Claims
- 1. A compound represented by the structure shown in formula 1, ##STR132## wherein 3 tautomers of the same structure are shown, wherein R.sub.1 is
- ______________________________________a) --CH--(C.sub.3 --C.sub.6 cycloalkyl).sub.2, b) diphenylmethyl, c) diphenylethyl, d) diphenylethenyl, e) diphenylpropyl, f) phenylcyclobutyl; g) --CH(CH.sub.2 -phenyl).sub.2, h) 5,6,7,8,9-tetrahydro-5H-benzocycloheptenyl, i) 1,2,3,4-tetrahydro-naphthalenyl, substituted with zero, one (1) or two (2) --O-- (C.sub.1-6 alkyl) or --CH.sub.3, - j) 8 STR133## - k) 9 STR134## - l) 0 STR135## - m) 1 STR136## - n) 2 STR137## - o) 3 STR138## - or p) 4 #STR139##______________________________________
- wherein R.sub.1-1 is
- a) --C.sub.1-10 alkyl,
- b) --C.sub.2-10 alkenyl,
- c) --C.sub.3-7 cycloalkyl,
- d) --(C.sub.1-6 alkyl)--(C.sub.3-7 cycloalkyl),
- e) --CH.sub.2 --C(O)--O--((H or (C.sub.1-6 alkyl)),
- f) --(C.sub.0-6 alkyl)--R.sub.1-100,
- g) --(C.sub.0-6 alkyl)--R.sub.1-500, or
- h) --(C.sub.0-6 alkyl)--CH.dbd.CH--R.sub.1-100 ;
- wherein R.sub.1-2 is
- a) -halo,
- b) -trifluoromethyl,
- c) --C.sub.3-7 cycloalkyl,
- d) --C.sub.2-10 alkenyl,
- e) --(C.sub.0-6 alkyl)--((CH.sub.2)CH.sub.2 --O--).sub.q --(C.sub.1-6 alkyl),
- f) --R.sub.1-100,
- g) --C(O)--O--(C.sub.0-6 alkyl)--R.sub.1-100,
- h) --R.sub.1-500,
- i) --C(O)--R.sub.1-500 or
- j) --O--R.sub.1-500 ;
- wherein R.sub.1-100 is
- a) phenyl, substituted with zero (0) to three (3) of RA.sub.1,
- b) naphthyl, substituted with zero (0) to three (3) of RA.sub.1,
- c) biphenyl, substituted with zero (0) to three (3) of RA.sub.1,
- d) perhalophenyl;
- wherein R.sub.1-500 is
- a 5- or 6-membered saturated or unsaturated ring containing from one (1) to four (4) heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur; and substituted with zero (0) to three (3) RA.sub.1 ; and including any bicyclic group in which any of the above heterocyclic rings is fused to a benzene ring, C.sub.3 -C.sub.8 cycloalkyl, or another heterocycle; and substituted with zero (0) to three (3) RA.sub.1 ; and if chemically feasible, the nitrogen and sulfur atoms may be in the oxidized forms;
- wherein RA.sub.1 is
- a) halo,
- b) --H
- c) --N-methyl-piperazino,
- d) --C.sub.1-8 alkyl, substituted with zero (0) to three (3) halo,
- e) --C.sub.2-8 alkenyl,
- f) --C.sub.3-7 cycloalkyl,
- g) --(C.sub.0-6 alkyl)--RA.sub.1-RA-12
- h) --(C.sub.1-6 alkyl)-phenyl, substituted with zero (0) to three (3) RA.sub.1-RA-120 ;
- i) --(C.sub.0-6 alkyl)--RA.sub.1-RA-15
- j) --OH,
- k) --O--(C.sub.1-6 alkyl), substituted with zero (0) to three (3) hydroxy,
- l) --(C.sub.1-6 alkyl)--O-(C.sub.1-6 alkyl), substituted with zero (0) to three (3) hydroxy,
- m) --O--(C.sub.2-7 alkenyl), substituted with zero (0) to three (3) hydroxy,
- n) --(C.sub.1-6 alkyl)--O-(C.sub.2-7 alkenyl), substituted with zero (0) to three (3) hydroxy,
- o) (o-) or (m-)--O-(C.sub.1-6 alkyl)--CH.dbd.CH.sub.2,
- p) --(CH.sub.2 -O).sub.q --C.sub.1-3 alkyl,
- q) --O--(CH.sub.2 CH.sub.2 --O--).sub.q --CH.sub.3,
- r) --CH(O),
- s) --C(O)--(C.sub.1-6 alkyl),
- t) --C(O)--O--(C.sub.1-6 alkyl),
- u) --C(O)--N(H or C.sub.1-5 alkyl).sub.2,
- v) --SO.sub.3 H,
- w) --SO.sub.2 --RA.sub.1-RA-12,
- x) --(C.sub.0-6 alkyl)--SO.sub.2 -(C.sub.0-6 alkyl)--RA.sub.1-RA-12,
- y) --(C.sub.0-6 alkyl)--SO.sub.2 -(C.sub.0-6 alkyl)--RA.sub.1-RA-15,
- z) --CN,
- a1) --NH.sub.2,
- b1) --NH--(C.sub.1-6 alkyl),
- c1) -mono or -di(C.sub.1-6 alkyl)amino,
- d1) -diethylamino,
- e1) --(C.sub.0-6 alkyl)--NH--C(NH(H or C.sub.1-5 alkyl)).dbd.NCN,
- f1) --(C.sub.0-6 alkyl)--NH--C(NH(H or C.sub.1-5 alkyl)).dbd.CHNO.sub.2,
- g1) --(C.sub.0-6 alkyl)--NH--C(O)--O--(C.sub.1-6 alkyl)--RA.sub.1-RA-12
- h1) --(C.sub.0-6 alkyl)--NH--C(O)--O--(C.sub.1-6 alkyl)--RA.sub.1-RA-15,
- i1) --(C.sub.0-6 alkyl)--NH--C(O)--N(C.sub.1-3 alkyl).sub.2,
- j1) --(C.sub.0-6 alkyl)--NH--C(O)--NH--RA.sub.1-RA-12,
- k1) --(C.sub.0-6 alkyl)--NH--SO.sub.2 --NH--RA.sub.1-RA-12,
- l1) --NH--C(O)--NH--SO.sub.2 --RA.sub.1-RA-12,
- m1) --(C.sub.0-6 alkyl)--NH--C(SCH.sub.3).dbd.CHNO.sub.2,
- n1) --(C.sub.0-6 alkyl)--NH--C(SCH.sub.3).dbd.NCN),
- o1) --NH--AA--P.sub.1,
- p1) --NO.sub.2,
- q1) --(C.sub.0-6 alkyl)--N.sub.3,
- r1) ##STR140## s1) --N.dbd.C--(NH--CH(C.sub.2-6 alkyl).sub.2).sub.2, t1) --NR.sub.40 R.sub.41,
- u1) --NH--P(O)(C.sub.1-4 alkyl)--RA.sub.1-RA-12,
- v1) --NH--P(O)(RA.sub.1-RA-12 -RA.sub.1-RA-12,
- w1) --NH--P(O)(O--R.sub.11)--(RA.sub.1-RA-12),
- x1) --NH--C(S)--NH--R.sub.42, or
- y1) --NH--C(S)--CH.sub.2 --R.sub.42 ;
- z1) --(C.sub.1-6 alkyl)--G.sub.1-1 --CH.dbd.CH--RA.sub.1-RA-12,
- a2) --(C.sub.0-6 alkyl)--G.sub.1-1 --CH.dbd.CH--RA.sub.1-RA-15,
- b2) --(C.sub.0-6 alkyl)--G.sub.1-1 --(C.sub.1-10 alkyl), substituted with zero (0) to three (3) halo,
- c2) --(C.sub.0-6 alkyl)--G.sub.1-1 --(C.sub.2-5 alkenyl),
- d2) --G.sub.1-1 --CH((C.sub.1-6 alkyl))--NH--C(O)--O--(C.sub.1-6 alkyl),
- e2) --G.sub.1-1 --CH((C.sub.1-6 alkyl)--RA.sub.1-RA-15)--NH--C(O)--O--(C.sub.1-6 alkyl),
- f2) --G.sub.1-1 --(C.sub.1-6 alkyl)--CH(NH--C(O)--O--(C.sub.1-6 alkyl)--RA.sub.1-RA-12)--C(O)--O--(C.sub.1-6 alkyl)--RA.sub.1-RA-12,
- g2) --(C.sub.0-6 alkyl)--G.sub.1-2 --(C.sub.1-12 alkyl),
- h2) --G.sub.1-2 --(C.sub.1-6 alkyl)-halo,
- i2) --G.sub.1-2 --(C.sub.1-6 alkyl)--NH.sub.2.
- j2) --G.sub.1-2 --(C.sub.1-6 alkyl)--NH--C(O)--O--(C.sub.1-6 alkyl),
- k2) --G.sub.1-2 --(C.sub.1-6 alkyl)--CH(NH--C(O)--O--(C.sub.1-6 alkyl))--C(O)--O--(C.sub.1-6 alkyl),
- l2) --G.sub.1-2 --(C.sub.0-6 alkyl)--CH(NH--C(O)--O--(C.sub.1-6 alkyl))--(C.sub.1-6 alkyl)--RA.sub.1-RA-15,
- m2) --G.sub.1-2 --(C.sub.1-6 alkyl)--CH(NH.sub.2)--C(O)--OH,
- n2) --G.sub.1-2 --(C.sub.1-6 alkyl)--C(O)--O--(C.sub.1-6 alkyl),
- o2) --G.sub.1-2 --(C.sub.1-6 alkyl)--(C.sub.3-6 cycloalkyl),
- p2) --(C.sub.0-6 alkyl)--G.sub.1-2 --(C.sub.O-6 alkyl)--RA.sub.1-RA-12,
- q2) --(C.sub.0-6 alkyl)--G.sub.1-2 --(C.sub.0-6 alkyl)--RA.sub.1-RA-15,
- r2) --G.sub.1-2 --(C.sub.0-6 alkyl)--O--RA.sub.1-RA-12,
- s2) --(C.sub.0-6 alkyl)--G.sub.1-2 --(C.sub.0-6 alkyl)--O--(C.sub.1-6 alkyl),
- t2) --G.sub.1-2 --(C.sub.1-6 alkyl)--C(O)--RA.sub.1-RA-15,
- u2) --G.sub.1-2 --(C.sub.1-6 alkyl)--C(O)--NH--(C.sub.1-6 alkyl)--RA.sub.1-RA-15,
- v2) --G.sub.1-2 --(C.sub.1-6 alkyl)--S--RA.sub.1-RA-15,
- w2) --(C.sub.0-6 alkyl)--G.sub.1-2 --O--(C.sub.1-6 alkyl)--RA.sub.1-RA-12,
- x2) --(C.sub.0-6 alkyl)--G.sub.1-2 --O--(C.sub.1-6 alkyl)--RA.sub.1-RA-15,
- y2) --G.sub.1-2 --CH.dbd.CH.sub.2,
- z2) --G.sub.1-2 --CH.dbd.CH--RA.sub.1-RA-12,
- a3) --G.sub.1-2 --N(R.sub.42).sub.2,
- b3) --G.sub.1-2 --NH.sub.2,
- c3) --G.sub.1-2 --(C.sub.1-6 alkyl)-phthalimido,
- d3) --G.sub.1-2 -(pentafluoro)-phenyl,
- e3) --G.sub.1-2 --(C.sub.1-6 alkyl)-bicyclo[2.2.1]heptane,
- f3) --G.sub.1-2 --H, or
- g3) --(C.sub.2-6 alkyl)--R.sub.30 ;
- wherein G.sub.1-1 is
- a) --NH--C(O)--,
- b) --NH--SO.sub.2 --,
- c) --NH--C(O)--NH--, or
- d) --SO.sub.2 --NH--;
- wherein G.sub.1-2 is
- a) --NH--C(O)--,
- b) --C(O)--NH--,
- c) --NH--SO.sub.2 --,
- d) --SO.sub.2 --NH--,
- e) --NH--SO.sub.2 --NH--,
- f) --C(O)--O--,
- g) --O--C(O)--,
- h) --N((C.sub.1-6 alkyl)--RA.sub.1-RA-12)--C(O)--,
- i) --NH--C(O)--NH,
- j) --N((C.sub.1-6 alkyl)--RA.sub.1-RA-12)--SO.sub.2 --, or
- k) --N((C.sub.0-6 alkyl)--(C.sub.1-6 alkyl))--SO.sub.2 --;
- wherein RA.sub.2 and RA.sub.3 are defined independently and are the same as RA.sub.1 ;
- wherein RA.sub.1-RA-12 is
- a) -phenyl, substituted with zero (0) to three (3) RA.sub.1-RA-12-AXA, or
- b) -naphthyl, substituted with zero (0) to three (3) RA.sub.1-RA-12-AXA ;
- wherein RA.sub.1-RA-15 is
- a 5- or 6-membered saturated or unsaturated ring containing from one (1) to four (4) heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur; and including any bicyclic group in which any of the above heterocyclic rings is fused to a benzene ring, C.sub.3 -C.sub.8 cycloalkyl, or another heterocycle; and substituted with zero (0) to three (3) RA.sub.1-RA-15-AXA ;
- wherein RA.sub.1-RA-120, RA.sub.2-RA-120 and RA.sub.3-RA-120, are defined independently and are
- a) --C.sub.1 -C.sub.4 alkyl,
- b) --C.sub.1 -C.sub.3 alkoxy,
- c) -dimethylamino,
- d) -diethylamino,
- e) --CF.sub.3,
- f) --CN,
- g) -halo,
- h) --NH.sub.2,
- i) --OH,
- j) --SO.sub.2 --NH.sub.2, or
- k) --C(O)--NH.sub.2 ;
- wherein RA.sub.1-RA-12-AXA or RA.sub.1-RA-15-AXA are independent and are,
- a) --H
- b) -halo,
- c) --NO.sub.2,
- d) --CN,
- e) --(C.sub.1-10 alkyl), substituted with zero (0) to three (3) halo,
- f) --(C.sub.0-6 alkyl)-phenyl, substituted with zero (0) to three (3) halo or hydroxy,
- g) --OH,
- h) --O--C.sub.1-5 alkyl,
- i) --(C.sub.0-6 alkyl)--O--(C.sub.1-6 alkyl), substituted with zero (0) to three (3) halo or hydroxy,
- j) --(C.sub.0-6 alkyl)--O--(C.sub.2-7 alkenyl), substituted with zero (0) to three (3) halo or hydroxy,
- k) --CH(O),
- l) --C(O)--(C.sub.1-6 alkyl),
- m) --C(O)OH,
- n) --C(O)O--(C.sub.1-5 alkyl),
- o) --C(O)--N(H or C.sub.1-6 alkyl).sub.2,
- p) --NH.sub.2,
- q) --NH--(C.sub.1-6 alkyl),
- r) -mono or di-(C.sub.1-6 alkyl)amino,
- s) --NH--OH,
- t) --NH--C(O)--(C.sub.1-3 alkyl),
- u) --(C.sub.0-6 alkyl)--NH--C(O)--phenyl,
- v) --(C.sub.0-6 alkyl)--NH--SO.sub.2 -phenyl,
- w) --(C.sub.0-6 alkyl)--N--N--phenyl, substituted with zero (0) or one (1) --N(C.sub.1 -C.sub.3 alkyl).sub.2, or
- x) --SO.sub.2 -phenyl, substituted with zero (0) to three (3) C.sub.1 -C.sub.5 alkyl;
- wherein R.sub.2 is
- a) --H,
- b) --C.sub.1-6 alkyl,
- c) --(C.sub.1-6 alkyl)--C.sub.3-7 cycloalkyl,
- d) --(C.sub.2-10 alkenyl)
- e) --(C.sub.1-6 alkyl)--R.sub.2-100,
- f) --(C.sub.1-6 alkyl)--R.sub.2-500,
- wherein R.sub.2-100 is independent of and defined the same as R.sub.1-100 wherein RA.sub.1 is RA.sub.2 ;
- wherein R.sub.2-500 is independent of and defined the same as R.sub.1-500 wherein RA.sub.1 is RA.sub.2 ;
- wherein RA.sub.2 is independent of and defined the same as RA.sub.1 ;
- wherein R.sub.3 is
- a) --C.sub.1-10 alkyl, substituted with zero (0) to five (5) halo,
- b) --C.sub.3-7 cycloalkyl,
- c) --C.sub.2-10 alkenyl,
- d) --(C.sub.1-6 alkyl)--CH.dbd.CH.sub.2
- e) --(C.sub.0-6 alkyl)--C(O)--O--(C.sub.1-6 alkyl),
- f) --(C.sub.0-6 alkyl)--(CH.sub.2 CH.sub.2 --O--).sub.q --(C.sub.1-6 alkyl),
- g) --(C.sub.1-6 alkyl)--R.sub.3-4,
- h) --(C.sub.0-6 alkyl)--CH.dbd.CH--R.sub.3-4,
- i) --(C.sub.2-10 alkenyl)--R.sub.3-4,
- j) --(C.sub.0-6 alkyl)--CH(R.sub.3-6)--(C.sub.0-6 alkyl)--R.sub.3-4,
- k) --(C.sub.0-6 alkyl)--CH(R.sub.3-6)--(C.sub.2-6 alkenyl)--R.sub.3-4,
- l) --(C.sub.0-6 alkyl)--C(O)--N(H or --C.sub.1-5 alkyl)--(C.sub.0-6 alkyl)--R.sub.3-4,
- m) --(C.sub.1-6 alkyl)--N(H or --C.sub.1-5 alkyl)--C(O)--R.sub.3-4,
- n) --(C.sub.1-6 alkyl)--N(H or --C.sub.1-5 alkyl)--C(O)--(C.sub.0-6 alkyl)--R.sub.3-4,
- o) --R.sub.3-100,
- except when R.sub.3-100 is phenyl and R.sub.1 is 1-phenylpropyl,
- p) --R.sub.3-500,
- q) --CH(R.sub.3-6)--CH(R.sub.3-6)--R.sub.3-4,
- r) --CH(C.sub.0-6 alkyl)--(C.sub.0-6 alkyl)--G.sub.3-1 --(C.sub.0-6 alkyl)--RA.sub.3-RA-12, or
- s) --CH(C.sub.0-6 alkyl)--(C.sub.0-6 alkyl)--G.sub.3-1 --(C.sub.0-6 alkyl)--RA.sub.3-RA-15 ;
- wherein G.sub.3-1 is
- a) --NH--C(O)--,
- b) --NH--SO.sub.2 --,
- c) --NH--CO--NH--, or
- d) --SO.sub.2 --NH--;
- wherein, R.sub.3-4 is
- a) -trifluoromethyl;
- b) -halo,
- c) --(C.sub.1-6 alkyl)
- d) --C.sub.3-7 cycloalkyl,
- e) --C.sub.2-10 alkenyl,
- f) --(C.sub.0-6 alkyl)--(CH.sub.2 CH.sub.2 --O--).sub.q --(C.sub.1-6 alkyl),
- g) --OH,
- h) --O--(C.sub.1-6 alkyl),
- i) --O--R.sub.3-500,
- j) --C(O)--R.sub.3-500,
- k) --C(O)--OH,
- l) --C(O)--O--(C.sub.1-6 alkyl),
- m) --C(O)--O--(C.sub.0-6 alkyl)--R.sub.3-100,
- n) --R.sub.3-100, or
- o) --R.sub.3-500 ;
- wherein R.sub.3-6 is
- a) --OH,
- b) --C.sub.1-0 alkyl,
- c) --(C.sub.0-6 alkyl)--C.sub.3 -C.sub.7 cycloalkyl,
- d) --(C.sub.1-6 alkyl)--CH.dbd.CH.sub.2,
- e) --(C.sub.0-6 alkyl)--R.sub.3-4,
- f) --(C.sub.1-6 alkyl)--R.sub.3-100, or
- g) --(C.sub.1-6 alkyl)--R.sub.3-500 ;
- wherein R.sub.3-9 is
- a) --(C.sub.1-6 alkyl),
- b) --(C.sub.2-7 alkenyl),
- c) --(C.sub.0-5 alkyl)--(C.sub.3-7 cycloalkyl),
- d) --(C.sub.0-6 alkyl)--RA.sub.3-RA-12, or
- e) --(C.sub.0-6 alkyl)--RA.sub.3-RA-15 ;
- wherein R.sub.3-100 is independent of and defined the same as R.sub.1-100 wherein RA.sub.1 is RA.sub.3 ;
- wherein R.sub.3-500 is independent of and defined the same as R.sub.1-100 wherein RA.sub.1 is RA.sub.3 ;
- wherein RA.sub.3 is independent of and defined the same as RA.sub.1 ;
- wherein RA.sub.3-RA-12, RA.sub.3-RA-15, RA.sub.3-RA-12-AXA and RA.sub.3-RA-15-AXA, are all independent of and defined the same as the corresponding R.sub.1 variables, which are: RA.sub.1-RA-12, RA.sub.1-RA-15, RA.sub.1-RA-12-AXA and RA.sub.1-RA-15-AXA, respectively,
- or wherein R.sub.2 and R.sub.3 can be taken together to form a ring comprised of the following groups,
- a) --(C.sub.5-9 cycloalkyl),
- b) --(C.sub.5-9 cycloalkyl) substituted with one to three: --OH, .dbd.N--OH, .dbd.O, R.sub.3-9,
- c) --(C.sub.1-5 alkyl substituted with zero to two R.sub.3-9)--R.sub.23 --(C.sub.1-5 alkyl substituted with zero to two R.sub.3-9)--,
- d) a 5- or 6-membered saturated ring containing one (1) or two (2) oxygen atoms, or or
- e) a double bond represented by the formula shown below; ##STR141## wherein R.sub.3-9 is a) --(C.sub.1-6 alkyl),
- b) --(C.sub.2-7 alkenyl),
- c) --(C.sub.0-6 alkyl)--(C.sub.3-7 cycloalkyl),
- d) --(C.sub.0-6 alkyl)--RA.sub.3-RA-12, or
- e) --(C.sub.0-6 alkyl)--RA.sub.3-RA-15 ;
- wherein R.sub.11 is
- a) --H,
- b) --C.sub.1 -C.sub.4 alkyl,
- c) --(RA.sub.3-RA-12), or
- d) pharmaceutically acceptable salts,
- wherein R.sub.23 is
- a) --O--,
- b) --C(O)--,
- c) --N(H)--,
- d) --N(R.sub.3-9)--,
- e) --N(C(O)--R.sub.3-9)--, or
- f) --N(C(O)--O--R.sub.3-9);
- wherein R.sub.30 is
- a) -morpholino,
- b) -piperidino,
- c) -piperazino,
- d) --OR.sub.40,
- e) -halo,
- f) ##STR142## g) --NR.sub.40 R.sub.41 ; wherein R.sub.40 and R.sub.41 are defined independently and are,
- a) --H,
- b) --C.sub.1 -C.sub.4 alkyl,
- c) phenyl, substituted with zero (0) to three (3) RA.sub.1-RA-120,
- wherein R.sub.42 is
- a) --C.sub.1 -C.sub.4 alkyl,
- b) --phenyl, substituted with zero (0) to three (3) RA.sub.1-RA-120, or
- c) --(C.sub.0-6 alkyl)-phenyl, substituted with zero (0) to three (3) RA.sub.1-RA-120 ;
- wherein RA.sub.2-RA-120 and RA.sub.3-RA-120 are independent of and defined the same as RA.sub.1-RA-120 ;
- wherein R.sub.50 and R.sub.51 are defined independently and are
- a) --(H or C.sub.1-6 alkyl),
- b) --(C.sub.0-6 alkyl)--RA.sub.3-RA-12, or
- c) --(C.sub.0-6 alkyl)--RA.sub.3-RA-15 ;
- wherein AA is an amino acid residue,
- wherein P.sub.1 is hydrogen or a nitrogen protecting group,
- wherein m and n are independently zero (0) to five (5) inclusive,
- wherein p and q are independently one (1) to five (5) inclusive,
- wherein z is one (1) to three (3) inclusive; and
- pharmaceutically acceptable salts, including bis salts, thereof,
- with the proviso that when R.sub.1 is 1-phenylpropyl and R.sub.2 is H, then R.sub.3 is not C.sub.1-5 alkyl, and
- with the proviso that when RA.sub.1 or RA.sub.3 is --G.sub.1-2 --(C.sub.0-6 alkyl)--O--RA.sub.1-RA-12, --(C.sub.0-6 alkyl)--G.sub.1-2 --(C.sub.0-6 alkyl)--O--(C.sub.0-6 alkyl), --(C.sub.0-6 alkyl)--G.sub.1-2 --O--(C.sub.1-6 alkyl)--RA.sub.1-RA-12, --(C.sub.0-6 alkyl)--G.sub.1-2 --O--(C.sub.1-6 alkyl)--RA.sub.1-RA-15, --G.sub.1-2 --N(R.sub.42).sub.2, or --G.sub.1-2 --NH.sub.2, then G.sub.1-2 is NOT, --C(O)--NH--, --NH--SO.sub.2 --, --SO.sub.2 --NH--, --NH--SO.sub.2 --NH--, --C(O)--O--, --NH--C(O)--NH, --N((C.sub.1-6 alkyl)--RA.sub.1-RA-12)--SO.sub.2 --, or --N((C.sub.0-6 alkyl)--(C.sub.1-6 alkyl))--SO.sub.2 --.
- 2. A compound selected from the following compounds
- BX-1)
- 5H-Furan-2-one,
- 5-benzyl-3-cyclopropylphenylmethyl-4-hydroxy-,
- BX-2)
- 2(5H)-Furanone, 3(cyclopropylphenylmethyl)--4-hydroxy-5-(2-phenylethyl)--,
- BX-3)
- 2(5H)-Furanone, 3-(cyclopropylphenylmethyl)--4-hydroxy-5-(3-phenylpropyl)--,
- BX-4)
- 2(5H)-Furanone, 3-(cyclopropylphenylmethyl)--4-hydroxy-5-propyl-,
- BX-5)
- 2(5H)-Furanone,
- 5-(2-cyclohexylethyl)--3-(cyclopropylphenylmethyl)-4-hydroxy-,
- BX-6)
- 2(5H)-Furanone, 3-(cyclopropylphenylmethyl)-4-hydroxy-5-(3-phenyl-2-propenyl)-,
- BX-7)
- 2(5H)-Furanone, 3-(cyclopropylphenylmethyl)-4-hydroxy-5-(1-hydroxy-3-phenyl-2-propenyl)-,
- BX-8)
- 2(5H)-Furanone, 3-(cyclopropylphenylmethy)-4-hydroxy-5-(1-hydroxy-3-phenylpropyl)--,
- BX-9)
- 2(5H)-Furanone, 4-hydroxy-5-(phenylmethyl)-3-(1-phenylpropyl)-,
- BX-10)
- 2(5H)-Furanone, 3-(cyclopropylphenylmethyl)-4-hydroxy-5-(1-methylethyl)-,
- BX-11)
- 2(5H)-Furanone, 5-butyl-3-(cyclopropylphenylmethyl)-4-hydroxy-,
- BX-12)
- 2(5H)-Furanone, 3-(cyclopropylphenylmethyl)-4-hydroxy-5,5-dipropyl-,
- BX-13)
- 2(5H)-Furanone, 3-(cyclopropylphenylmethyl)-4-hydroxy-5,5-bis(1-methylethyl)-,
- BX-14)
- 2(5H)-Furanone, 3-(cyclopropylphenylmethyl)-5,5-diethyl-4-hydroxy-,
- BX-15)
- 2(5H)-Furanone, 5,5-dibutyl-3-(cyclopropyl phenylmethyl)-4-hydroxy-,
- BX-16)
- 2(5H)-Furanone, 4-hydroxy-5-(2-phenylethyl)-3-(1-phenylpropyl)-.
- 3. A compound selected from the following compounds,
- CX-1) 1-Oxaspiro[4.4]non-3-en-2-one, 3-(cyclopropylphenylnethyl)-4-hydroxy-,
- CX-2) 1-Oxaspiro[4.7]dodec-3-en-2-one, 3-(cyclopropylphenylmethyl)-4-hydroxy-,
- CX-3) 2(5H)-Furanone, 3-(cyclopropylphenylmethyl)-4-hydroxy-methyl-5-(2-phenylethyl)-.
- 4. A compound selected from the following compounds,
- DX-1) 2(5H)-Furanone, 3-(cyclopropylphenylmethyl)-4-hydroxy-5-(3-phenylpropyl)-5-propyl-,
- DX-2) 2(5H)-Furanone, 3-(cyclopropylphenylmethyl)-hydroxy-5-methyl-5-(phenylmethyl)-,
- DX-3) 2(5H)-Furanone, 3-(cyclopropylphenylmethyl)-5-ethyl-4-hydroxy-5-(phenylmethyl)-,
- DX-4) 2(5H)-Furanone, 3-(cyclopropylphenylmethyl)-4-hydroxy-5-(phenylmethyl)-5-propyl-,
- DX-5) 2(5H)-Furanone, 3-(cyclopropylphenylmethyl)-4-hydroxy-5,5-bis(phenylmethyl)-,
- DX-6) 2(5H)-Furanone, 3-(cyclopropylphenylmethyl)-4-hydroxy-5-propyl-5-(3-pyridinylmethyl)-,
- DX-7) 2(5H)-Furanone, 3-(cyclopropylphenylmethyl)-5-ethyl-4-hydroxy-5-(2-phenyl-ethyl)-,
- DX-8) 2(5H)-Furanone, 3-(cyclopropylphenylmethyl)-4-hydroxy-5-(2-phenyl-ethyl)-5-propyl-,
- DX-9) 2(5H)-Furanone, 3-(cyclopropylphenylmethyl)-4-hydroxy-5,5-bis(2-phenylethyl)-,
- DX-10) 2(5H)-Furanone, 3-(cyclopropylphenylmethyl)-4-hydroxy-5-methyl-5-(3-phenylpropyl)-,
- DX-1 1) 2(5H)-Furanone, 3-(cyclopropylphenylmethyl)-5-ethyl-4-hydroxy-5-(3-phenylpropyl)-,
- DX-12) 2(5H)-Furanone, 5-butyl-3-(cyclopropylphenylmethyl)-4-hydroxy-5-(3-phenylpropyl)-,
- DX-13) 2(5H)-Furanone, 3-(cyclopropylphenylmethyl)-4-hydroxy-5,5-bis(3-phenylpropyl)-,
- DX-14) 2(5H)-Furanone, 5-(cyclopropylmethyl)-3-cyclopropylphenylmethyl)-hydroxy-5-(3-phenylpropyl)-,
- DX-15) 2(5H)-Furanone, 3-(cyclopropylphenylmethyl) hydroxy-5-(phenylmethyl)-5-(3-phenylpropyl)-,
- DX-16) 2(5H)-Furanone, 3-(cyclopropylphenylmethyl)-4-hydroxy-5-(3-phenylpropyl)-5-(2-propenyl)-,
- DX-17) 2(5H)-Furanone, 3-(cyclopropylphenylmethyl)-4-hydroxy-5-(l -methylethyl)-5-(3-phenylpropyl)-,
- DX-18) 2(5H)-Furanone, 3-(cyclopropylphenylmethyl)4-hydroxy-5-(2-phenyl-ethyl)-5-(3-phenylpropyl)-,
- DX-19) 2(5H)-Furanone, 3-(cyclopropylphenylmethyl) hydroxy-5-(1-methylpropyl)-5-(3-phenylpropyl)-,
- DX-20) 2(5H)-Furanone, 3-(cyclopropylphenylmethyl)-4-hydroxy-5-(2-methylpropyl)-5-(3-phenylpropyl)-.
- 5. A compound selected from the following compounds,
- FX-1) 2(5H)-Furanone, 3-(1,2-diphenylethyl)-4-hydroxy-5-(3-phenylpropyl)-,
- FX-2) 2(5H)-Furanone, 3-(diphenylmethyl)-4-hydroxy-5-(3-phenylpropyl)-,
- FX-3) 2(5H)-Furanone, 4-hydroxy-3-(1-phenyl-2-propenyl)-5-(3-phenylpropyl)-,
- FX-4) 2(5H)-Furanone, 4-hydroxy-3-(2-methyl-1-phenylpropyl)-5-(3-phenylpropyl)-,
- FX-5) 2(5H)-Furanone, 3-(2,2-dimethyl-1-phenylpropyl)-4-hydroxy-5-(3-phenylpropyl)-.
- 6. A compound selected from the following compounds,
- GX-1) 2(5H)-Furanone, 3-(cyclopropylphenylmethyl)-4-hydroxy-5-(1-(2-phenylethyl)pentyl)-,
- GX-2) 2(5H)-Furanone, 3-(cyclopropylphenylmethyl)-4-hydroxy-5-(1-(2-phenylethyl)pentyl)-,
- GX-3) 2(5H)-Furanone, 3-(cyclopropylphenylmethyl)-4-hydroxy-5-(1-methyl-3-phenylpropyl)-,
- GX-4) 2(5H)-Furanone, 3-(cyclopropylphenylmethyl)-5-(1,3-diphenylpropyl)-4-hydroxy-,
- GX-5) 2(5H)-Furanone, 3-(cyclopropylphenylmethyl)-5-(1-ethylpentyl)-4-hydroxy-,
- GX6) 2(5H)-Furanone, 3-(cyclopropylphenylmethyl)-4-hydroxy-5-(1-phenylpropyl)-,
- GX-7) 2(5H)-Furanone, 3-(cyclopropylphenylmethyl)-4-hydroxy-5-(1-phenylbutyl)-,
- GX-8) 2(5H)-Furanone, 3-(cyclopropylphenylmethyl)-5-(1-ethylpropyl)-4-hydroxy-.
- 7. A compound selected from the following compounds,
- HX-1) 2-Furanpropanoic acid, 4(cyclopropylphenylmethyl)-2,5-dihydro-3-hydroxy-5-oxo-.beta.-(2-phenylethyl)-, methyl ester,
- HX-2) 2(5H)-Furanone, 3-(cyclopropylphenylmethyl)-4-hydroxy-(1-(2-hydroxyethyl)-3-phenylpropyl)-
- 8. A compound selected from the following compounds,
- IX-1) 2(5H)-Furanone, 3-(cyclopropyl(3-nitrophenyl)methyl)-4-hydroxy-5,5-dipropyl-,
- IX-2) 2(5H)-Furanone, 4-hydroxy-3-(1-(3-nitrophenyl)propyl)-5,5-dipropyl-,
- IX-3) 1-Oxaspiro[4.5]dec-3-en-2-one, 3-(cyclopropylphenylmethyl)-4-hydroxy-,
- IX-4) 1-Oxaspiro[4.5]dec-3-en-2-one, 3-(cyclopropylphenylmethyl)-4-hydroxy -6-(2-phenylethyl)-,
- IX-5) 1-Oxaspiro[4.5]dec-3-en-2-one, 3-(cyclopropylphenylmethyl)-4-hydroxy-6-(2-phenylethyl)-,
- IX-6) 1-Oxaspiro[4.5]dec-3-en-2-one, 3-(cyclopropylphenylmethyl)-4-hydroxy-6-(2-phenylmethyl)-,
- IX-7) 1-Oxaspiro[4.5]dec-3-en-2-one, 3-(cyclopropylphenylmethyl)-4-hydroxy-6-(2-phenylmethyl)-,
- IX-8) 1-Oxaspiro[4.6]undec-3-en-2-one, 3-(cyclopropylphenylmethyl)-4-hydroxy-,
- IX-9) 2(5H)-Furanone, 5-ethyl-4-hydroxy-3-(2-methyl-1-phenylpropyl)-5-(phenylmethyl)-,
- IX-10) 2(5H)-Furanone, 5-ethyl-4-hydroxy-5-(phenylmethyl)-3-(1-phenylpropyl)-,
- IX-11) 2(5H)-Furanone, 3-((3-aminophenyl)cyclopropylmethyl)-4-hydroxy-5,5-dipropyl-,
- IX-12) 2(5H)-Furanone, 3-((3-aminophenyl)cyclopropylmethyl)-4-hydroxy-5,5-dipropyl-hydrochloride,
- IX-13) 2(5H)-Furanone, 3-(1-(3-aminophenyl)propyl)-4-hydroxy-5,5-dipropyl-,
- IX-14) Benzenesulfonamide, 4-cyano-N-(3-(cyclopropyl(2,5-dihydro-4-hydroxy-2-oxo-5,5-dipropyl-3-furanyl)methyl)phenyl)-,
- IX-15) Benzenesulfonamide, N-(3-(cyclopropyl(2,5-dihydro-4-hydroxy-2-oxo-5,5-dipropyl-3-furanyl)methyl)phenyl)-,
- IX-16) Benzenesulfonamide, N-(3-(cyclopropyl(2,5-dihydro-4-hydroxy-2-oxo-5,5-dipropyl-3-furanyl)methyl)phenyl)-4-fluoro-,
- IX-17) 1H-Imidazole-4-sulfonamide, N-(3-(cyclopropyl(2,5-dihydro-4-hydroxy-2-oxo-5,5-dipropyl-3-furanyl)methyl)phenyl)-1-methyl-,
- IX-18) 8-Quinolinesulfonamide, N-(3-(cyclopropyl(2,5-dihydrohydroxy-2-oxo-5,5-dipropyl-3-furanyl)methyl)phenyl)-,
- IX-19) 1-Naphthalenesulfonamide, N-(3-(cyclopropyl(2,5-dihydro-4-hydroxy-2-oxo-5,5-dipropyl-3-furanyl)methyl)phenyl)-,
- IX-20) Benzenesulfonamide, N-(3-(1-(2,5-dihydro-4-hydroxy-2-oxo-5,5-ipropyl-3-furanyl)propyl)phenyl)-
- IX-21) Benzenesulfonamide, 4-Cyano-N-(3-(1-(4-hydroxy-2-oxo-5,5-dipropyl-2,5-dihydrofuran-3-yl)-3-methyl-butyl)-phenyl)-,
- IX-22) 1H-Imidazole-4-sulfonamide, N-(3-(1-(4-hydroxy-2-oxo-5,5-dipropyl-2,5-dihydrofuran-3-yl)-3-methyl-butyl)-phenyl)-1-methyl-,
- IX-23) Benzenesulfonamide, 4-Cyano-N-(3-(1-(4-hydroxy-2-oxo-5,5-dipropyl-2,5-dihydrofuran-3-yl)-2-methyl-propyl)-phenyl)-,
- IX-24) 1H-Imidazole-4-sulfonamide, N-(3-(1-(4-hydroxy-2-oxo-5,5-dipropyl-2,5-dihydrofuran-3-yl)-2-methyl-propyl)-phenyl)-1-methyl-,
- IX-25) Benzenesulfonamide, 4-Cyano-N-(3-(1-(4-hydroxy-2-oxo-5,5-dipropyl-2,5-dihydrofuran-3-yl)-2,2-dimethyl-propyl)-phenyl)-,
- IX-26) 1H-Imidazole-4-sulfonamide, N-(3-(1-(4-hydroxy-2-oxo-5,5-dipropyl-2,5-dihydrofuran-3-yl)-2,2-dimethyl-propyl)-phenyl)-1-methyl-,
- IX-27) Benzenesulfonamide, N-(3-(1-(2,5-dihydro-4-hydroxy-2-oxo-5-(phenylmethyl)-5-propyl-3-furanyl)-2-methylpropyl)phenyl)-,
- IX-28) Benzenesulfonamide, 4cyano-N-(3-(1-(2,5-dihydro-4-hydroxy-2-oxo-5-(phenylmethyl)-5-propyl-3-furanyl)-2-methylpropyl)phenyl)-,
- IX-29) Benzenesulfonamide, N-(3-(1-(2,5-dihydro-4-hydroxy-2-oxo-5-(phenylmethyl)-5-propyl-3-furanyl)-2-methylpropyl)phenyl)-4fluoro-,
- IX-30) 1H-Imidazole-4-sulfonamnide, N-(3-(1-(2,5-dihydro-4-hydroxy-2-oxo-5-(phenyl methyl)-5-propyl-3-furanyl)-2-methylpropyl)phenyl)-1-methyl-,
- IX-31) 8-Quinolinesulfonamide, N-(3-(1-(2,5-dihydro-4-hydroxy-2-oxo-5-(phenylmethyl)-5-propyl-3-furanyl)-2-methylpropyl)phenyl)-,
- IX-32) Carbamic acid, (3-(cyclopropyl(2,5-dihydro-4-hydroxy-2-oxo-5,5-dipropyl-3-furanyl)methyl)phenyl)-, phenylmethyl ester,
- IX-33) 1-Oxaspiro[4.5]dec-3-en-2-one, 3-(cyclopropylphenylmethyl)-4-hydroxy-6-ethyl-,
- IX-34) 1-Oxaspiro[4.5]dec-3-en-2-one, 3-(cyclopropylphenylmethyl)-4-hydroxy-6-etyl-,
- IX-35) 5-cyano-2-pyridinesulfonamide, N-(3-(cyclopropyl (2,5-dihydro-4-hydroxy-2-oxo-5,5-dipropyl-3-furanyl)methyl)phenyl)-,
- IX-36) 1H-Imidazole-2-sulfonamide, N-(3-(cyclopropyl(2,5-dihydro-4-hydroxy-2-oxo-5,5-dipropyl-3-furanyl)methyl)phenyl)-,
- IX-37) 1-Methyl-1H-imidazole-2-sulfonamide, N-(3-(cyclopropyl(2,5-dihydro-4-hydroxy-2-oxo-5,5-dipropyl-3-furanyl)methyl)phenyl)-,
- IX-38) 2-Quinolinesulfonamide, N-(3-(cyclopropyl(2,5-dihydro-4-hydroxy-2-oxo-5,5-dipropyl-3-furanyl)methyl)phenyl)-,
- IX-39) Benzenesulfonamide, 4-cyano-N-(3-(1-(4-hydroxy-2-oxo-5,5-dipropyl-2,5-dihydro-furan-3-yl)-2-phenyl-ethyl)-phenyl)-,
- IX-40) 1H-Imidazole-4-sulfonamide, N-(3-(1-(4-hydroxy-2-oxo-5,5-dipropyl-2,5-dihydrofuran-3-yl)-2-phenyl-ethyl)-phenyl)-1-methyl-,
- IX-41) Benzenesulfonamide, 4-cyano-N-(3-(cyclopentyl(2,5-dihydro-4-hydroxy-2-oxo-5,5-dipropyl-3-furanyl)methyl)phenyl)-,
- IX-42) 1H-Imidazole-4-sulfonamide, N-(3-(cyclopentyl(2,5-dihydro-4-hydroxy-2-oxo-5,5-dipropyl-3-furanyl)methyl)phenyl)-1-methyl-,
- IX-43) Benzenesulfonamide, 4-cyano-N-(3-(cyclopropyl-(5,5-dibenzyl-4-hydroxy-2-oxo-2,5-dihydro-3-furanyl)methyl)phenyl)-,
- IX-44) Benzenesulfonamide, N-(3-(cyclopropyl-(5,5-dibenzyl-4-hydroxy-2-oxo-2,5-dihydro-3-furanyl)methyl)phenyl)-4-fluoro-,
- IX-45) 1H-Imidazole-4-sulfonamide, N-(3-(cyclopropyl-(5,5-dibenzyl-4-hydroxy-2-oxo-2,5-dihydro-3-furanyl)methyl)phenyl)-1-methyl-,
- IX-46) 8-Quinolinesulfonamide, N-(3-(cyclopropyl-(5,5-dibenzyl-4-hydroxy-2-oxo-2,5-dihydro-3-furanyl)methyl)phenyl)-,
- IX-47) Benzenesulfonamide, 4-cyano-N-(3-((5,5-dipropyl-4-hydroxy-2-oxo-2,5-dihydro-3-furanyl)-phenyl-methyl)phenyl)-,
- IX-48) 1H-Imidazole-4-sulfonamide, N-(3-((5,5-dipropyl-4-hydroxy-2-oxo-2,5-dihydro-3-furanyl)-phenyl-methyl)phenyl-1-methyl-,
- IX-49) Benzenesulfonamide, 4cyano-3-cyclopentyl-N-(3-(cyclopentyl(2,5-dihydro-4-hydroxy-2-oxo-5,5-dipropyl-3-furanyl)methyl)phenyl-,
- IX-50) 1H-Tetrazole-5-sulfonamide, N-(3-(cyclopropyl-(4-hydroxy-2-oxo-5,5-dipropyl-2,5-dihydro-furan-3-yl)-methyl)-phenyl)-1-phenyl-,
- IX-51) 1H-Benzoimidazole-2-sulfonamide, N-(3-(cyclopropyl-(4-hydroxy-2-oxo-5,5-dipropyl-2,5-dihydro-furan-3-yl)-methyl)-phenyl)-,
- IX-52) 2-Pyridinesulfonamide, N-(3-(cyclopropyl-(4-hydroxy-2-oxo-5,5-propyl-2,5-dihydro-furan-3-yl)-methyl)-phenyl)-,
- IX-53) 1H-Imidazole-4-sulfonamide, N-(3-(1-(4-hydroxy-2-oxo-5,5-dipropyl-2,5-dihydro-furan-3-yl)-2,2-dimethyl-propyl)-phenyl)-1-methyl-,
- IX-54) Benzenesulfonamide, 4-Cyano-N-(3-(1-(4-hydroxy-2-oxo-5,5-dipropyl-2,5-dihydro-furan-3-yl)-2,2-dimethyl-propyl)-phenyl)-,
- IX-55) 2-Pyrimidinesulfonamide, N-(3-(cyclopropyl-(4-hydroxy-2-oxo-5,5-dipropyl-2,5-dihydro-furan-3-yl)-methyl)-phenyl)-,
- IX-56) Benzenesulfonamide 4-Cyano-N-(3-(4-hydroxy-2-oxo-5,5-dipropyl-2,5-dihydro-furan-3-ylmethyl)-phenyl)-,
- IX-57) 1H-Tetrazole-5-sulfonamide, N-(3-(cyclopropyl-(4-hydroxy-2-oxo-5,5-dipropyl-2,5-dihydro-furan-3-yl)-methyl)-phenyl)-1-methyl-,
- IX-58) 3-(Cyclopropyl-phenyl-methyl)-4-hydroxy-2-oxo-1-oxa-8-aza-spiro[4.5]dec-3-ene-8-carboxylic acid.
- 9. A compound selected from the following compounds,
- JX-1) 3-(Cyclopropyl-phenyl-methyl)-4-hydroxy-5-(3-phenyl-propylidene)-5H-furan-2-one,
- JX-2) 5-Benzylidene-3-(cyclopropyl-phenyl-methyl)-4-hydroxy-5H-furan-2-one,
- JX-3) 3-(Cyclopropyl-phenyl-methyl)-4-hydroxy-5-propylidene-5H-furan-2-one,
- JX-4) 5-Butylidene-3-(cyclopropyl-phenyl-methyl)-4-hydroxy-5H-furan-2-one, or
- OX-1) 3-(Cyclopropyl-phenyl-methyl)-4-hydroxy-2-oxo-1-oxa-8-aza-spiro[4.5]dec-3-ene -8-carboxylic acid tert-butyl ester,
- OX-2) 3-(Cyclopropyl-phenyl-methyl)-4-hydroxy-1-oxa-8-aza-spiro[4.5]dec-3-en-2-one.
- 10. A compound selected from the following compounds,
- a) 2-Pyrimidinesulfonamide, N-(3-(cyclopropyl(2,5-dihydro-4-hydroxy-2-oxo-5,5-dipropyl-3-furanyl)methyl)phenyl)-,
- b) 2-Quinazolinesulfonamide, N-(3-(cyclopropyl(2,5-dihydro-4-hydroxy-2-oxo-5,5-dipropyl-3-furanyl)methyl)phenyl)-,
- c) 4-Thiazolesulfonamide, N-(3-(cyclopropyl(2,5-dihydro-4-hydroxy-2-oxo-5,5-dipropyl-3-furanyl)methyl)phenyl)-,
- d) 7H-Purine-6-sulfonamide, N-(3-(cyclopropyl(2,5-dihydro-4-hydroxy-2-oxo-5,5-dipropyl-3-furanyl)methyl)phenyl)-,
- e) Benzenesulfonamide, N-(3-(cyclopropyl-(5,5-dibenzyl-4-hydroxy-2-oxo-2,5-dihydro-3-furanyl)methyl)phenyl)-,
- f) 2-Pyridinesulfonamide, N-(3-(cyclopropyl-(5,5-dibenzyl-4-hydroxy-2-oxo-2,5-dihydro-3-furanyl)methyl)phenyl)-,
- g) 5-cyano-2-pyridinesulfonamide, N-(3-(cyclopropyl-(5,5-dibenzyl-4-hydroxy-2-oxo-2,5-dihydro-3-furanyl)methyl)phenyl)-,
- h) 2-Quinolinesulfonamide, N-(3-(cyclopropyl-(5,5-benzylhydroxy-2-oxo-2,5-dihydro-3-furanyl)methyl)phenyl)-,
- i) 2-Pyrimidinesulfonamide, N-(3-(cyclopropyl-(5,5-dibenzyl-4-hydroxy-2-oxo-2,5-dihydro-3-furanyl)methyl)phenyl)-,
- j) 2-Quinazolinesulfonamide, N-(3-(cyclopropyl-(5,5-dibenzyl-4-hydroxy-2-oxo-2,5-dihydro-3-furanyl)methyl)phenyl)-,
- k) 1H-Benzimidazole-2-sulfonamide, N-(3-(cyclopropyl-(5,5-dibenzyl-4-hydroxy-2-oxo-2,5-dihydro-3-furanyl)methyl)phenyl)-,
- l) 1H-Imidazole-2-sulfonamide, N-(3-(cyclopropyl-(5,5-dibenzyl-4-hydroxy-2-oxo-2,5-dihydro-3-furanyl)methyl)phenyl)-,
- m) 4-Thiazolesulfonamide, N-(3-(cyclopropyl-(5,5-dibenzyl-4-hydroxy-2-oxo-2,5-dihydro-3-furanyl)methyl)phenyl)-,
- n) 7H-Purine-6-sulfonamide, N-(3-(cyclopropyl-(5,5-dibenzyl-4-hydroxy-2-oxo-2,5-dihydro-3-furanyl)methyl)phenyl)-,
- o) Benzenesulfonamide, N-(3-(1-(4-hydroxy-2-oxo-5,5-dipropyl-2,5-dihydro-3-furanyl)-2,2-dimethyl-propyl)-phenyl)-,
- p) 2-Pyridinesulfonamide, N-(3-(1-(4-hydroxy-2-oxo-5,5-dipropyl-2,5-dihydro-3-furanyl)-2,2-dimethyl-propyl)-phenyl)-,
- q) 5-cyano-2-pyridinesulfonamide, N-(3-(1-(4-hydroxy-2-oxo-5,5-dipropyl-2,5-dihydro-3-furanyl)-2,2-dimethyl-propyl)-phenyl)-,
- r) 2-Quinolinesulfonamide, N-(3-(1-(4-hydroxy-2-oxo-5,5-dipropyl-2,5-dihydro-3-furanyl)-2,2-dimethyl-propyl)-phenyl)-,
- s) 2-Pyrimidinesulfonamide, N-(3-(1-(4-hydroxy-2-oxo-5,5-dipropyl-2,5-dihydro-3-furanyl)-2,2-dimethyl-propyl)-phenyl)-,
- t) 2-Quinazolinesulfonamide, N-(3-(1-(4-hydroxy-2-oxo-5,5-dipropyl-2,5-dihydro-3-furanyl)-2,2-dimethyl-propyl)-phenyl)-,
- u) 1H-Benzimidazole-2-sulfonamide, N-(3-(1-(4-hydroxy-2-oxo5,5-dipropyl-2,5-dihydro-3-furanyl)-2,2-dimethyl-propyl)-phenyl)-,
- v) 1H-Imidazole-2-sulfonamide, N-(3-(1-(4-hydroxy-2-oxo-5,5-dipropyl-2,5-dihydro-3-furanyl)-2,2-dimethyl-propyl)-phenyl)-,
- w) 4-Thiazolesulfonamide, N-(3-(1-(4-hydroxy-2-oxo-5,5-dipropyl-2,5-dihydro-3-furanyl)-2,2-dimethyl-propyl)-phenyl)-,
- x) 7H-Purine-6-sulfonamide, N-(3-(1-(4-hydroxy-2-oxo-5,5-ipropyl-2,5-dihydro-3-furanyl)-2,2-dimethyl-propyl)-phenyl)-,
- y) Benzenesulfonamide, N-3-(1-(5,5-dibenzyl-4-hydroxy-2-oxo-2,5-dihydro-3-furanyl)-2,2-dimethyl-propyl)-phenyl)-,
- z) Benzenesulfonamide, 4cyano-N-3-(1-(5,5-dibenzyl-4-hydroxy-2-oxo-2,5-dihydro-3-furanyl)-2,2-dimethyl-propyl)-phenyl)-,
- a1) 1H-Imidazole-4-sulfonamide, N-3-(1-(5,5-dibenzyl-4-hydroxy-2-oxo-2,5-dihydro-3-furanyl)-2,2-dimethyl-propyl)-phenyl)-1-methyl-,
- b1) 2-Pyridinesulfonamide, N-3-(1-(5,5-dibenzyl-4-hydroxy-2-oxo-2,5-dihydro-3-furanyl)-2,2-dimethyl-propyl)-phenyl)-,
- c1) 5-cyano-2-pyridinesulfonamide, N-3-(1-(5,5-dibenzyl-4-hydroxy-2-oxo-2,5-dihydro-3-furanyl)-2,2-dimethyl-propyl)-phenyl)-,
- d1) 2-Quinolinesulfonamide, N-3-(1-(5,5-dibenzyl-hydroxy-2-oxo-2,5-dihydro-3-furanyl)-2,2-dimethyl-propyl)-phenyl)-,
- e1) 2-Pyrimidinesulfonamide, N-3-(1-(5,5-dibenzyl-4-hydroxy-2-oxo-2,5-dihydro-3-furanyl)-2,2-dimethyl-propyl)-phenyl)-,
- f1) 2-Quinazolinesulfonamide, N-3-(1-(5,5-dibenzyl-4-hydroxy-2-oxo-2,5-dihydro-3-furanyl)-2,2-dimethyl-propyl)-phenyl)-,
- g1) 1H-Benzimidazole-2-sulfonamide, N-3-(1-(5,5-dibenzyl-4-hydroxy-2-oxo-2,5-dihydro-3-furanyl)-2,2-dimethyl-propyl)-phenyl)-,
- h1) 1H-Imidazole-2-sulfonamide, N-3-(1-(5,5-dibenzyl-4-hydroxy-2-oxo-2,5-dihydro-3-furanyl)-2,2-dimethyl-propyl)-phenyl)-,
- i1) 4-Thiazolesulfonamide, N-3-(1-(5,5-dibenzyl-4-hydroxy-2-oxo-2,5-dihydro-3-furanyl)-2,2-dimethyl-propyl)-phenyl)-,
- j1) 7H-Purine-6-sulfonamide, N-3-(1-(5,5-dibenzyl-hydroxy-2-oxo-2,5-dihydro-3-furanyl)-2,2-dimethyl-propyl)-phenyl)-.
- 11. A compound of claim 1 selected from the following compounds,
- a) N-(3-(Cyclopropyl-(4-hydroxy-2-oxo-5,5-dipropyl-2,5-dihydro-3-furanyl)-methyl)-phenyl)--N-methyl-benzenesulfonamide,
- b) 4-yano-N-(3-(cyclopropyl-(4-hydroxy-2-oxo-5,5-dipropyl-2,5-dihydro-3-furanyl)-methyl)-phenyl)--N-methyl-benzenesulfonamide,
- c) 1-Methyl-1H-imidazole-4-sulfonic acid (3-(cyclopropyl-(4-hydroxy-2-oxo-5,5-dipropyl-2,5-dihydro-3-furanyl)-methyl)-phenyl)-methyl-amide,
- d) Pyridine-2-sulfonic acid (3-(cyclopropyl-(4-hydroxy-2-oxo-5,5-dipropyl-2,5-dihydro-3-furanyl)-methyl)-phenyl)-methyl-amide,
- e) 5-Cyano-pyridine-2-sulfonic acid (3-(cyclopropyl-(4-hydroxy-2-oxo-5,5-dipropyl-2,5-dihydro-3-furanyl)-methyl)-phenyl)-methyl-amide,
- f) Quinoline-2-sulfonic acid (3-(cyclopropyl-(4-hydroxy-2-oxo-5,5-dipropyl-2,5-dihydro-3-furanyl)-methyl)-phenyl)-methyl-amide,
- g) Pyrimidine-2-sulfonic acid (3-(cyclopropyl-(4-hydroxy-2-oxo-5,5-dipropyl-2,5-dihydro-3-furanyl)-methyl)-phenyl)-methyl-amide,
- h) Quinazoline-2-sulfonic acid (3-(cyclopropyl-(4-hydroxy-2-oxo-5,5-dipropyl-2,5-dihydro-3-furanyl)-methyl)-phenyl)-methyl-amide,
- i) 1H-Benzimidazole-2-sulfonic acid (3-(cyclopropyl-(4-hydroxy-2-oxo-5,5-dipropyl-2,5-dihydro-3-furanyl)-methyl)-phenyl)-methyl-amide,
- j) 1H-Imidazole-2-sulfonic acid (3-(cyclopropyl-(4-hydroxy-2-oxo-5,5-dipropyl-2,5-dihydro-3-furanyl)-methyl)-phenyl)-methyl-amide,
- k) Thiazole-4-sulfonic acid (3-(cyclopropyl-(4-hydroxy-2-oxo-5,5-dipropyl-2,5-dihydro-3-furanyl)-methyl)-phenyl)-methyl-amide,
- l) 7H-Purine-6-sulfonic acid (3-(cyclopropyl-(4-hydroxy-2-oxo-5,5-dipropyl-2,5-dihydro-3-furanyl)-methyl)-phenyl)-methyl-amide,
- m) N-(3-(1-(4-hydroxy-2-oxo-5,5-dipropy-2,5-dihydro-3-furanyl)-2,2-ethyl-propyl)-phenyl)--N-methyl-benzenesulfonamide,
- n) 4-Cyano-N-(3-(1-(4-hydroxy-2-oxo-5,5-dipropyl-2,5-dihydro-3-furanyl)-2,2-dimethyl-propyl)-phenyl)-N-methyl-benzenesulfonamide,
- o) 1-Methyl-1H-imidazole-4-sulfonic acid (3-(1-(4-hydroxy-2-oxo-5,5-dipropyl-2,5-dihydro-3-furanyl)-2,2-dimethyl-propyl)-phenyl)-methyl-amide,
- p) Pyridine-2-sulfonic acid (3-(1-(4-hydroxy-2-oxo-5,5-dipropyl-2,5-dihydro-3-furanyl)-2,2-dimethyl-propyl)-phenyl)-methyl-amide,
- q) 5-Cyano-pyridine-2-sulfonic acid (3-(1-(4-hydroxy-2-oxo-5,5-dipropyl-2,5-dihydro-3-furanyl)-2,2-dimethyl-propyl)-phenyl)-methyl-amide,
- r) Quinoline-2-sulfonic acid (3-(1-(4-hydroxy-2-oxo-5,5-dipropyl-2,5-dihydro-3-furanyl)-2,2-dimethyl-propyl)-phenyl)-methyl-amide,
- s) Pyrimidine-2-sulfonic acid (3-(1-(4-hydroxy-2-oxo-5,5-dipropyl-2,5-dihydro-3-furanyl)-2,2-dimethyl-propyl)-phenyl)-methyl-amide,
- t) Quinazoline-2-sulfonic acid (3-(1-(4-hydroxy-2-oxo-5,5-dipropyl-2,5-dihydro-3-furanyl)-2,2-dimethyl-propyl)-phenyl)-methyl-amide,
- u) 1H-Benzimidazole-2-sulfonic acid (3-(1-(4-hydroxy-2-oxo-5,5-dipropyl-2,5-dihydro-3-furanyl)-2,2-dimethyl-propyl)-phenyl)-methyl-amide,
- v) 1H-Imidazole-2-sulfonic acid (3-(1-(4-hydroxy-2-oxo-5,5-dipropyl-2,5-dihydro-3-furanyl)-2,2-dimethyl-propyl)-phenyl)-methyl-amide,
- w) Thiazole-4-sulfonic acid (3-(1-(4-hydroxy-2-oxo-5,5-dipropyl-2,5-dihydro-3-furanyl)-2,2-dimethyl-propyl)-phenyl)-methyl-amide,
- x) 7H-Purine-6-sulfonic acid (3-(1-(4-hydroxy-2-oxo-5,5-dipropyl-2,5-dihydro-3-furanyl)-2,2-dimethyl-propyl)-phenyl)-methyl-amide,
- y) N-(3-(Cyclopropyl-(5,5-dibenzyl-4-hydroxy-2-oxo-2,5-dihydro-3-furanyl)-methyl)-phenyl)-N-methyl-benzenesulfonamide,
- z) 4-Cyano-N-(3-(cyclopropyl-(5,5-dibenzyl-4-hydroxy-2-oxo-2,5-dihydro-3-furanyl)-methyl)-phenyl)-N-methyl-benzenesulfonamide,
- a1) 1-Methyl-1H-imidazole-4-sulfonic acid (3-(cyclopropyl-(5,5-dibenzyl-4-hydroxy-2-oxo-2,5-dihydro-3-furanyl)-methyl)-phenyl)-methyl-amide,
- b1) Pyridine-2-sulfonic acid (3-(cyclopropyl-(5,5-dibenzyl-4-hydroxy-2-oxo-2,5-dihydro-3-furanyl)-methyl)-phenyl)-methyl-amide,
- c1) 5-Cyano-pyridine-2-sulfonic acid (3-(cyclopropyl-(5,5-dibenzyl-4-hydroxy-2-oxo-2,5-dihydro-3-furanyl)-methyl)-phenyl)-methyl-amide,
- d1) Quinoline-2-sulfonic acid (3-(cyclopropyl-(5,5-dibenzyl-4-hydroxy-2-oxo-2,5-dihydro-3-furanyl)-methyl)-phenyl)-methyl-amide,
- e1) Pyrimidine-2-sulfonic acid (3-(cyclopropyl-(5,5-dibenzyl-4-hydroxy-2-oxo-2,5-dihydro-3-furanyl)-methyl)-phenyl)-methyl-amide,
- f1) Quinazoline-2-sulfonic acid (3-(cyclopropyl-(5,5-dibenzyl-4-hydroxy-2-oxo-2,5-dihydro-3-furanyl)-methyl)-phenyl)-methyl-amide,
- g1) 1H-Benzimidazole-2-sulfonic acid (3-(cyclopropyl-(5,5-dibenzyl-4-hydroxy-2-oxo-2,5-dihydro-3-furanyl)-methyl)-phenyl)-methyl-amide,
- h1) 1H-Imidazole-2-sulfonic acid (3-(cyclopropyl-(5,5-dibenzyl-4-hydroxy-2-oxo-2,5-dihydro-3-furanyl)-methyl)-phenyl)-methyl-amide,
- i1) Thiazole-4-sulfonic acid (3-(cyclopropyl-(5,5-dibenzyl-4-hydroxy-2-oxo-2,5-hydro-3-furanyl)-methyl)-phenyl)-methyl-amide,
- j1) 7H-Purine-6-sulfonic acid (3-(cyclopropyl-(5,5-dibenzyl-4-hydroxy-2-oxo-2,5-dihydro-3-furanyl)-methyl)-phenyl)-methyl-amide,
- k1) N-(3-(1-(5,5-dibenzyl-4-hydroxy-2-oxo-2,5-dihydro-3-furanyl)-2,2-methyl-propyl)-phenyl)-N-methyl-benzenesulfonamide,
- l1) 4-yano-N-(3-(1-(5,5-dibenzyl-4-hydroxy-2-oxo-2,5-dihydro-3-furanyl)-2,2-dimethyl-propyl)-phenyl)-N-methyl-benzenesulfonamide,
- m1) 1-Methyl-1H-imidazole-4-sulfonic acid (3-(1-(5,5-dibenzyl-4-hydroxy-2-oxo-2,5-dihydro-3-furanyl)-2,2-dimethyl-propyl)-phenyl)-methyl-amide,
- n1) Pyridine-2-sulfonic acid (3-(1-(5,5-dibenzyl-4-hydroxy-2-oxo-2,5-dihydro-3-furanyl)-2,2-dimethyl-propyl)-phenyl)-methyl-amide,
- o1) 5-Cyano-pyridine-2-sulfonic acid (3-(1-(5,5-dibenzyl-4-hydroxy-2-oxo-2,5-dihydro-3-furanyl)-2,2-dimethyl-propyl)-phenyl)-methyl-amide,
- p1) Quinoline-2-sulfonic acid (3-(1-(5,5-dibenzyl-4-hydroxy-2-oxo-2,5-dihydro-3-furanyl)-2,2-dimethyl-propyl)-phenyl)-methyl-amide,
- q1) Pyrimidine-2-sulfonic acid (3-(1-(5,5-dibenzyl-4-hydroxy-2-oxo-2,5-dihydro-3-furanyl)-2,2-dimethyl-propyl)-phenyl)-methyl-amide,
- r1) Quinazoline-2-sulfonic acid (3-(1-(5,5-dibenzyl-4-hydroxy-2-oxo-2,5-dihydro-3-furanyl)-2,2-dimethyl-propyl)-phenyl)-methyl-amide,
- s1) 1H-Benzimidazole-2-sulfonic acid (3-(1-(5,5-dibenzyl-4-hydroxy-2-oxo-2,5-dihydro-3-furanyl)-2,2-dimethyl-propyl)-phenyl)-methyl-amide,
- t1) 1H-Imidazole-2-sulfonic acid (3-(1-(5,5-dibenzyl-4-hydroxy-2-oxo-2,5-dihydro-3-furanyl)-2,2-dimethyl-propyl)-phenyl)-methyl-amide,
- u1) Thiazole-4-sulfonic acid (3-(1-(5,5-dibenzyl-4-hydroxy-2-oxo-2,5-dihydro-3-furanyl)-2,2-dimethyl-propyl)-phenyl)-methyl-amide,
- v1) 7H-Purine-6-sulfonic acid (3-(1-(5,5-dibenzyl-4-hydroxy-2-oxo-2,5-dihydro-3-furanyl)-2,2-dimethyl-propyl)-phenyl)-methyl-amide.
- 12. A compound selected from the following compounds,
- a) 3-((3-Benzenesulfonylmethyl-phenyl)-cyclopropyl-methyl)-4-hydroxy-5,5-dipropyl-5H-furan-2-one,
- b) 4-(3-(Cyclopropyl-(4-hydroxy-2-oxo-5,5-dipropyl-2,5-dihydro-furan-3-yl)-methyl)-phenylmethanesulfonyl)-benzonitrile,
- c) 3-(Cyclopropyl-(3-(1-methyl-1H-imidazole-4-sulfonylmethyl)-phenyl)-methyl)-4-hydroxy-5,5-dipropyl-5H-furan-2-one,
- d) 3-(Cyclopropyl-(3-(pyridine-2-sulfonylmethyl)-phenyl)-methyl)4-hydroxy-5,5-dipropyl-5H-furan-2-one,
- e) 6-(3-(Cyclopropyl-(4-hydroxy-2-oxo-5,5-dipropyl-2,5-hydro-furan-3-yl)-methyl)-phenylmethanesulfonyl)-nicotinonitrile,
- f) 3-(Cyclopropyl-(3-(quinoline-2-sulfonylmethyl)-phenyl)-methyl)-4-hydroxy-5,5-dipropyl-5H-furan-2one,
- g) 3-(Cyclopropyl-(3-(pyrimidine-2-sulfonylmethyl)-phenyl)-methyl)-4-hydroxy-5,5-dipropyl-5H-furan-2-one,
- h) 3-(Cyclopropyl-(3-(quinazoline-2-sulfonylmethyl)-phenyl)-methyl)-4-hydroxy-5,5-dipropyl-5H-furan-2-one,
- i) 3-((3-(1H-Benzimidazole-2-sulfonylmethyl)-phenyl)-cyclopropyl-methyl)-4-hydroxy-5,5-dipropyl-5H-furan-2-one,
- j) 3-(Cyclopropyl-(3-(1H-imidazole-2-sulfonylmethyl)-phenyl)-methyl)-4-hydroxy-5,5-dipropyl-5H-furan-2-one,
- k) 3-(Cyclopropyl-(3-(thiazole-4-sulfonylmethyl)-phenyl)-methyl)-4-hydroxy-5,5-dipropyl-5H-furan-2-one,
- l) 3-(Cyclopropyl-(3-(7H-purine-6-sulfonylmethyl)-phenyl)-methyl)-4-hydroxy-5,5-dipropyl-5H-furan-2-one,
- m) 3-(1-(3-Benzenesulfonylmethyl-phenyl)-2,2-dimethyl-propyl)-4-hydroxy-5,5-dipropyl-5H-furan-2-one,
- n) 4(3-(1-(4-Hydroxy-2-oxo-5,5-dipropyl-2,5-dihydro-furan-3-yl)-2,2-dimethyl-propyl)-phenylmethanesulfonyl)-benzonitrile,
- o) 3-(2,2-Dimethyl-1-(3-(1-methyl-1H-imidazole-4-sulfonylmethyl)-phenyl)-propyl)-4-hydroxy-5,5-dipropyl-5H-furan-2-one,
- p) 3-(2,2-Dimethyl-1-(3-(pyridine-2-sulfonylmethyl)-phenyl)-propyl)-4-hydroxy-5,5-dipropyl-5H-furan-2-one,
- q) 6-(3-(1-(4-Hydroxy-2-oxo-5,5-dipropyl-2,5-dihydro-furan-3-yl)-2,2-dimethyl-propyl)-phenylmethanesulfonyl)-nicotinonitrile,
- r) 3-(2,2-Dimethyl-1-(3-(quinoline-2-sulfonylmethyl)-phenyl)-propyl)-4-hydroxy-5,5-dipropyl-5H-furan-2-one,
- s) 3-(2,2-Dimethyl-1-(3-(pyrimidine-2-sulfonylmethyl)-phenyl)-propyl)-4-hydroxy-5,5-dipropyl-5H-furan-2-one,
- t) 3-(2,2-Dimethyl-1-(3-(quinazoline-2-sulfonylmethyl)-phenyl)-propyl)-4-hydroxy-5,5-dipropyl-5H-furan-2-one,
- u) 3-(1-(3-(1H-Benzimidazole-2-sulfonylmethyl)-phenyl)-2,2-dimethyl-propyl)-hydroxy-5,5-dipropyl-5H-furan-2-one,
- v) 4-Hydroxy-3-(1-(3-(1H-imidazole-2-sulfonylmethyl)-phenyl)-2,2-dimethyl-propyl)-5,5-dipropyl-5H-furan-2-one,
- w) 3-(2,2-Dimethyl-1-(3-(thiazole-4-sulfonylmethyl)-phenyl)-propyl)-hydroxy-5,5-dipropyl-5H-furan-2-one,
- x) 3-(2,2-Dimethyl-1-(3-(7H-purine-6-sulfonylmethyl)-phenyl)-propyl)-4-hydroxy-5,5-dipropyl-5H-furan-2-one,
- y) 3-((3-Benzenesulfonylmethyl-phenyl)-cyclopropyl-methyl)-5,5-dibenzyl-4-hydroxy-5H-furan-2-one,
- z) 4-(3-(Cyclopropyl-(5,5-dibenzyl-4-hydroxy-2-oxo-2,5-dihydro-furan-3-yl)-methyl)-phenylmethanesulfonyl)-benzonitrile,
- a1) 5,5-Dibenzyl-3-(cyclopropyl-(3-(1-methyl-1H-imidazole-4-sulfonylmethyl)-phenyl)-methyl)-4-hydroxy-5H-furan-2-one,
- b1) 5,5-Dibenzyl-3-(cyclopropyl-(3-(pyridine-2-sulfonylmethyl)-phenyl)-methyl)-4-hydroxy-5H-furan-2-one,
- c1) 6-(3-(Cyclopropyl-(5,5-dibenzyl-4-hydroxy-2-oxo-2,5-ydro-furan-3-yl)-methyl)-phenylmethanesulfonyl)-nicotinonitrile,
- d1) 5,5-Dibenzyl-3-(cyclopropyl-(3-(quinoline-2-sulfonylmethyl)-phenyl)-methyl)-4-hydroxy-5H-furan-2-one,
- e1) 5,5-Dibenzyl-3-(cyclopropyl-(3-(pyrimidine-2-sulfonylmethyl)-phenyl)-methyl)-4-hydroxy-5H-furan-2-one,
- f1) 5,5-Dibenzyl-3-(cyclopropyl-(3-(quinazoline-2-sulfonylmethyl)-phenyl)-methyl)-4-hydroxy-5H-furan-2-one,
- g1) 3-((3-(1H-Benzimidazole-2-sulfonylmethyl)-phenyl)-cyclopropyl-methyl)-5,5-dibenzyl-4-hydroxy-5H-furan-2-one,
- h1) 5,5-Dibenzyl-3-(cyclopropyl-(3-(1H-imidazole-2-sulfonylmethyl)-phenyl)-methyl) hydroxy-5H-furan-2-one,
- i1) 5,5-Dibenzyl-3-(cyclopropyl-(3-(thiazole-4-sulfonylmethyl)-phenyl)-methyl)-4-hydroxy-5H-furan-2-one,
- j1) 5,5-Dibenzyl-3-(cyclopropyl-(3-(7H-purine-6-sulfonylmethyl)-phenyl)-methyl)-4-hydroxy-5H-furan-2-one,
- k1) 3-(1-(3-Benzenesulfonylmethyl-phenyl)-2,2dimethyl-propyl)-5,5-dibenzyl-4-hydroxy-5H-furan-2-one,
- l1) 4-(3-(1-(5,5-Dibenzyl-4-hydroxy-2-oxo-2,5-dihydro-furan-3-yl)-2,2-dimethyl-propyl)-phenylmethanesulfonyl)-benzonitrile,
- m1) 5,5-Dibenzyl-3-(2,2-dimethyl-1-(3-(1-methyl-1H-imidazole-4-sulfonylmethyl)-phenyl)-propyl)-4-hydroxy-5H-furan-2-one,
- n1) 5,5-Dibenzyl-3-(2,2-dimethyl-1-(3-(pyridine-2-sulfonylmethyl)-phenyl)-propyl)-4-hydroxy-5H-furan-2-one,
- o1) 6-(3-(1-(5,5-Dibenzyl-4-hydroxy-2-oxo-2,5-dihydro-furan-3-yl)-2,2-dimethyl-propyl)-phenylmethanesulfonyl)-nicotinonitrile,
- p1) 5,5-Dibenzyl-3-(2,2-dimethyl-1-(3-(quinoline-2-sulfonylmethyl)-phenyl)-propyl)-4-hydroxy-5H-furan-2-one,
- q1) 5,5-Dibenzyl-3-(2,2-dimethyl-1-(3-(pyrimidine-2-sulfonylmethyl)-phenyl)-propyl)-4-hydroxy-5H-furan-2-one,
- r1) 5,5-Dibenzyl-3-(2,2-dimethyl-1-(3-(quinazoline-2-sulfonylmethyl)-phenyl)-propyl)-4-hydroxy-5H-furan-2-one,
- s1) 3-(1-(3-(1H-Benzimidazole-2-sulfonylmethyl)-phenyl)-2,2-dimethyl-propyl)-5,5-dibenzyl-4-hydroxy-5H-furan-2-one,
- t1) 5,5-Dibenzyl-4-hydroxy-3-(1-(3-(1H-imidazole-2-sulfonylmethyl)-phenyl)-2,2-dimethyl-propyl)-5H-furan-2-one,
- u1) 5,5-Dibenzyl-3-(2,2-dimethyl-1-(3-(thiazole-4-sulfonylmethyl)-phenyl)-propyl)4-hydroxy-5H-furan-2-one,
- v1) 5,5-Dibenzyl-3-(2,2-dimethyl-1-(3-(7H-purine-6-sulfonylmethyl)-phenyl)-propyl)-4-hydroxy-5H-furan-2-one.
- 13. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and an effective amount of a compound described in claim 1.
- 14. A method of administering an effective amount of a compound described by claim 1 to a patient in need thereof for the treatment of AIDS and diseases caused by all variants of HIV comprising administering an effective amount of said compound to said patient.
- 15. A compound represented by the structure shown in formula 1, ##STR143## wherein 3 tautomers of the same structure are shown, wherein R.sub.1 is ##STR144## wherein R.sub.1-1 is a) --(C.sub.1-5 alkyl),
- b) --(C.sub.2-5 alkenyl),
- c) --(C.sub.3-7 cycloalkyl),
- d) --(C.sub.3-5 cycloalkyl),
- e) -cyclopropyl,
- f) --(C.sub.1-5 alkyl)--(C.sub.3-7 cycloalkyl),
- g) --R.sub.1-100, or
- h) --(C.sub.1 -C.sub.5 alkyl)--R.sub.1-100 ;
- wherein R.sub.1-2 is --R.sub.1-100, or --R.sub.1-500 ;
- wherein R.sub.1-100 is
- a) phenyl, substituted with zero (0) to three (3) of RA.sub.1,
- b) naphthyl, substituted with zero (0) to three (3) of RA.sub.1,
- c) biphenyl, substituted with zero (0) to three (3) of RA.sub.1,
- d) perhalophenyl;
- wherein R.sub.1-500 is
- a 5- or 6-membered saturated or unsaturated ring containing from one (1) to four (4) heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur; and substituted with zero (0) to three (3) RA.sub.1 ; and including any bicyclic group in which any of the above heterocyclic rings is fused to a benzene ring, C.sub.3 -C.sub.8 cycloalkyl, or another heterocycle; and substituted with zero (0) to three (3) RA.sub.1 ; and if chemically feasible, the nitrogen and sulfur atoms may be in the oxidized forms;
- wherein RA.sub.1 is
- a) --H,
- b) --(C.sub.1-5 alkyl),
- c) --(C.sub.2-5 alkenyl),
- d) --OH,
- e) --O--(C.sub.1-5 alkyl),
- f) --O--(C.sub.2-5 alkenyl),
- g) --C(O)OH,
- h) --C(O)(C.sub.1-5 alkyl),
- i) --C(O)--RA.sub.1-3,
- wherein RA.sub.1-3 is any N-terminus substituted amino acid,
- j) --C(O)--N(H)RA.sub.1-1,
- k) --CN,
- l) --NH.sub.2 (para or meta positions),
- m) --N(H)(C.sub.1-5 alkyl) (para or meta positions),
- n) --N(C.sub.1-5 alkyl).sub.2,
- o) --N(H)RA.sub.1-4,
- wherein RA.sub.1-4 is any C-terminus substituted amino acid,
- p) --N(H)C(O)--RA.sub.1-1 (para or meta positions),
- q) --N(H)C(O)--O--RA.sub.1-1 (para or meta positions),
- r) --N(H)(SO.sub.2)--RA.sub.1-2,
- s) --N(C.sub.1-6 alkyl)(SO.sub.2)--RA.sub.1-2,
- t) --N(CH.sub.3)(SO.sub.2)--RA.sub.1-2,
- u) --NO.sub.2,
- v) --PO.sub.3 H,
- w) --SO.sub.3 H,
- x) --SO.sub.2 NH.sub.2,
- y) --(C.sub.0-6 alkyl)--SO.sub.2 --RA.sub.1-RA-12,
- z) --(C.sub.0-6 alkyl)--SO.sub.2 --RA.sub.1-RA-15,
- a1) -halo,
- b1) --RA.sub.1-RA-12, or
- c1) --RA.sub.1-RA-15 ;
- wherein RA.sub.1-1 is
- a) --(C.sub.1-5 alkyl),
- b) --(C.sub.1-5 alkyl)--C(O)--O--(C.sub.1-5 alkyl),
- c) --(C.sub.1-5 alkyl)--NH.sub.2,
- d) --(C.sub.1-5 alkyl)--N(H)C(O)--O--(C.sub.1-5 alkyl),
- e) --(C.sub.1-5 alkyl)--C((H)(NH.sub.2))--C(O)OH,
- f) --RA.sub.1-RA-12,
- g) --RA.sub.1-RA-15,
- h) --(C.sub.1-5 alkyl)-RAX,
- i) --(C.sub.1-5 alkyl)--O-RAX,
- j) --C(O)--RA.sub.1-1-3,
- wherein RA.sub.1-1-3 is any N-terminus amino acid,
- k) --N(H)--RA.sub.1-1-4, or
- wherein RA.sub.1-1-4 is any C-terminus amino acid,
- l) --R.sub.1-500 ;
- wherein RA.sub.1-2 is
- a) -RAX,
- b) --(C.sub.1-5 alkyl)-RAX,
- c) --(C.sub.1-5 alkyl)--O-RAX,
- d) --RA.sub.1-RA-12,
- e) --RA.sub.1-RA-15,
- f) --(C.sub.1 -C.sub.5 alkyl)--R.sub.1-RA-12,
- g) --(C.sub.1 -C.sub.5 alkyl)--RA.sub.1-RA-15,
- h) --(C.sub.1 -C.sub.5 alkyl)--O--RA.sub.1-RA-12, or
- i) --(C.sub.1 -C.sub.5 alkyl)--O--RA.sub.1-RA-15 ;
- wherein RA.sub.2 and RA.sub.3 are defined independently and are independent of and defined the same as RA.sub.1 ;
- wherein G.sub.1-1 is
- a) --NH--C(O)--,
- b) --NH--SO.sub.2 --,
- c) --NH--C(O)--NH--, or
- d) --SO.sub.2 --NH--;
- wherein G.sub.1-2 is
- a) --NH--C(O)--,
- b) --C(O)--NH--,
- c) --NH--SO.sub.2 --,
- d) --SO.sub.2 --NH--,
- e) --NH--SO.sub.2 --NH--,
- f) --C(O)--O--,
- g) --O--C(O)--,
- h) --N((C.sub.1-6 alkyl)--RA.sub.1-RA-12)--C(O)--,
- i) --NH--C(O)--NH,
- j) --N((C.sub.1-6 alkyl)-RA.sub.1-RA-12)--SO.sub.2 --, or
- k) --N((C.sub.0-6 alkyl)--(C.sub.1-6 alkyl))--SO.sub.2 --;
- wherein RA.sub.2 and RA.sub.3 are defined independently and are the same as RA.sub.1 ;
- wherein RA.sub.1-RA-12 is
- a) -phenyl, substituted with zero (0) to three (3) RA.sub.1-RA-12-AXA, or
- b) -naphthyl, substituted with zero (0) to three (3) RA.sub.1-RA-12-AXA ;
- wherein RA.sub.1-RA-15 is
- a 5- or 6-membered saturated or unsaturated ring containing from one (1) to four (4) heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur; and including any bicyclic group in which any of the above heterocyclic rings is fused to a benzene ring, C.sub.3 -C.sub.8 cycloalkyl, or another heterocycle; and substituted with zero (0) to three (3) RA.sub.1-RA-15-AXA ;
- wherein RA.sub.1-RA-120, RA.sub.2-RA-120 and RA.sub.3-RA-120, are defined independently and are
- a) --C.sub.1 -C.sub.4 alkyl,
- b) --C.sub.1 -C.sub.3 alkoxy,
- c) -dimethylamino,
- d) -diethylamino,
- e) --CF.sub.3,
- f) --CN,
- g) -halo,
- h) --NH.sub.2,
- i) --OH,
- j) --SO.sub.2 --NH.sub.2, or
- k) --C(O)--NH.sub.2 ;
- wherein RA.sub.1-RA-12-AXA or RA.sub.1-RA-15-AXA are independent and are,
- a) --H
- b) -halo,
- c) --NO.sub.2,
- d) --CN,
- e) --(C.sub.1-10 alkyl), substituted with zero (0) to three (3) halo,
- f) --(C.sub.0-6 alkyl)-phenyl, substituted with zero (0) to three (3) halo or hydroxy,
- g) --OH,
- h) --O--C.sub.1-5 alkyl,
- i) --(C.sub.0-6 alkyl)--O--(C.sub.1-6 alkyl), substituted with zero (0) to three (3) halo or hydroxy,
- j) --(C.sub.0-6 alkyl)--O--(C.sub.2-7 alkenyl), substituted with zero (0) to three (3) halo or hydroxy,
- k) --CH(O),
- l) --C(O)--(C.sub.1-6 alkyl),
- m) --C(O)OH,
- n) --C(O)O--(C.sub.1-5 alkyl),
- o) --C(O)--N(H or C.sub.1-6 alkyl).sub.2,
- p) --NH.sub.2,
- q) --NH--(C.sub.1-6 alkyl),
- r) -mono or di-(C.sub.1-6 alkyl)amino,
- s) --NH--OH,
- t) --NH--C(O)--(C.sub.1-3 alkyl),
- u) --(C.sub.0-6 alkyl)--NH--C(O)-phenyl,
- v) --(C.sub.0-6 alkyl)--NH--SO.sub.2 -phenyl,
- w) --(C.sub.0-6 alkyl)--N.dbd.N-phenyl, substituted with zero (0) or one (1) --N(C.sub.1 -C.sub.3 alkyl).sub.2, or
- x) --SO.sub.2 -phenyl, substituted with zero (0) to three (3) C.sub.1 -C.sub.5 alkyl;
- wherein R.sub.2 is
- a) --H,
- b) --C.sub.1-6 alkyl,
- c) --(C.sub.1-6 alkyl)--C.sub.3-7 cycloalkyl,
- d) --(C.sub.2-10 alkenyl)
- e) --(C.sub.1-6 alkyl)--R.sub.2-100,
- f) --(C.sub.1-6 alkyl)--R.sub.2-500,
- wherein R.sub.2-100 is independent of and defined the same as R.sub.1-100 wherein RA.sub.1 is RA.sub.2 ;
- wherein R.sub.2-500 is independent of and defined the same as R.sub.1-500 wherein RA.sub.1 is RA.sub.2 ;
- wherein RA.sub.2 is independent of and defined the same as RA.sub.1 ;
- wherein R.sub.3 is
- a) --(C.sub.1-5 alkyl),
- b) --(C.sub.6-10 alkyl),
- c) --(C.sub.2-5 alkenyl),
- d) --(C.sub.6-10 alkenyl),
- e) --(C.sub.1-6 alkyl)--CH.dbd.CH.sub.2,
- f) --(C.sub.1-5 alkyl)--(C.sub.3-7 cycloalkyl),
- g) --(C.sub.1-5 alkyl)--O--(CH.sub.2 CH.sub.2 O).sub.q --CH.sub.3,
- h) --(C.sub.1-6 alkyl)--R.sub.3-4,
- i) --(C.sub.2-6 alkenyl)--R.sub.3-4,
- j) --CH(R.sub.3-6)--R.sub.3-4,
- k) --CH(R.sub.3-6)--(C.sub.1-6 alkyl)--R.sub.3-4,
- l) --CH(R.sub.3-6)--(C.sub.2-6 alkenyl)--R.sub.3-4,
- m) --R.sub.3-100,
- n) --(C.sub.1-5 alkyl)--R.sub.3-100,
- o) --(C.sub.3-4 alkyl)-RAX
- p) --H or --(C.sub.1-5 alkyl),
- q) -n propyl-RAX,
- r) --3-phenylpropyl,
- s) --R.sub.3-500,
- t) --(C.sub.1-5 alkyl)--R.sub.3-500,
- u) --(C.sub.3-4 alkyl)--R.sub.3-500,
- v) -n propyl-R.sub.3-500,
- w) --C(H)(OH)--R.sub.3-1,
- x) --(C.sub.1-5 alkyl)--C(H)(OH)--R.sub.3-1,
- y) --C(O)--R.sub.3-1,
- z) --(C.sub.1-5 alkyl)--C(O)--R.sub.3-1,
- a1) --(C.sub.1-5 alkyl)--N(H)R.sub.3-1,
- b1) --(C.sub.1-5 alkyl)--N((C.sub.1-5 alkyl)((C.sub.1-5 alkyl)--R.sub.3-1),
- c1) --(C.sub.1-5 alkyl)--N(H)C(O)--R.sub.3-1,
- d1) --C(O)--N(H)R.sub.3-1, or
- e1) --(C.sub.1-5 alkyl)--C(O)--N(H)R.sub.3-1 ;
- wherein R.sub.3-1 is
- a) --NH--C(O)--,
- b) --NH--SO.sub.2 --,
- c) --NH--CO--NH--, or
- d) --SO.sub.2 --NH--;
- wherein, R.sub.3-4 is
- a) --OH,
- b) --O--(C.sub.1-6 alkyl),
- c) --C(O)--OH,
- d) --C(O)--O--(C.sub.1-6 alkyl),
- e) --(C.sub.1-6 alkyl),
- f) --(C.sub.3-6 cycloalkyl),
- g) --R.sub.3-100, or
- h) --R.sub.3-500 ;
- wherein R.sub.3-6 is
- a) --OH,
- b) --C.sub.1-10 alkyl,
- c) --(C.sub.0-6 alkyl)--C.sub.3 -C.sub.7 cycloalkyl,
- d) --(C.sub.1-6 alkyl)--CH.dbd.CH.sub.2,
- e) --(C.sub.0-6 alkyl)--R.sub.3-4,
- f) --(C.sub.1-6 alkyl)--R.sub.3-100, or
- g) --(C.sub.1-6 alkyl)--R.sub.3-500 ;
- wherein R.sub.3-9 is
- a) --(C.sub.1-6 alkyl),
- b) --(C.sub.0-6 alkyl)--RA.sub.3-RA-12, or
- c) --(C.sub.0-6 alkyl)--RA.sub.3-RA-15 ;
- wherein R.sub.3-100 is independent of and defined the same as R.sub.1-100 ;
- wherein R.sub.3-500 is independent of and defined the same as R.sub.1-500 ;
- wherein RA.sub.3 is independent of and defined the same as RA.sub.1 ;
- wherein RA.sub.3-RA-12, RA.sub.3-RA-15, RA.sub.3-RA-12-AXA and RA.sub.3-RA-15-AXA, are all independent of and defined the same as the corresponding R.sub.1 variables, which are: RA.sub.1-RA-12, RA.sub.1-RA-15, RA.sub.1-RA-12-AXA and RA.sub.1-RA-15-AXA, respectively,
- wherein R.sub.2 and R.sub.3 can be taken together to form a ring comprised of the following groups,
- a) (C.sub.5-9 cycloalkyl),
- b) (C.sub.5-9 cycloalkyl) substituted with one to two --R.sub.3-9, or
- c) --(C.sub.1-5 alkyl substituted with zero to one R.sub.3-9)--R.sub.23 --(C.sub.1-5 alkyl);
- wherein R.sub.3-9 is
- a) --(C.sub.1-6 alkyl),
- b) --(C.sub.0-6 alkyl)--RA.sub.3-RA-12, or
- c) --(C.sub.0-6 alkyl)--RA.sub.3-RA-15 ;
- or wherein R.sub.2 and R.sub.3 can be taken together to form a double bond represented by formula 50, shown below, ##STR145## wherein R.sub.11 is a) --H,
- b) --C.sub.1 -C.sub.4 alkyl,
- c) --(RA.sub.3-RA-12), or
- d) pharmaceutically acceptable salts,
- wherein R.sub.23 is
- a) --O--,
- b) --C(O)--,
- c) --N(H)--,
- d) --N(R.sub.3-9)--,
- e) --N(C(O)--R.sub.3-9)--, or
- f) --N(C(O)--O--R.sub.3-9);
- wherein R.sub.30 is
- a) -morpholino,
- b) -piperidino,
- c) -piperazino,
- d) --OR.sub.40,
- e) -halo,
- f) ##STR146## g) --NR.sub.40 R.sub.41 ; wherein R.sub.40 and R.sub.41 are defined independently and are,
- a) --H,
- b) --C.sub.1 -C.sub.4 alkyl,
- c) phenyl, substituted with zero (0) to three (3) RA.sub.1-RA-120,
- wherein R.sub.42 is
- a) --C.sub.1 -C.sub.4 alkyl,
- b) -phenyl, substituted with zero (0) to three (3) RA.sub.1-RA-120, or
- c) --(C.sub.0-6 alkyl)-phenyl, substituted with zero (0) to three (3) RA.sub.1-RA-120 ;
- wherein RA.sub.2-RA-120 and RA.sub.3-RA-120 are independent of and defined the same as RA.sub.1-RA-120 ;
- wherein R.sub.50 and R.sub.51 are defined independently and are
- a) --(H or C.sub.1-6 alkyl),
- b) --(C.sub.0-6 alkyl)--RA.sub.3-RA-12, or
- c) --(C.sub.0-6 alkyl)--RA.sub.3-RA-15 ;
- wherein AA is an amino acid residue,
- wherein P.sub.1 is hydrogen or a nitrogen protecting group,
- wherein m and n are independently zero (0) to five (5) inclusive,
- wherein p and q are independently one (1) to five (5) inclusive,
- wherein z is one (1) to three (3) inclusive; and
- pharmaceutically acceptable salts, including bis salts, thereof,
- with the proviso that when R.sub.1 is 1-phenylpropyl and R.sub.2 is H, then R.sub.3 is not C.sub.1-5 alkyl, and
- with the proviso that when RA.sub.1 or RA.sub.3 is --G.sub.1-2 --(C.sub.0-6 alkyl)--O--RA.sub.1-RA-12, --(C.sub.0-6 alkyl)--G.sub.1-2 --(C.sub.0-6 alkyl)--O--(C.sub.0-6 alkyl), --(C.sub.0-6 alkyl)--G.sub.1-2 --O--(C.sub.1-6 alkyl)--RA.sub.1-RA-12, --(C.sub.0-6 alkyl)--G.sub.1-2 --O--(C.sub.1-6 alkyl)--RA.sub.1-RA-15, --G.sub.1-2 --N(R.sub.42).sub.2, or --G.sub.1-2 --NH.sub.2, then G.sub.1-2 is NOT, --C(O)--NH--, --NH--SO.sub.2 --, --SO.sub.2 --NH--, --NH--SO.sub.2 --NH--, --C(O)--O--, --NH--C(O)--NH, --N((C.sub.1-6 alkyl)--RA.sub.1-RA-12)--SO.sub.2 --, or --N((C.sub.0-6 alkyl)--(C.sub.1-6 alkyl))--SO.sub.2 --.
- 16. A compound represented by the structure shown in formula 1, ##STR147## wherein 3 tautomers of the same structure are shown, wherein R.sub.1 is ##STR148## wherein R.sub.1-1 is a) --(C.sub.1-5 alkyl),
- b) --(C.sub.2-5 alkenyl),
- c) --(C.sub.3-7 cycloalkyl),
- d) --(C.sub.3-5 cycloalkyl),
- e) -cyclopropyl,
- f) --(C.sub.1-5 alkyl)--(C.sub.3-7 cycloalkyl),
- g) --R.sub.1-100, or
- h) --(C.sub.1 -C.sub.5 alkyl)--R.sub.1-100 ;
- wherein R.sub.1-2 is --R.sub.1-100, or --R.sub.1-500 ;
- wherein R.sub.1-100 is
- a) phenyl, substituted with zero (0) to three (3) of RA.sub.1,
- b) naphthyl, substituted with zero (0) to three (3) of RA.sub.1,
- c) biphenyl, substituted with zero (0) to three (3) of RA.sub.1,
- d) perhalophenyl;
- wherein R.sub.1-500 is
- a 5- or 6-membered saturated or unsaturated ring containing from one (1) to four (4) heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur; and substituted with zero (0) to three (3) RA.sub.1 ; and including any bicyclic group in which any of the above heterocyclic rings is fused to a benzene ring, C.sub.3 -C.sub.8 cycloalkyl, or another heterocycle; and substituted with zero (0) to three (3) RA.sub.1 ; and if chemically feasible, the nitrogen and sulfur atoms may be in the oxidized forms;
- wherein RA.sub.1 is
- a) --H,
- b) --(C.sub.1-5 alkyl),
- c) --(C.sub.2-5 alkenyl),
- d) --OH,
- e) --O--(C.sub.1-5 alkyl),
- f) --O--(C.sub.2-5 alkenyl),
- g) --C(O)OH,
- h) --C(O)(C.sub.1-5 alkyl),
- i) --C(O)--RA.sub.1-3,
- wherein RA.sub.1-3 is any N-terminus substituted amino acid,
- j) --C(O)--N(H)RA.sub.1-1,
- k) --CN,
- l) --NH.sub.2 (para or meta positions),
- m) --N(H)(C.sub.1-5 alkyl) (para or meta positions),
- n) --N(C.sub.1-5 alkyl).sub.2,
- o) --N(H)RA.sub.1-4,
- wherein RA.sub.1-4 is any C-terminus substituted amino acid,
- p) --N(H)C(O)--RA.sub.1-1 (para or meta positions),
- q) --N(H)C(O)--O--RA.sub.1-1 (para or meta positions),
- r) --N(H)(SO.sub.2)--RA.sub.1-2,
- s) --N(C.sub.1-6 alkyl)(SO.sub.2)--RA.sub.1-2,
- t) --N(CH.sub.3)(SO.sub.2)--RA.sub.1-2,
- u) --NO.sub.2,
- v) --PO.sub.3 H,
- w) --SO.sub.3 H,
- x) --SO.sub.2 NH.sub.2,
- y) --(C.sub.0-6 alkyl)--SO.sub.2 --RA.sub.1-RA-12,
- z) --(C.sub.0-6 alkyl)--SO.sub.2 --RA.sub.1-RA-15,
- a1) -halo,
- b1) --RA.sub.1-RA-12, or
- c1) --RA.sub.1-RA-15 ;
- wherein RA.sub.1-1 is
- a) --(C.sub.1-5 alkyl),
- b) --(C.sub.1-5 alkyl)--C(O)--O--(C.sub.1-5 alkyl),
- c) --(C.sub.1-5 alkyl)--NH.sub.2,
- d) --(C.sub.1-5 alkyl)--N(H)C(O)--O--(C.sub.1-5 alkyl),
- e) --(C.sub.1-5 alkyl)--C((H)(NH.sub.2))--C(O)OH,
- f) --R.sub.1-RA-12,
- g) --R.sub.1-RA-15,
- h) --(C.sub.1-5 alkyl)-RAX,
- i) --(C.sub.1-5 alkyl)--O-RAX,
- j) --C(O)--RA.sub.1-1-3,
- wherein RA.sub.1-1-3 is any N-terminus amino acid,
- k) --N(H)--RA.sub.1-1-4, or
- wherein RA.sub.1-1-4 is any C-terminus amino acid,
- l) --R.sub.1-500 ;
- wherein RA.sub.1-2 is
- a) -RAX,
- b) --(C.sub.1-5 alkyl)-RAX,
- c) --(C.sub.1-5 alkyl)--O-RAX,
- d) --RA.sub.1-RA-12,
- e) --RA.sub.1-RA-15,
- f) --(C.sub.1 -C.sub.5 alkyl)--RA.sub.1-RA-12,
- g) --(C.sub.1 -C.sub.5 alkyl)--RA.sub.1-RA-15,
- h) --(C.sub.1 -C.sub.5 alkyl)--O--RA.sub.1-RA-12, or
- i) --(C.sub.1 -C.sub.5 alkyl)--O--RA.sub.1-RA-15 ;
- wherein RA.sub.2 and RA.sub.3 are defined independently and are independent of and defined the same as RA.sub.1 ;
- wherein G.sub.1-1 is
- a) --NH--C(O)--,
- b) --NH--SO.sub.2 --,
- c) --NH--C(O)--NH--, or
- d) --SO.sub.2 --NH--;
- wherein G.sub.1-2 is
- a) --NH--C(O)--,
- b) --C(O)--NH--,
- c) --NH--SO.sub.2 --,
- d) --SO.sub.2 --NH--,
- e) --NH--SO.sub.2 --NH--,
- f) --C(O)--O--,
- g) --O--C(O)--,
- h) --N((C.sub.1-6 alkyl)--RA.sub.1-RA-12)--C(O)--,
- i) --NH--C(O)--NH,
- j) --N((C.sub.1-6 alkyl)--RA.sub.1-RA-12)--SO.sub.2 --, or
- k) --N((C.sub.0-6 alkyl)--(C.sub.1-6 alkyl))--SO.sub.2 --;
- wherein RA.sub.2 and RA.sub.3 are defined independently and are the same as RA.sub.1 ;
- wherein RA.sub.1-RA-12 is
- a) -phenyl, substituted with zero (0) to three (3) RA.sub.1-RA-12-AXA, or
- b) -naphthyl, substituted with zero (0) to three (3) RA.sub.1-RA-12-AXA,
- wherein RA.sub.1-RA-15 is
- a 5- or 6-membered saturated or unsaturated ring containing from one (1) to four (4) heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur; and including any bicyclic group in which any of the above heterocyclic rings is fused to a benzene ring, C.sub.3 -C.sub.8 cycloalkyl, or another heterocycle; and substituted with zero (0) to three (3) RA.sub.1-RA-15-AXA ;
- wherein RA.sub.1-RA-120, RA.sub.2-RA-120 and RA.sub.3-RA-120, are defined independently and are
- a) --C.sub.1 -C.sub.4 alkyl,
- b) --C.sub.1 -C.sub.3 alkoxy,
- c) -dimethylamino,
- d) -diethylamino,
- e) --CF.sub.3,
- f) --CN,
- g) -halo,
- h) --NH.sub.2,
- i) --OH,
- j) --SO.sub.2 --NH.sub.2, or
- k) --C(O)--NH.sub.2 ;
- wherein RA.sub.1-RA-12-AXA or RA.sub.1-RA-15-AXA are independent and are,
- a) --H
- b) -halo,
- c) --NO.sub.2,
- d) --CN,
- e) --(C.sub.1-10 alkyl), substituted with zero (0) to three (3) halo,
- f) --(C.sub.0-6 alkyl)-phenyl, substituted with zero (0) to three (3) halo or hydroxy,
- g) --OH,
- h) --O--C.sub.1-5 alkyl,
- i) --(C.sub.0-6 alkyl)--O--(C.sub.1-6 alkyl), substituted with zero (0) to three (3) halo or hydroxy,
- j) --(C.sub.0-6 alkyl)--O--(C.sub.2-7 alkenyl), substituted with zero (0) to three (3) halo or hydroxy,
- k) --CH(O),
- l) --C(O)--(C.sub.1-6 alkyl),
- m) --C(O)OH,
- n) --C(O)O--(C.sub.1-5 alkyl),
- o) --C(O)--N(H or C.sub.1-6 alkyl).sub.2,
- p) --NH.sub.2,
- q) --NH--(C.sub.1-6 alkyl),
- r) -mono or di-(C.sub.1-6 alkyl)amino,
- s) --NH--OH,
- t) --NH--C(O)--(C.sub.1-3 alkyl),
- u) --(C.sub.0-6 alkyl)--NH--C(O)-phenyl,
- v) --(C.sub.0-6 alkyl)--NH--SO.sub.2 -phenyl,
- w) --(C.sub.0-6 alkyl)--N.dbd.N-phenyl, substituted with zero (0) or one (1) --N(C.sub.1 -C.sub.3 alkyl).sub.2, or
- x) --SO.sub.2 -phenyl, substituted with zero (0) to three (3) C.sub.1 -C.sub.5 alkyl;
- wherein R.sub.2 is
- a) --H,
- b) --C.sub.1-6 alkyl,
- c) --(C.sub.1-6 alkyl)--C.sub.3-7 cycloalkyl,
- d) --(C.sub.2-10 alkenyl)
- e) --(C.sub.1-6 alkyl)--R.sub.2-100,
- f) --(C.sub.1-6 alkyl)--R.sub.2-500,
- wherein R.sub.2-100 is independent of and defined the same as R.sub.1-100 wherein RA.sub.1 is RA.sub.2 ;
- wherein R.sub.2-500 is independent of and defined the same as R.sub.1-500 wherein RA.sub.1 is RA.sub.2 ;
- wherein RA.sub.2 is independent of and defined the same as RA.sub.1 ;
- wherein R.sub.3 is
- a) --(C.sub.1-5 alkyl),
- b) --(C.sub.6-10 alkyl),
- c) --(C.sub.2-5 alkenyl),
- d) --(C.sub.6-10 alkenyl),
- e) --(C.sub.1-6 alkyl)--CH.dbd.CH.sub.2,
- f) --(C.sub.1-5 alkyl)--(C.sub.3-7 cycloalkyl),
- g) --(C.sub.1-5 alkyl)--O--(CH.sub.2 CH.sub.2 O).sub.q --CH.sub.3,
- h) --(C.sub.1-6 alkyl)--R.sub.3-4,
- i) --(C.sub.2-6 alkenyl)--R.sub.3-4,
- j) --CH(R.sub.3-6)--R.sub.3-4,
- k) --CH(R.sub.3-6)--(C.sub.1-6 alkyl)--R.sub.3-4,
- l) --CH(R.sub.3-6)--(C.sub.2-6 alkenyl)--R.sub.3-4,
- m) --R.sub.3-100,
- n) --(C.sub.1-5 alkyl)--R.sub.3-100,
- o) --(C.sub.3-4 alkyl)-RAX
- p) --H or --(C.sub.1-5 alkyl),
- q) -n propyl-RAX,
- r) --3-phenylpropyl,
- s) --R.sub.3-500,
- t) --(C.sub.1-5 alkyl)--R.sub.3-500,
- u) --(C.sub.3-4 alkyl)--R.sub.3-500,
- v) -n propyl-R.sub.3-500,
- w) --C(H)(OH)--R.sub.3-1,
- x) --(C.sub.1-5 alkyl)--C(H)(OH)--R.sub.3-1,
- y) --C(O)--R.sub.3-1,
- z) --C.sub.1-5 alkyl)--C(O)--R.sub.3-1,
- a1) --(C.sub.1-5 alkyl)--N(H)R.sub.3-1,
- b1) --(C.sub.1-5 alkyl)-N((C.sub.1-5 alkyl)((C.sub.1-5 alkyl)--R.sub.3-1),
- c1) --(C.sub.1-5 alkyl)--N(H)C(O)--R.sub.3-1,
- d1) --C(O)--N(H)R.sub.3-1, or
- e1) --(C.sub.1-5 alkyl)--C(O)--N(H)R.sub.3-1 ;
- wherein R.sub.3-1 is
- a) --NH--C(O)--,
- b) --NH--SO.sub.2 --,
- c) --NH--CO--NH--, or
- d) --SO.sub.2 --NH--;
- wherein, R.sub.3-4 is
- a) --OH,
- b) --O--(C.sub.1-6 alkyl),
- c) --C(O)--OH,
- d) --C(O)--O--(C.sub.1-6 alkyl),
- e) --(C.sub.1-6 alkyl),
- f) --(C.sub.3-6 cycloalkyl),
- g) --R.sub.3-100, or
- h) --R.sub.3-500 ;
- wherein R.sub.3-6 is
- a) --OH,
- b) --C.sub.1-10 alkyl,
- c) --(C.sub.0-6 alkyl)--C.sub.3 -C.sub.7 cycloalkyl,
- d) --(C.sub.1-6 alkyl)--CH.dbd.CH.sub.2,
- e) --(C.sub.0-6 alkyl)--R.sub.3-4,
- f) --(C.sub.1-6 alkyl)--R.sub.3-100, or
- g) --(C.sub.1-6 alkyl)--R.sub.3-500 ;
- wherein R.sub.3-9 is
- a) --(C.sub.1-6 alkyl),
- b) --(C.sub.0-6 alkyl)--RA.sub.3-RA-12, or
- c) --(C.sub.0-6 alkyl)--RA.sub.3-RA-15 ;
- wherein R.sub.3-100 is independent of and defined the same as R.sub.1-100 ;
- wherein R.sub.3-500 is independent of and defined the same as R.sub.1-500 ;
- wherein RA.sub.3 is independent of and defined the same as RA.sub.1 ;
- wherein RA.sub.3-RA-12, RA.sub.3-RA-15, RA.sub.3-RA-12-AXA and RA.sub.3-RA-15-AXA, are all independent of and defined the same as the corresponding R.sub.1 variables, which are: RA.sub.1-RA-12, RA.sub.1-RA-15, RA.sub.1-RA-12-AXA and RA.sub.1-RA-15-AXA, respectively,
- wherein R.sub.2 and R.sub.3 can be taken together to form a ring comprised of the following groups,
- a) (C.sub.5-9 cycloalkyl),
- b) (C.sub.5-9 cycloalkyl) substituted with one to two --R.sub.3-9, or
- c) --(C.sub.1-5 alkyl substituted with zero to one R.sub.3-9)--R.sub.23 --(C.sub.1-5 alkyl);
- wherein R.sub.3-9 is
- a) --(C.sub.1-6 alkyl),
- b) --(C.sub.0-6 alkyl)--RA.sub.3-RA-12, or
- c) --(C.sub.0-6 alkyl)--RA.sub.3-RA-15 ;
- or
- wherein R.sub.2 and R.sub.3 can be taken together to form a double bond represented by formula 50, shown below, ##STR149## wherein R.sub.11 is a) --H,
- b) --C.sub.1 -C.sub.4 alkyl,
- c) --(RA.sub.3-RA-12), or
- d) pharmaceutically acceptable salts,
- wherein R.sub.23 is
- a) --O--,
- b) --C(O)--,
- c) --N(H)--,
- d) --N(R.sub.3-9)--,
- e) --N(C(O)--R.sub.3-9)--, or
- f) --N(C(O)--O--R.sub.3-9);
- wherein R.sub.30 is
- a) -morpholino,
- b) -piperidino,
- c) -piperazino,
- d) --OR.sub.40,
- e) -halo,
- f) ##STR150## g) --NR.sub.40 R.sub.41 ; wherein R.sub.40 and R.sub.41 are defined independently and are,
- a) --H,
- b) --C.sub.1 -C.sub.4 alkyl,
- c) phenyl, substituted with zero (0) to three (3) RA.sub.1-RA-120,
- wherein R.sub.42 is
- a) --C.sub.1 -C.sub.4 alkyl,
- b) -phenyl, substituted with zero (0) to three (3) RA.sub.1-RA-120, or
- c) --(C.sub.0-6 alkyl)-phenyl, substituted with zero (0) to three (3) RA.sub.1-RA-120 ;
- wherein RA.sub.2-RA-120 and R.sub.3-RA-120 are independent of and defined the same as RA.sub.1-RA-120 ;
- wherein R.sub.50 and R.sub.51 are defined independently and are
- a) --(H or C.sub.1-6 alkyl),
- b) --(C.sub.0-6 alkyl)--RA.sub.3-RA-12, or
- c) --(C.sub.0-6 alkyl)--RA.sub.3-RA-15 ;
- wherein AA is an amino acid residue,
- wherein P.sub.1 is hydrogen or a nitrogen protecting group,
- wherein m and n are independently zero (0) to five (5) inclusive,
- wherein p and q are independently one (1) to five (5) inclusive,
- wherein z is one (1) to three (3) inclusive; and
- pharmaceutically acceptable salts, including bis salts, thereof,
- with the proviso that when R.sub.1 is 1-phenylpropyl and R.sub.2 is H, then R.sub.3 is not C.sub.1-5 alkyl, and
- with the proviso that when RA.sub.1 or RA.sub.3 is --G.sub.1-2 --(C.sub.0-6 alkyl)--O--RA.sub.1-RA-12, --(C.sub.0-6 alkyl)--G.sub.1-2 --(C.sub.0-6 alkyl)--O--(C.sub.0-6 alkyl), --(C.sub.0-6 alkyl)--G.sub.1-2 --O--(C.sub.1-6 alkyl)--RA.sub.1-RA-12, --(C.sub.0-6 alkyl)--G.sub.1-2 --O--(C.sub.1-6 alkyl)--RA.sub.1-RA-15, --G.sub.1-2 --N(R.sub.42).sub.2, or --G.sub.1-2 --NH.sub.2, then G.sub.1-2 is NOT, --C(O)--NH--, --NH--SO.sub.2 --, --SO.sub.2 --NH--, --NH--SO.sub.2 --NH--, --C(O)--O--, --NH--C(O)--NH, --N((C.sub.1-6 alkyl)--RA.sub.1-RA-12)--SO.sub.2 --, or --N((C.sub.0-6 alkyl)--(C.sub.1-6 alkyl))--SO.sub.2 --.
- 17. A compound represented by the structure shown in formula 1, ##STR151## wherein 3 tautomers of the same structure are shown, wherein R.sub.1 is ##STR152## wherein R.sub.1-1 is a) --(C.sub.1-5 alkyl),
- b) --(C.sub.2-5 alkenyl),
- c) --(C.sub.3-7 cycloalkyl),
- d) --(C.sub.3-5 cycloalkyl),
- e) -cyclopropyl,
- f) --(C.sub.1-5 alkyl)--(C.sub.3-7 cycloalkyl),
- g) --R.sub.1-100, or
- h) --(C.sub.1 -C.sub.5 alkyl)--R.sub.1-100 ;
- wherein R.sub.1-2 is --R.sub.1-100, or --R.sub.1-500 ;
- wherein R.sub.1-100 is
- a) phenyl, substituted with zero (0) to three (3) of RA.sub.1,
- b) naphthyl, substituted with zero (0) to three (3) of RA.sub.1,
- c) biphenyl, substituted with zero (0) to three (3) of RA.sub.1,
- d) perhalophenyl;
- wherein R.sub.1-500 is
- a 5- or 6-membered saturated or unsaturated ring containing from one (1) to four (4) heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur; and substituted with zero (0) to three (3) RA.sub.1 ; and including any bicyclic group in which any of the above heterocyclic rings is fused to a benzene ring, C.sub.3 -C.sub.8 cycloalkyl, or another heterocycle; and substituted with zero (0) to three (3) RA.sub.1 ; and if chemically feasible, the nitrogen and sulfur atoms may be in the oxidized forms;
- wherein RA.sub.1 is
- a) --H,
- b) --(C.sub.1-5 alkyl),
- c) --O--(C.sub.1-5 alkyl),
- d) --C(O)--RA.sub.1-3,
- wherein RA.sub.1-3 is any N-terminus substituted amino acid,
- e) --C(O)--N(H)RA.sub.1 l,,
- f) --NH.sub.2 (para or meta positions),
- g) --N(H)(C.sub.1-5 alkyl) (para or meta positions),
- h) --N(C.sub.1-5 alkyl).sub.2,
- i) --N(H)RA.sub.1-4,
- wherein RA.sub.1-4 is any C-terminus substituted amino acid,
- j) --N(H)C(O)--RA.sub.1-1 (para or meta positions),
- k) --N(H)C(O)--O--RA.sub.1-1 (para or meta positions),
- l) --N(H)(SO.sub.2)--RA.sub.1-2,
- m) --N(CH.sub.3)(SO.sub.2 --RA.sub.1-2,
- n) --NO.sub.2,
- o) --SO.sub.2 NH.sub.2,
- p) --(C.sub.1-3 alkyl)--SO.sub.2 --RA.sub.1-RA-12,
- q) --(C.sub.1-3 alkyl)--SO.sub.2 --RA.sub.1-RA-15,
- r) -halo,
- wherein RA.sub.1-1 is
- a) --(C.sub.1-5 alkyl),
- b) --(C.sub.1-5 alkyl)--C(O)--O--(C.sub.1-5 alkyl),
- c) --(C.sub.1-5 alkyl)--NH.sub.2,
- d) --(C.sub.1-5 alkyl)--N(H)C(O)--O--(C.sub.1-5 alkyl),
- e) --(C.sub.1-5 alkyl)--C((H)(NH.sub.2))--C(O)OH,
- f) --RA.sub.1-RA-12,
- g) RA.sub.1-RA-15,
- h) --(C.sub.1-5 alkyl)-RAX,
- i) --(C.sub.1-5 alkyl)--O-RAX,
- j) --C(O)--RA.sub.1-1-3,
- wherein RA.sub.1-1-3 is any N-terminus amino acid,
- k) --N(H)--RA.sub.1-1-4, or
- wherein RA.sub.1-1-4 is any C-terminus amino acid,
- l) --R.sub.1-500 ;
- wherein RA.sub.1-2 is
- a) -RAX,
- b) --(C.sub.1-5 alkyl)-RAX,
- c) --(C.sub.1-5 alkyl)--O-RAX,
- d) --RA.sub.1-RA-12,
- e) --RA.sub.1-RA-15,
- f) --(C.sub.1 -C.sub.5 alkyl)--RA.sub.1-RA-12,
- g) --(C.sub.1 -C.sub.5 alkyl)--RA.sub.1-RA-15,
- h) --(C.sub.1 -C.sub.5 alkyl)--O--RA.sub.1-RA-12, or
- i) --(C.sub.1 -C.sub.5 alkyl)--O--RA.sub.1-RA-15 ;
- wherein RA.sub.2 and RA.sub.3 are defined independently and are independent of and defined the same as RA.sub.1 ;
- wherein G.sub.1-1 is
- a) --NH--C(O)--,
- b) --NH--SO.sub.2 --,
- c) --NH--C(O)--NH--, or
- d) --SO.sub.2 --NH--;
- wherein G.sub.1-2 is
- a) --NH--C(O)--,
- b) --C(O)--NH--,
- c) --NH--SO.sub.2 --,
- d) --SO.sub.2 --NH--,
- e) --NH--SO.sub.2 --NH--,
- f) --C(O)--O--,
- g) --O--C(O)--,
- h) --N((C.sub.1-6 alkyl)--RA.sub.1-RA-12)--C(O)--,
- i) --NH--C(O)--NH,
- j) --N((C.sub.1-6 alkyl)--RA.sub.1-RA-12)--SO.sub.2 --, or
- k) --N((C.sub.0-6 alkyl)--(C.sub.1-6 alkyl))--SO.sub.2 --;
- wherein RA.sub.2 and RA.sub.3 are defined independently and are the same as RA.sub.1 ;
- wherein RA.sub.1-RA-12 is
- a) -phenyl, substituted with zero (0) to three (3) RA.sub.1-RA-12-AXA, or
- b) -naphthyl, substituted with zero (0) to three (3) RA.sub.1-RA-12-AXA ;
- wherein RA.sub.1-RA-15 is
- a 5- or 6-membered saturated or unsaturated ring containing from one (1) to four (4) heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur; and including any bicyclic group in which any of the above heterocyclic rings is fused to a benzene ring, C.sub.3 -C.sub.8 cycloalkyl, or another heterocycle; and substituted with zero (0) to three (3) RA.sub.1-RA-15-AXA ;
- wherein RA.sub.1-RA-120, RA.sub.2-RA-120 and RA.sub.3-RA-120, are defined independently and are
- a) --C.sub.1 -C.sub.4 alkyl,
- b) --C.sub.1 -C.sub.3 alkoxy,
- c) -dimethylamino,
- d) -diethylamino,
- e) --CF.sub.3,
- f) --CN,
- g) -halo,
- h) --NH.sub.2,
- i) --OH,
- j) --SO.sub.2 --NH.sub.2, or
- k) --C(O)--NH.sub.2 ;
- wherein RA.sub.1-RA-12-AXA or RA.sub.1-RA-15-AXA are independent and are,
- a) --H
- b) -halo,
- c) --NO.sub.2,
- d) --CN,
- e) --(C.sub.1-10 alkyl), substituted with zero (0) to three (3) halo,
- f) --(C.sub.0-6 alkyl)-phenyl, substituted with zero (0) to three (3) halo or hydroxy,
- g) --OH,
- h) --O--C.sub.1-5 alkyl,
- i) --(C.sub.0-6 alkyl)--O--(C.sub.1-6 alkyl), substituted with zero (0) to three (3) halo or hydroxy,
- j) --(C.sub.0-6 alkyl)--O--(C.sub.2-7 alkenyl), substituted with zero (0) to three (3) halo or hydroxy,
- k) --CH(O),
- l) --C(O)--(C.sub.1-6 alkyl),
- m) --C(O)OH,
- n) --C(O)O--(C.sub.1-5 alkyl),
- o) --C(O)--N(H or C.sub.1-6 alkyl).sub.2,
- p) --NH.sub.2,
- q) --NH--(C.sub.1-6 alkyl),
- r) -mono or di--(C.sub.1-6 alkyl)amino,
- s) --NH--OH,
- t) --NH--C(O)--(C.sub.1-3 alkyl),
- u) --(C.sub.0-6 alkyl)--NH--C(O)-phenyl,
- v) --(C.sub.0-6 alkyl)--NH--SO.sub.2 -phenyl,
- w) --(C.sub.0-6 alkyl)--N.dbd.N-phenyl, substituted with zero (0) or one (1) --N(C.sub.1 -C.sub.3 alkyl).sub.2, or
- x) --SO.sub.2 -phenyl, substituted with zero (0) to three (3) C.sub.1 -C.sub.5 alkyl;
- wherein R.sub.2 is
- a) --H,
- b) --C.sub.1-6 alkyl,
- c) --(C.sub.1-6 alkyl)--C.sub.3-7 cycloalkyl,
- d) --(C.sub.2-10 alkenyl)
- e) --(C.sub.1-6 alkyl)--R.sub.2-100,
- f) --(C.sub.1-4 alkyl)--R.sub.2-500,
- wherein R.sub.2-100 is independent of and defined the same as R.sub.1-100 wherein RA.sub.1 is RA.sub.2 ;
- wherein R.sub.2-500 is independent of and defined the same as R.sub.1-500 wherein RA.sub.1 is RA.sub.2 ;
- wherein RA.sub.2 is independent of and defined the same as RA.sub.1 ;
- wherein R.sub.3 is
- a) --(C.sub.1-5 alkyl),
- b) --(C.sub.6-10 alkyl),
- c) --(C.sub.2-5 alkenyl),
- d) --(C.sub.6-10 alkenyl),
- e) --(C.sub.1-6 alkyl)--CH.dbd.CH.sub.2,
- f) --(C.sub.1-5 alkyl)--(C.sub.3-7 cycloalkyl),
- g) --(C.sub.1-5 alkyl)--O--(CH.sub.2 CH.sub.2 O).sub.q --CH.sub.3,
- h) --(C.sub.1-6 alkyl)--R.sub.3-4,
- i) --(C.sub.2-6 alkenyl)--R.sub.3-4,
- j) --CH(R.sub.3-6)--R.sub.3-4),
- k) --CH(R.sub.3-6)--(C.sub.1-6 alkyl)--R.sub.3-4,
- l) --CH(R.sub.3-6)--(C.sub.2-6 alkenyl)--R.sub.3-4,
- m) --R.sub.3-100,
- n) --(C.sub.1-5 alkyl)--R.sub.3-100,
- o) --(C.sub.3-4 alkyl)-RAX
- p) --H or --(C.sub.1-5 alkyl),
- q) -n propyl-RAX,
- r) --3-phenylpropyl,
- s) --R.sub.3-500,
- t) --(C.sub.1-5 alkyl)--R.sub.3-500,
- u) --(C.sub.3-4 alkyl)--R.sub.3-500,
- v) -n propyl--R.sub.3-500,
- w) --C(H)(OH)--R.sub.3-1,
- x) --(C.sub.1-5 alkyl)--C(H)(OH)--R.sub.3-1,
- y) --C(O)--R.sub.3-1,
- z) --(C.sub.1-5 alkyl)--C(O)--R.sub.3-1,
- a1) --(C.sub.1-5 alkyl)--N(H)R.sub.3-1,
- b1) --(C.sub.1-5 alkyl)--N((C.sub.1-5 alkyl)((C.sub.1-5 alkyl)--R.sub.3-1),
- c1) --(C.sub.1-5 alkyl)--N(H)C(O)--R.sub.3-1,
- d1) --C(O)--N(H)R.sub.3-1, or
- e1) --(C.sub.1-5 alkyl)--C(O)--N(H)R.sub.3-1 ;
- wherein R.sub.3-1 is
- a) --NH--C(O)--,
- b) --NH--SO.sub.2 --,
- c) --NH--CO--NH--, or
- d) --SO.sub.2 --NH--;
- wherein, R.sub.3-4 is
- a) --OH,
- b) --O--(C.sub.1-6 alkyl),
- c) --C(O)--OH,
- d) --C(O)--O--(C.sub.1-6 alkyl),
- e) --(C.sub.1-6 alkyl),
- f) --(C.sub.3-6 cycloalkyl),
- g) --R.sub.3-100, or
- h) --R.sub.3-500 ;
- wherein R.sub.3-6 is
- a) --OH,
- b) --C.sub.1-10 alkyl,
- c) --(C.sub.0-6 alkyl)--C.sub.3 -C.sub.7 cycloalkyl,
- d) --(C.sub.1-6 alkyl)--CH.dbd.CH.sub.2,
- e) --(C.sub.0-6 alkyl)--R.sub.3-4,
- f) --(C.sub.1-6 alkyl)--R.sub.3-100, or
- g) --(C.sub.1-6 alkyl)--R.sub.3-500 ;
- wherein R.sub.3-9 is
- a) --(C.sub.1-6 alkyl),
- b) --(C.sub.0-6 alkyl)--RA.sub.3-RA-12, or
- c) --(C.sub.0-6 alkyl)--RA.sub.3-RA-15 ;
- wherein R.sub.3-100 is independent of and defined the same as R.sub.1-100 ;
- wherein R.sub.3-500 is independent of and defined the same as R.sub.1-500 ;
- wherein RA.sub.3 is independent of and defined the same as RA.sub.1 ;
- wherein RA.sub.3-RA-12, RA.sub.3-RA-15, RA.sub.3-RA-12-AXA and RA.sub.3-RA-15-AXA, are all independent of and defined the same as the corresponding R.sub.1 variables, which are: RA.sub.1-RA-12, RA.sub.1-RA-15, RA.sub.1-RA-12-AXA and RA.sub.1-RA-15-AXA, respectively,
- wherein R.sub.2 and R.sub.3 can be taken together to form a ring comprised of the following groups,
- a) (C.sub.5-9 cycloalkyl),
- b) (C.sub.5-9 cycloalkyl) substituted with one to two --R.sub.3-9, or
- c) --(C.sub.1-5 alkyl substituted with zero to one R.sub.3-9)--R.sub.23 --(C.sub.1-5 alkyl);
- wherein R.sub.3-9 is
- a) --(C.sub.1-6 alkyl),
- b) --(C.sub.0-6 alkyl)--RA.sub.3-RA-12, or
- c) --(C.sub.0-6 alkyl)--RA.sub.3-RA-15 ;
- or
- wherein R.sub.2 and R.sub.3 can be taken together to form a double bond represented by formula 50, shown below, ##STR153## wherein R.sub.11 is a) --H,
- b) --C.sub.1 -C.sub.4 alkyl,
- c) --(RA.sub.3-RA-12), or
- d) pharmaceutically acceptable salts,
- wherein R.sub.23 is
- a) --O--,
- b) --C(O)--,
- c) --N(H)--,
- d) --N(R.sub.3-9)--,
- e) --N(C(O)--R.sub.3-9)--, or
- f) --N(C(O)--O--R.sub.3-9);
- wherein R.sub.30 is
- a) -morpholino,
- b) -piperidino,
- c) -piperazino,
- d) --OR.sub.40,
- e) -halo,
- f) ##STR154## g) --NR.sub.40 R.sub.41 ; wherein R.sub.40 and R.sub.41 are defined independently and are,
- a) --H,
- b) --C.sub.1 -C.sub.4 alkyl,
- c) phenyl, substituted with zero (0) to three (3) RA.sub.1-RA-120,
- wherein R.sub.42 is
- a) --C.sub.1 -C.sub.4 alkyl,
- b) -phenyl, substituted with zero (0) to three (3) RA.sub.1-RA-120, or
- c) --(C.sub.0-6 alkyl)-phenyl, substituted with zero (0) to three (3) RA.sub.1-RA-120 ;
- wherein RA.sub.2-RA-120 and RA.sub.3-RA-120 are independent of and defined the same as RA.sub.1-RA-120 ;
- wherein R.sub.50 and R.sub.51 are defined independently and are
- a) --(H or C.sub.1-6 alkyl),
- b) --(C.sub.0-6 alkyl)--RA.sub.3-RA-12, or
- c) --(C.sub.0-6 alkyl)-RA.sub.3-RA-15 ;
- wherein AA is an amino acid residue,
- wherein P.sub.1 is hydrogen or a nitrogen protecting group,
- wherein m and n are independently zero (0) to five (5) inclusive,
- wherein p and q are independently one (1) to five (5) inclusive,
- wherein z is one (1) to three (3) inclusive; and
- pharmaceutically acceptable salts, including bis salts, thereof,
- with the proviso that when R.sub.1 is 1-phenylpropyl and R.sub.2 is H, then R.sub.3 is not C.sub.1-5 alkyl, and
- with the proviso that when RA.sub.1 or RA.sub.3 is --G.sub.1-2 --(C.sub.0-6 alkyl)--O--RA.sub.1-RA-12, --(C.sub.0-6 alkyl)--G.sub.1-2 --(C.sub.0-6 alkyl)--O--(C.sub.0-6 alkyl), --(C.sub.0-6 alkyl)--G.sub.1-2 --O--(C.sub.1-6 alkyl)--RA.sub.1-RA-12, --(C.sub.0-6 alkyl)--G.sub.1-2 --O--(C.sub.1-6 alkyl)--RA.sub.1-RA-15, --G.sub.1-2 --N(R.sub.42).sub.2, or --G.sub.1-2 --NH.sub.2, then G.sub.1-2 is NOT, --C(O)--NH--, --NH--SO.sub.2 --, --SO.sub.2 --NH--, --NH--SO.sub.2 --NH--, --C(O)--O--, --NH--C(O)--NH, --N((C.sub.1-6 alkyl)--RA.sub.1-RA-12)--SO.sub.2 --, or --N((C.sub.0-6 alkyl)--(C.sub.1-6 alkyl))--SO.sub.2 --.
- 18. A compound represented by the structure shown in formula 1, ##STR155## wherein 3 tautomers of the same structure are shown, wherein R.sub.1 is ##STR156## wherein R.sub.1-1 is a) --C.sub.1-5 alkyl),
- b) --(C.sub.2-5 alkenyl),
- c) --(C.sub.3-7 cycloalkyl),
- d) --(C.sub.3-5 cycloalkyl),
- e) -cyclopropyl,
- f) --(C.sub.1-5 alkyl)--(C.sub.3-7 cycloalkyl),
- g) --R.sub.1-100, or
- h) --(C.sub.1 -C.sub.5 alkyl)--R.sub.1-100 ;
- wherein R.sub.1-2 is --R.sub.1-100, or --R.sub.1-500 ;
- wherein R.sub.1-100 is
- a) phenyl, substituted with zero (0) to three (3) of RA.sub.1,
- b) naphthyl, substituted with zero (0) to three (3) of RA.sub.1,
- c) biphenyl, substituted with zero (0) to three (3) of RA.sub.1,
- d) perhalophenyl;
- wherein R.sub.1-500 is
- a 5- or 6-membered saturated or unsaturated ring containing from one (1) to four (4) heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur; and substituted with zero (0) to three (3) RA.sub.1 ; and including any bicyclic group in which any of the above heterocyclic rings is fused to a benzene ring, C.sub.3 -C.sub.8 cycloalkyl, or another heterocycle; and substituted with zero (0) to three (3) RA.sub.1 ; and if chemically feasible, the nitrogen and sulfur atoms may be in the oxidized forms;
- wherein RA.sub.1 is
- a) --H,
- b) --(C.sub.1-5 alkyl),
- c) --O--(C.sub.1-5 alkyl),
- d) --C(O)--RA.sub.1-3,
- wherein RA.sub.1-3 is any N-terminus substituted amino acid,
- e) --C(O)--N(H)RA.sub.1-1,
- f) --NH.sub.2 (para or meta positions),
- g) --N(H)(C.sub.1-5 alkyl) (para or meta positions),
- h) --N(C.sub.1-5 alkyl).sub.2,
- i) --N(H)RA.sub.1-4,
- wherein RA.sub.1-4 is any C-terminus substituted amino acid,
- j) --N(H)C(O)--RA.sub.1-1 (para or meta positions),
- k) --N(H)C(O)--O--RA.sub.1-1 (para or meta positions),
- l) --N(H)(SO.sub.2)--RA.sub.1-2,
- m) --N(CH.sub.3)(SO.sub.2)--RA.sub.1-2,
- n) --NO.sub.2,
- o) --SO.sub.2 NH.sub.2,
- p) --(C.sub.1-3 alkyl)--SO.sub.2 --RA.sub.1-RA-12,
- q) --(C.sub.1-3 alkyl)--SO.sub.2 --RA.sub.1-RA-15,
- r) -halo,
- wherein RA.sub.1-1 is
- a) --(C.sub.1-5 alkyl),
- b) --(C.sub.1-5 alkyl)--C(O)--O--(C.sub.1-5 alkyl),
- c) --(C.sub.1-5 alkyl)--NH.sub.2,
- d) --(C.sub.1-5 alkyl)--N(H)C(O)--O--(C.sub.1-5 alkyl),
- e) --(C.sub.1-5 alkyl)--C((H)(NH.sub.2))--C(O)OH,
- f) --RA.sub.1-RA-12,
- g) --RA.sub.1-RA-15,
- h) --(C.sub.1-5 alkyl)-RAX,
- i) --(C.sub.1-5 alkyl)--O-RAX,
- j) --C(O)--RA.sub.1-1-3,
- wherein RA.sub.1-1-3 is any N-terminus amino acid,
- k) --N(H)--RA.sub.1-1-4, or
- wherein RA.sub.1-1-4 is any C-terminus amino acid,
- l) --R.sub.1-500 ;
- wherein RA.sub.1-2 is
- a) -RAX,
- b) --(C.sub.1-5 alkyl)-RAX,
- c) --(C.sub.1-5 alkyl)--O-RAX,
- d) --RA.sub.1-RA-12,
- e) --RA.sub.1-RA-15,
- f) --(C.sub.1 -C.sub.5 alkyl)--RA.sub.1-RA-12,
- g) --(C.sub.1 -C.sub.5 alkyl)--RA.sub.1-RA-15,
- h) --(C.sub.1 -C.sub.5 alkyl)--O--RA.sub.1-RA-12, or
- i) --(C.sub.1 -C.sub.5 alkyl)--O--RA.sub.1-RA-15 ;
- wherein RA.sub.2 and RA.sub.3 are defined independently and are independent of and defined the same as RA.sub.1 ;
- wherein G.sub.1-1 is
- a) --NH--C(O)--,
- b) --NH--SO.sub.2 --,
- c) --NH--C(O)--NH--, or
- d) --SO.sub.2 --NH--;
- wherein G.sub.1-2 is
- a) --NH--C(O)--,
- b) --C(O)--NH--,
- c) --NH--SO.sub.2 --,
- d) --SO.sub.2 --NH--,
- e) --NH--SO.sub.2 --NH--,
- f) --C(O)--O--,
- g) --O--C(O)--,
- h) --N((C.sub.1-6 alkyl)--RA.sub.1-RA-12)--C(O)--,
- i) --NH--C(O)--NH,
- j) --N((C.sub.1-6 alkyl)--RA.sub.1-RA-12)--SO.sub.2 --, or
- k) --N((C.sub.0-6 alkyl)--(C.sub.1-6 alkyl))--SO.sub.2 --;
- wherein RA.sub.2 and RA.sub.3 are defined independently and are the same as RA.sub.1 ;
- wherein RA.sub.1-RA-12 is
- a) -phenyl, substituted with zero (0) to three (3) RA.sub.1-RA-12-AXA, or
- b) -naphthyl, substituted with zero (0) to three (3) RA.sub.1-RA-12-AXA ;
- wherein RA.sub.1-RA-15 is
- a 5- or 6-membered saturated or unsaturated ring containing from one (1) to four (4) heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur; and including any bicyclic group in which any of the above heterocyclic rings is fused to a benzene ring, C.sub.3 -C.sub.8 cycloalkyl, or another heterocycle; and substituted with zero (0) to three (3) RA.sub.1-RA-15-AXA ;
- wherein RA.sub.1-RA-120, RA.sub.2-RA-120 and RA.sub.3-RA-120, are defined independently and are
- a) --C.sub.1 -C.sub.4 alkyl,
- b) --C.sub.1 -C.sub.3 alkoxy,
- c) -dimethylamino,
- d) -diethylamino,
- e) --CF.sub.3,
- f) --CN,
- g) -halo,
- h) --NH.sub.2,
- i) --OH,
- j) --SO.sub.2 --NH.sub.2, or
- k) --C(O)--NH.sub.2 ;
- wherein RA.sub.1-RA-12-AXA or RA.sub.1-RA-15-AXA are independent and are,
- a) --H
- b) -halo,
- c) --NO.sub.2,
- d) --CN,
- e) --(C.sub.1-10 alkyl), substituted with zero (0) to three (3) halo,
- f) --(C.sub.0-6 alkyl)-phenyl, substituted with zero (0) to three (3) halo or hydroxy,
- g) --OH,
- h) --O--C.sub.1-5 alkyl,
- i) --(C.sub.0-6 alkyl)--O--(C.sub.1-6 alkyl), substituted with zero (0) to three (3) halo or hydroxy,
- j) --(C.sub.0-6 alkyl)--O--(C.sub.2-7 alkenyl), substituted with zero (0) to three (3) halo or hydroxy,
- k) --CH(O),
- l) --C(O)--(C.sub.1-6 alkyl),
- m) --C(O)OH,
- n) --C(O)O--(C.sub.1-5 alkyl),
- o) --C(O)--N(H or C.sub.1-6 alkyl).sub.2,
- p) --NH.sub.2,
- q) --NH--(C.sub.1-6 alkyl),
- r) -mono or di --(C.sub.1-6 alkyl)amino,
- s) --NH--OH,
- t) --NH--C(O)--(C.sub.1-3 alkyl),
- u) --(C.sub.0-6 alkyl)--NH--C(O)-phenyl,
- v) --(C.sub.0-6 alkyl)--NH--SO.sub.2 -phenyl,
- w) --(C.sub.0-6 alkyl)--N.dbd.N-phenyl, substituted with zero (0) or one (1) --N(C.sub.1 -C.sub.3 alkyl).sub.2, or
- x) --SO.sub.2 -phenyl, substituted with zero (0) to three (3) C.sub.1 -C.sub.5 alkyl;
- wherein R.sub.2 is
- a) --C.sub.3-4 alkyl,
- b) -n-propyl,
- c) --(C.sub.1-5 alkyl)--C.sub.3-5 cycloalkyl,
- d) --(C.sub.2-5 alkenyl)
- e) --(C.sub.1-5 alkyl)--R.sub.2-100,
- f) --(C.sub.1-5 alkyl)--R.sub.2-500,
- wherein R.sub.2-100 is independent of and defined the same as R.sub.1-100 wherein RA.sub.1 is RA.sub.2 ;
- wherein R.sub.2-500 is independent of and defined the same as R.sub.1-500 wherein RA.sub.1 is RA.sub.2 ;
- wherein RA.sub.2 is independent of and defined the same as RA.sub.1 ;
- wherein R.sub.3 is
- a) --(C.sub.1-5 alkyl),
- b) --(CH.sub.2 --CH.dbd.CH.sub.2),
- c) --(C.sub.1-5 alkyl)--(C.sub.3-5 cycloalkyl),
- d) --(C.sub.1-5 alkyl)--O--(CH.sub.2 CH.sub.2 O).sub.q --CH.sub.3,
- e) --(C.sub.1-6 alkyl)--R.sub.3-4,
- f) --(C.sub.2-6 alkenyl)--R.sub.3-4,
- g) --R.sub.3-100,
- h) --(C.sub.1-4 alkyl)--R.sub.3-100,
- i) --H or --(C.sub.1-5 alkyl),
- j) --CH.sub.2 -RAX
- k) -n propyl-RAX,
- l) --3-phenylpropyl,
- m) --R.sub.3-500,
- n) --CH.sub.2 -RAX
- o) -n propyl-R.sub.3-500,
- p) --C(H)(OH)--R.sub.3-1,
- q) --(C.sub.1-5 alkyl)--C(H)(OH)--R.sub.3-1,
- r) --C(O)--R.sub.3-1,
- s) --(C.sub.1-4 alkyl)--C(O)--R.sub.3-1,
- t) --(C.sub.1-4 alkyl)--N(H)R.sub.3-1,
- u) --(C.sub.1-4 alkyl)--N((C.sub.1-4 alkyl)((C.sub.1-4 alkyl)--R.sub.3-1),
- v) --(C.sub.1-4 alkyl)--N(H)C(O)--R.sub.3-1,
- w) --C(O)--N(H)R.sub.3-1, or
- x) --(C.sub.1-4 alkyl)--C(O)--N(H)R.sub.3-1 ;
- wherein R.sub.3-1 is
- a) --NH--C(O)--,
- b) --NH--SO.sub.2 --,
- c) --NH--CO--NH--, or
- d) --SO.sub.2 --NH--;
- wherein, R.sub.3-4 is
- a) --OH,
- b) --O--(C.sub.1-6 alkyl),
- c) --C(O)--OH,
- d) --C(O)--O--(C.sub.1-6 alkyl),
- e) --(C.sub.1-6 alkyl),
- f) --(C.sub.3-6 cycloalkyl),
- g) --R.sub.3-100, or
- h) --R.sub.3-500 ;
- wherein R.sub.3-6 is
- a) --OH,
- b) --C.sub.1-10 alkyl,
- c) --(C.sub.0-6 alkyl)--C.sub.3 -C.sub.7 cycloalkyl,
- d) --(C.sub.1-6 alkyl)--CH.dbd.CH.sub.2,
- e) --(C.sub.0-6 alkyl)--R.sub.3-4,
- f) --(C.sub.1-6 alkyl)--R.sub.3-100, or
- g) --(C.sub.1-6 alkyl)--R.sub.3-500 ;
- wherein R.sub.3-9 is
- a) --(C.sub.1-6 alkyl),
- b) --(C.sub.0-6 alkyl)--RA.sub.3-RA-12, or
- c) --(C.sub.0-6 alkyl)--RA.sub.3-RA-15 ;
- wherein R.sub.3-100 is independent of and defined the same as R.sub.1-100 ;
- wherein R.sub.3-500 is independent of and defined the same as R.sub.1-500 ;
- wherein RA.sub.3 is independent of and defined the same as RA.sub.1 ;
- wherein RA.sub.3-RA-12, RA.sub.3-RA-15, RA.sub.3-RA-12-AXA and RA.sub.3-RA-15-AXA, are all independent of and defined the same as the corresponding R.sub.1 variables, which are: RA.sub.1-RA-12, RA.sub.1-RA-15, RA.sub.1-RA-12-AXA and RA.sub.1-RA-15-AXA, respectively,
- wherein R.sub.2 and R.sub.3 can be taken together to form a ring comprised of the following groups,
- a) (C.sub.5-9 cycloalkyl),
- b) (C.sub.5-9 cycloalkyl) substituted with one to two --R.sub.3-9, or
- c) --(C.sub.1-5 alkyl substituted with zero to one R.sub.3-9)--R.sub.23 --(C.sub.1-5 alkyl);
- wherein R.sub.3-9 is
- a) --(C.sub.1-6 alkyl),
- b) --(C.sub.0-6 alkyl)--RA.sub.3-RA-12, or
- c) --(C.sub.0-6 alkyl)--RA.sub.3-RA-15 ;
- or
- wherein R.sub.2 and R.sub.3 can be taken together to form a double bond represented by formula 50, shown below, ##STR157## wherein R.sub.11 is a) --H,
- b) --C.sub.1 -C.sub.4 alkyl
- c) --(RA.sub.3-RA-12), or
- d) pharmaceutically acceptable salts,
- wherein R.sub.23 is
- a) --O--,
- b) --C(O)--,
- c) --N(H)--,
- d) --N(R.sub.3-9)--,
- e) --N(C(O)--R.sub.3-9)--, or
- f) --N(C(O)--O--R.sub.3-9);
- wherein R.sub.30 is
- a) -morpholino,
- b) -piperidino,
- c) -piperazino,
- d) --OR.sub.40,
- e) -halo,
- f) ##STR158## g) --NR.sub.40 R.sub.41 ; wherein R.sub.40 and R.sub.41 are defined independently and are,
- a) --H,
- b) --C.sub.1 -C.sub.4 alkyl,
- c) phenyl, substituted with zero (0) to three (3) RA.sub.1-RA-120,
- wherein R.sub.42 is
- a) --C.sub.1 -C.sub.4 alkyl,
- b) -phenyl, substituted with zero (0) to three (3) RA.sub.1-RA-120, or
- c) --(C.sub.0-6 alkyl)-phenyl, substituted with zero (0) to three (3) RA.sub.1-RA-120 ;
- wherein RA.sub.2-RA-120 and RA.sub.3-RA-120 are independent of and defined the same as RA.sub.1-RA-120 ;
- wherein R.sub.50 and R.sub.51 are defined independently and are
- a) --(H or C.sub.1-6 alkyl),
- b) --(C.sub.0-6 alkyl)--RA.sub.3-RA-12, or
- c) --(C.sub.0-6 alkyl)--RA.sub.3-RA-15 ;
- wherein AA is an amino acid residue,
- wherein P.sub.1 is hydrogen or a nitrogen protecting group,
- wherein m and n are independently zero (0) to five (5) inclusive,
- wherein p and q are independently one (1) to five (5) inclusive,
- wherein z is one (1) to three (3) inclusive; and
- pharmaceutically acceptable salts, including bis salts, thereof,
- with the proviso that when R.sub.1 is 1-phenylpropyl and R.sub.2 is H, then R.sub.3 is not C.sub.1-5 alkyl, and
- with the proviso that when RA.sub.1 or RA.sub.3 is --G.sub.1-2 --(C.sub.0-6 alkyl)--O--RA.sub.1-RA-12, --(C.sub.0-6 alkyl)--G.sub.1-2 --(C.sub.0-6 alkyl)--O--(C.sub.0-6 alkyl), --(C.sub.0-6 alkyl)--G.sub.1-2 --O--(C.sub.1-6 alkyl)--RA.sub.1-RA-12, --(C.sub.0-6 alkyl)--G.sub.1-2 --O--(C.sub.1-6 alkyl)--RA.sub.1-RA-15, --G.sub.1-2 --N(R.sub.42).sub.2, or --G.sub.1-2 --NH.sub.2, then G.sub.1-2 is NOT, --C(O)--NH--, --NH--SO.sub.2 --, --SO.sub.2 --NH--, --NH--SO.sub.2 --NH--, -C(O)--O--, --NH--C(O)--NH, --N((C.sub.1-6 alkyl)--R.sub.1-RA-12)--SO.sub.2 --, or --N((C.sub.0-6 alkyl)--(C.sub.1-6 alkyl))--SO.sub.2 --.
- 19. A compound represented by the structure shown in formula 1, ##STR159## wherein 3 tautomers of the same structure are shown, wherein R.sub.1 is ##STR160## wherein R.sub.1-1 is a) --(C.sub.1-5 alkyl),
- b) --(C.sub.2-5 alkenyl),
- c) --(C.sub.3-7 cycloalkyl),
- d) --(C.sub.3-5 cycloalkyl),
- e) -cyclopropyl,
- f) --(C.sub.1-5 alkyl)--(C.sub.3-7 cycloalkyl),
- g) --R.sub.1-100, or
- h) --(C.sub.1 -C.sub.5 alkyl)--R.sub.1-100 ;
- wherein R.sub.1-2 is --R.sub.1-100, or --R.sub.1-500 ;
- wherein R.sub.1-100 is
- a) phenyl, substituted with zero (0) to three (3) of RA.sub.1,
- wherein R.sub.1-500 is
- a 5- or 6-membered saturated or unsaturated ring containing from one (1) to four (4) heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur; and substituted with zero (0) to three (3) RA.sub.1 ; and including any bicyclic group in which any of the above heterocyclic rings is fused to a benzene ring, C.sub.3 -C.sub.8 cycloalkyl, or another heterocycle; and substituted with zero (0) to three (3) RA.sub.1 ; and if chemically feasible, the nitrogen and sulfur atoms may be in the oxidized forms;
- wherein RA.sub.1 is
- a) --H,
- b) --(C.sub.1-5 alkyl),
- c) --O--(C.sub.1-5 alkyl),
- d) --C(O)--RA.sub.1-3,
- wherein RA.sub.1-3 is any N-terminus substituted amino acid,
- e) --C(O)--N(H)RA.sub.1-1,
- f) --NH.sub.2 (para or meta positions),
- g) --N(H)(C.sub.1-5 alkyl) (para or meta positions),
- h) --N(C.sub.1-5 alkyl).sub.2,
- i) --N(H)RA.sub.1-4,
- wherein RA.sub.1-4 is any C-terminus substituted amino acid,
- j) --N(H)C(O)--RA.sub.1-1 (para or meta positions),
- k) --N(H)C(O)--O--RA.sub.1-1 (para or meta positions),
- l) --N(H)(SO.sub.2)--RA.sub.1-2,
- m) --N(CH.sub.3)(SO.sub.2)--RA.sub.1-2,
- n) --NO.sub.2,
- o) --SO.sub.2 NH.sub.2,
- p) --(C.sub.1-3 alkyl)--SO.sub.2 --RA.sub.1-RA-12,
- q) --(C.sub.1-3 alkyl)--SO.sub.2 --RA.sub.1-RA-15,
- r) -halo,
- wherein RA.sub.1-1 is
- a) --(C.sub.1-5 alkyl),
- b) --(C.sub.1-5 alkyl)--C(O)--O--(C.sub.1-5 alkyl),
- c) --(C.sub.1-5 alkyl)--NH.sub.2,
- d) --(C.sub.1-5 alkyl)--N(H)C(O)--O--(C.sub.1-5 alkyl),
- e) --(C.sub.1-5 alkyl)--C((H)(NH.sub.2))--C(O)OH,
- f) --RA.sub.1-RA-12,
- g) --RA.sub.1-RA-15,
- h) --(C.sub.1-5 alkyl)-RAX,
- i) --(C.sub.1-5 alkyl)--O-RAX,
- j) --C(O)--RA.sub.1-1-3,
- wherein RA.sub.1-1-3 is any N-terminus amino acid,
- k) --N(H)--RA.sub.1-1-4, or
- wherein RA.sub.1-2 is any C-terminus amino acid,
- l) --R.sub.1-500 ;
- wherein RA.sub.1-2 is
- a) -RAX,
- b) --(C.sub.1-5 alkyl)-RAX,
- c) --(C.sub.1-5 alkyl)--O-RAX,
- d) --RA.sub.1-RA-12,
- e) --RA.sub.1-RA-15,
- f) --(C.sub.1 -C.sub.5 alkyl)--RA.sub.1-RA-12,
- g) --(C.sub.1 -C.sub.5 alkyl)--RA.sub.1-RA-15,
- h) --(C.sub.1 -C.sub.5 alkyl)--O--RA.sub.1-RA-12, or
- i) --(C.sub.1 -C.sub.5 alkyl)--O--RA.sub.1-RA-15 ;
- wherein RA.sub.2 and RA.sub.3 are defined independently and are independent of and defined the same as RA.sub.1 ;
- wherein G.sub.1-1 is
- a) --NH--C(O)--,
- b) --NH--SO.sub.2 --,
- c) --NH--C(O)--NH--, or
- d) --SO.sub.2 --NH--;
- wherein G.sub.1-2 is
- a) --NH--C(O)--,
- b) --C(O)--NH--,
- c) --NH--SO.sub.2 --,
- d) --SO.sub.2 --NH--,
- e) --NH--SO.sub.2 --NH--,
- f) --C(O)--O--,
- g) --O--C(O)--,
- h) --N((C.sub.14 alkyl)--RA.sub.1-RA-12)--C(O)--,
- i) --NH--C(O)--NH,
- j) --N((C.sub.1-6 alkyl)--RA.sub.1-RA-12)--SO.sub.2 --, or
- k) --N((C.sub.0-6 alkyl)--(C.sub.1-6 alkyl))--SO.sub.2 --;
- wherein RA.sub.2 and RA.sub.3 are defined independently and are the same as RA.sub.1 ;
- wherein RA.sub.1-RA-12 is
- a) -phenyl, substituted with zero (0) to three (3) RA.sub.1-RA-12-AXA, or
- b) -naphthyl, substituted with zero (0) to three (3) RA.sub.1-RA-12-AXA ;
- wherein RA.sub.1-RA-15 is
- a 5- or 6-membered saturated or unsaturated ring containing from one (1) to four (4) heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur; and including any bicyclic group in which any of the above heterocyclic rings is fused to a benzene ring, C.sub.3 -C.sub.8 cycloalkyl, or another heterocycle; and substituted with zero (0) to three (3) RA.sub.1-RA-15-AXA ;
- wherein RA.sub.1-RA-120, RA.sub.2-RA-120 and RA.sub.3-RA-120, are defined independently and are
- a) --C.sub.1 -C.sub.4 alkyl,
- b) --C.sub.1 -C.sub.3 alkoxy,
- c) -dimethylamino,
- d) -diethylamino,
- e) --CF.sub.3,
- f) --CN,
- g) -halo,
- h) --NH.sub.2,
- i) --OH,
- j) --SO.sub.2 --NH.sub.2, or
- k) --C(O)--NH.sub.2 ;
- wherein RA.sub.1-RA-12-AXA or RA.sub.1-RA-15-AXA are independent and are,
- a) --H
- b) -halo,
- c) --NO.sub.2,
- d) --CN,
- e) --(C.sub.1-10 alkyl), substituted with zero (0) to three (3) halo,
- f) --(C.sub.0-6 alkyl)-phenyl, substituted with zero (0) to three (3) halo or hydroxy,
- g) --OH,
- h) --O--C.sub.1-5 alkyl,
- i) --(C.sub.0-6 alkyl)--O--(C.sub.1-6 alkyl), substituted with zero (0) to three (3) halo or hydroxy,
- j) --(C.sub.0-6 alkyl)--O--(C.sub.2-7 alkenyl), substituted with zero (0) to three (3) halo or hydroxy,
- k) --CH(O), 1) --C(O)--(C.sub.1-6 alkyl),
- m) --C(O)OH,
- n) --C(O)O--(C.sub.1-5 alkyl),
- o) --C(O)--N(H or C.sub.1-6 alkyl).sub.2,
- p) --NH.sub.2,
- q) --NH--(C.sub.1-6 alkyl),
- r) -mono or di --(C.sub.1-6 alkyl)amino,
- s) --NH--OH,
- t) --NH--C(O)--(C.sub.1-3 alkyl),
- u) --(C.sub.0-6 alkyl)--NH--C(O)-phenyl,
- v) --(C.sub.0-6 alkyl)--NH--SO.sub.2 -phenyl, w) --(C.sub.0-6 alkyl)--N.dbd.N-phenyl, substituted with zero (0) or one (1) --N(C.sub.1 -C.sub.3 alkyl).sub.2, or
- x) --SO.sub.2 -phenyl, substituted with zero (0) to three (3) C.sub.1 -C.sub.5 alkyl;
- wherein R.sub.2 is
- a) --C.sub.3-4 alkyl,
- b) -n-propyl,
- c) --C.sub.1-5 alkyl)--C.sub.3-5 cycloalkyl,
- d) --(C.sub.2-5 alkenyl)
- e) --(C.sub.1-5 alkyl)--R.sub.2-100,
- f) --(C.sub.1-5 alkyl)--R.sub.2-500,
- wherein R.sub.2-100 is independent of and defined the same as R.sub.1-100 wherein RA.sub.1 is RA.sub.2 ;
- wherein R.sub.2-500 is independent of and defined the same as R.sub.1-500 wherein RA.sub.1 is RA.sub.2 ;
- wherein RA.sub.2 is independent of and defined the same as RA.sub.1 ;
- wherein R.sub.3 is
- a) --(C.sub.1-5 alkyl),
- b) --(CH.sub.2 --CH.dbd.CH.sub.2),
- c) --(C.sub.1-5 alkyl)--(C.sub.3-5 cycloalkyl),
- d) --(C.sub.1-5 alkyl)--O--(CH.sub.2 CH.sub.2 O).sub.q --CH.sub.3,
- e) --(C.sub.1-6 alkyl)--R.sub.3-4,
- f) --(C2-6 alkenyl)--R.sub.3-4,
- g) --R.sub.3-100,
- h) --(C.sub.1-4 alkyl)--R.sub.3-100,
- i) --H or --(C.sub.1-5 alkyl),
- j) --CH.sub.2 -RAX
- k) -n propyl-RAX,
- l) --3-phenylpropyl,
- m) --R.sub.3-500,
- n) --CH.sub.2 -RAX
- o) -n propyl-R.sub.3-500,
- p) --C(H)(OH)--R.sub.3-1,
- q) --(C.sub.1-5 alkyl)--C(H)(OH)--R.sub.3-1,
- r) --C(O)--R.sub.3-1,
- s) --(C.sub.1-4 alkyl)--C(O)--R.sub.3-1,
- t) --(C.sub.1-4 alkyl)--N(H)R.sub.3-1,
- u) --(C.sub.1-4 alkyl)--N((C.sub.1-4 alkyl)((C.sub.1-4 alkyl)--R.sub.3-1),
- v) --(C.sub.1-4 alkyl)--N(H)C(O)--R.sub.3-1,
- w) --C(O)--N(H)R.sub.3-1, or
- x) --(C.sub.1-4 alkyl)--C(O)--N(H)R.sub.3-1 ;
- wherein R.sub.3-1 is
- a) --NH--C(O)--,
- b) --NH--SO.sub.2 --,
- c) --NH--CO--NH--, or
- d) --SO.sub.2 --NH--;
- wherein, R.sub.3-4 is
- a) --OH,
- b) --O--(C.sub.1-6 alkyl),
- c) --C(O)--OH,
- d) --C(O)--O--(C.sub.1-6 alkyl),
- e) --(C.sub.1-6 alkyl),
- f) --(C.sub.3-6 cycloalkyl),
- g) --R.sub.3-100, or
- h) --R.sub.3-500 ;
- wherein R.sub.3-6 is
- a) --OH,
- b) --C.sub.1-10 alkyl,
- c) --(C.sub.0-6 alkyl)--C.sub.3 -C.sub.7 cycloalkyl,
- d) --(C.sub.1-6 alkyl)--CH.dbd.CH.sub.2,
- e) --(C.sub.0-6 alkyl)--R.sub.3-4,
- f) --(C.sub.1-6 alkyl)--R.sub.3-100, or
- g) --(C.sub.1-6 alkyl)--R.sub.3-500 ;
- wherein R.sub.3-9 is
- a) --(C.sub.1-6 alkyl),
- b) --(C.sub.0-6 alkyl)--RA.sub.3-RA-12, or
- c) --(C.sub.0-6 alkyl)--RA.sub.3-RA-15 ;
- wherein R.sub.3-100 is independent of and defined the same as R.sub.1-100 ;
- wherein R.sub.3-500 is independent of and defined the same as R.sub.1-500 ;
- wherein RA.sub.3 is independent of and defined the same as RA.sub.1 ;
- wherein RA.sub.3-RA-12, RA.sub.3-RA-15, RA.sub.3-RA-12-AXA and RA.sub.3-RA-15-AXA, are all independent of and defined the same as the corresponding R.sub.1 variables, which are: RA.sub.1-RA-12, RA.sub.1-RA-15, RA.sub.1-RA-12-AXA and RA.sub.1-RA-15-AXA, respectively,
- wherein R.sub.2 and R.sub.3 can be taken together to form a ring comprised of the following groups,
- a) (C.sub.5-9 cycloalkyl),
- b) (C.sub.5-9 cycloalkyl) substituted with one to two --R.sub.3-9, or
- c) --C.sub.1-5 alkyl substituted with zero to one R.sub.3-9)--R.sub.23 --(C.sub.1-5 alkyl);
- wherein R.sub.3-9 is
- a) --(C.sub.1-6 alkyl),
- b) --(C.sub.0-6 alkyl)--RA.sub.3-RA-12, or
- c) --(C.sub.0-6 alkyl)--RA.sub.3-RA-15 ;
- or
- wherein R.sub.2 and R.sub.3 can be taken together to form a double bond represented by formula 50, shown below, ##STR161## wherein R.sub.11 is a) --H,
- b) --C.sub.1 -C.sub.4 alkyl,
- c) --(RA.sub.3-RA-12), or
- d) pharmaceutically acceptable salts,
- wherein R.sub.23 is
- a) --O--,
- b) --C(O)--,
- c) --N(H)--,
- d) --N(R.sub.3-9)--,
- e) --N(C(O)--R--.sub.3-9)--, or
- f) --N(C(O)--O--R.sub.3-9);
- wherein R.sub.30 is
- a) -morpholino,
- b) -piperidino,
- c) -piperazino,
- d) --OR.sub.40,
- e) -halo,
- f) ##STR162## g) --NR.sub.40 R.sub.41 ; wherein R.sub.40 and R.sub.41 are defined independently and are,
- a) --H,
- b) --C.sub.1 -C.sub.4 alkyl,
- c) phenyl, substituted with zero (0) to three (3) RA.sub.1-RA-120,
- wherein R.sub.42 is
- a) --C.sub.1 -C.sub.4 alkyl,
- b) -phenyl, substituted with zero (0) to three (3) RA.sub.1-RA-120, or
- c) --(C.sub.0-6 alkyl)-phenyl, substituted with zero (0) to three (3) RA.sub.1-RA-120 ;
- wherein RA.sub.2-RA-120 and RA.sub.3-RA-120 are independent of and defined the same as RA.sub.1-RA-120 ;
- wherein R.sub.50 and R.sub.51 are defined independently and are
- a) --(H or C.sub.1-6 alkyl),
- b) --(C.sub.0-6 alkyl)--RA.sub.3-RA-12, or
- c) --(C.sub.0-6 alkyl)--RA.sub.3-RA-15 ;
- wherein AA is an amino acid residue,
- wherein P.sub.1 is hydrogen or a nitrogen protecting group,
- wherein m and n are independently zero (0) to five (5) inclusive,
- wherein p and q are independently one (1) to five (5) inclusive,
- wherein z is one (1) to three (3) inclusive; and
- pharmaceutically acceptable salts, including bis salts, thereof,
- with the proviso that when R.sub.1 is 1-phenylpropyl and R.sub.2 is H, then R.sub.3 is not C.sub.1-5 alkyl, and
- with the proviso that when RA.sub.1 or RA.sub.3 is --G.sub.1-2 --(C.sub.0-6 alkyl)--O--RA.sub.1-RA-12, --(C.sub.0-6 alkyl)--G.sub.1-2 --(C.sub.0-6 alkyl)--O--(C.sub.0-6 alkyl), --(C.sub.0-6 alkyl)--G.sub.1-2 --O--(C.sub.1-6 alkyl)--RA.sub.1-RA-12, --(C.sub.0-6 alkyl)--G.sub.1-2 --O--(C.sub.1-6 alkyl)--RA.sub.1-RA-15, --G.sub.1-2 --N(R.sub.42).sub.2, or --G.sub.1-2 --NH.sub.2, then G.sub.1-2 is NOT, --C(O)--NH--, --NH--SO.sub.2 --, --SO.sub.2 --NH--, --NH--SO.sub.2 --NH--, -C(O)--O--, --NH--C(O)--NH, --N((C.sub.1-6 alkyl)--RA.sub.1-RA-12)--SO.sub.2 --, or --N((C.sub.0-6 alkyl)--(C.sub.1-6 alkyl))--SO.sub.2 --.
- 20. A compound represented by the structure shown in formula 1, ##STR163## wherein 3 tautomers of the same structure are shown, wherein R.sub.1 is --CH(R.sub.1-1)--R.sub.1-2 ;
- wherein R.sub.1-1 is
- a) --(C.sub.1-5 alkyl),
- b) --(C.sub.2-5 alkenyl),
- c) --(C.sub.3-7 cycloalkyl),
- d) --(C.sub.3-5 cycloalkyl),
- e) -cyclopropyl,
- f) --(C.sub.1-5 alkyl)--(C.sub.3-7 cycloalkyl),
- g) --R.sub.1-100, or
- h) --(C.sub.1-5 alkyl)--R.sub.1-100 ;
- wherein R.sub.1-2 is --R.sub.1-100, or --R.sub.1-500 ;
- wherein R.sub.1-100 is
- a) phenyl, substituted with zero (0) to three (3) of RA.sub.1,
- wherein R.sub.1-500 is
- a 5- or 6-membered saturated or unsaturated ring containing from one (1) to four (4) heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur; and substituted with zero (0) to three (3) RA.sub.1 ; and including any bicyclic group in which any of the above heterocyclic rings is fused to a benzene ring, C.sub.3 -C.sub.8 cycloalkyl, or another heterocycle; and substituted with zero (0) to three (3) RA.sub.1 ; and if chemically feasible, the nitrogen and sulfur atoms may be in the oxidized forms;
- wherein RA.sub.1 is
- a) --H,
- b) --(C.sub.1-5 alkyl),
- c) --O--(C.sub.1-5 alkyl),
- d) --C(O)--RA.sub.1-3,
- wherein RA.sub.1-3 is any N-terminus substituted amino acid,
- e) --C(O)--N(H)RA.sub.1-1,
- f) --NH.sub.2 (para or meta positions),
- g) --N(H)(C.sub.1-5 alkyl) (para or meta positions),
- h) --N(C.sub.1-5 alkyl).sub.2,
- i) --N(H)RA.sub.1-4,
- wherein RA.sub.1-4 is any C-terminus substituted amino acid,
- j) --N(H)C(O)--RA.sub.1-1 (para or meta positions),
- k) --N(H)C(O)--O--RA.sub.1-1 (para or meta positions),
- l) --N(H)(SO.sub.2)--RA.sub.1-2,
- m) --N(CH.sub.3)(SO.sub.2)--RA.sub.1-2,
- n) --NO.sub.2,
- o) --SO.sub.2 NH.sub.2,
- p) --(C.sub.1-3 alkyl)--SO.sub.2 --RA.sub.1-RA-12,
- q) --(C.sub.1-3 alkyl)--SO.sub.2 --RA.sub.1-RA-15,
- r) -halo,
- wherein RA.sub.1-1 is
- a) --(C.sub.1-5 alkyl),
- b) --(C.sub.1-5 alkyl)--C(O)--O--(C.sub.1-5 alkyl),
- c) --(C.sub.1-5 alkyl)--NH.sub.2,
- d) --(C.sub.1-5 alkyl)--N(H)C(O)--O--(C.sub.1-5 alkyl),
- e) --(C.sub.1-5 alkyl)--C((H)(NH.sub.2))--C(O)OH,
- f) --RA.sub.1-RA-12,
- g) --RA.sub.1-RA-15,
- h) --(C.sub.1-5 alkyl)-RAX,
- i) --(C.sub.1-5 alkyl)--O-RAX,
- j) --C(O)--RA.sub.1-1-3,
- wherein RA.sub.1-1-3 is any N-terminus amino acid,
- k) --N(H)--RA.sub.1-1-4, or
- wherein RA.sub.1-1-4 is any C-terminus amino acid,
- l) --R.sub.1-500 ;
- wherein RA.sub.1-2 is
- a) -RAX
- b) --(C.sub.1-5 alkyl)-RAX,
- c) --(C.sub.1-5 alkyl)--O-RAX,
- d) --RA.sub.1-RA-12,
- e) --RA.sub.1-RA-15,
- f) --(C.sub.1 -C.sub.5 alkyl)--RA.sub.1-RA-12,
- g) --(C.sub.1 -C.sub.5 alkyl)--RA.sub.1-RA-15,
- h) --(C.sub.1 -C.sub.5 alkyl)--O--RA.sub.1-RA-12, or
- i) --(C.sub.1 -C.sub.5 alkyl)--O--RA.sub.1-RA-15 ;
- wherein RA.sub.2 and RA.sub.3 are defined independently and are independent of and defined the same as RA.sub.1 ;
- wherein G.sub.1-1 is
- a) --NH--C(O)--,
- b) --NH--SO.sub.2 --,
- c) --NH--C(O)--NH--, or
- d) --SO.sub.2 --NH--;
- wherein G.sub.1-2 is
- a) --NH--C(O)--,
- b) --C(O)--NH--,
- c) --NH--SO.sub.2 --,
- d) --SO.sub.2 --NH--,
- e) --NH--SO.sub.2 --NH--,
- f) --C(O)--O--,
- g) --O--C(O)--,
- h) --N((C.sub.1-6 alkyl)--RA.sub.1-RA-12)--C(O)--,
- i) --NH--C(O)--NH,
- j) --N((C.sub.1-6 alkyl)--RA.sub.1-RA-12)--SO.sub.2 --, or
- k) --N((C.sub.0-6 alkyl)--(C.sub.1-6 alkyl))--SO.sub.2 --;
- wherein RA.sub.2 and RA.sub.3 are defined independently and are the same as RA.sub.1 ;
- wherein RA.sub.1-RA-12 is
- a) -phenyl, substituted with zero (0) to three (3) RA.sub.1-RA-12-AXA, or
- b) -naphthyl, substituted with zero (0) to three (3) RA.sub.1-RA-12-AXA ;
- wherein RA.sub.1-RA-15 is
- a 5- or 6-membered saturated or unsaturated ring containing from one (1) to four (4) heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur; and including any bicyclic group in which any of the above heterocyclic rings is fused to a benzene ring, C.sub.3 -C.sub.8 cycloalkyl, or another heterocycle; and substituted with zero (0) to three (3) RA.sub.1-RA-15-AXA ;
- wherein RA.sub.1-RA-120, RA.sub.2-RA-120 and RA.sub.3-RA-120, are defined independently and are
- a) --C.sub.1 -C.sub.4 alkyl,
- b) --C.sub.1 -C.sub.3 alkoxy,
- c) -dimethylamino,
- d) -diethylamino,
- e) --CF.sub.3,
- f) --CN,
- g) -halo,
- h) --NH.sub.2,
- i) --OH,
- j) --SO.sub.2 --NH.sub.2, or
- k) --C(O)--NH.sub.2 ;
- wherein RA.sub.1-RA-12-AXA or RA.sub.1-RA-15-AXA are independent and are,
- a) --H
- b) -halo,
- c) --NO.sub.2,
- d) --CN,
- e) --(C.sub.1-10 alkyl), substituted with zero (0) to three (3) halo,
- f) --(C.sub.0-6 alkyl)-phenyl, substituted with zero (0) to three (3) halo or hydroxy,
- g) --OH,
- h) --O--C.sub.1-5 alkyl,
- i) --(C.sub.0-6 alkyl)--O--(C.sub.1-6 alkyl), substituted with zero (0) to three (3) halo or hydroxy,
- j) --(C.sub.0-6 alkyl)--O--(C.sub.2-7 alkenyl), substituted with zero (0) to three (3) halo or hydroxy,
- k) --CH(O),
- l) --C(O)--(C.sub.1-6 alkyl),
- m) --C(O)OH,
- n) --C(O)O--(C.sub.1-5 alkyl),
- o) --C(O)--N(H or C.sub.1-6 alkyl).sub.2,
- p) --NH.sub.2,
- q) --NH--(C.sub.1-6 alkyl),
- r) -mono or di --(C.sub.1-6 alkyl)amino,
- s) --NH--OH,
- t) --NH--C(O)--(C.sub.1-3 alkyl),
- u) --(C.sub.0-6 alkyl)--NH--C(O)-phenyl,
- v) --(C.sub.0-6 alkyl)--NH--SO.sub.2 -phenyl,
- w) --(C.sub.0-6 alkyl)--N.dbd.N-phenyl, substituted with zero (0) or one (1) --N(C.sub.1 -C.sub.3 alkyl).sub.2, or
- x) --SO.sub.2 -phenyl, substituted with zero (0) to three (3) C.sub.1 -C.sub.5 alkyl;
- wherein R.sub.2 is
- a) --C.sub.3-4 alkyl,
- b) -n-propyl,
- c) --(C.sub.1-5 alkyl)--C.sub.3-5 cycloalkyl,
- d) --(C.sub.2-5 alkenyl)
- e) --C.sub.1-5 alkyl)--R.sub.2-100,
- f) --(C.sub.1-5 alkyl)--R.sub.2-500,
- wherein R.sub.2-100 is independent of and defined the same as R.sub.1-100 wherein RA.sub.1 is RA.sub.2 ;
- wherein R.sub.2-500 is independent of and defined the same as R.sub.1-500 wherein RA.sub.1 is RA.sub.2 ;
- wherein RA.sub.2 is independent of and defined the same as RA.sub.1 ;
- wherein R.sub.3 is
- a) --(C.sub.1-5 alkyl),
- b) --(CH.sub.2 --CH.dbd.CH.sub.2),
- c) --(C.sub.1-5 alkyl)--(C.sub.3-5 cycloalkyl),
- d) --(C.sub.1-5 alkyl)--O--(CH.sub.2 CH.sub.2 O).sub.q --CH.sub.3,
- e) --(C.sub.1-6 alkyl)--R.sub.3-4,
- f) --(C.sub.2-6 alkenyl)--R.sub.3-4,
- g) --R.sub.3-100)
- h) --(C.sub.1-4 alkyl)--R.sub.3-100,
- i) --H or --(C.sub.1-5 alkyl),
- j) --CH.sub.2 -RAX
- k) -n propyl-RAX,
- l) --3-phenylpropyl,
- m) --R.sub.3-500,
- n) --CH.sub.2 -RAX
- o) -n propyl-R.sub.3-500,
- p) --C(H)(OH)--R.sub.3-1,
- q) --(C.sub.1-5 alkyl)--C(H)(OH)--R.sub.3-1,
- r) --C(O)--R.sub.3-1,
- s) --(C.sub.1-4 alkyl)--C(O)--R.sub.3-1,
- t) --(C.sub.1-4 alkyl)--N(H)R.sub.3-1,
- u) --(C.sub.1-4 alkyl)--N((C.sub.1-4 alkyl)((C.sub.1-4 alkyl)--R.sub.3-1),
- v) --(C.sub.1-4 alkyl)--N(H)C(O)--R.sub.3-1,
- w) --C(O)--N(H)R.sub.3-1, or
- x) --(C.sub.1-4 alkyl)--C(O)--N(H)R.sub.3-1 ;
- wherein R.sub.3-1 is
- a) --NH--C(O)--,
- b) --NH--SO.sub.2 --,
- c) --NH--CO--NH--, or
- d) --SO.sub.2 --NH--;
- wherein, R.sub.3-4 is
- a) --OH,
- b) --O--(C.sub.1-6 alkyl),
- c) --C(O)--OH,
- d) --C(O)--O--(C.sub.1-6 alkyl),
- e) --(C.sub.1-6 alkyl),
- f) --(C.sub.3-6 cycloalkyl),
- g) --R.sub.3-100, or
- wherein R.sub.3-6 is
- a) --OH,
- b) --C.sub.1-10 alkyl,
- c) --(C.sub.0-6 alkyl)--C.sub.3 -C.sub.7 cycloalkyl,
- d) --(C.sub.1-6 alkyl)--CH.dbd.CH.sub.2,
- e) --(C.sub.0-6 alkyl)--R.sub.3-4,
- f) --(C.sub.1-6 alkyl)--R.sub.3-100, or
- g) --(C.sub.1-6 alkyl)--R.sub.3-500 ;
- wherein R.sub.3-9 is
- a) --(C.sub.1-6 alkyl),
- b) --(C.sub.0-6 alkyl)--RA.sub.3-RA-12, or
- c) --(C.sub.0-6 alkyl)--RA.sub.3-RA-15 ;
- wherein R.sub.3-100 is independent of and defined the same as R.sub.1-100 ;
- wherein R.sub.3-500 is independent of and defined the same as R.sub.1-500 ;
- wherein RA.sub.3 is independent of and defined the same as RA.sub.1 ;
- wherein RA.sub.3-RA-12, RA.sub.3-RA-15, RA.sub.3-RA-12-AXA and RA.sub.3-RA-15-AXA, are all independent of and defined the same as the corresponding R.sub.1 variables, which are: RA.sub.1-RA-12, RA.sub.1-RA-15, RA.sub.1-RA-12-AXA and RA.sub.1-RA-15-AXA, respectively,
- wherein R.sub.2 and R.sub.3 can be taken together to form a ring comprised of the following groups,
- a) (C.sub.5-9 cycloalkyl),
- b) (C.sub.5-9 cycloalkyl) substituted with one to two --R.sub.3-9, or
- c) --(C.sub.1-5 alkyl substituted with zero to one R.sub.3-9)--R.sub.23 --(C.sub.1-5 alkyl);
- wherein R.sub.3-9 is
- a) --(C.sub.1-6 alkyl),
- b) --(C.sub.0-6 alkyl)--RA.sub.3-RA-12, or
- c) --(C.sub.0-6 alkyl)-RA.sub.3-RA-15 ;
- or
- wherein R.sub.2 and R.sub.3 can be taken together to form a double bond represented by formula 50, shown below, ##STR164## wherein R.sub.11 is a) --H,
- b) --C.sub.1 -C.sub.4 alkyl,
- c) --(RA.sub.3-RA-12), or
- d) pharmaceutically acceptable salts,
- wherein R.sub.23 is
- a) --O--,
- b) --C(O)--,
- c) --N(H)--,
- d) --N(R.sub.3-9)--,
- e) --N(C(O)--R.sub.3-9)--, or
- f) --N(C(O)--O--R.sub.3-9);
- wherein R.sub.30 is
- a) -morpholino,
- b) -piperidino,
- c) -piperazino,
- d) --OR.sub.40,
- e) -halo,
- f) ##STR165## g) --NR.sub.40 R.sub.41 ; wherein R.sub.40 and R.sub.41 are defined independently and are,
- a) --H,
- b) --C.sub.1 -C.sub.4 alkyl,
- c) phenyl, substituted with zero (0) to three (3) RA.sub.1-RA-120,
- wherein R.sub.42 is
- a) --C.sub.1 -C.sub.4 alkyl,
- b) -phenyl, substituted with zero (0) to three (3) RA.sub.1-RA-120, or
- c) --(C.sub.0-6 alkyl)-phenyl, substituted with zero (0) to three (3) RA.sub.1-RA-120 ;
- wherein RA.sub.2-RA-120 and RA.sub.3-RA-120 are independent of and defined the same as RA.sub.1-RA-120 ;
- wherein R.sub.50 and R.sub.51 are defined independently and are
- a) --(H or C.sub.1-6 alkyl),
- b) --(C.sub.0-6 alkyl)--RA.sub.3-RA-12, or
- c) --(C.sub.0-6 alkyl)--RA.sub.3-RA-15 ;
- wherein AA is an amino acid residue,
- wherein P.sub.1 is hydrogen or a nitrogen protecting group,
- wherein m and n are independently zero (0) to five (5) inclusive,
- wherein p and q are independently one (1) to five (5) inclusive,
- wherein z is one (1) to three (3) inclusive; and
- pharmaceutically acceptable salts, including bis salts, thereof,
- with the proviso that when R.sub.1 is 1-phenylpropyl and R.sub.2 is H, then R.sub.3 is not C.sub.1-5 alkyl, and
- with the proviso that when RA.sub.1 or RA.sub.3 is --G.sub.1-2 --(C.sub.0-6 alkyl)--O--RA.sub.1-RA-12, --(C.sub.0-6 alkyl)--G.sub.1-2 --(C.sub.0-6 alkyl)--O--(C.sub.0-6 alkyl), --(C.sub.0-6 alkyl)--G.sub.1-2 --O--(C.sub.1-6 alkyl)--RA.sub.1-RA-12, --(C.sub.0-6 alkyl)--G.sub.1-2 --O--(C.sub.1-6 alkyl)--RA.sub.1-RA-15, --G.sub.1-2 --N(R.sub.42).sub.2, or --G.sub.1-2 --NH.sub.2, then G.sub.1-2 is NOT, --C(O)--NH--, --NH--SO.sub.2 --, --SO.sub.2 --NH--, --NH--SO.sub.2 --NH--, --C(O)--O--, --NH--C(O)--NH, --N((C.sub.1-6 alkyl)--RA.sub.1-RA-12)--SO.sub.2 --, or --N((C.sub.0-6 alkyl)--(C.sub.1-6 alkyl))--SO.sub.2 --.
- 21. A compound represented by the structure shown in formula 1, ##STR166## wherein 3 tautomers of the same structure are shown, wherein R.sub.1 is --CH(R.sub.1-1)--R.sub.1-2 ;
- wherein R.sub.1-1 is
- a) --(C.sub.1-5 alkyl),
- b) --(C.sub.3-5 cycloalkyl),
- c) -cyclopropyl,
- wherein R.sub.1-2 is --R.sub.1-100 or --R.sub.1-500 ;
- wherein R.sub.1-100 is
- a) phenyl, substituted with zero (0) to three (3) of RA.sub.1,
- wherein R.sub.1-500 is
- a 5- or 6-membered saturated or unsaturated ring containing from one (1) to four (4) heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur; and substituted with zero (0) to three (3) RA.sub.1 ; and including any bicyclic group in which any of the above heterocyclic rings is fused to a benzene ring, C.sub.3 -C.sub.8 cycloalkyl, or another heterocycle; and substituted with zero (0) to three (3) RA.sub.1 ; and if chemically feasible, the nitrogen and sulfur atoms may be in the oxidized forms;
- wherein RA.sub.1 is
- a) --H,
- b) --(C.sub.1-5 alkyl),
- c) --O--(C.sub.1-5 alkyl),
- wherein RA.sub.1-4 is any C-terminus substituted amino acid,
- j) --N(H)C(O)--RA.sub.1-1 (para or meta positions),
- k) --N(H)C(O)--O--RA.sub.1-1 (para or meta positions),
- l) --N(H)(SO.sub.2)--RA.sub.1-2,
- m) --N(CH.sub.3)(SO.sub.2)--RA.sub.1-2,
- n) --NO.sub.2,
- o) --SO.sub.2 NH.sub.2,
- p) --(C.sub.1-3 alkyl)--SO.sub.2 --RA.sub.1-RA-12,
- q) --(C.sub.1-3 alkyl)--SO.sub.2 --RA.sub.1-RA-15,
- r) -halo,
- wherein RA.sub.1-1 is
- a) --C.sub.1-5 alkyl),
- b) --(C.sub.1-5 alkyl)--C((H)(NH.sub.2))--C(O)OH,
- wherein RA.sub.1-2 is
- a) -RAX,
- b) --(C.sub.1-5 alkyl)-RAX,
- c) --(C.sub.1-5 alkyl)--O-RAX,
- d) --RA.sub.1-RA-12,
- e) --RA.sub.1-RA-15,
- f) --(C.sub.1 -C.sub.5 alkyl)--R.sub.1-RA-12,
- g) --(C.sub.1 -C.sub.5 alkyl)--RA.sub.1-RA-15,
- h) --(C.sub.1 -C.sub.5 alkyl)--O--RA.sub.1-RA-12, or
- i) --(C.sub.1 -C.sub.5 alkyl)--O--RA.sub.1-RA-15 ;
- wherein RA.sub.2 and RA.sub.3 are defined independently and are independent of and defined the same as RA.sub.1 ;
- wherein G.sub.1-1 is
- a) --NH--C(O)--,
- b) --NH--SO.sub.2 --,
- c) --NH--C(O)--NH--, or
- d) --SO.sub.2 --NH--;
- wherein G.sub.1-2 is
- a) --NH--C(O)--,
- b) --C(O)--NH--,
- c) --NH--SO.sub.2 --,
- d) --SO.sub.2 --NH--,
- e) --NH--SO.sub.2 --NH--,
- f) --C(O)--O--,
- g) --O--C(O)--,
- h) --N((C.sub.1-6 alkyl)--RA.sub.1-RA-12)--C(O)--,
- i) --NH--C(O)--NH,
- j) --N((C.sub.1-6 alkyl)--R.sub.1-RA-12)--SO.sub.2 --, or
- k) --N((C.sub.0-6 alkyl)--(C.sub.1-6 alkyl))--SO.sub.2 --;
- wherein RA.sub.2 and RA.sub.3 are defined independently and are the same as RA.sub.1 ;
- wherein RA.sub.1-RA-12 is
- a) -phenyl, substituted with zero (0) to three (3) RA.sub.1-RA-12 -AXA, or
- b) -naphthyl, substituted with zero (0) to three (3) RA.sub.1-RA-12-AXA ;
- wherein RA.sub.1-RA-15 is
- a 5- or 6-membered saturated or unsaturated ring containing from one (1) to four (4) heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur; and including any bicyclic group in which any of the above heterocyclic rings is fused to a benzene ring, C.sub.3 -C.sub.8 cycloalkyl, or another heterocycle; and substituted with zero (0) to three (3) RA.sub.1-RA-15-AXA ;
- wherein RA.sub.1-RA-120, RA.sub.2-RA-120 and RA.sub.3-RA-120, are defined independently and are
- a) --C.sub.1 -C.sub.4 alkyl,
- b) --C.sub.1 -C.sub.3 alkoxy,
- c) -dimethylamino,
- d) -diethylamino,
- e) --CF.sub.3,
- f) --CN,
- g) -halo,
- h) --NH.sub.2,
- i) --OH,
- j) --SO.sub.2 --NH.sub.2, or
- k) --C(O)--NH.sub.2 ;
- wherein RA.sub.1-RA-12-AXA or RA.sub.1-RA-15-AXA are independent and are,
- a) --H
- b) -halo,
- c) --NO.sub.2,
- d) --CN,
- e) --(C.sub.1-10 alkyl), substituted with zero (0) to three (3) halo,
- f) --(C.sub.0-6 alkyl)-phenyl, substituted with zero (0) to three (3) halo or hydroxy,
- g) --OH,
- h) --O--C.sub.1-5 alkyl,
- i) --(C.sub.0-6 alkyl)--O--(C.sub.1-6 alkyl), substituted with zero (0) to three (3) halo or hydroxy,
- j) --(C.sub.0-6 alkyl)--O--(C.sub.2-7 alkenyl), substituted with zero (0) to three (3) halo or hydroxy,
- k) --CH(O),
- l) --C(O)--(C.sub.1-6 alkyl),
- m) --C(O)OH,
- n) --C(O)O--(C.sub.1-5 alkyl),
- o) --C(O)--N(H or C.sub.1-6 alkyl).sub.2,
- p) --NH.sub.2,
- q) --NH--(C.sub.1-6 alkyl),
- r) -mono or di-(C.sub.1-6 alkyl)amino,
- s) --NH--OH,
- t) --NH--C(O)--(C.sub.1-3 alkyl),
- u) --(C.sub.0-6 alkyl)--NH--C(O)-phenyl,
- v) --(C.sub.0-6 alkyl)--NH--SO.sub.2 -phenyl,
- w) --(C.sub.0-6 alkyl)--N.dbd.N-phenyl, substituted with zero (0) or one (1) --N(C.sub.1 -C.sub.3 alkyl).sub.2, or
- x) --SO.sub.2 -phenyl, substituted with zero (0) to three (3) C.sub.1 -C.sub.5 alkyl;
- wherein R.sub.2 is
- a) --C.sub.3-4 alkyl,
- b) -n-propyl,
- c) --(C.sub.1-5 alkyl)--C.sub.3-5 cycloalkyl,
- d) --(C.sub.2-5 alkenyl)
- e) --(C.sub.1-5 alkyl)--R.sub.2-100,
- f) --(C.sub.1-5 alkyl)--R.sub.2-500,
- wherein R.sub.2-100 is independent of and defined the same as R.sub.1-100 wherein RA.sub.1 is RA.sub.2 ;
- wherein R.sub.2-500 is independent of and defined the same as R.sub.1-500 wherein RA.sub.1 is RA.sub.2 ;
- wherein RA.sub.2 is independent of and defined the same as RA.sub.1 ;
- wherein R.sub.3 is
- a) --(C.sub.1-5 alkyl),
- b) --(CH.sub.2 --CH.dbd.CH.sub.2),
- c) --(C.sub.1-5 alkyl)--(C.sub.3-5 cycloalkyl),
- d) --(C.sub.1-5 alkyl)--O--(CH.sub.2 CH.sub.2 O).sub.q --CH.sub.3,
- e) --(C.sub.1-6 alkyl)--R.sub.3-4,
- f) --(C.sub.2-6 alkenyl)--R.sub.3-4,
- g) --R.sub.3-100,
- h) --(C.sub.1-4 alkyl)--R.sub.3-100,
- i) --H or --(C.sub.1-5 alkyl),
- j) --CH.sub.2 -RAX
- k) -n propyl-RAX,
- l) --3-phenylpropyl,
- m) --R.sub.3-500,
- n) --CH.sub.2 -RAX
- o) -n propyl-R.sub.3-500,
- p) -benzyl,
- wherein R.sub.3-1 is
- a) --NH--C(O)--,
- b) --NH--SO.sub.2 --,
- c) --NH--CO--NH--, or
- d) --SO.sub.2 --NH--;
- wherein, R.sub.3-4 is
- a) --OH,
- b) --O--(C.sub.1-6 alkyl),
- c) --C(O)--OH,
- d) --C(O)--O--(C.sub.1-6 alkyl),
- e) --(C.sub.1-6 alkyl),
- f) --(C.sub.3-6 cycloalkyl),
- g) --R.sub.3-100, or
- h) --R.sub.3-500 ;
- wherein R.sub.3-6 is
- a) --OH,
- b) --C.sub.1-10 alkyl,
- c) --(C.sub.0-6 alkyl)--C.sub.3 -C.sub.7 cycloalkyl,
- d) --(C.sub.1-6 alkyl)--CH.dbd.CH.sub.2,
- e) --(C.sub.0-6 alkyl)--R.sub.3-4,
- f) --(C.sub.1-6 alkyl)--R.sub.3-100, or
- g) --(C.sub.1-6 alkyl)--R.sub.3-500 ;
- wherein R.sub.3-9 is
- a) --(C.sub.1-6 alkyl),
- b) --(C.sub.0-6 alkyl)--RA.sub.3-RA-12, or
- c) --(C.sub.0-6 alkyl)--RA.sub.3-RA-15 ;
- wherein R.sub.3-100 is independent of and defined the same as R.sub.1-100 ;
- wherein R.sub.3-500 is independent of and defined the same as R.sub.1-500 ;
- wherein RA.sub.3 is independent of and defined the same as RA.sub.1 ;
- wherein RA.sub.3-RA-12, RA.sub.3-RA-15, RA.sub.3-RA-12-AXA and RA.sub.3-RA-15-AXA, are all independent of and defined the same as the corresponding R.sub.1 variables, which are: RA.sub.1-RA-12, RA.sub.1-RA-15, RA.sub.1-RA-12-AXA and RA.sub.1-RA-15-AXA, respectively,
- wherein R.sub.2 and R.sub.3 can be taken together to form a ring comprised of the following groups,
- a) (C.sub.5-9 cycloalkyl),
- b) (C.sub.5-9 cycloalkyl) substituted with one to two --R.sub.3-9, or
- c) --(C.sub.1-5 alkyl substituted with zero to one R.sub.3-9)--R.sub.23 --(C.sub.1-5 alkyl);
- wherein R.sub.3-9 is
- a) --(C.sub.1-6 alkyl),
- b) --(C.sub.0-4 alkyl)--RA.sub.3-RA-12, or
- c) --(C.sub.0-6 alkyl)--RA.sub.3-RA-15 ;
- or
- wherein R.sub.2 and R.sub.3 can be taken together to form a double bond represented by formula 50, shown below, ##STR167## wherein R.sub.11 is a) --H,
- b) --C.sub.1 -C.sub.4 alkyl,
- c) --(RA.sub.3-RA-12), or
- d) pharmaceutically acceptable salts,
- wherein R.sub.23 is
- a) --O--,
- b) --C(O)--,
- c) --N(H)--,
- d) --N(R.sub.3-9)--,
- e) --N(C(O)--R.sub.3-9)--, or
- f) --N(C(O)--O--R.sub.3-9);
- wherein R.sub.30 is
- a) -morpholino,
- b) -piperidino,
- c) -piperazino,
- d) --OR.sub.40,
- e) -halo,
- f) ##STR168## g) --NR.sub.40 R.sub.41 ; wherein R.sub.40 and R.sub.41 are defined independently and are,
- a) --H,
- b) --C.sub.1 -C.sub.4 alkyl,
- c) phenyl, substituted with zero (0) to three (3) RA.sub.1-RA-120,
- wherein R.sub.42 is
- a) --C.sub.1 -C.sub.4 alkyl,
- b) -phenyl, substituted with zero (0) to three (3) RA.sub.1-RA-120, or
- c) --(C.sub.0-6 alkyl)-phenyl, substituted with zero (0) to three (3) RA.sub.1-RA-120 ;
- wherein R.sub.2-RA-120 and RA.sub.3-RA-120 are independent of and defined the same as RA.sub.1-RA-120 ;
- wherein R.sub.50 and R.sub.51 are defined independently and are
- a) --(H or C.sub.1-6 alkyl),
- b) --(C.sub.0-6 alkyl)--RA.sub.3-RA-12, or
- c) --(C.sub.0-6 alkyl)--RA.sub.3-RA-15 ;
- wherein AA is an amino acid residue,
- wherein P.sub.1 is hydrogen or a nitrogen protecting group,
- wherein m and n are independently zero (0) to five (5) inclusive,
- wherein p and q are independently one (1) to five (5) inclusive,
- wherein z is one (1) to three (3) inclusive; and
- pharmaceutically acceptable salts, including bis salts, thereof,
- with the proviso that when R.sub.1 is 1-phenylpropyl and R.sub.2 is H, then R.sub.3 is not C.sub.1-5 alkyl, and
- with the proviso that when RA.sub.1 or RA.sub.3 is --G.sub.1-2 --(C.sub.0-6 alkyl)--O--R.sub.1-RA-12, --(C.sub.0-6 alkyl)--G.sub.1-2 --(C.sub.0-6 alkyl)--O--(C.sub.0-6 alkyl), --(C.sub.0-6 alkyl)-G.sub.1-2 --O--(C.sub.1-6 alkyl)--RA.sub.1-RA-12, --(C.sub.0-6 alkyl)--G.sub.1-2 --O--(C.sub.1-6 alkyl)--RA.sub.1-RA-15, --G.sub.1-2 --N(R.sub.42).sub.2, or --G.sub.1-2 --NH.sub.2, then G.sub.1-2 is NOT, --C(O)--NH--, --NH--SO.sub.2 --, --SO.sub.2 --NH--, --NH--SO.sub.2 --NH--, --C(O)--O--, --NH--C(O)--NH, --N((C.sub.1-6 alkyl)--RA.sub.1-RA-12)--SO.sub.2 --, or --N((C.sub.0-6 alkyl)--(C.sub.1-6 alkyl))--SO.sub.2 --.
- 22. A compound represented by the structure shown in formula 1, ##STR169## Formula 1 wherein 3 tautomers of the same structure are shown,
- wherein R.sub.1 is --CH(R.sub.1-1)--R.sub.1-2 ;
- wherein R.sub.1-1 is
- a) --(C.sub.1-5 alkyl),
- b) --(C.sub.3-5 cycloalkyl),
- c) -cyclopropyl,
- wherein R.sub.1-2 is --R.sub.1-100, or --R.sub.1-500 ;
- wherein R.sub.1-100 is
- a) phenyl, substituted with zero (0) to three (3) of RA.sub.1,
- wherein R.sub.1-500 is
- a 5- or 6-membered saturated or unsaturated ring containing from one (1) to four (4) heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur; and substituted with zero (0) to three (3) RA.sub.1 ; and including any bicyclic group in which any of the above heterocyclic rings is fused to a benzene ring, C.sub.3 -C.sub.8 cycloalkyl, or another heterocycle; and substituted with zero (0) to three (3) RA.sub.1 ; and if chemically feasible, the nitrogen and sulfur atoms may be in the oxidized forms;
- wherein RA.sub.1 is
- a) --H,
- b) --(C.sub.1-5 alkyl),
- c) --O--(C.sub.1-5 alkyl),
- wherein RA.sub.1-4 is any C-terminus substituted amino acid,
- j) --N(H)C(O)--RA.sub.1-1 (para or meta positions),
- k) --N(H)C(O)--O--RA.sub.1-1 (para or meta positions),
- l) --N(H)(SO.sub.2)--RA.sub.1-2,
- m) --N(CH.sub.3)(SO.sub.2)--RA.sub.1-2,
- n) --NO.sub.2,
- o) --SO.sub.2 NH.sub.2,
- p) --(C.sub.1-3 alkyl)--SO.sub.2 --RA.sub.1-RA-12,
- q) --(C.sub.1-3 alkyl)--SO.sub.2 --RA.sub.1-RA-15,
- r) -halo,
- wherein RA.sub.1-1 is
- a) --(C.sub.1-5 alkyl),
- b) --(C.sub.1-5 alkyl)--C((H)(NH.sub.2))--C(O)OH,
- wherein RA.sub.1-2 is
- a) -RAX,
- b) --(C.sub.1-5 alkyl)-RAX,
- c) --(C.sub.1-5 alkyl)--O-RAX,
- d) --RA.sub.1-RA-12)
- e) --RA.sub.1-RA-15)
- f) --(C.sub.1 -C.sub.5 alkyl)--RA.sub.1-RA-12,
- g) --(C.sub.1 -C.sub.5 alkyl)--RA.sub.1-RA-15,
- h) --(C.sub.1 -C.sub.5 alkyl)--O--RA.sub.1-RA-12, or
- i) --(C.sub.1 -C.sub.5 alkyl)--O--RA.sub.1-RA-15 ;
- wherein RA.sub.2 and RA.sub.3 are defined independently and are independent of and defined the same as RA.sub.1 ;
- wherein G.sub.1-1 is
- a) --NH--C(O)--,
- b) --NH--SO.sub.2 --,
- c) --NH--C(O)--NH--, or
- d) --SO.sub.2 --NH--;
- wherein G.sub.1-2 is
- a) --NH--C(O)--,
- b) --C(O)--NH--,
- c) --NH--SO.sub.2 --,
- d) --SO.sub.2 --NH--,
- e) --NH--SO.sub.2 --NH--,
- f) --C(O)--O--,
- g) --O--C(O)--,
- h) --N((C.sub.1-6 alkyl)--RA.sub.1-RA-12)--C(O)--,
- i) --NH--C(O)--NH,
- j) --N((C.sub.1-6 alkyl)--RA.sub.1-RA-12)--SO.sub.2 --, or
- k) --N((C.sub.0-6 alkyl)--(C.sub.1-6 alkyl))--SO.sub.2 --;
- wherein RA.sub.2 and RA.sub.3 are defined independently and are the same as RA.sub.1 ;
- wherein --RA.sub.1-RA-12, --RA.sub.2-RA-12, and --RA.sub.3-RA-12 are defined independently as phenyl, cyanophenyl, fluorophenyl, naphthyl; or phenyl or naphthyl--substituted with 1 to 3 groups of --(C.sub.1-6 alkyl), cyano, halo, hydroxy or --(C.sub.1-6 alkoxy);
- wherein --RA.sub.1-RA-15, --RA.sub.2-RA-15, and --RA.sub.3-RA-15 are defined independently as pyridinyl, cyano-pyridinyl, quinolinyl, pyrimidinyl, quinazolinyl, benzimidazolyl, imidazolyl, methyl-imidazolyl, thiazolyl or purinyl; or pyridinyl, quinolinyl, pyrimidinyl, quinazolinyl, benzimidazolyl, imidazolyl, thiazolyl, or purinyl--substituted with 1 to 3 groups of --(C.sub.1-6 alkyl), cyano, halo, hydroxy or --(C.sub.1-6 alkoxy);
- wherein R.sub.2 and R.sub.3 can be taken together to form a ring comprised of the following groups,
- a) (C.sub.6 cycloalkyl),
- b) (C.sub.6 cycloalkyl)--R.sub.3-9, or
- c) --(C.sub.2 alkyl substituted with zero to one R.sub.3-9)--R.sub.23 --(C.sub.2 alkyl substituted with zero to one R.sub.3-9)--.
- wherein RA.sub.1-RA-120, R.sub.2-RA-120 and RA.sub.3-RA-120, are defined independently and are
- a) --C.sub.1 -C.sub.4 alkyl,
- b) --C.sub.1 -C.sub.3 alkoxy,
- c) -dimethylamino,
- d) -diethylamino,
- e) --CF.sub.3,
- f) --CN,
- g) -halo,
- h) --NH.sub.2,
- i) --OH,
- j) --SO.sub.2 --NH.sub.2, or
- k) --C(O)--NH.sub.2 ;
- wherein RA.sub.1-RA-12-AXA or RA.sub.1-RA-15-AXA are independent and are,
- a) --H
- b) -halo,
- c) --NO.sub.2,
- d) --CN,
- e) --(C.sub.1-10 alkyl), substituted with zero (0) to three (3) halo,
- f) --(C.sub.0-6 alkyl)-phenyl, substituted with zero (0) to three (3) halo or hydroxy,
- g) --OH,
- h) --O--C.sub.1-5 alkyl,
- i) --(C.sub.0-6 alkyl)--O--(C.sub.1-6 alkyl), substituted with zero (0) to three (3) halo or hydroxy,
- j) --(C.sub.0-6 alkyl)--O--(C.sub.2-7 alkenyl), substituted with zero (0) to three (3) halo or hydroxy,
- k) --CH(O),
- l) --C(O)--(C.sub.1-6 alkyl),
- m) --C(O)OH,
- n) --C(O)O--(C.sub.1-5 alkyl),
- o) --C(O)--N(H or C.sub.1-6 alkyl).sub.2,
- p) --NH.sub.2,
- q) --NH--(C.sub.1-6 alkyl),
- r) -mono or di-(C.sub.1-6 alkyl)amino,
- s) --NH--OH,
- t) --NH--C(O)--(C.sub.1-3 alkyl),
- u) --(C.sub.0-6 alkyl)--NH--C(O)-phenyl,
- v) --(C.sub.0-6 alkyl)--NH--SO.sub.2 -phenyl,
- w) --(C.sub.0-6 alkyl)--N.dbd.N-phenyl, substituted with zero (0) or one (1) --N(C.sub.1 -C.sub.3 alkyl).sub.2, or
- x) --SO.sub.2 -phenyl, substituted with zero (0) to three (3) C.sub.1 -C.sub.5 alkyl;
- wherein R.sub.2 is
- a) --C.sub.3-4 alkyl,
- b) -n-propyl,
- c) --(C.sub.1-5 alkyl)--C.sub.3-5 cycloalkyl,
- d) --(C.sub.2-5 alkenyl)
- e) --(C.sub.1-5 alkyl)--R.sub.2-100,
- f) --(C.sub.1-5 alkyl)--R.sub.2-500,
- wherein R.sub.2-100 is independent of and defined the same as R.sub.1-100 wherein RA.sub.1 is RA.sub.2 ;
- wherein R.sub.2-500 is independent of and defined the same as R.sub.1-500 wherein RA.sub.1 is RA.sub.2 ;
- wherein RA.sub.2 is independent of and defined the same as RA.sub.1 ;
- wherein R.sub.3 is
- a) --(C.sub.1-5 alkyl),
- b) --(CH.sub.2 --CH.dbd.CH.sub.2),
- c) --(C.sub.1-5 alkyl)--(C.sub.3-5 cycloalkyl),
- d) --(C.sub.1-5 alkyl)--O--(CH.sub.2 CH.sub.2 O).sub.q --CH.sub.3,
- e) --(C.sub.1-6 alkyl)--R.sub.3-4,
- f) --(C.sub.2-6 alkenyl)--R.sub.3-4,
- g) --R.sub.3-100,
- h) --(C.sub.1-4 alkyl)--R.sub.3-100,
- i) --H or --(C.sub.1-5 alkyl),
- j) --CH.sub.2 -RAX
- k) -n propyl-RAX,
- l) --3-phenylpropyl,
- m) --R.sub.3-500,
- n) --CH.sub.2 -RAX
- o) -n propyl-R.sub.3-500,
- p) -benzyl,
- wherein R.sub.3-1 is
- a) --NH--C(O)--,
- b) --NH--SO.sub.2 --,
- c) --NH--CO--NH--, or
- d) --SO.sub.2 --NH--;
- wherein, R.sub.3-4 is
- a) --OH,
- b) --O--(C.sub.1-6 alkyl),
- c) --C(O)--OH,
- d) --C(O)--O--(C.sub.1-6 alkyl),
- e) --(C.sub.1-6 alkyl),
- f) --(C.sub.3-6 cycloalkyl),
- g) --R.sub.3-100, or
- h) --R.sub.3-500 ;
- wherein R.sub.3-6 is
- a) --OH,
- b) --C.sub.1-10 alkyl,
- c) --(C.sub.0-6 alkyl)--C.sub.3 -C.sub.7 cycloakyl
- d) --(C.sub.1-6 alkyl)--CH.dbd.CH.sub.2,
- e) --(C.sub.0-6 alkyl)--R.sub.3-4,
- f) --(C.sub.1-6 alkyl)--R.sub.3-100, or
- g) --(C.sub.1-6 alkyl)--R.sub.3-500 ;
- wherein R.sub.3-9 is
- a) --(C.sub.1-6 alkyl),
- b) --(C.sub.0-6 alkyl)--RA.sub.3-RA-12, or
- c) --(C.sub.0-6 alkyl)--RA.sub.3-RA-15 ;
- wherein R.sub.3-100 is independent of and defined the same as R.sub.1-100 ;
- wherein R.sub.3-500 is independent of and defined the same as R.sub.1-500 ;
- wherein RA.sub.3 is independent of and defined the same as RA.sub.1 ;
- wherein RA.sub.3-RA-12, RA.sub.3-RA-15, RA.sub.3-RA-12-AXA and RA.sub.3-RA-15-AXA, are all independent of and defined the same as the corresponding R.sub.1 variables, which are: RA.sub.1-RA-12, RA.sub.1-RA-15, RA.sub.1-RA-12-AXA and RA.sub.1-RA-15-AXA, respectively,
- wherein R.sub.2 and R.sub.3 can be taken together to form a ring comprised of the following groups,
- a) (C.sub.5-9 cycloalkyl),
- b) (C.sub.5-9 cycloalkyl) substituted with one to two --R.sub.3-9, or
- c) --(C.sub.1-5 alkyl substituted with zero to one R.sub.3-9)--R.sub.23 --(C.sub.1-5 alkyl);
- wherein R.sub.3-9 is
- a) --(C.sub.1-6 alkyl),
- b) --(C.sub.0-6 alkyl)--RA.sub.3-RA-12, or
- c) --(C.sub.0-6 alkyl)--RA.sub.3-RA-15 ;
- or
- wherein R.sub.2 and R.sub.3 can be taken together to form a double bond represented by formula 50, shown below, ##STR170## wherein R.sub.11 is a) --H,
- b) --C.sub.1 -C.sub.4 alkyl,
- c) --(RA.sub.3-RA-12), or
- d) pharmaceutically acceptable salts,
- wherein R.sub.23 is
- a) --O--,
- b) --C(O)--,
- c) --N(H)--,
- d) --N(R.sub.3-9)--,
- e) --N(C(O)--R.sub.3-9)--, or
- f) --N(C(O)--O--R.sub.3-9);
- wherein R.sub.30 is
- a) -morpholino,
- b) -piperidino,
- c) -piperazino,
- d) -OR.sub.40,
- e) -halo,
- f) ##STR171## g) --NR.sub.40 R.sub.41 ; wherein R.sub.40 and R.sub.41 are defined independently and are,
- a) --H,
- b) --C.sub.1 -C.sub.4 alkyl,
- c) phenyl, substituted with zero (0) to three (3) RA.sub.1-RA-120,
- wherein R.sub.42 is
- a) --C.sub.1 -C.sub.4 alkyl,
- b) -phenyl, substituted with zero (0) to three (3) RA.sub.1-RA-120, or
- c) --(C.sub.0-6 alkyl)-phenyl, substituted with zero (0) to three (3) RA.sub.1-RA-120 ;
- wherein RA.sub.2-RA-120 and RA.sub.3-RA-120 are independent of and defined the same as RA.sub.1-RA-120 ;
- wherein R.sub.50 and R.sub.51 are defined independently and are
- a) --(H or C.sub.1-6 alkyl),
- b) --(C.sub.0-6 alkyl)--RA.sub.3-RA-12, or
- c) --(C.sub.0-6 alkyl)--RA.sub.3-RA-15 ;
- wherein AA is an amino acid residue,
- wherein P.sub.1 is hydrogen or a nitrogen protecting group,
- wherein m and n are independently zero (0) to five (5) inclusive,
- wherein p and q are independently one (1) to five (5) inclusive,
- wherein z is one (1) to three (3) inclusive; and
- pharmaceutically acceptable salts, including bis salts, thereof,
- with the proviso that when R.sub.1 is 1-phenylpropyl and R.sub.2 is H, then R.sub.3 is not C.sub.1-5 alkyl, and
- with the proviso that when RA.sub.1 or RA.sub.3 is --G.sub.1-2 --(C.sub.0-6 alkyl)--O--RA.sub.1-RA-12, --(C.sub.0-6 alkyl)--G.sub.1-2 --(C.sub.0-6 alkyl)--O--(C.sub.0-6 alkyl), --(C.sub.0-6 alkyl)--G.sub.1-2 --O--(C.sub.1-6 alkyl)--RA.sub.1-RA-12, --(C.sub.0-6 alkyl)--G.sub.1-2 --O--(C.sub.1-6 alkyl)--RA.sub.1-RA-15, --G.sub.1-2 --N(R.sub.42).sub.2, or --G.sub.1-2 --NH.sub.2, then G.sub.1-2 is NOT, --C(O)--NH--, --NH--SO.sub.2 --, --SO.sub.2 --NH--, --NH--SO.sub.2 --NH--, --C(O)--O--, --NH--C(O)--NH, --N((C.sub.1-6 alkyl)--RA.sub.1-RA-12)--SO.sub.2 --, or --N((C.sub.0-6 alkyl)--(C.sub.1-6 alkyl))--SO.sub.2 --.
- 23. A compound represented by the structure shown in formula 1, ##STR172## wherein 3 tautomers of the same structure are shown, wherein R.sub.1 is --CH(R.sub.1-1)--R.sub.1-2 ;
- wherein R.sub.1-1 is
- a) --(C.sub.1-5 alkyl),
- b) --(C.sub.3-5 cycloalkyl),
- c) -cyclopropyl,
- wherein R.sub.1-2 is --R.sub.1-100, or --R.sub.1-500 ;
- wherein R.sub.1-100 is
- a) phenyl, substituted with zero (0) to three (3) of RA.sub.1,
- wherein R.sub.1-500 is
- a 5- or 6-membered saturated or unsaturated ring containing from one (1) to four (4) heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur; and substituted with zero (0) to three (3) RA.sub.1 ; and including any bicyclic group in which any of the above heterocyclic rings is fused to a benzene ring, C.sub.3 -C.sub.8 cycloalkyl, or another heterocycle; and substituted with zero (0) to three (3) RA.sub.1 ; and if chemically feasible, the nitrogen and sulfur atoms may be in the oxidized forms;
- wherein RA.sub.1 is
- a) --H,
- b) --(C.sub.1-5 alkyl),
- c) --O--(C.sub.1-5 alkyl),
- wherein RA.sub.1-4 is any C-terminus substituted amino acid,
- j) --N(H)C(O)--RA.sub.1-1 (para or meta positions),
- k) --N(H)C(O)--O--RA.sub.1-1 (para or meta positions),
- l) --N(H)(SO.sub.2)--RA.sub.1-2,
- m) --N(CH.sub.3)(SO.sub.2)--RA.sub.1-2,
- n) --NO.sub.2,
- o) --SO.sub.2 NH.sub.2,
- p) --(C.sub.1-3 alkyl)--SO.sub.2 --RA.sub.1-RA-12,
- q) --(C.sub.1-3 alkyl)--SO.sub.2 --RA.sub.1-RA-15,
- r) -halo,
- wherein RA.sub.1-1 is
- a) --(C.sub.1-5 alkyl),
- b) --(C.sub.1-5 alkyl)--C((H)(NH.sub.2))--C(O)OH,
- wherein RA.sub.1-2 is
- a) -RAX
- b) --(C.sub.1-5 alkyl)-RAX,
- c) --(C.sub.1-5 alkyl)--O-RAX,
- d) --RA.sub.1-RA-12,
- e) --RA.sub.1-RA-15,
- f) --(C.sub.1 -C.sub.5 alkyl)--RA.sub.1-RA-12,
- g) --(C.sub.1 -C.sub.5 alkyl)--RA.sub.1-RA-15,
- h) --(C.sub.1 -C.sub.5 alkyl)--O--RA.sub.1-RA-12, or
- i) --(C.sub.1 -C.sub.5 alkyl)--O--RA.sub.1-RA-15 ;
- wherein RA.sub.2 and RA.sub.3 are defined independently and are independent of and defined the same as RA.sub.1 ;
- wherein G.sub.1-1 is
- a) --NH--C(O)--,
- b) --NH--SO.sub.2 --,
- c) --NH--C(O)--NH--, or
- d) --SO.sub.2 --NH--;
- wherein G.sub.1-2 is
- a) --NH--C(O)--,
- b) --C(O)--NH--,
- c) --NH--SO.sub.2 --,
- d) --SO.sub.2 --NH--,
- e) --NH--SO.sub.2 --NH--,
- f) --C(O)--O--,
- g) --O--C(O)--,
- h) --N((C.sub.1-6 alkyl)--RA.sub.1-RA-12)--C(O)--,
- i) --NH--C(O)--NH,
- j) --N((C.sub.1-6 alkyl)--RA.sub.1-RA-12)--SO.sub.2 --, or
- k) --N((C.sub.0-6 alkyl)--(C.sub.1-6 alkyl))--SO.sub.2 --;
- wherein RA.sub.2 and RA.sub.3 are defined independently and are the same as RA.sub.1 ;
- wherein --RA.sub.1-RA-12, is phenyl, fluorophenyl or cyanophenyl;
- wherein --RA.sub.1-RA-15, is
- 1-methyl-4-imidazolyl, 2-pyridinyl, 5-cyano-2-pyridinyl, 2-quinolinyl, 8-quinolinyl, 2-pyrimidinyl, 2-quinazolinyl, 2-benzimidazolyl, 2-imidazolyl, 4-thiazolyl, 6-purinyl;
- wherein R.sub.2-100 and R.sub.3-100 are defined independently and are,
- phenyl,
- benzyl, or
- phenyl or benzyl, substituted with one, two, or three of the following, --(C.sub.1-5 alkyl), -hydroxy, --O--(C.sub.1-5 alkyl), or -halo;
- wherein --RA.sub.2-RA-12, and --RA.sub.3-RA-12 are defined independently as phenyl, cyanophenyl, fluorophenyl, naphthyl; or phenyl or naphthyl--substituted with 1 to 3 groups of --(C.sub.1-6 alkyl), cyano, halo, hydroxy or --(C.sub.1-6 alkoxy);
- wherein --RA.sub.2-RA-15, and --RA.sub.3-RA-15 are defined independently as pyridinyl, cyano-pyridinyl, quinolinyl, pyrimidinyl, quinazolinyl, benzimidazolyl, imidazolyl, methylimidazolyl, thiazolyl or purinyl; or pyridinyl, quinolinyl, pyrimidinyl, quinazolinyl, benzimidazolyl, imidazolyl, thiazolyl, or purinyl--substituted with 1 to 3 groups of --(C.sub.1-6 alkyl), cyano, halo, hydroxy or --(C.sub.1-6 alkoxy);
- wherein R.sub.2 and R.sub.3 can be taken together to form a ring comprised of the following groups,
- a) (C.sub.6 cycloalkyl),
- b) (C.sub.6 cycloalkyl)--R.sub.3-9, or
- c) --(C.sub.2 alkyl substituted with zero to one R.sub.3-9)--R.sub.23 --(C.sub.2 alkyl substituted with zero to one R.sub.3-9)--.
- wherein RA.sub.1-RA-120, RA.sub.2-RA-120 and RA.sub.3-RA-120, are defined independently and are
- a) --C.sub.1 -C.sub.4 alkyl,
- b) --C.sub.1 -C.sub.3 alkoxy,
- c) -dimethylamino,
- d) -diethylamino,
- e) --CF.sub.3,
- f) --CN,
- g) -halo,
- h) --NH.sub.2,
- i) --OH,
- j) --SO.sub.2 --NH.sub.2, or
- k) --C(O)--NH.sub.2 ;
- wherein RA.sub.1-RA-12-AXA or RA.sub.1-RA-15-AXA are independent and are,
- a) --H
- b) -halo,
- c) --NO.sub.2,
- d) --CN,
- e) --(C.sub.1-10 alkyl), substituted with zero (0) to three (3) halo,
- f) --(C.sub.0-6 alkyl)-phenyl, substituted with zero (0) to three (3) halo or hydroxy,
- g) --OH,
- h) --O--C.sub.1-5 alkyl,
- i) --(C.sub.0-6 alkyl)--O--(C.sub.1-6 alkyl), substituted with zero (0) to three (3) halo or hydroxy,
- j) --(C.sub.0-6 alkyl)--O--(C.sub.2-7 alkenyl), substituted with zero (0) to three (3) halo or hydroxy,
- k) --CH(O),
- l) --C(O)--(C.sub.1-6 alkyl),
- m) --C(O)OH,
- n) --C(O)O--(C.sub.1-5 alkyl),
- o) --C(O)--N(H or C.sub.1-6 alkyl).sub.2,
- p) --NH.sub.2,
- q) --NH--(C.sub.1-6 alkyl),
- r) -mono or di-(C.sub.1-6 alkyl)amino,
- s) --NH--OH,
- t) --NH--C(O)--(C.sub.1-3 alkyl),
- u) --(C.sub.0-6 alkyl)--NH--C(O)-phenyl,
- v) --(C.sub.0-4 alkyl)--NH--SO.sub.2 -phenyl,
- w) --(C.sub.0-6 alkyl)--N.dbd.N-phenyl, substituted with zero (0) or one (1) --N(C.sub.1 -C.sub.3 alkyl).sub.2, or
- x) --SO.sub.2 -phenyl, substituted with zero (0) to three (3) C.sub.1 -C.sub.5 alkyl;
- wherein R.sub.2 is
- a) --C.sub.3-4 alkyl
- b) -n-propyl,
- c) --(C.sub.1-5 alkyl)--C.sub.3-5 cycloalkyl,
- d) --(C.sub.2-5 alkenyl)
- e) --(C.sub.1-5 alkyl)--R.sub.2-100,
- f) --(C.sub.1-5 alkyl)--R.sub.2-500,
- wherein R.sub.2-100 is independent of and defined the same as R.sub.1-100 wherein RA.sub.1 is RA.sub.2 ;
- wherein R.sub.2-500 is independent of and defined the same as R.sub.1-500 wherein RA.sub.1 is RA.sub.2 ;
- wherein RA.sub.2 is independent of and defined the same as RA.sub.1 ;
- wherein R.sub.3 is
- a) --(C.sub.1-5 alkyl),
- b) --(CH.sub.2 --CH.dbd.CH.sub.2),
- c) --C.sub.1-5 alkyl)--(C.sub.3-5 cycloalkyl),
- d) --(C.sub.1-5 alkyl)--O--(CH.sub.2 CH.sub.2 O).sub.q --CH.sub.3,
- e) --(C.sub.1-6 alkyl)--R.sub.3-4,
- f) --(C.sub.2-6 alkenyl)--R.sub.3-4,
- g) --R.sub.3-100,
- h) --(C.sub.1-4 alkyl)--R.sub.3-100,
- i) --H or --(C.sub.1-5 alkyl),
- j) --CH.sub.2 -RAX
- k) -n propyl-RAX,
- l) --3-phenylpropyl,
- m) --R.sub.3-500,
- n) --CH.sub.2 -RAX
- o) -n propyl-R.sub.3-500,
- p) -benzyl,
- wherein R.sub.3-1 is
- a) --NH--C(O)--,
- b) --NH--SO.sub.2 --,
- c) --NH--CO--NH--, or
- d) --SO.sub.2 --NH--;
- wherein, R.sub.3-4 is
- a) --OH)
- b) --O--(C.sub.1-6 alkyl),
- c) --C(O)--OH,
- d) --C(O)--O--(C.sub.1-6 alkyl),
- e) --(C.sub.1-6 alkyl),
- f) --(C.sub.3-6 cycloalkyl),
- g) --R.sub.3-100, or
- h) --R.sub.3-500 ;
- wherein R.sub.3-6 is
- a) --OH,
- b) --C.sub.1-10 alkyl,
- c) --(C.sub.0-6 alkyl)--C.sub.3 -C.sub.7 cycloalkyl,
- d) --(C.sub.1-6 alkyl)--CH.dbd.CH.sub.2,
- e) --(C.sub.0-6 alkyl)--R.sub.3-4,
- f) --(C.sub.1-6 alkyl)--R.sub.3-100, or
- g) --(C.sub.1-6 alkyl)--R.sub.3-500 ;
- wherein R.sub.3-9 is
- a) --(C.sub.1-6 alkyl),
- b) --(C.sub.0-6 alkyl)--RA.sub.3-RA-12, or
- c) --(C.sub.0-6 alkyl)--RA.sub.3-RA-15 ;
- wherein R.sub.3-100 is independent of and defined the same as R.sub.1-100 ;
- wherein R.sub.3-500 is independent of and defined the same as R.sub.1-500 ;
- wherein RA.sub.3 is independent of and defined the same as RA.sub.1 ;
- wherein RA.sub.3-RA-12, RA.sub.3-RA-15, RA.sub.3-RA-12-AXA and RA.sub.3-RA-15-AXA, are all independent of and defined the same as the corresponding R.sub.1 variables, which are: RA.sub.1-RA-12, RA.sub.1-RA-15, RA.sub.1-RA-12-AXA and RA.sub.1-RA-15-AXA, respectively,
- wherein R.sub.2 and R.sub.3 can be taken together to form a ring comprised of the following groups,
- a) (C.sub.5-9 cycloalkyl),
- b) (C.sub.5-9 cycloalkyl) substituted with one to two --R.sub.3-9, or
- c) --(C.sub.1-5 alkyl substituted with zero to one R.sub.3-9)--R.sub.23 --(C.sub.1-5 alkyl);
- wherein R.sub.3-9 is
- a) --(C.sub.1-6 alkyl),
- b) --(C.sub.0-6 alkyl)--RA.sub.3-RA-12, or
- c) --(C.sub.0-6 alkyl)--RA.sub.3-RA-15 ;
- or
- wherein R.sub.2 and R.sub.3 can be taken together to form a double bond represented by formula 50, shown below, ##STR173## wherein R.sub.11 is a) --H,
- b) --C.sub.1 -C.sub.4 alkyl,
- c) --(RA.sub.3-RA-12), or
- d) pharmaceutically acceptable salts,
- wherein R.sub.23 is
- a) --O--,
- b) --C(O)--,
- c) --N(H)--,
- d) --N(R.sub.3-9)--,
- e) --N(C(O)--R.sub.3-9)--, or
- f) --N(C(O)--O--R.sub.3-9);
- wherein R.sub.30 is
- a) -morpholino,
- b) -piperidino,
- c) -piperazino,
- d) --OR.sub.40,
- e) -halo,
- f) ##STR174## g) --NR.sub.40 R.sub.41 ; wherein R.sub.40 and R.sub.41 are defined independently and are,
- a) --H,
- b) --C.sub.1 -C.sub.4 alkyl,
- c) phenyl, substituted with zero (0) to three (3) RA.sub.1-RA-120,
- wherein R.sub.42 is
- a) --C.sub.1 -C.sub.4 alkyl,
- b) -phenyl, substituted with zero (0) to three (3) RA.sub.1-RA-120, or
- c) --(C.sub.0-6 alkyl)-phenyl, substituted with zero (0) to three (3) RA.sub.1-RA-120 ;
- wherein RA.sub.2-RA-120 and RA.sub.3-RA-120 are independent of and defined the same as RA.sub.1-RA-120 ;
- wherein R.sub.50 and R.sub.51 are defined independently and are
- a) --(H or C.sub.1-6 alkyl),
- b) --(C.sub.0-6 alkyl)--RA.sub.3-RA-12, or
- c) --(C.sub.0-6 alkyl)--RA.sub.3-RA-15 ;
- wherein AA is an amino acid residue,
- wherein P.sub.1 is hydrogen or a nitrogen protecting group,
- wherein m and n are independently zero (0) to five (5) inclusive,
- wherein p and q are independently one (1) to five (5) inclusive,
- wherein z is one (1) to three (3) inclusive; and
- pharmaceutically acceptable salts, including bis salts, thereof,
- with the proviso that when R.sub.1 is 1-phenylpropyl and R.sub.2 is H, then R.sub.3 is not C.sub.1-5 alkyl, and
- with the proviso that when RA.sub.1 or RA.sub.3 is --G.sub.1-2 --(C.sub.0-6 alkyl)--O--R.sub.1-RA-12, --(C.sub.0-6 alkyl)--G.sub.1-2 --(C.sub.0-6 alkyl)--O--(C.sub.0-6 alkyl), --(C.sub.0-6 alkyl)--G.sub.1-2 --O--(C.sub.1-6 alkyl)--RA.sub.1-RA-12, --(C.sub.0-6 alkyl)--G.sub.1-2 --O--(C.sub.1-6 alkyl)--RA.sub.1-RA-15, --G.sub.1-2 --N(R.sub.42).sub.2, or --G.sub.1-2 --NH.sub.2, then G.sub.1-2 is NOT, --C(O)--NH--, --NH--SO.sub.2 --, --SO.sub.2 --NH--, --NH--SO.sub.2 --NH--, --C(O)--O--, --NH--C(O)--NH, --N((C.sub.1-6 alkyl)--R.sub.1-RA-12)--SO.sub.2 --, or --N((C.sub.0-6 alkyl)--(C.sub.1-6 alkyl))--SO.sub.2 --.
- 24. A compound represented by the structure shown in formula 1, ##STR175## wherein 3 tautomers of the same structure are shown, wherein R.sub.1 is --CH(R.sub.1-1)--R.sub.1-2 ;
- wherein R.sub.1-1 is
- a) --(C.sub.1-5 alkyl),
- b) --(C.sub.3-5 cycloalkyl),
- c) -cyclopropyl,
- wherein R.sub.1-2 is --R.sub.1-100, or --R.sub.1-500 ;
- wherein R.sub.1-100 is
- a) phenyl, substituted with zero (0) to three (3) of RA.sub.1,
- wherein R.sub.1-500 is
- a 5- or 6-membered saturated or unsaturated ring containing from one (1) to four (4) heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur; and substituted with zero (0) to three (3) RA.sub.1 ; and including any bicyclic group in which any of the above heterocyclic rings is fused to a benzene ring, C.sub.3 -C.sub.8 cycloalkyl, or another heterocycle; and substituted with zero (0) to three (3) RA.sub.1 ; and if chemically feasible, the nitrogen and sulfur atoms may be in the oxidized forms;
- wherein RA.sub.1 is
- a) --H,
- b) --(C.sub.1-5 alkyl),
- c) --O--(C.sub.1-5 alkyl),
- wherein RA.sub.1-4 is any C-terminus substituted amino acid,
- j) --N(H)C(O)--RA.sub.1-1 (para or meta positions),
- k) --N(H)C(O)--O--RA.sub.1-1 (para or meta positions),
- l) --N(H)(SO.sub.2)--RA.sub.1-2,
- m) --N(CH.sub.3)(SO.sub.2)--RA.sub.1-2,
- n) --NO.sub.2,
- o) --SO.sub.2 NH.sub.2,
- p) --(C.sub.1-3 alkyl)--SO.sub.2 --RA.sub.1-RA-12,
- q) --(C.sub.1-3 alkyl)--SO.sub.2 --RA.sub.1-RA-15,
- r) -halo,
- wherein RA.sub.1-1 is
- a) --(C.sub.1-5 alkyl),
- b) --(C.sub.1-5 alkyl)--C((H)(NH.sub.2))--C(O)OH,
- wherein RA.sub.1-2 is
- a) -RAX,
- b) --(C.sub.1-5 alkyl)-RAX,
- c) --(C.sub.1-5 alkyl)--O-RAX,
- d) --RA.sub.1-RA-12,
- e) --RA.sub.1-RA-15,
- f) --(C.sub.1 -C.sub.5 alkyl)--RA.sub.1-RA-12,
- g) --(C.sub.1 -C.sub.5 alkyl)--RA.sub.1-RA-15,
- h) --(C.sub.1 -C.sub.5 alkyl)--O--R.sub.1-RA-12, or
- i) --(C.sub.1 -C.sub.5 alkyl)--O--RA.sub.1-RA-15 ;
- wherein RA.sub.2 and RA.sub.3 are defined independently and are independent of and defined the same as RA.sub.1 ;
- wherein G.sub.1-1 is
- a) --NH--C(O)--,
- b) --NH--SO.sub.2 --,
- c) --NH--C(O)--NH--, or
- d) --SO.sub.2 --NH--;
- wherein G.sub.1-2 is
- a) --NH--C(O)--,
- b) --C(O)--NH--,
- c) --NH--SO.sub.2 --,
- d) --SO.sub.2 --NH--,
- e) --NH--SO.sub.2 --NH--,
- f) --C(O)--O--,
- g) --O--C(O)--,
- h) --N((C.sub.1-6 alkyl)--R.sub.1-RA-12)--C(O)--,
- i) --NH--C(O)--NH,
- j) --N((C.sub.1-6 alkyl)--RA.sub.1-RA-12)--SO.sub.2 --, or
- k) --N((C.sub.0-6 alkyl)--(C.sub.1-6 alkyl))--SO.sub.2 --;
- wherein RA.sub.2 and RA.sub.3 are defined independently and are the same as RA.sub.1 ;
- wherein --RA.sub.1-RA-12, is phenyl, fluorophenyl or cyanophenyl;
- wherein --RA.sub.1-RA-15, is
- 1-methyl-4-imidazolyl, 2-pyridinyl, 5-cyano-2-pyridinyl, 2-quinolinyl, 8-quinolinyl, 2-pyrimidinyl, 2-quinazolinyl, 2-benzimidazolyl, 2-imidazolyl, 4-thiazolyl, 6-purinyl;
- wherein R.sub.2-500 and R.sub.3-100 are defined independently and are,
- a) phenyl, substituted with zero (0) to three (3) RA.sub.2-RA-12-AXA, or
- b) naphthyl, substituted with zero (0) to three (3) RA.sub.2-RA-12-AXA ;
- wherein R.sub.2-500 and R.sub.3-500 are defined independently and are,
- a 5- or 6-membered saturated or unsaturated ring containing from one (1) to four (4) heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur; and including any bicyclic group in which any of the above heterocyclic rings is fused to a benzene ring, C.sub.3 -C.sub.8 cycloalkyl, or another heterocycle; and substituted with zero (0) to three (3) RA.sub.2-RA-15-AXA ;
- wherein RA.sub.2-RA-12-AXA RA.sub.2-RA-15-AXA are are defined independently and are,
- a) --H,
- b) -halo,
- c) --NO.sub.2,
- d) --CN,
- e) --C.sub.1-10 alkyl, substituted with zero (0) to three (3) halo,
- f) --(C.sub.0-6 alkyl)-phenyl, substituted with zero (0) to three (3) hydroxy or halo,
- g) --OH,
- h) --O--C.sub.1-5 alkyl,
- i) --(C.sub.0-6 alkyl)--O--(C.sub.1-6 alkyl), substituted with zero (0) to three (3) hydroxy or halo,
- j) --(C.sub.0-6 alkyl)--O--(C.sub.2-7 alkenyl), substituted with zero (0) to three (3) hydroxy or halo,
- k) --CH(O),
- l) --C(O)--(C.sub.1-6 alkyl),
- m) --C(O)OH,
- n) --C(O)O--(C.sub.1-5 alkyl),
- o) --C(O)--N(H or C.sub.1-6 alkyl).sub.2,
- p) --NH.sub.2,
- q) --NH--(C.sub.1-6 alkyl),
- r) mono or di-(C.sub.1-6 alkyl)amino,
- s) --NH--OH,
- t) --NH--C(O)--(C.sub.1-3 alkyl),
- u) --(C.sub.0-6 alkyl)--NH--C(O)-phenyl,
- v) --(C.sub.0-6 alkyl)--NH--SO.sub.2 -phenyl,
- w) --(C.sub.0-6 alkyl)--N.dbd.N-phenyl, substituted by zero (0) or one (1) --N(C.sub.1 -C.sub.3 alkyl).sub.2, or
- x) --SO.sub.2 -phenyl, substituted with zero (0) to three (3) C.sub.1 -C.sub.5 alkyl;
- wherein R.sub.2 and R.sub.3 can be taken together to form a ring comprised of the following groups,
- a) (C.sub.5-9 cycloalkyl),
- b) (C.sub.5-9 cycloalkyl) substituted with one R.sub.3-9,
- c) --(C.sub.1-5 alkyl substituted with zero to one R.sub.3-9)--R.sub.3 --(C.sub.1-5 alkyl).
- wherein RA.sub.1-RA-120, RA.sub.2-RA-120 and RA.sub.3-RA-120, are defined independently and are
- a) --C.sub.1 -C.sub.4 alkyl,
- b) --C.sub.1 -C.sub.3 alkoxy,
- c) -dimethylamino,
- d) -diethylamino,
- e) --CF.sub.3,
- f) --CN,
- g) -halo,
- h) --NH.sub.2,
- i) --OH,
- j) --SO.sub.2 --NH.sub.2, or
- k) --C(O)--NH.sub.2 ;
- wherein RA.sub.1-RA-12-AXA or RA.sub.1-RA-15-AXA are independent and are,
- a) --H
- b) -halo,
- c) --NO.sub.2,
- d) --CN,
- e) --(C.sub.1-10 alkyl), substituted with zero (0) to three (3) halo,
- f) --(C.sub.0-6 alkyl)-phenyl, substituted with zero (0) to three (3) halo or hydroxy,
- g) --OH,
- h) --O--C.sub.1-5 alkyl,
- i) --(C.sub.0-6 alkyl)--O--(C.sub.1-6 alkyl), substituted with zero (0) to three (3) halo or hydroxy,
- j) --(C.sub.0-6 alkyl)--O--(C.sub.2-7 alkenyl), substituted with zero (0) to three (3) halo or hydroxy,
- k) --CH(O),
- l) --C(O)--(C.sub.1-6 alkyl),
- m) --C(O)OH,
- n) --C(O)O--(C.sub.1-5 alkyl),
- o) --C(O)--N(H or C.sub.1-6 alkyl).sub.2,
- p) --NH.sub.2,
- q) --NH--(C.sub.1-6 alkyl),
- r) -mono or di --(C.sub.1-6 alkyl)amino,
- s) --NH--OH,
- t) --NH--C(O)--(C.sub.1-3 alkyl),
- u) --(C.sub.0-6 alkyl)--NH--C(O)-phenyl,
- v) --(C.sub.0-6 alkyl)--NH--SO.sub.2 -phenyl,
- w) --(C.sub.0-6 alkyl)--N.dbd.N-phenyl, substituted with zero (0) or one (1) --N(C.sub.1 -C.sub.3 alkyl).sub.2, or
- x) --SO.sub.2 -phenyl, substituted with zero (0) to three (3) C.sub.1 -C.sub.5 alkyl;
- wherein R.sub.2 is
- a) --C.sub.3-4 alkyl,
- b) -n-propyl,
- c) --(C.sub.1-5 alkyl)--C.sub.3-5 cycloalkyl,
- d) --(C.sub.2-5 alkenyl)
- e) --(C.sub.1-5 alkyl)--R.sub.2-100,
- f) --C.sub.1-5 alkyl)--R.sub.2-500,
- wherein R.sub.2-100 is independent of and defined the same as R.sub.1-100 wherein RA.sub.1 is RA.sub.2 ;
- wherein R.sub.2-500 is independent of and defined the same as R.sub.1-500 wherein RA.sub.1 is RA.sub.2 ;
- wherein RA.sub.2 is independent of and defined the same as RA.sub.1 ;
- wherein R.sub.3 is
- a) --(C.sub.1-5 alkyl),
- b) --(CH.sub.2 --CH.dbd.CH.sub.2),
- c) --(C.sub.1-5 alkyl)--(C.sub.3-5 cycloalkyl),
- d) --(C.sub.1-5 alkyl)--O--(CH.sub.2 CH.sub.2 O).sub.q --CH.sub.3,
- e) --(C.sub.1-6 alkyl)--R.sub.3-4,
- f) --(C.sub.2-6 alkenyl)--R.sub.3-4,
- g) --R.sub.3-100,
- h) --(C.sub.1-4 alkyl)--R.sub.3-100,
- i) --H or --(C.sub.1-5 alkyl),
- j) --CH.sub.2 -RAX
- k) -n propyl-RAX,
- l) --3-phenylpropyl,
- m) --R.sub.3-500,
- n) --CH.sub.2 -RAX
- o) -n propyl-R.sub.3-500,
- p) -benzyl,
- wherein R.sub.3-1 is
- a) --NH--C(O)--,
- b) --NH--SO.sub.2 --,
- c) --NH--CO--NH--, or
- d) --SO.sub.2 --NH--;
- wherein, R.sub.3-4 is
- a) --OH,
- b) --O--(C.sub.1-6 alkyl),
- c) --C(O)--OH,
- d) --C(O)--O--(C.sub.1-6 alkyl),
- e) --(C.sub.1-6 alkyl),
- f) --(C.sub.3-6 cycloalkyl),
- g) --R.sub.3-100, or
- h) --R.sub.3-500 ;
- wherein R.sub.3-6 is
- a) --OH,
- b) --C.sub.1-10 alkyl,
- c) --(C.sub.0-6 alkyl)--C.sub.3 -C.sub.7 cycloalkyl,
- d) --(C.sub.1-6 alkyl)--CH.dbd.CH.sub.2,
- e) --(C.sub.0-6 alkyl)--R.sub.3-4,
- f) --(C.sub.1-6 alkyl)--R.sub.3-100, or
- g) --(C.sub.1-6 alkyl)--R.sub.3-500 ;
- wherein R.sub.3-9 is
- a) --(C.sub.1-6 alkyl),
- b) --(C.sub.0-6 alkyl)--RA.sub.3-RA-12, or
- c) --(C.sub.0-6 alkyl)--RA.sub.3-RA-15 ;
- wherein R.sub.3-100 is independent of and defined the same as R.sub.1-100 ;
- wherein R.sub.3-500 is independent of and defined the same as R.sub.1-500 ;
- wherein RA.sub.3 is independent of and defined the same as RA.sub.1 ;
- wherein RA.sub.3-RA-12, RA.sub.3-RA-15, RA.sub.3-RA-12-AXA and RA.sub.3-RA-15-AXA, are all independent of and defined the same as the corresponding R.sub.1 variables, which are: RA.sub.1-RA-12, RA.sub.1-RA-15, RA.sub.1-RA-12-AXA and RA.sub.1-RA-15-AXA, respectively,
- wherein R.sub.2 and R.sub.3 can be taken together to form a ring comprised of the following groups,
- a) (C.sub.5-9 cycloalkyl),
- b) (C.sub.5-9 cycloalkyl) substituted with one to two --R.sub.3-9, or
- c) --(C.sub.1-5 alkyl substituted with zero to one R.sub.3-9)--R.sub.23 --(C.sub.1-5 alkyl);
- wherein R.sub.3-9 is
- a) --(C.sub.1-6 alkyl),
- b) --(C.sub.0-6 alkyl)--RA.sub.3-RA-12, or
- c) --(C.sub.0-6 alkyl)--RA.sub.3-RA-15 ;
- or
- wherein R.sub.2 and R.sub.3 can be taken together to form a double bond represented by formula 50, shown below, ##STR176## wherein R.sub.11 is a) --H,
- b) --C.sub.1 -C.sub.4 alkyl,
- c) --(RA.sub.3-RA-12), or
- d) pharmaceutically acceptable salts,
- wherein R.sub.23 is
- a) --O--,
- b) --C(O)--,
- c) --N(H)--,
- d) --N(R.sub.3-9)--,
- e) --N(C(O)--R.sub.3-9)--, or
- f) --N(C(O)--O--R.sub.3-9);
- wherein R.sub.30 is
- a) -morpholino,
- b) -piperidino,
- c) -piperazino,
- d) --OR.sub.40,
- e) -halo,
- f) ##STR177## g) --NR.sub.40 R.sub.41 ; wherein R.sub.40 and R.sub.41 are defined independently and are,
- a) --H,
- b) --C.sub.1 -C.sub.4 alkyl,
- c) phenyl, substituted with zero (0) to three (3) RA.sub.1-RA-120,
- wherein R.sub.42 is
- a) --C.sub.1 -C.sub.4 alkyl,
- b) -phenyl, substituted with zero (0) to three (3) RA.sub.1-RA-120, or
- c) --(C.sub.0-6 alkyl)-phenyl, substituted with zero (0) to three (3) RA.sub.1-RA-120 ;
- wherein RA.sub.2-RA-120 and RA.sub.3-RA-120 are independent of and defined the same as RA.sub.1-RA-120 ;
- wherein R.sub.50 and R.sub.51 are defined independently and are
- a) --(H or C.sub.1-6 alkyl),
- b) --(C.sub.0-6 alkyl)--RA.sub.3-RA-12, or
- c) --(C.sub.0-6 alkyl)--RA.sub.3-RA-15 ;
- wherein AA is an amino acid residue,
- wherein P.sub.1 is hydrogen or a nitrogen protecting group,
- wherein m and n are independently zero (0) to five (5) inclusive,
- wherein p and q are independently one (1) to five (5) inclusive,
- wherein z is one (1) to three (3) inclusive; and
- pharmaceutically acceptable salts, including bis salts, thereof,
- with the proviso that when R.sub.1 is 1-phenylpropyl and R.sub.2 is H, then R.sub.3 is not C.sub.1-5 alkyl, and
- with the proviso that when RA.sub.1 or RA.sub.3 is --G.sub.1-2 --(C.sub.0-6 alkyl)--O--RA.sub.1-RA-12, --(C.sub.0-6 alkyl)--G.sub.1-2 --(C.sub.0-6 alkyl)--O--(C.sub.0-6 alkyl), --(C.sub.0-6 alkyl)--G.sub.1-2 --O--(C.sub.1-6 alkyl)--RA.sub.1-RA-12, --(C.sub.0-6 alkyl)--G.sub.1-2 --O--(C.sub.1-6 alkyl)--R.sub.1-RA-15, --G.sub.1-2 --N(R.sub.42).sub.2, or --G.sub.1-2 --NH.sub.2, then G.sub.1-2 is NOT, --C(O)--NH--, --NH--SO.sub.2 --, --SO.sub.2 --NH--, --NH--SO.sub.2 --NH--, --C(O)--O--, --NH--C(O)--NH, --N((C.sub.1-6 alkyl)--R.sub.1-RA-12)--SO.sub.2 --, or --N((C.sub.0-6 alkyl)--(C.sub.1-6 alkyl))--SO.sub.2 --.
- 25. A compound represented by the structure shown in formula 1, ##STR178## wherein 3 tautomers of the same structure are shown, wherein R.sub.1 is --CH(R.sub.1-1)--R.sub.1-2 ;
- wherein R.sub.1-1 is
- a) --(C.sub.1-5 alkyl),
- b) --(C.sub.3-5 cycloalkyl),
- c) -cyclopropyl,
- wherein R.sub.1-2 is --R.sub.1-100, or --R.sub.1-500 ;
- wherein R.sub.1-100 is
- a) phenyl, substituted with zero (0) to three (3) of RA.sub.1,
- wherein R.sub.1-500 is
- a 5- or 6-membered saturated or unsaturated ring containing from one (1) to four (4) heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur; and substituted with zero (0) to three (3) RA.sub.1 ; and including any bicyclic group in which any of the above heterocyclic rings is fused to a benzene ring, C.sub.3 -C.sub.8 cycloalkyl, or another heterocycle; and substituted with zero (0) to three (3) RA.sub.1 ; and if chemically feasible, the nitrogen and sulfur atoms may be in the oxidized forms;
- wherein RA.sub.1 is
- a) --H,
- b) --(C.sub.1-5 alkyl),
- c) --O--(C.sub.1-5 alkyl),
- wherein RA.sub.1-4 is any C-terminus substituted amino acid,
- j) --N(H)C(O)--RA.sub.1-1 (para or meta positions),
- k) --N(H)C(O)--O--RA.sub.1-1 (para or meta positions),
- l) --N(H)(SO.sub.2)--RA.sub.1-2,
- m) --N(CH.sub.3)(SO.sub.2)--RA.sub.1-2,
- n) --NO.sub.2,
- o) --SO.sub.2 NH.sub.2,
- p) --(C.sub.1-3 alkyl)--SO.sub.2 --RA.sub.1-RA-12,
- q) --(C.sub.1-3 alkyl)--SO.sub.2 --RA.sub.1-RA-15,
- r) -halo,
- wherein RA.sub.1-1 is
- a) --(C.sub.1-5 alkyl),
- b) --(C.sub.1-5 alkyl)--C((H)(NH.sub.2))--C(O)OH,
- wherein RA.sub.1-2 is
- a) -RAX,
- b) --(C.sub.1-5 alkyl)-RAX,
- c) --(C.sub.1-5 alkyl)--O-RAX,
- d) --RA.sub.1-RA-12,
- e) --RA.sub.1-RA-15,
- f) --(C.sub.1 -C.sub.5 alkyl)--RA.sub.1-RA-12,
- g) --(C.sub.1-5 alkyl)--RA.sub.1-RA-15,
- h) --(C.sub.1 -C.sub.5 alkyl)--O--RA.sub.1-RA-12, or
- i) --(C.sub.1 -C.sub.5 alkyl)--O--R.sub.1-RA-15 ;
- wherein RA.sub.2 and RA.sub.3 are defined independently and are independent of and defined the same as RA.sub.1 ;
- wherein G.sub.1-1 is
- a) --NH--C(O)--,
- b) --NH--SO.sub.2 --,
- c) --NH--C(O)--NH--, or
- d) --SO.sub.2 --NH--;
- wherein G.sub.1-2 is
- a) --NH--C(O)--,
- b) --C(O)--NH--,
- c) --NH--SO.sub.2 --,
- d) --SO.sub.2 --NH--,
- e) --NH--SO.sub.2 --NH--,
- f) --C(O)--O--,
- g) --O--C(O)--,
- h) --N((C.sub.1-6 alkyl)--RA.sub.1-RA-12)--C(O)--,
- i) --NH--C(O)--NH,
- j) --N((C.sub.1-6 alkyl)--R.sub.1-RA-12)--SO.sub.2 --, or
- k) --N((C.sub.0-6 alkyl)--(C.sub.1-6 alkyl))--SO.sub.2 --;
- wherein RA.sub.2 and RA.sub.3 are defined independently and are the same as RA.sub.1 ; wherein --RA.sub.1-RA-12, is phenyl, fluorophenyl or cyanophenyl;
- wherein --RA.sub.1-RA-15, is
- 1-methyl-4-imidazolyl, 2-pyridinyl, 5-cyano-2-pyridinyl, 2-quinolinyl, 8-quinolinyl, 2-pyrimidinyl, 2-quinazolinyl, 2-benzimidazolyl, 2-imidazolyl, 4-thiazolyl, 6-purinyl;
- wherein R.sub.2-100 and R.sub.3-100 are defined independently and are,
- a) phenyl, substituted with zero (0) to three (3) RA.sub.2-RA-12-AXA, or
- b) naphthyl, substituted with zero (0) to three (3) RA.sub.2-RA-12-AXA ;
- wherein R.sub.2-500 and R.sub.3-500 are defined independently and are,
- a 5- or 6-membered saturated or unsaturated ring containing from one (1) to four (4) heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur; and including any bicyclic group in which any of the above heterocyclic rings is fused to a benzene ring, C.sub.3 -C.sub.8 cycloalkyl, or another heterocycle; and substituted with zero (0) to three (3) RA.sub.2-RA-15-AXA ;
- wherein RA.sub.2-RA-12-AXA or RA.sub.2-RA-15-AXA are are defined independently and are,
- a) --H,
- b) -halo,
- c) --NO.sub.2,
- d) --CN,
- e) --C.sub.1-10 alkyl, substituted with zero (0) to three (3) halo,
- f) --(C.sub.0-6 alkyl)-phenyl, substituted with zero (0) to three (3) hydroxy or halo,
- g) --OH,
- h) --O--C.sub.1-5 alkyl,
- i) --(C.sub.0-6 alkyl)--O--(C.sub.1-6 alkyl), substituted with zero (0) to three (3) hydroxy or halo,
- j) --(C.sub.0-6 alkyl)--O--(C.sub.2-7 alkenyl), substituted with zero (0) to three (3) hydroxy or halo,
- k) --CH(O),
- l) --C(O)--(C.sub.1-6 alkyl),
- m) --C(O)OH,
- n) --C(O)O--(C.sub.1-5 alkyl),
- o) --C(O)--N(H or C.sub.1-6 alkyl).sub.2,
- p) --NH.sub.2,
- q) --NH--(C.sub.1-6 alkyl),
- r) mono or di --(C.sub.1-6 alkyl)amino,
- s) --NH--OH,
- t) --NH--C(O)--(C.sub.1-3 alkyl),
- u) --(C.sub.0-6 alkyl)--NH--C(O)-phenyl,
- v) --(C.sub.0-4 alkyl)--NH--SO.sub.2 -phenyl,
- w) --(C.sub.0-6 alkyl)--N.dbd.N-phenyl, substituted by zero (0) or one (1) --N(C.sub.1 -C.sub.3 alkyl).sub.2, or
- x) --SO.sub.2 -phenyl, substituted with zero (0) to three (3) C.sub.1 -C.sub.5 alkyl;
- wherein R.sub.2 and R.sub.3 can be taken together to form a ring comprised of the following groups,
- a) (C.sub.5-9 cycloalkyl),
- b) (C.sub.5-9 cycloalkyl) substituted with one R.sub.3-9,
- c) --(C.sub.1-5 alkyl substituted with zero to one R.sub.3-9)--R.sub.23 --(C.sub.1-5 alkyl).
- wherein RA.sub.1-RA-120, RA.sub.2-RA-120 and RA.sub.3-RA-120, are defined independently and are
- a) --C.sub.1 -C.sub.4 alkyl,
- b) --C.sub.1 -C.sub.3 alkoxy,
- c) -dimethylamino,
- d) -diethylamino,
- e) --CF.sub.3,
- f) --CN,
- g) -halo,
- h) --NH.sub.2,
- i) --OH,
- j) --SO.sub.2 --NH.sub.2, or
- k) --C(O)--NH.sub.2 ;
- wherein RA.sub.1-RA-12-AXA or RA.sub.1-RA-15-AXA are independent and are,
- a) --H
- b) -halo,
- c) --NO.sub.2,
- d) --CN,
- e) --(C.sub.1-10 alkyl), substituted with zero (0) to three (3) halo,
- f) --(C.sub.0-6 alkyl)-phenyl, substituted with zero (0) to three (3) halo or hydroxy,
- g) --OH,
- h) --O--C.sub.1-5 alkyl,
- i) --(C.sub.0-6 alkyl)--O--(C.sub.1-6 alkyl), substituted with zero (0) to three (3) halo or hydroxy,
- j) --(C.sub.0-6 alkyl)--O--(C.sub.2-7 alkenyl), substituted with zero (0) to three (3) halo or hydroxy,
- k) --CH(O),
- l) --C(O)--(C.sub.1-6 alkyl),
- m) --C(O)OH,
- n) --C(O)O--(C.sub.1-5 alkyl),
- o) --C(O)--N(H or C.sub.1-6 alkyl).sub.2,
- p) --NH.sub.2,
- q) --NH--(C.sub.1-6 alkyl),
- r) -mono or di --(C.sub.1-6 alkyl)amino,
- s) --NH--OH,
- t) --NH--C(O)--(C.sub.1-3 alkyl),
- u) --(C.sub.0-6 alkyl)--NH--C(O)-phenyl,
- v) --(C.sub.0-6 alkyl)--NH--SO.sub.2 -phenyl,
- w) --(C.sub.0-6 alkyl)--N.dbd.N-phenyl, substituted with zero (0) or one (1) --N(C.sub.1 -C.sub.3 alkyl).sub.2, or
- x) --SO.sub.2 -phenyl, substituted with zero (0) to three (3) C.sub.1 -C.sub.5 alkyl;
- wherein R.sub.2 is
- a) --C.sub.3-4 alkyl,
- b) -n-propyl,
- c) --(C.sub.1-5 alkyl)--C.sub.3-5 cycloalkyl,
- d) --(C.sub.2-5 alkenyl)
- e) --(C.sub.1-5 alkyl)--R.sub.2-100,
- f) --(C.sub.1-5 alkyl)--R.sub.2-500,
- wherein R.sub.2-100 is independent of and defined the same as R.sub.1-100 wherein RA.sub.1 is RA.sub.2 ;
- wherein R.sub.2-500 is independent of and defined the same as R.sub.1-500 wherein RA.sub.1 is RA.sub.2 ;
- wherein RA.sub.2 is independent of and defined the same as RA.sub.1 ;
- wherein R.sub.3 is
- a) --(C.sub.1-5 alkyl),
- b) --(CH.sub.2 --CH.dbd.CH.sub.2),
- c) --C.sub.1-5 alkyl)--(C.sub.3-5 cycloalkyl),
- d) --(C.sub.1-5 alkyl)--O--(CH.sub.2 CH.sub.2 O).sub.q --CH.sub.3,
- e) --(C.sub.1-6 alkyl)--R.sub.3-4,
- f) --(C.sub.1-6 alkenyl)--R.sub.3-4,
- g) --R.sub.3-100,
- h) --(C.sub.1-4 alkyl)--R.sub.3-100,
- i) --H or --(C.sub.1-5 alkyl),
- j) --CH.sub.2 -RAX
- k) -n propyl-RAX,
- l) --3-phenylpropyl,
- m) --R.sub.3-500,
- n) --CH.sub.2 -RAX
- o) -n propyl-R.sub.3-500,
- p) -benzyl,
- wherein R.sub.3-1 is
- a) --NH--C(O)--,
- b) --NH--SO.sub.2 --,
- c) --NH--CO--NH--, or
- d) --SO.sub.2 --NH--;
- e) --(C.sub.1-5 alkyl),
- f) --(C.sub.2-5 alkenyl),
- g) --(C.sub.1-2 alkyl)--(C.sub.3-7 cycloalkyl),
- h) --(C.sub.1-2 alkyl)--R.sub.3-100, or
- i) --(C.sub.1 2 alkyl)--R.sub.3-500 ;
- wherein, R.sub.3-4 is
- a) --OH,
- b) --O--(C.sub.1-6 alkyl),
- c) --C(O)--OH,
- d) --C(O)--O--(C.sub.1-6 alkyl),
- e) --(C.sub.1-6 alkyl),
- f) --(C.sub.3-4 cycloalkyl),
- g) --R.sub.3-100, or
- h) --R.sub.3-500 ;
- wherein R.sub.3-6 is
- a) --OH,
- b) --C.sub.1-10 alkyl,
- c) --(C.sub.0-6 alkyl)--C.sub.3 -C.sub.7 cycloalkyl,
- d) --(C.sub.1-4 alkyl)--CH.dbd.CH.sub.2,
- e) --(C.sub.0-6 alkyl)--R.sub.3-4,
- f) --(C.sub.1-6 alkyl)--R.sub.3-100, or
- g) --(C.sub.1-4 alkyl)--R.sub.3-500 ;
- wherein R.sub.3-9 is
- a) --(C.sub.1-6 alkyl),
- b) --(C.sub.0-6 alkyl)--RA.sub.3-RA-12, or
- c) --(C.sub.0-4 alkyl)--RA.sub.3-RA-15 ;
- wherein R.sub.3-100 is independent of and defined the same as R.sub.1-100 ;
- wherein R.sub.3-500 is independent of and defined the same as R.sub.1-500 ;
- wherein RA.sub.3 is independent of and defined the same as RA.sub.1 ;
- wherein RA.sub.3-RA-12, RA.sub.3-RA-15, RA.sub.3-RA-12-AXA and RA.sub.3-RA-15-AXA, are all independent of and defined the same as the corresponding R.sub.1 variables, which are: RA.sub.1-RA-12, RA.sub.1-RA-15, RA.sub.1-RA-12-AXA and RA.sub.1-RA-15-AXA, respectively,
- wherein R.sub.2-100 and R.sub.3-100 are defined independently and are,
- phenyl,
- benzyl, or
- phenyl or benzyl, substituted with one, two, or three of the following, --(C.sub.1-5 alkyl), -hydroxy, --O--(C.sub.1-5 alkyl), or -halo;
- or
- wherein R.sub.2 and R.sub.3 can be taken together to form a ring comprised of the following groups,
- a) (C.sub.6 cycloalkyl),
- b) (C.sub.6 cycloalkyl) substituted with one R.sub.3-9, or
- c) --(C.sub.2 alkyl substituted with zero to one R.sub.3-9)--R.sub.23 --(C.sub.2 alkyl);
- wherein R.sub.3-9 is
- a) --(C.sub.1-6 alkyl),
- b) --(C.sub.0-6 alkyl)--RA.sub.3-RA-12, or
- c) --(C.sub.0-6 alkyl)--RA.sub.3-RA-15 ;
- or
- wherein R.sub.2 and R.sub.3 can be taken together to form a double bond represented by formula 50, shown below, ##STR179## wherein R.sub.11 is a) --H,
- b) --C.sub.1 -C.sub.4 alkyl,
- c) --(RA.sub.3-RA-12), or
- d) pharmaceutically acceptable salts,
- wherein R.sub.23 is
- a) --O--,
- b) --C(O)--,
- c) --N(H)--,
- d) --N(R.sub.3-9)--,
- e) --N(C(O)--R.sub.3-9)--, or
- f) --N(C(O)--O--R.sub.3-9);
- wherein R.sub.30 is
- a) -morpholino,
- b) -piperidino,
- c) -piperazino,
- d) -OR.sub.40,
- e) -halo,
- f) ##STR180## g) --NR.sub.40 R.sub.41 ; wherein R.sub.40 and R.sub.41 are defined independently and are,
- a) --H,
- b) --C.sub.1 -C.sub.4 alkyl,
- c) phenyl, substituted with zero (0) to three (3) RA.sub.1-RA-120,
- wherein R.sub.4 is
- a) --C.sub.1 -C.sub.4 alkyl,
- b) -phenyl, substituted with zero (0) to three (3) RA.sub.1-RA-120, or
- c) --(C.sub.0-6 alkyl)-phenyl, substituted with zero (0) to three (3) RA.sub.1-RA-120 ;
- wherein RA.sub.2-RA-120 and RA.sub.3-RA-120 are independent of and defined the same as RA.sub.1-RA-120 ;
- wherein R.sub.50 and R.sub.51 are defined independently and are
- a) --(H or C.sub.1-6 alkyl),
- b) --(C.sub.0-6 alkyl)--RA.sub.3-RA-12, or
- c) --(C.sub.0-6 alkyl)--RA.sub.3-RA-15 ;
- wherein AA is an amino acid residue,
- wherein P.sub.1 is hydrogen or a nitrogen protecting group,
- wherein m and n are independently zero (0) to five (5) inclusive,
- wherein p and q are independently one (1) to five (5) inclusive,
- wherein z is one (1) to three (3) inclusive; and
- pharmaceutically acceptable salts, including bis salts, thereof,
- with the proviso that when R.sub.1 is 1-phenylpropyl and R.sub.2 is H, then R.sub.3 is not C.sub.1-5 alkyl, and
- with the proviso that when RA.sub.1 or RA.sub.3 is --G.sub.1-2 --(C.sub.0-6 alkyl)--O--RA.sub.1-RA-12, --(C.sub.0-6 alkyl)--G.sub.1-2 --(C.sub.0-6 alkyl)--O--(C.sub.0-6 alkyl), --(C.sub.0-6 alkyl)--G.sub.1-2 --O--(C.sub.1-6 alkyl)--R.sub.1-RA-12, --(C.sub.0-6 alkyl)--G.sub.1-2 --O--(C.sub.1-6 alkyl)--RA.sub.1-RA-15, --G.sub.1-2 --N(R.sub.42).sub.2, or --G.sub.1-2 --NH.sub.2, then G.sub.1-2 is NOT, --C(O)--NH--, --NH--SO.sub.2 --, --SO.sub.2 --NH--, --NH--SO.sub.2 --NH--, --C(O)--O--, --NH--C(O)--NH, --N((C.sub.1-6 alkyl)--RA.sub.1-RA-12)--SO.sub.2 --, or --N((C.sub.0-6 alkyl)--(C.sub.1-6 alkyl))--SO.sub.2 --.
Parent Case Info
The present application is a 371 (national phase) patent application of International Patent Application No. PCT/U.S.94/09,533, International Filing Date Sep. 7, 1994, which is a continuation-in-part patent application of U.S. patent application Ser. No. 08/238,820, filed May 6, 1994, now abandoned, which is a continuation-in-part patent application of U.S. patent application Ser. No. 08/123,029, filed Sep. 17, 1993, now abandoned.
PCT Information
| Filing Document |
Filing Date |
Country |
Kind |
102e Date |
371c Date |
| PCT/US94/09533 |
9/7/1994 |
|
|
7/28/1997 |
7/28/1997 |
| Publishing Document |
Publishing Date |
Country |
Kind |
| WO95/07901 |
3/23/1995 |
|
|
Foreign Referenced Citations (1)
| Number |
Date |
Country |
| 0 202 589 A2 |
Nov 1986 |
EPX |
Continuation in Parts (2)
|
Number |
Date |
Country |
| Parent |
238820 |
May 1994 |
|
| Parent |
123029 |
Sep 1993 |
|
Patent Grant
5977169
