significant effect on heart rate. The preliminary structure-activity relationships were also discussed in the present paper.

Discovery of 4'-[(imidazol-1-yl)methyl]biphenyl-2-sulfonamides as dual endothelin/angiotensin II receptor antagonists.

A series of 4'-[(imidazol-1-yl)methyl]biphenylsulfonamides has potent antagonist activity against both angiotensin II AT(1) and endothelin ET(A) receptors. Such dual-acting antagonists could have utility in the treatment of hypertension, heart failure, an

Substituted biphenylsulfonamide endothelin antagonists

Compounds of the formula inhibit the activity of endothelin. The symbols are defined as follows: R2 and R3 are each independently (a) hydrogen; (b) alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, aryl, aryloxy, aralkyl or aralkoxy, any of which may be substituted with Z1, Z2 and Z3; (c) halo; (d) hydroxyl; (e) cyano; (f) nitro; (g) -C(O)H or -C(O)R6; (h) -CO2H or -CO2R6; (i) -SH, -S(O)nR6, -S(O)m-OH, -S(O)m-OR6, -O-S(O)m-R6, -O-S(O)mOH or -O-S(O)m-OR6; (j) -Z4-NR7R8; or (k) -Z4-N(R11)-Z5-NR9R10; and the remaining symbols are as defined in the specification.

Biphenylsulfonamide endothelin antagonists: Structure-activity relationships of a series of mono- and disubstituted analogues and pharmacology of the orally active endothelin antagonist 2'-amino-N-(3,4- dimethyl-5-isoxazolyl)-4'-(2-methylpropyl)[1,1'-biphenyl]-2-sulfonamide (BMS- 187308)

Substitution at the ortho position of N-(3,4-dimethyl-5-isoxazolyl) benzenesulfonamide led to the identification of the biphenylsulfonamides as a novel series of endothelin-A (ETA) selective antagonists. Appropriate substitutions on the pendant phenyl ring led to improved binding as well as functional activity. A hydrophobic group such as isobutyl or isopropoxyl was found to be optimal at the 4'-position. Introduction of an amino group at the 2'-position also led to improved analogues. Combination of the optimal 4'- isobutyl substituent with the 2'-amino function afforded an analogue (20, BMS-187308) with improved ET(A) binding affinity and functional activity. Compound 20 also has good oral activity in inhibiting the pressor effect caused by an ET-1 infusion in rats. Doses of 10 and 30 μmol/kg iv 20 attenuated the pressor responses due to the administration of exogenous ET-1 to conscious monkeys, indicating that the compound inhibits the in vivo activity of endothelin-1 in nonhuman primates.

Substituted biphenyl isoxazole sulfonamides

Compounds of the formula STR1 inhibit the activity of endothelin. The symbols are defined as follows: R1, R2, R3 and R4 are each directly bonded to a ring carbon and are each independently (a) hydrogen; (b) alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, aryl, aryloxy, aralkyl or aralkoxy, any of which may be substituted with Z1, Z2 and Z3 ; (c) halo; (d) hydroxyl; (e) cyano; (f) nitro; (g) --C(O)H or --C(O)R5 ; (h) --CO2 H or --CO2 R5 ; (i) --Z4 --NR6 R7 ; (j) --Z4 --N(R10)--Z5 --NR8 R9 ; or (k) R3 and R4 together may also be alkylene or alkenylene, either of which may be substituted with Z1, Z2 and Z3, completing a 4- to 8-membered saturated, unsaturated or aromatic ring together with the carbon atoms to which they are attached; and the remaining symbols are as defined in the specification.

N-Isoxazolyl-biphenylsulfonamide derivatives, their preparation and their use as endothelin antagonists

A compound of the formula I an enantiomer, diastereomer or pharmaceutically acceptable salt thereof, wherein: one of X and Y is N and the other is O; R2,R3,R4 and R5 are each independently (a) hydrogen;(b) alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, aryl, aryloxy, aralkyl or aralkoxy, any of which may be substituted with Z1, Z2 and Z3;(c) halo;(d) hydroxyl;(e) cyano;(f) nitro;(g)-C(O)H or-C(O)R6;(h)-CO2H or-CO2R6;(i)-SH,-S(O)nR6 ,-S(O)m-OH,-S(O)m-OR6,-O-S(O)m-R6,-O-S(O)mOH or-O-S(O)m-OR6;(j)-Z4-NR7R8; or(k)-Z4-N(R11)-Z5-NR9 R10; R4 and R5 together are alkylene or alkenylene, either of which may be substituted with Z1,Z2 and Z3, completing a 4-to 8-membered saturated, unsaturated or aromatic ring together with the carbon atoms to which they are attached; G1 is (a) hydrogen; or(b) alkyl; G2 is (a) hydroxyalkyl;(b)-(CH2)mOR6; or(c)-(CH2)m-NR12 R13;(d) mono-to hexa-halo substituted alkyl; or(e)-(CH2)n OR14; and the remaining symbols are as defined in the description.The compounds of formula I are antagonists of ET-1, ET-2 and /or ET-3 and are useful in treatment of conditions associated with increased ET levels (e.g., dialysis, trauma and surgery) and of all endothelin-dependent disorders. They are thus inter alia useful as antihypertensive agents.

PHENYL SULFONAMIDE ENDOTHELIN ANTAGONISTS

Compounds of the formula STR1 inhibit the activity of endothelin. The symbols are defined as follows: R 1, R 2 and R. sup.3 are each independently(a) hydrogen, except that R. sup.1 is other than hydrogen;(b) alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, aryl, aryloxy, aralkyl or aralkoxy, any of which may be substituted with Z 1, Z 2 and Z. sup.3 ;(c) halo;(d) hydroxyl;(e) cyano; (f) nitro; (g)--C(O)H or--C(O)R 6 ;(h)--CO 2 H or--CO 2 R 6 ; (i)--SH,--S(O) n R 6,--S(O) m--OH,--S(O) m--OR 6,--O--S(O) m--R 6,--O--S(O) m OH or--O--S(O) m--OR. sup.6 ;(j)--Z. sup.4--NR 7 R 8 ; or (k)--Z 4--N(R 11--Z 5--NR 9 R 10 ; and the remaining symbols are as defined in the specification.