| 摘要 |
<p>Phenol derivs. of formula (I) and their salts are new. R1 = H, 1-6C alkyl, 3-8C cycloalkyl, Ph-(1-3C)alkyl, or Ph opt. substd. by halogen, 1-4C alkyl or 1-4C alkoxy; R2 = 1-10C alkyl, 2-6C alkenyl, benzyl or 2-phenethyl; R3 = H, Br or Cl; Z = 0, NR or S(O)p; or CR5R6-Z = CH=CH; m = 0-4; A = bond, O, S(O)p, NR', CO or CH(OH); n = 0-4; Q = bond, O, S(O)p or NR"; R4 = CN, OH, SC(=NH)NH2, NR14R15, COR9, 5-tetrazolyl or a gp. (II)-(VIII); R, R', R" = H or 1-3C alkyl; R5, R6 = H 1-3C alkyl, Ph or PhCH2; R9 = OH, 1-4C alkoxy, NH-OH or NR14R15; R10 = H, OH, 1-4C alkoxy, halogen, 1-4C alkyl, NH2, mono- or di(1-3C)alkylamino or 1-3C alkanoylamino; R11 = (X)r-COR9, O-(X)r-COR9, (X)r-T-CN, O-(X)r-T-CN, (X)r-W-tetrazole or O-(X)r-W-tetrazole; X = CR16R17; R12 = H or 1-3C alkyl; R13 = H or Me; R14, R15 = H or 1-3C alkyl; or NR14R15 = morpholino or N-methylpiperazino; R16, R17 = H or 1-3C alkyl; r = 0-4; s = 1-4; T = direct bond or S; W = direct bond, O, NH, N-(1-3C alkyl) or S(O)p; and p = 0, 1 or 2. - Intermediates of formula (IX) are also new. G = halogen, OH, SH, NR18R19 or P.(Ph)3Y; R18, R19 = H or 1-3C alkyl, and Y = halogen. (0/0) EPAB- EP-132366 B Phenol derivs. of formula (I) and their salts are new. R1 = H, 1-6C alkyl, 3-8C cycloalkyl, Ph-(1-3C)alkyl, or Ph opt. substd. by halogen, 1-4C alkyl or 1-4C alkoxy; R2 = 1-10C alkyl, 2-6C alkenyl, benzyl or 2-phenethyl; R3 = H, Br or Cl; Z = 0, NR or S(O)p; or CR5R6-Z = CH=CH; m = 0-4; A = bond, O, S(O)p, NR', CO or CH(OH); n = 0-4; Q = bond, O, S(O)p or NR"; R4 = CN, OH, SC(=NH)NH2, NR14R15, COR9, 5-tetrazolyl or a gp. (II)-(VIII); R, R', R" = H or 1-3C alkyl; R5, R6 = H 1-3C alkyl, Ph or PhCH2; R9 = OH, 1-4C alkoxy, NH-OH or NR14R15; R10 = H, OH, 1-4C alkoxy, halogen, 1-4C alkyl, NH2, mono- or di(1-3C)alkylamino or 1-3C alkanoylamino; R11 = (X)r-COR9, O-(X)r-COR9, (X)r-T-CN, O-(X)r-T-CN, (X)r-W-tetrazole or O-(X)r-W-tetrazole; X = CR16R17; R12 = H or 1-3C alkyl; R13 = H or Me; R14, R15 = H or 1-3C alkyl; or NR14R15 = morpholino or N-methylpiperazino; R16, R17 = H or 1-3C alkyl; r = 0-4; s = 1-4; T = direct bond or S; W = direct bond, O, NH, N-(1-3C alkyl) or S(O)p; and p = 0, 1 or 2. - Intermediates of formula (IX) are also new. G = halogen, OH, SH, NR18R19 or P.(Ph)3Y; R18, R19 = H or 1-3C alkyl, and Y = halogen. (106pp Dwg.No.0/0) - EP-132366 B A compound of the Formula I and pharmaceutically acceptable salts thereof, wherein: R1 is hydrogen, C1 - C8 alkyl, C3 - C8 cycloalkyl, phenyl-substituted-(C1 - C3 alkyl), phenyl, or phenyl substituted with halo, C1 - C4 alkyl, or C1 - C4 alkoxy; R2 is C1 - C10 alkyl, C2 - C6 alkenyl, benzyl, or 2-phenylethyl; R3 is hydrogen, bromo, or chloro; Z is -O-, -NR-, or gp (i) m is 0 - 4; A is a bond, -O-, (i) -NR'-, -CO or -CHOH-; n is O - 4; Q is a bond, -O-, (i) or -NR"-; and R4 is -CN, Y, (ii), (iii), (iv), (v), (vi), (vii), (viii) or (Y) where each or R, R', and R" is independently hydrogen or C1 - C3 alkyl; R10 is hydrogen, hydroxy, C1 - C4 alkoxy,halo, C1 - C4 alkyl, amino, mono-, or di-(C1 - C3 alkyl)amino, or (C1 - C3 alkyl)CONH-; R11 is -(CR16R17)r - COR9, -O-(CR16R17)s-COR9, -(CR16R17)r-TCN, -O-(CR16R17)s-T-CN, -CR16R17)r-WY or -O-(CR16R17)s-WY R9 is hydroxy, C1 - C4 alkoxy, -NHOH, or NR14R15; R12 is hydrogen or C1 - C3 alkyl; R13 is hydrogen or methyl; each of R14 and R15 is independently hydrogen, C1 - C3 alkyl, or when taken together with the nitrogen atom form a morpholine or N-methyl piperazine ring; each of R16 and R17 is independently hydrogen or C1 - C3 alkyl; r is O - 4; s is 1 - 4; T is a bond or -S-; W is a bond -O-, -NR"'-, or (i) R"' is hydrogen or C1 - C3 alkyl; and p is O, 1, or 2; provided that; (a) when R4 is -CN, Q may only be a bond and n may not be O; (b) when A is -O-, (i), -NR'-, or -CHOH-, and Z is -O-, (i), or -NR-, m may not be O; (c) when A is -O-, (i) -NR'-, or -CHOH-, and Q is -O-, (i), or -NR"-, n may not be O; (d) when Z is -O-, (i), or -NR-, Q is -O-, (i), or -NR"-, and A is a bond, m and n may not both be O; and (e) if A is =CO (1) when Z is (i), m may not be O, (2) when Q is (i) n may not be O, and (3) when Z is -O- or -NR- and Q is -O- or -NR"-, m and m may not both be O. (58pp)n GBAB- GB2143530 B A compound of the formula (I) and pharmaceutically acceptable salts thereof, wherein: R1 is hydrogen, C1-C6 alkyl, C3-C8 cycloalkyl, phenyl-substituted-(C1-C3 alkyl), phenyl, or phenyl substituted with halo, C1-C4 alkyl, or C1-C4 alkoxy; R2 is C1-C10 alkyl, C2-C6 alkenyl, benzyl, or 2-phenylethyl; R3 is hydrogen, bromo, or chloro; X is -O-, -NR-, or S(O)p, or when taken together, -CR5R6-Z- is -CH=CH-; m is 0-4; A is a bond, -O-, S(O)p, -NR'-CO, or -CHOH-; n is 0-4; Q is a bond. -O-. S(O)p-, or NR''-; and R4 is -CN, hydroxy, -SC(=NH)NH2, -NR14-R15, COR9, (II)-(IX); -COR9, where each of R, R', and R'' is independently hydrogen or C1-C3 alkyl; each of R5 and R6 is independently hydrogen, C1-C3 alkyl, phenyl, or benzyl, R9 is hydroxy, C1-C4 alkoxy, -NHOH, or -NR14R15; R10 is hydrogen, hydroxy, C1-C4 alkoxy, halo, C1-C4 alkyl, amino, mono- or di-(C1-C3 alkyl)amino, or (C1-C3 alkyl)CONH; R11 is -(CR16R17)r-COR9, -O-(CR16R17)s-COR9, -(CR16R17)r-TCN, -O-(CR16R17)s-T-CN, (X) or (XI) R12 is hydrogen or C1-C3 alkyl; R13 is hydrogen or methyl; each of R14 and R15 is independently hydrogen, C1-C3 alkyl, or when taken together with the nitrogen atom form a morpholine or N-methyl piperazine ring; each of R16 and R17 is independently hydrogen or C1-C3 alkyl; T is a bond or -S-; W is a bond, -O-. -NR'''-, S(O)p, or R''' is hydrogen or C1-C3 alkyl; and p is 0, 1, or 2; provided that: (a) when R4 is -CN, -COR9, hydroxy, -NR11R12, or -SC(=NH)NH2, W may only be a bond and n may not be 0, (b) when A is -O-, S(O)p, -NR'-, or -CHOH-, and Z is -O-, S(O)p, or -NR-, m may not be O; (c) when A is -O-, S(O)p, -NR'-, or -CHOH-, and Q is -O-. S(O)p, or -NR'', n may not be O; (d) when Z is -O-, S(O)p, or -NR-, Q is -O-, S(O)p, or -NR''-, and A is a bond, m and n may not both be O; and (e) if A is CO-, (1) when Z is S(O)p, m may not be O, (2) when Q is S(O)p, n may not be O, and (3) when Z is -O- or -NR- and Q is -O- or -NR''-, m and n may not both be O. - GB2143530 B A compound of the formula (I) and pharmaceutically acceptable salts thereof, wherein: R1 is hydrogen, C1-C6 alkyl, C3-C8 cycloalkyl, phenyl-substituted-(C1-C3 alkyl), phenyl, or phenyl substituted with halo, C1-C4 alkyl, or C1-C4 alkoxy; R2 is C1-C10 alkyl, C2-C6 alkenyl, benzyl, or 2-phenylethyl; R3 is hydrogen, bromo, or chloro; X is -O-, -NR-, or S(O)p, or when taken together, -CR5R6-Z- is -CH =CH-; m is 0-4; A is a bond, -O-, S(O)p, -NR'-CO, or -CHOH-; n is 0-4; Q is a bond. -O-. S(O)p-, or NR''-; and R4 is -CN, hydroxy, -SC( =NH)NH2, -NR14-R15, COR9, (II)-(IX); -COR9, where each of R, R', and R'' is independently hydrogen or C1-C3 alkyl; each of R5 and R6 is independently hydrogen, C1-C3 alkyl, phenyl, or benzyl, R9 is hydroxy, C1-C4 alkoxy, -NHOH, or -NR14R15; R10 is hydrogen, hydroxy, C1-C4 alkoxy, halo, C1-C4 alkyl, amino, mono- or di-(C1-C3 alkyl)amino, or (C1-C3 alkyl)CONH; R11 is -(CR16R17)r-COR9, -O-(CR16R17)s-COR9, -(CR16R17)r-TCN, -O-(CR16R17)s-T-CN, (X) or (XI) R12 is hydrogen or C1-C3 alkyl; R13 is hydrogen or methyl; each of R14 and R15 is independently hydrogen, C1-C3 alkyl, or when taken together with the nitrogen atom form a morpholine or N-methyl piperazine ring; each of R16 and R17 is independently hydrogen or C1-C3 alkyl; T is a bond or -S-; W is a bond, -O-. -NR'''-, S(O)p, or R''' is hydrogen or C1-C3 alkyl; and p is 0, 1, or 2; provided that: (a) when R4 is -CN, -COR9, hydroxy, -NR11R12, or -SC( =NH)NH2, W may only be a bond and n may not be 0, (b) when A is -O-, S(O)p, -NR'-, or -CHOH-, and Z is -O-, S(O)p, or -NR-, m may not be O; (c) when A is -O-, S(O)p, -NR'-, or -CHOH-, and Q is -O-. S(O)p, or -NR'', n may not be O; (d) when Z is -O-, S(O)p, or -NR-, Q is -O-, S(O)p, or -NR''-, and A is a bond, m and n may not both be O; and (e) if A is CO-, (1) when Z is S(O)p, m may not be O, (2) when Q is S(O)p, n may not be O, and (3) when Z is -O- or -NR- and Q is -O- or -NR''-, m and n may not both be O. USAB- US5105017 A New benzene derivs. of formula (VI) where R1 is 1-6C alkyl, 3-8C cycloalkyl, Ph opt. substd. by 1-3C alkyl, halo or 1-4C-alkyl or -alkoxy; R2 is 1-10C alkyl, 2-6C alkenyl, benzyl or 2-PhEt; R3 is H, Br or Cl; R5 and R6 are each H, 1-3C alkyl, Ph or benzyl; G is Cl Br, I, OH, SH, -NR18R19 or Ph3PX' where R18 and R19 are each H or 1-3C alkyl and X' is C1, Br or I. - A typical cpd. is 4-acetyl-3-hydroxy-2-propylbenzyl chloride. - (XVI) may be prepd. e.g. by treating 3-methyloxybenzyl chloride with dialkylamine, then with base and R2-halide.</p> |
