Claims
- 1. A compound of the formula: ##STR13## wherein: R.sup.1 is H, halogen, --CF.sub.3, --CN, --NO.sub.2, or N.sub.3 ;
- R.sup.2 is lower alkyl, lower alkenyl, lower alkynyl, --F.sub.3, --CH.sub.2 F, --CHF.sub.2, --CH.sub.2 CF.sub.3, substituted or unsubstituted phenyl, substituted or unsubstituted benzyl, substituted or unsubstituted 2-phenethyl, or two R.sup.2 groups joined to the same carbon may form a ring of up to 8 members containing 0-2 heteroatoms chosen from O, S, and N;
- R.sup.3 is Hor R.sup.2 ;
- R.sup.4 is halogen, --NO.sub.2, --CN, --OR.sup.3, --SR.sup.3, NR.sup.3 R.sup.3, NR.sup.3 C(O)R.sup.7 or R.sup.3 ;
- R.sup.5 is H, halogen, --NO.sub.2, --N.sub.3, --CN, --SR.sup.2, --NR.sup.3 R.sup.3, --OR.sup.3, lower alkyl, or --C(O)R.sup.3 ;
- R.sup.6 is --(CH.sub.2).sub.s --C(R.sup.7 R.sup.7)--(CH.sub.2).sub.s --R.sup.8 or --CH.sub.2 C(O)NR.sup.12 R.sup.12 ;
- R.sup.7 is H or C.sub.1 -C.sub.4 alkyl;
- R.sup.8 is A) a monocyclic or bicyclic heterocyclic radical containing from 3 to 12 nuclear carbon atoms and 1 or 2 nuclear heteroatoms selected from N, S or O and with each ring in the heterocyclic radical being formed of 5 or 6 atoms, or
- B) the radical W-R.sup.9 ;
- R.sup.9 contains up to 20 carbon atoms and is (1) an alkyl group or (2) an alkylcarbonyl group of an organic acyclic or monocyclic carboxylic acid containing not more than 1 heteroatom in the ring;
- R.sup.10 is --SR.sup.11, --OR.sup.12, or --NR.sup.12 R.sup.12 ;
- R.sup.11 is lower alkyl, --C(O)R.sup.14, unsubstituted phenyl, or unsubstituted benzyl;
- R.sup.12 is H, R.sup.11, or two R.sup.12 groups joined to the same N may form a ring of 5 or 6 members containing 1-2 heteroatoms chosen from O, S, and N;
- R.sup.13 is lower alkyl, lower alkenyl, lower alkynyl, --CF.sub.3, or substituted or unsubstituted phenyl, benzyl, or 2-phenethyl;
- R.sup.14 is H or R.sup.13 ;
- R.sup.15 is R.sup.3 or halogen;
- R.sup.16 is H, C.sub.1 -C.sub.4 alkyl, or OH;
- R.sup.17 is lower alkyl, lower alkenyl, lower alkynyl, or substituted or unsubstituted phenyl, benzyl, or 2-phenethyl;
- R.sup.18 is lower alkyl, lower alkenyl, lower alkynyl, --CF.sub.3, or substituted or unsubstituted phenyl, benzyl, or 2-phenethyl;
- R.sup.19 is lower alkyl, lower alkenyl, lower alkynyl, --CF.sub.3, or substituted or unsubstituted phenyl, benzyl, or 2-phenethyl;
- R.sup.20 is H, C.sub.1 -C.sub.4 alkyl, substituted or unsubstituted phenyl, benzyl, phenethyl, or pyridinyl or two R.sup.20 groups joined to the same N may form a saturated ring of 5 or 6 members containing 1-2 heteroatoms chosen from O, S, and N;
- R.sup.21 is H or R.sup.17 ;
- R.sup.22 is R.sup.4, CHR.sup.7 OR.sup.3, or CHR.sup.7 SR.sup.2 ;
- m and m' are independently 0-8;
- n and n' are independently 0 or 1,
- p and p' are independently 0-8;
- m+n+p is 1-10 when r is 1 and X.sup.2 is O, S, S(O), or S(O).sub.2 ;
- m+n+p is 0-10 when r is 1 and X.sup.2 is CR.sup.3 R.sup.16 ;
- m+n+p is 0-10 when r is 0;
- m'+n'+p' is 0-10;
- r and r' are independently 0 or 1;
- s is 0-3;
- Q.sup.1 is --C(O)OR.sup.3, 1H(or 2H)-tetrazol-5-yl, -C(O)OR.sup.6, --C(O)NHS(O).sub.2 R.sup.13, --CN, --C(O)NR.sup.12 R.sup.12, --NR.sup.21 S(O).sub.2 R.sup.13, --NR.sup.12 C(O)NR.sup.12 R.sup.12, --NR.sup.21 C(O)R.sup.28, --OC(O)NR.sup.12 R.sup.12, --C(O)R.sup.19, --S(O)R.sup.18, --S(O).sub.2 R.sup.18, --S(O).sub.2 NR.sup.12 R.sup.12, --NO.sub.2, --NR.sup.21 C(O)OR.sup.17, --C(NR.sup.12 R.sup.12)=NR.sup.12, --C(R.sup.13)=NOH; or if Q.sup.1 is --C(O)OH and R.sup.22 is --OH, --SH, --CHR.sup.7 OH or --NHR.sup.3, then Q.sup.1 and R.sup.22 and the carbons through which they are attached may form a heterocyclic ring by loss of water;
- Q.sup.2 is OH or NR.sup.20 R.sup.20 ;
- W is O, S, or NR.sup.3 ;
- X.sup.2 and X.sup.3 are independently O, S, S(O), S(O).sub.2, or CR.sup.3 R.sup.16 with the proviso that at least one is S or S(O).sub.2 ;
- Y is ##STR14## Z.sup.1 and Z.sup.2 are independently --HET(--R.sup.3 --R.sup.5)--; HET is the diradical of a benzene, a pyridine, a furan, or a thiophene; and the pharmaceutically acceptable salts thereof.
- 2. A compound of claim 1 wherein:
- R.sup.1 is H, halogen, CF.sub.3, or --CN;
- R.sup.2 is C.sub.1 -C.sub.4 alkyl, --CF.sub.3, --CHF.sub.2, --CH.sub.2 F, or two R.sup.2 groups joined to the same carbon may form a ring of up to 6 carbons;
- R.sup.3 is H or R.sup.2 ;
- CR.sup.3 R.sup.22 may be the radical of a standard amino acid;
- R.sup.4 is --OR.sup.3, --SR.sup.3, NR.sup.3 R.sup.3, NHC(O)CH.sub.3, or R.sup.3 ;
- R.sup.5 is H or halogen;
- R.sup.6 is --(CH.sub.2).sub.s --C(R.sup.7 R.sup.7)--(CH.sub.2).sub.s --R.sup.8 or -CH.sub.2 C(O)NR.sup.12 R.sup.12 ;
- R.sup.7 is H or C.sub.1 -C.sub.4 alkyl;
- R.sup.8 is A) a monocyclic or bicyclic heterocyclic radical containing from 3 to 12 nuclear carbon atoms and 1 or 2 nuclear heteroatoms selected from N, S or O and with each ring in the heterocyclic radical being formed of 5 or 6 atoms, or
- B) the radical W-R.sup.9 ;
- R.sup.9 contains up to 20 carbon atoms and is (1) an alkyl group or (2) an alkylcarbonyl group;
- R.sup.10 is --SR.sup.11, --OR.sup.12, or --NR.sup.12 R.sup.12 ;
- R.sup.11 is lower alkyl, --C(O)R.sup.14, unsubstituted phenyl, or unsubstituted benzyl;
- R.sup.12 is H, R.sup.11, or two R.sup.12 groups joined to the same N may form a ring of 5 or 6 members containing 1-2 heteroatoms chosen from O, S, and N;
- R.sup.13 is lower alkyl, --CF.sub.3, or substituted or unsubstituted phenyl, benzyl, or 2-phenethyl;
- R.sup.14 is H or R.sup.13 ;
- R.sup.15 is R.sup.3 or halogen;
- R.sup.16 is H, C.sub.1 -C.sub.4 alkyl, or OH;
- R.sup.22 is R.sup.4, --CH.sub.2 OR.sup.3, or --CH.sub.2 SR.sup.2 ;
- m and m' are independently 0-4;
- n and n' are independently 0 or 1;
- p and p' are independently 0-4;
- m+n+p is 1-9 when r is 1 and X.sup.2 is O or S;
- m+n+p is 0-9 when r is 1 and X.sup.2 is CR.sup.3 R.sup.16 ;
- m+n+p is 0-9 when r is 0;
- m'+n'+p'is 1-9;
- r and r' are independently 0 or 1;
- s is 0-3;
- Q.sup.1 is --C(O)OR.sup.3, 1H(or 2H)-tetrazol-5-yl, --C(O)OR.sup.6, --C(O)NHS(O).sub.2 R.sup.13, --C(O)NR.sup.12 R.sup.12, --NHS(O).sub.2 R.sup.13 ; or if Q.sup.1 is C(O)OH and R.sup.22 is --OH, --SH, --CH.sub.2 OH or --NHR.sup.3 then Q.sup.1 and R.sup.22 and the carbons through which they are attached may form a heterocyclic ring by loss of water;
- Q.sup.2 is OH;
- W is O, S, or NH;
- X.sup.2 and X.sup.3 are independently O, S, or CR.sup.3 R.sup.16 ;
- Y is ##STR15## Z.sup.1 and Z.sup.2 are independently --HET(--R.sup.3 --R.sup.5)--; HET is the diradical of a benzene, pyridine, furan, or thiophene; and the pharmaceutically acceptable salts thereof.
- 3. A compound of claim 1 wherein the R.sup.22 .alpha. to Q.sup.1 is lower alkyl, CF.sub.3 or substituted or unsubstituted phenyl.
- 4. A compound of claim 1 of the Formula Ia: ##STR16## wherein: R.sup.1 is H, halogen, CN, or CF.sub.3 ;
- Rhu 22 is R.sup.3, --CH.sub.2 OR.sup.3, or --CH.sub.2 SR.sup.2 ;
- Q.sup.1 is --C(O)OH, 1H(or 2H)-tetrazol-5-yl, --C(O)NHS(O).sub.2 R.sup.13, --C(O)NR.sup.12 R.sup.12, or --NHS(O).sub.2 R.sup.13 ;
- m' is 2 or 3;
- p' is 0 or 1;
- m+p is 1-5; and the pharmaceutically acceptable salts thereof.
- 5. A compound of claim 4 wherein m is 0.
- 6. A compound of claim 4 wherein the carbon .alpha. to Q.sup.1 is lower alkyl-substituted.
- 7. A compound of claim 1 of the Formula Ib: ##STR17## wherein: R.sup.1 is H, halogen, CN, or CF.sub.3 ;
- R.sup.22 is R.sup.3 , --CH.sub.2 OR.sup.3, or --CH.sub.2 SR.sup.2 ;
- Q.sup.1 is --C(O)OH, 1H(or 2H)-tetrazol-5-yl, --C(O)NHS(O).sub.2 R.sup.13, --C(O)NR.sup.12 R.sup.12, or --NHS(O).sub.2 R.sup.13 ;
- m is0, 2, or3;
- p is0or 1;
- p' is 1-4;
- m+p is 0-4; and the pharmaceutically acceptable salts thereof.
- 8. A compound of claim 1 of Formula I' ##STR18## wherein the substituents are as follows:
- __________________________________________________________________________ * R.sup.1 Y A B__________________________________________________________________________ 1 RS 7-Cl CHCH.sub.2 CH SCH.sub.2 CHMeCO.sub.2 H (CH.sub.2).sub.2 (1,2-phe)CMe.sub.2 OH 2 RS 7-Cl CH.sub.2 CH.sub.2 SCH.sub.2 CHMeCO.sub.2 H (CH.sub.2).sub.2 (1,2-phe)(1-c-Bu)OH 3 RS 7-Cl CH.sub.2 CH.sub.2 CH SCH.sub.2 CHEtCO.sub.2 H (CH.sub.2).sub.2 (4-Cl-1,2-phe)CMe.sub.2 OH 4 RS 7-Cl CH.sub.2 CH.sub.2 SCH.sub.2 CHMeCO.sub.2 H (1,3-phe)C.sub.2 OH 5 RS 7-Cl CHCH.sub.2 CH S(CH.sub.2).sub.2 CMe.sub.2 OH (CH.sub.2).sub.2 (1,2-phe)CO.sub.2 H 6 S 7-Cl CH.sub.2 CH.sub.2 SCH.sub.2 (S)CHEtCO.sub.2 H (CH.sub.2).sub.2 (1,2-phe)CMe.sub.2 OH 7 S 7-Cl CH.sub.2 CH.sub.2 SCH.sub.2 (R)CH(NH.sub.2)Co.sub.2 H (CH.sub.2).sub.2 (1,2-phe)CMe.sub.2 OH 8 S 7-Cl CH.sub.2 CH.sub.2 SCH.sub.2 (S)CHMeCO.sub.2 H (CH.sub.2).sub.2 (1,2-phe)CMe.sub.2 OH 9 S 7-Cl CH.sub.2 CH2 SCH.sub.2 (S)CH(n-Pr)CO.sub.2 H (CH.sub.2).sub.2 (1,2-phe)CMe.sub.2 OH10 RS 7-Cl CH.sub.2 CH.sub.2 CH SCH.sub.2 CHEtCO.sub.2 H (CH.sub.2).sub.2 (1,2-phe)CMe.sub.2 OH11 RS 7-Cl CHCBr.sub.2 CH SCH.sub.2 CHEtCO.sub.2 H (CH.sub.2).sub.2 (1,2-phe)CMe.sub.2 OH12 RS 7-Cl CH.sub.2 CH.sub.2 SCH.sub.2 CMe.sub.2 CO.sub.2 H (CH.sub.2).sub.2 (1,2-phe)CMe.sub.2 OH13 RS 7-Cl CH.sub.2 CH.sub.2 SCH.sub.2 CHMeCO.sub.2 H (CH.sub.2).sub.2 (1,2-phe)CMe.sub.2 OH14 RS 7-Cl CH.sub.2 CH.sub.2 S(CH.sub.2).sub.2 CO.sub.2 H (CH.sub.2).sub.2 (1,2-phe)CMe.sub.2 OH15 RS 7-Br CH.sub.2 CH.sub.2 SCH.sub.2 CHMeCO.sub.2 H (CH.sub.2).sub.2 (1,2-phe)CMe.sub.2 OH16 RS 7-Cl CH.sub.2 CH.sub.2 S(CH.sub.2)CMe.sub.2 OH (CH.sub.2).sub.2 (1,2-phe)CHMeCO.sub.2 H17 RS 7-Cl CH.sub.2 CH.sub.2 SCH.sub.2 CHEtCO.sub.2 H S(CH.sub.2).sub.2 CMe.sub.2 OH18 S 7-Cl CH.sub.2 CH.sub.2 SCH.sub.2 CHMeCO.sub.2 H (CH.sub.2).sub.2 (1,2-phe)C(CF.sub.3).sub. 2 OH19 RS 7-Cl CHCH.sub.2 CH SCH.sub.2 CHEtCO.sub.2 H (CH.sub.2).sub.2 (1,3-phe)CMe.sub.2 OH20 RS 7-Cl CHCH.sub.2 CH SCH.sub. 2 CHEtCO.sub.2 H SCH.sub.2 CMe.sub.2 CMe.sub.2 OH21 RS 7-Cl CH.sub.2 CH.sub.2 S(CH.sub.2).sub.2 CMe.sub.2 OH (CH.sub.2).sub.2 (1,2-phe)CO.sub.2 H22 RS 7-Cl CH.sub.2 CH.sub.2 S(CH.sub.2).sub.2 CMe.sub.2 OH (CH.sub.2).sub.2 (1,2-phe)CONH.sub.223 RS 7-Cl CH.sub.2 CH.sub.2 SCH.sub.2 CHMeCO.sub.2 H SCH.sub.2 (1,2-phe)CMe.sub.2 OH24 RS 7-CF.sub.3 CH.sub.2 CH.sub.2 SCH.sub.2 CHMeCO.sub.2 H (CH.sub.2).sub.2 (1,4-phe)CMe.sub.2 OH25 RS 7-Cl CH.sub.2 CH.sub.2 SCH.sub.2 CH(OMe)CO.sub.2 H (CH.sub.2).sub.2 (1,2-phe)CMe.sub.2 OH26 RS 7-Cl CHCH.sub.2 CH SCH.sub.2 CHEtCO.sub.2 H (CH.sub.2).sub.2 (1,2-phe)CH(CF.sub.3)OH27 RS H CHCH.sub.2 CH SCH.sub.2 CHMeCO.sub.2 H (CH.sub.2).sub.2 (1,2-phe)CMe.sub.2 OH28 RS H CH.sub.2 CH.sub.2 SCH.sub.2 CHEtCO.sub.2 H (CH.sub.2).sub.2 (1,2-phe)CMe.sub.2 OH29 RS 7-Br CH.sub.2 CH.sub.2 SCH.sub.2 CHEtCO.sub.2 H (CH.sub.2).sub.2 (4-Br-1,2-phe)CMe.sub.2 OH30 RS 7-CN CH.sub.2 CH.sub.2 SCH.sub.2 CHEtCO.sub.2 H (CH.sub.2).sub.2 (1,2-phe)CMeEtOH31 RS 7-Br CHCH.sub.2 CH SCH.sub.2 CHEtCO.sub.2 H (CH.sub.2).sub.2 (1,2-phe)CEt.sub.2 OH32 RS 7-Cl CH.sub.2 CH.sub.2 SCH.sub.2 CHMeCO.sub.2 H (CH.sub.2).sub.2 (1,2-phe)CMe.sub.2 NH.sub.233 RS 7-Cl CHCH.sub.2 CH SCH.sub.2 CHEtCO.sub.2 H (CH.sub.2).sub.2 (1,2-phe)CHMeNHMe34 RS 7-Br CH.sub.2 CH.sub.2 SCH.sub.2 CHEtCO.sub.2 H (CH.sub.2).sub.2 (1,2-phe)CHMeNMe.sub.235 RS 7-Cl CH.sub.2 CH.sub.2 SCH.sub.2 CHEtCO.sub.2 H (CH.sub.2).sub.2 (2,5-fur)CMe.sub.2 OH36 RS 7-Cl CH.sub.2 CH.sub.2 SCH.sub.2 CHEtCO.sub.2 H (CH.sub.2).sub.2 (2,6-pye)CMe.sub.2 OH37 RS 7-Cl CH.sub.2 CH.sub.2 SCH.sub.2 CHEtCO.sub.2 H (CH.sub.2).sub.2 (4,2-pye)CMe.sub.2 OH38 RS 7-Cl CHCH.sub.2 CH SCH.sub.2 CHEtCO.sub.2 H (2,5-thio)CMe.sub.2 OH39 RS 7-Cl CH.sub.2 CH.sub.2 SCH.sub.2 CHEtCO.sub.2 H (3,2-pye)CMe.sub.2 OH40 RS 7-Br CH.sub.2 CH.sub.2 SCH.sub.2 CHEtCO.sub.2 H (1,4-phe)CMe.sub.2 OH41 RS 7-Cl CH.sub.2 CH.sub.2 SCH.sub.2 CHMeCONHS(O).sub.2 Me (CH.sub.2).sub.2 (1,2-phe)CMe.sub.2 OH42 RS 7-Cl CH.sub.2 CH.sub.2 SCH.sub.2 CHMeCONH.sub.2 (CH.sub.2).sub.2 (1,2-phe)CMe.sub.2 OH43 RS 7-Cl CH.sub.2 CH.sub.2 SCH.sub.2 CHMeTz (CH.sub.2).sub.2 (1,2-phe)CMe.sub.2 OH44 RS 7-Cl CHCH.sub.2 CH SCH.sub.2 CHEtTz (CH.sub.2).sub.2 (1,2-phe)CMe.sub.2 OH45 RS 7-Cl CHCH.sub.2 CH SCH.sub.2 CHEtCONHS(O).sub.2 CF.sub.3 (CH.sub.2).sub.2 (1,2-phe)CMe.sub.2 OH46 RS 7-Cl CH.sub.2 CH.sub.2 SCH.sub.2 CHMeNO.sub.2 (CH.sub.2).sub.2 (1,2-phe)CMe.sub.2 OH47 RS 7-Cl CH.sub.2 CH.sub.2 S(CH.sub.2).sub.2 CONHS(O).sub.2 Ph (CH.sub.2).sub.2 (1,2-phe)CMe.sub.2 OH48 RS 7-Cl CH.sub.2 CH.sub.2 SCH.sub.2 CHEtCO.sub.2 H (CH.sub.2).sub.2 (1,2-phe)CH.sub.2 CMe.sub.2 OH49 RS 7-Cl CHCH.sub.2 CH SCH.sub.2 CHEtCO.sub.2 H (CH.sub.2).sub.3 (1,2-phe)CMe.sub.2 OH50 S 7-Cl CH.sub.2 CH.sub.2 SCH.sub.2 CH(CH.sub.2 CH.dbd.CH.sub.2)CO.sub.2 H (CH.sub.2).sub.2 (1,2-phe)CMe.sub.2 OH51 S 7-Cl CHCH.sub.2 CH SCH.sub.2 CHEtCO.sub.2 H (CH.sub.2).sub.2 (1,2-phe)CHMeOH52 S 7-Cl CH.sub.2 CH.sub.2 SCH.sub.2 CH(CH.sub.2 SMe)CO.sub.2 H (CH.sub.2).sub.2 (1,2-Phe)CMe.sub.2 OH53 S 7-Cl CHCH.sub.2 CH SCH.sub.2 CH(c-Pr)CO.sub.2 H (CH.sub.2).sub.2 (1,2-phe)CMe.sub.2 OH54 S 7-Cl CH.sub.2 CH.sub.2 SCH.sub.2 CH(CH.sub.2 C.tbd.CH)CO.sub.2 H (CH.sub.2).sub.2 (1,2-phe)CMe.sub.2 OH55 S 7-Cl CH.sub.2 CH.sub.2 SCH.sub.2 CHPhCO.sub.2 H (CH.sub.2).sub.2 (1,2-phe)CMe.sub.2 OH56 RS 7-Cl CH.sub.2 CH.sub.2 SCH.sub.2 CHEtCO.sub.2 H (1,2-phe)CMe.sub.2 OH57 RS 7-Cl CH.sub.2 CH.sub.2 S(CH.sub.2).sub.2 CMe.sub.2 OH (1,3-phe)CO.sub.2 H58 RS 7-Cl CH.sub.2 CH.sub.2 S(CH.sub.2).sub.2 CO.sub.2 H CH.sub.2 CHOH(1,3-phe)CN.sub.4 H59 RS 7-Cl CH.sub.2 CH.sub.2 S(CH.sub.2).sub.2 CO.sub.2 H CH.sub.2 CHOH(1,4-phe)CN.sub.4 H60 S 7-Cl CH.sub.2 CH.sub.2 S(CH.sub.2).sub.2 CO.sub.2 H CH.sub.2).sub.2 (1,2-phe)CMe.sub.2 OH61 S 7-Cl CH.sub.2 CH.sub.2 SCH.sub.2 CHCF.sub.3 CO.sub.2 H CH.sub.2).sub.2 (1,2-phe)CMe.sub.2 OH62 S 7-Cl CH.sub.2 CH.sub.2 S(CH.sub.2).sub.3 CO.sub.2 H (CH.sub.2).sub.2 (1,2-phe)CMe.sub.2 OH63 S 7-Cl CH.sub.2 CH.sub.2 S(CH.sub. 2).sub.2 CHMeCO.sub.2 H (CH.sub.2).sub.2 (1,2-phe)CMe.sub.2 OH64 S 7-Cl CH.sub.2 CH.sub.2 S(O).sub.2 CH.sub.2 (S)CHEtCO.sub.2 H (CH.sub.2).sub.2 (1,2-phe)CMe.sub.2 OH65 S 7-Cl CH.sub.2 CH.sub.2 SCH.sub.2 CH(CH.sub.2 OMe)CO.sub.2 H (CH.sub.2).sub.2 (1,2-phe)CMe.sub.2 OH66 S 7-Cl CH.sub.2 CH.sub.2 S(CH.sub.2).sub.2 CMe.sub.2 OH (CH.sub.2).sub.2 (1,2-phe)CO.sub.2 H67 R 7-Cl CH.sub.2 CH.sub.2 S(CH.sub.2).sub.2 CMe.sub.2 OH (CH.sub.2).sub.2 (1,2-phe)CO.sub.2 H68 S 7-Cl CH.sub.2 CH.sub.2 SCH.sub.2 (S)CHEtCO.sub.2 H (CH.sub.2).sub.2 (1,3-phe)CMe.sub.2 OH69 S 7-Cl CH.sub.2 CH.sub.2 SCH.sub.2 CHEtCO.sub.2 H (CH.sub.2).sub.2 (1,3-phe)(1,1-c-Bu)OH70 S 7-Cl CH.sub.2 CH.sub.2 S(CH.sub.2).sub.2 CMe.sub.2 OH (CH.sub.2).sub.3 (1,2-phe)COOH71 R 7-Cl CH.sub.2 CH.sub.2 S(CH.sub.2).sub.2 CO.sub.2 H S(CH.sub.2).sub.2 (1,-c-Pen)OH72 S 7-Cl CH.sub.2 CH.sub.2 SCH.sub.2 CH(CH.sub.2 CF.sub.3)CO.sub.2 H (CH.sub.2).sub.2 (1,2-phe)CMe.sub.2 OH73 S 7-Cl CH.sub.2 CH.sub. 2 S(CH.sub.2).sub.2 CMe.sub.2 OH (CH.sub.2).sub.2 (4-C1-1,2-phe)CO.sub.2 H74 R 7-Cl CH.sub.2 CH.sub.2 SCH.sub.2 (S)CHEtCONHS(O).sub.2 Me (CH.sub.2).sub.2 (1,2-phe)CMe.sub.2 OH75 S 7-Cl CH.sub.2 CH.sub.2 S(CH.sub.2).sub.2 CMeOH (CH.sub.2).sub.2 (1,3-phe)CMe.sub.2 CO.sub.2 H76 S 7-Cl CH.sub.2 CH.sub.2 S(CH.sub.2).sub.2 CMeOH (CH.sub.2).sub.2 (1,3-phe)CHMeCO.sub.2 H77 S 7-Cl CH.sub.2 CH.sub.2 S(CH.sub.2).sub.3 CMe.sub.2 OH (CH.sub.2).sub.2 (1,2-Phe)CO.sub.2 H78 S 7-Cl CH.sub.2 CH.sub.2 SCH.sub.2 (S)CHEtCO.sub.2 H (CH.sub.2).sub.2 (1,4-phe)CMe.sub.2 OH79 RS 7-Cl CH.sub.2 CH.sub.2 S(CH.sub.2).sub.2 CMe.sub.2 OH (CH.sub.2).sub.2 (1,3-phe)CN.sub.4 H80 S 7-Cl CH.sub.2 CH.sub.2 S(CH.sub.2).sub.3 CMe.sub.2 OH (CH.sub.2).sub.2 (1,2-phe)CHMeCO.sub.2 H81 S 7-Cl CH.sub.2 CH.sub.2 S(CH.sub.2).sub.3 CMe.sub.2 OH (CH.sub.2).sub.2 (1,2-phe)CHMeCONHS(O).sub .2 CH.sub.382 S 7-Cl CH.sub.2 CH.sub.2 S(CH.sub.2).sub.2 CMe.sub.2 OH (CH.sub.2).sub.3 (1,2-phe)CO.sub.2 H83 R 7-Cl CH.sub.2 CH.sub.2 S(O).sub.2 CH.sub.2 (S)CHEtCO.sub.2 H (CH.sub.2).sub.2 (1,2-phe)CMe.sub.2 OH84 S 7-Cl CH.sub.2 CH.sub.2 S(CH.sub.2).sub.2 CMe.sub.2 OH (CH.sub.2).sub.2 (4-Cl-1,2-phe)CHMeCO.sub. 2 H85 S 7-Cl CH.sub.2 CH.sub.2 SCH.sub.2 (S)CHMeCO.sub.2 H (CH.sub.2).sub.2 (1,2-phe)CH.sub.2 CMe.sub.2 OH86 S 7-Cl CH.sub.2 CH.sub.2 S(CH.sub.2).sub.2 CME.sub.2 OH (CH.sub.2).sub.2 (1,2-phe)CO.sub.2 Me87 S 7-Cl CH.sub.2 CH.sub.2 S(CH.sub.2).sub.3 CMe.sub.2 OH (CH.sub.2).sub.2 (4-Cl-1,2-phe)CO.sub.2 H88 R 7-Cl CH.sub.2 CH.sub.2 S(CH.sub.2).sub.2 CMe.sub.2 OH (CH.sub.2).sub.2 (4-Cl-1,2-phe)CO.sub.2 H89 S 7-Cl CH.sub.2 CH.sub.2 S(CH.sub.2).sub.3 CMe.sub.2 OH (CH.sub.2).sub.2 (1,2-phe)CMe.sub.2 CO.sub.2 H90 S 7-Cl CH.sub.2 CH.sub.2 S(CH.sub.2).sub.2 CMe.sub.2 OH (CH.sub.2).sub.3 (R)CHMe.sub.2 CO.sub.2 H91 S 7-Cl CH.sub.2 CH.sub.2 S(CH.sub.2).sub.3 CEt.sub.2 OH (CH.sub.2).sub.2 (1,2-phe)CO.sub.2 H92 S 7-Cl CH.sub.2 CH.sub.2 S(CH.sub. 2).sub.3 CEt.sub.2 OH (CH.sub.2).sub.2 (1,2-phe)CHMeCO.sub.2 H93 R 7-Cl CH.sub.2 CH.sub.2 SCHMeCH.sub.2 CO.sub.2 H (CH.sub.2).sub.2 (1,2-phe)CMe.sub.2 OH94 S 7-Cl CH.sub.2 CH.sub.2 S(CH.sub.2).sub.3 CMe.sub.2 OH (CH.sub.2).sub.2 (1,2-phe)CHEtCO.sub.2 H95 S 7-Cl CH.sub.2 CH.sub.2 S(CH.sub.2).sub.3 CMe.sub.2 OH (CH.sub.2).sub.2 (1,2-phe)CH(n-Pr)CO.sub.2 H96 S 7-Cl CH.sub.2 CH.sub.2 S(CH.sub.2).sub.3 CMe.sub.2 OH (CH.sub.2).sub.2 (1,2-phe)CH(i-Pr)CO.sub.2 H97 R 7-Cl CH.sub.2 CH.sub.2 SCH.sub.2 MeCHMeCO.sub.2 H (CH.sub.2).sub.2 (1,2-phe)CMe.sub.2 OH98 R 7-Cl CH.sub.2 CH.sub.2 S(CH.sub.2).sub.2 CMe.sub.2 OH (CH.sub.2).sub.3 (R)CHMeCO.sub.2 H99 R 7-Cl CH.sub.2 CH.sub.2 SCH.sub.2 (S)CHMeCN.sub.4 H (CH.sub.2).sub.2 (1,2-phe)CMe.sub.2 OH100 S 7-Cl CH.sub.2 CH.sub.2 SCH.sub.2 (S)CHMeCO.sub.2 H (CH.sub.2).sub.2 (3-OH-1,4-phe)CHMeOH101 S 7-Cl CH.sub.2 CH.sub.2 S(CH.sub.2).sub.3 CHMeOH (CH.sub.2).sub.2 (1,2-phe)CHMeCO.sub.2 H102 R 7-Cl CH.sub.2 CH.sub.2 S(S)CHMeCH.sub.2 CO.sub.2 H (CH.sub.2).sub.2 (1,2-phe)CMe.sub.2 OH103 R 7-Cl CH.sub.2 CH.sub.2 S(R)CHMeCH.sub.2 CO.sub.2 H (CH.sub.2).sub.2 (1,2-phe)CMe.sub.2 OH104 R 7-Cl CH.sub.2 CH.sub.2 S(S)CHMe(S)CHMeCO.sub.2 H (CH.sub.2).sub.2 (1,2-phe)CMe.sub.2 OH105 R 7-Cl CH.sub.2 CH.sub.2 S(R)CHMe(R)CHMeCO.sub.2 H (CH.sub.2).sub.2 (1,2-phe)CMe.sub.2 OH106 R 7-Cl CH.sub.2 CH.sub.2 SCHEtCH.sub.2 CO.sub.2 H (CH.sub.2).sub.2 (1,2-phe)CMe.sub.2 OH107 S 7-Cl CH.sub.2 CH.sub.2 S(CH.sub.2).sub.3 CHMeOH (CH.sub.2).sub.2 (1,2-phe)CHEtCO.sub.2 H108 S 7-Cl CH.sub.2 CH.sub.2 SCH.sub.2 (S)CHMeCO.sub.2 H (CH.sub.2).sub.2 (1,2-phe)CH(OH)CH.sub.2 (OH)Ph109 R 7-Cl CH.sub.2 CH.sub.2 SCMe.sub.2 CH.sub.2 CO.sub.2 H (CH.sub.2).sub.2 (1,2-phe)CMe.sub.2 OH110 R 7-Cl CH.sub.2 CH.sub.2 SCH.sub.2 CHMeCH.sub.2 CO.sub.2 H (CH.sub.2).sub.2 (1,2-phe)CMe.sub.2 OH111 R 7-Cl CH.sub.2 CMe.sub.2 SCH.sub.2 (1,1-c-Pr)CH.sub.2 CO.sub.2 H (CH.sub.2).sub.2 (1,2-phe)CMe.sub.2 OH112 S 7-Cl CMe.sub.2 CH.sub.2 SCH.sub.2 (1,1-c-Pr)CH.sub.2 CO.sub.2 H (CH.sub.2).sub.2 (1,2-phe)CO.sub.2 H113 S 7-Cl Me.sub.2 H.sub.2 CH.sub.2 S(CH.sub.2).sub.3 CMe.sub.2 OH (CH.sub.2).sub.2 (1,2-phe)(R)CHEtCO.sub.2 H114 S 7-Cl CH.sub.2 CH.sub.2 S(CH.sub.2).sub.3 CMe.sub.2 OH (CH.sub.2).sub.2 (1,2-phe)(S)CHEtCO.sub.2 H115 S 7-Cl CH.sub.2 CH.sub.2 S(CH.sub.2).sub.3 CMe.sub.2 OH (CH.sub.2).sub.2 (4-Cl-1,2-phe)CHEtCO.sub. 2 H116 S 7-Cl CH.sub.2 CH.sub.2 S(CH.sub.2).sub.3 CMe.sub.2 OH (CH.sub.2).sub.2 (1,2-phe)CEt.sub.2 CO.sub.2 H117 S 7-Cl CH.sub.2 CH.sub.2 S(CH.sub.2).sub.3 CMe.sub.2 OH (CH.sub.2).sub.2 (1,2-phe)CH.sub.2 CO.sub.2 H118 S 7-Cl CH.sub.2 CH.sub.2 S(CH.sub.2).sub.3 CMe.sub.2 OH (CH.sub.2).sub.2 (1,2-phe)CH(OH)CO.sub.2 H119 S 7-Cl CHMeCHMe SCH.sub.2 (1,1-c-Pr)CH.sub.2 CO.sub.2 H (CH.sub.2).sub.2 (1,2-phe)CHEtCO.sub.2 H120 S 7-Cl CH.sub.2 CH.sub.2 S(CH.sub.2).sub.3 CMe.sub.2 OH (CH.sub.2).sub.2 CHMeCH.sub.2 CO.sub.2 H121 R 7-Cl CH.sub.2 CH.sub.2 SCH.sub.2 CMe.sub.2 CH.sub.2 CO.sub.2 H (CH.sub.2).sub.2 (1,2-phe)CMe.sub.2 OH122 R 7-Cl CH.sub.2 CH.sub.2 S(CH.sub.2).sub.4 CMe.sub.2 OH (CH.sub.2).sub.2 (1,2-phe)CHEtCO.sub.2 H123 S 7-F CH.sub.2 CH.sub.2 SCH.sub.2 CMe.sub.2 CH.sub.2 CO.sub.2 H (CH.sub.2).sub.2 (1,2-phe)CO.sub.2 H124 S 7-Br CH.sub.2 CH.sub.2 SCH.sub.2 CMe.sub.2 CH.sub.2 CO.sub.2 H (CH.sub.2).sub.2 (1,2-phe)CO.sub.2 H125 S 7-I CH.sub.2 CH.sub.2 SCH.sub.2 (1,1-c-Pr)CH.sub.2 CO.sub.2 H (CH.sub.2).sub.2 (1,2-phe)CMe.sub.2 OH126 S 7-CF.sub.3 CH.sub.2 CH.sub.2 SCH.sub.2 CMe.sub.2 CH.sub.2 CO.sub.2 H (CH.sub.2).sub.2 (1,2-phe)CHMeCO.sub.2 H127 S 7-CN CH.sub.2 CH.sub.2 SCH.sub.2 CMe.sub.2 CH.sub.2 CO.sub.2 H (CH.sub.2).sub.2 (1,2-phe)CHEtCO.sub.2 H128 S 7-NO.sub.2 CH.sub.2 CH.sub.2 SCH.sub.2 (1,1-c-Pr)CH.sub.2 CO.sub.2 H (CH.sub.2).sub.2 (1,2-phe)CMe.sub.2 OH129 R 7-N.sub.3 CH.sub.2 CH.sub.2 SCH.sub.2 (1,1-c-Pr)CH.sub.2 CO.sub.2 H (CH.sub.2).sub.2 (1,2-phe)CMe.sub.2 OH130 RS 7-Cl CH.sub.2 CH.sub.2 S(CH.sub.2).sub.2 CMe.sub.2 OH (CH.sub.2).sub.2 CMe.sub.2 CH.sub.2 CO.sub.2 H131 R 7-Cl CH.sub.2 CH.sub.2 S(1,2-phe)CH.sub.2 CO.sub.2 H (CH.sub.2).sub.2 (1,2-phe)CMe.sub.2 OH132 R 7-Cl CH.sub.2 CH.sub.2 S(CH.sub.2).sub.3 CMe.sub.2 OH (CH.sub.2).sub.2 (1,2-phe)CHEtCO.sub.2 H133 S 7-Cl CH.sub.2 CH.sub.2 S(CH.sub.2).sub.2 CMe.sub.2 OH (CH.sub.2).sub.2 (1,2-phe)CHEtCO.sub.2 H134 S 7-Cl CH.sub.2 CH.sub.2 S(CH.sub.2).sub.3 CMe(4-Cl-Ph)OH (CH.sub.2).sub.2 (1,2-phe)CHEtCO.sub.2 H135 R 7-Cl CH.sub.2 CH.sub.2 SCH.sub.2 (1,2-phe)CMe.sub.2 OH (CH.sub.2).sub.2 CMe.sub.2 CH.sub.2 CO.sub.2 H136 R 7-Cl CH.sub.2 CH.sub.2 SCH.sub.2 (1,1-c-Pr)CH.sub.2 CO.sub.2 H (CH.sub.2).sub.2 (1,2-phe)CMe.sub.2 OH137 R 7-Cl CH.sub.2 CH.sub.2 SCH.sub.2 (1,1-c-Bu)CH.sub.2 CO.sub.2 H (CH.sub.2).sub.2 (1,2-phe)CMe.sub.2 OH138 R 7-Cl CH.sub.2 CH.sub.2 SCH.sub.2 CMe.sub.2 CHMeCO.sub.2 H (CH.sub.2).sub.2 1,2-phe)CMe.sub.2 OH139 S 7-Cl CH.sub.2 CH.sub.2 SCH.sub.2 (1,2-phe)CMe.sub.2 OH (CH.sub.2).sub.2 CMe.sub.2 CH.sub.2 CO.sub.2 H140 R 7-Cl CH.sub.2 CH.sub.2 SCHMeCMe.sub.2 CH.sub.2 CO.sub.2 H (CH.sub.2).sub.2 (1,2-phe)CMe.sub.2 OH141 R 7-Cl CH.sub.2 CH.sub.2 S(1,1-c-Pr)CH.sub.2 CO.sub.2 H (CH.sub.2).sub.2 (1,2-phe)CMe.sub.2 OH142 R 7-Cl CH.sub.2 CH.sub.2 S(1,1-c-Pr)CHMeCO.sub.2 H (CH.sub.2).sub.2 (1,2-phe)CMe.sub.2 OH143 R 7-Cl CH.sub.2 CH.sub.2 S(1,1-c-Pr)CH.sub.2 CO.sub.2 H (CH.sub.2).sub.2 (1,3-phe)CMe.sub.2 OH144 R 7-Cl CH.sub.2 CH.sub.2 S(1,1-c-Pr)CH.sub.2 CO.sub.2 H (CH.sub.2).sub.2 (1,2-phe)(1,1-c-Bu)OH145 R 7-Cl CH.sub.2 CH.sub.2 S(1,1-c-Pr)CH.sub.2 CO.sub.2 H (CH.sub.2).sub.2 (1,3-phe)(1,1-c-Bu)OH146 R 7-Cl CH.sub.2 CH.sub.2 SCH.sub.2 (1,1-c-Pr)CH.sub.2 CO.sub.2 H (CH.sub.2).sub.2 (1,3-phe)CMe.sub.2 OH147 R 7-Cl CHCH.sub.2 CH SCH.sub.2 (1,1-c-Pr)CH.sub.2 CO.sub.2 H (CH.sub.2).sub.2 (1,2-phe)CMe.sub.2 OH148 R 7-Cl CHCH.sub.2 CH S(1,1-c-Pr)CH.sub.2 CO.sub.2 H (CH.sub.2).sub.2 (1,2-phe)CMe.sub.2 OH149 R 7-Cl CHCH.sub.2 CH SCMe.sub.2 CH.sub.2 CO.sub.2 H (CH.sub.2).sub.2 (1,2-phe)CMe.sub.2 OH150 R 7-Cl CHCH.sub.2 CH S(1,1-c-Pr)(S)CHMeCO.sub.2 H (CH.sub.2).sub.2 (1,2-phe)CMe.sub.2 OH151 R 7-Cl CHCH.sub.2 CH S(1,1-c-Pr)CHMeCO.sub.2 H (CH.sub.2).sub.2 (1,3-phe)CMe.sub.2 OH152 R 7-Cl CHCH.sub.2 CH S(1,1-c-Pr)CH.sub.2 CO.sub.2 H (CH.sub.2).sub.2 (1,2-phe)(1,1-c-Bu)OH153 R 7-Cl CHCH.sub.2 CH S(1,1-c-Pr)CH.sub.2 CO.sub.2 H (CH.sub.2).sub.2 (1,3-phe)(1,1-c-Bu)OH154 S 7-Cl CH.sub.2 CH.sub.2 SCH.sub.2 CHEtCO.sub.2 H (CH.sub.2).sub.2 (1,2-phe)CMe.sub.2 OH155 S 7-Cl CH.sub.2 CH.sub.2 SCH.sub.2 (1,2-phe)CMe.sub.2 OH CH.sub.2).sub.2 (1,2-phe)CHEtCO.sub.2 H156 S 7-Cl CH.sub.2 CH.sub.2 S(CH.sub.2).sub.2 CMe.sub.2 OH (CH.sub.2).sub.2 (1,2-phe)CH.sub.2 CO.sub.2 H157 S 7-Cl CH.sub.2 CH.sub.2 SCH.sub.2 (1,2-phe)CHMe.sub.2 OH (CH.sub.2).sub.2 (1,2-phe)CH.sub.2 CO.sub.2 H158 S 7-Cl CH.sub.2 CH.sub.2 S(CH.sub.2).sub.2 CMe.sub.2 OH (CH.sub.2).sub.2 (4-Cl-1,2-phe)CH.sub.2 CO.sub.2 H159 S 7-Cl CH.sub.2 CH.sub.2 SCH.sub.2 (1,2-phe)CMe.sub.2 OH (CH.sub.2).sub.2 (4-Cl-1,2-phe)CH.sub.2 CO.sub.2 H160 R 7-Cl CH.sub.2 CH.sub.2 SCH.sub.2 CMe.sub.2 CH.sub.2 CO.sub.2 H (CH.sub.2).sub.4 (1,2-phe)CMe.sub.2 OH161 S 7-Cl CH.sub.2 CH.sub.2 S(CH.sub.2).sub.3 CMe.sub.2 OH (CH.sub.2).sub.2 (4-Cl-1,2-phe)CH.sub.2 CO.sub.2 H162 S 7-Cl CH.sub.2 CH.sub.2 SCH.sub.2 (1,2-phe)CMe.sub.2 OH (CH.sub.2).sub.2 (1,1-c-Pr)CH.sub.2 CO.sub.2 H__________________________________________________________________________
- 9. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 1 and a pharmaceutically acceptable carrier.
- 10. The pharmaceutical composition of claim 9 additionally comprising an effective amount of a second active ingredient selected from the group consisting of non-steroidal anti-inflammatory drugs; peripheral analgesic agents; cyclooxygenase inhibitors; leukotriene antagonists; leukotriene bisynthesis inhibitors; H2-receptor antagonists; antihistaminic agents; prostaglandin antagonists; thromboxane antagonists; thromboxane synthetase inhibitors; and ACE antagonists.
- 11. A pharmaceutical composition according to claim 10, wherein the second active ingredient is a non-steroidal anti-inflammatory drug.
- 12. A pharmaceutical composition of claim 11, wherein the weight ratio of said compound of claim 1 to said second active ingredient ranges from about 1000: 1 to 1: 1000.
- 13. A method of preventing the synthesis, the action, or the release of SRS-A or leukotrienes in a mammal which comprises administering to said mammal an effective amount of a compound of claim 1.
- 14. The method of claim 13 wherein the mammal is man.
- 15. A method of treating asthma in a mammal comprising administering to a mammal in need of such treatment a therapeutically effective amount of a compound of claim 1.
- 16. A method of treating inflammatory deseases of the eye in a mammal which comprises administering to a mammal in need of such treatment a therapeutically effective amount of a compound of claim 1.
- 17. The method of claim 16 wherein the mammal is man.
CROSS-REFERENCE
This is a CIP of U.S. Ser. No. 596,844, Oct. 12, 1990, abandoned.
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4833161 |
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|
4851409 |
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|
5104882 |
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Continuation in Parts (1)
|
Number |
Date |
Country |
Parent |
596844 |
Oct 1990 |
|