US 5,204,344 AGranted

(Quinolin-2-ylmethoxy)indoles as inhibitors of the biosynthesis of leukotrienes

AssigneeMerck Frosst Canada, Inc.

InventorsPetpiboon Prasit, Rejean Fortin, John H. Hutchinson, Michel L. Belley, Serge Leger, John Gillard, Richard Frenette

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Abstract

Compounds having the formula I: ##STR1## are inhibitors of leukotriene biosynthesis. These compounds are useful as anti-asthmatic, anti-allergic, anti-inflammatory, and cytoprotective agents. They are also useful in treating diarrhea, hypertension, angina, platelet aggregation, cerebral spasm, premature labor, spontaneous abortion, dysmenorrhea, and migraine.

Claims22

Dependent claims

A compound of the formula I:

##STR23## wherein:
R.sup.1, R.sup.2, R.sup.3, R.sup.4 and R.sup.10 are independently hydrogen, halogen, lower alkyl, lower alkenyl, lower alkynyl, --CF.sub.3, --CN, --NO.sub.2, --N.sub.3, --C(OH)R.sup.11 R.sup.11, --CO.sub.2 R.sup.12, --SR.sup.14, --S(O)R.sup.14, --S(O).sub.2 R.sup.14, --S(O).sub.2 NR.sup.15 R.sup.15, --OR.sup.15, --NR.sup.15 R.sup.15, --C(O)R.sup.16 or --(CH.sub.2).sub.t R.sup.21 ;
R.sup.5 is hydrogen, --CH.sub.3, --CF.sub.3, --C(O)H, X.sup.1 --R.sup.6 or X.sup.2 --R.sup.7 ;
R.sup.6 and R.sup.9 are independently:
alkyl, --(CH.sub.2).sub.u Ph(R.sup.10).sub.2 or --(CH.sub.2).sub.u Th(R.sup.10).sub.2 ;
R.sup.7 is --CF.sub.3 or R.sup.6 ;
R.sup.8 is hydrogen or X.sup.3 --R.sup.9 ;
each R.sup.11 is independently hydrogen or lower alkyl, or two R.sup.11 's on same carbon atom are joined to form a cycloalkyl ring of 3 to 6 carbon atoms;
R.sup.12 is hydrogen, lower alkyl or --CH.sub.2 R.sup.21 ;
R.sup.13 is lower alkyl or --(CH.sub.2).sub.r R.sup.21 ;
R.sup.14 is --CF.sub.3 or R.sup.13 ;
R.sup.15 is hydrogen, --C(O)R.sup.16, R.sup.13, or two R.sup.15 's on the same nitrogen may be joined to form pyrrolidine, piperidine, morpholine, thiamorpholine, piperazine or N-methylpiperazine 2,5 dioxo-1-pyrrolidinyl, (3-pyridinylcarbonyl)amino, 1,3-dihydro-1,3-dioxo-2H-isoindol-2-yl, 1,3-dihydro-2H-isoindol-2-yl, 2,4-imidazolinedion-1-yl, 2,6-piperidinedion-1-yl, 2-imidazolyl, 2-oxo-1,3-dioxolen-4-yl, piperindin-1-yl, morpholin-1-yl or piperazin-1-yl;
R.sup.16 is hydrogen, --CF.sub.3, lower alkyl, lower alkenyl, lower alkynyl or --(CH.sub.2).sub.r R.sup.21 ;
R.sup.17 is --(CH.sub.2).sub.s --C(R.sup.18 R.sup.18)--(CH.sub.2).sub.s --R.sup.19 or --CH.sub.2 C(O)NR.sup.15 R.sup.15 ;
R.sup.18 is hydrogen or lower alkyl;
R.sup.19 is a) pyrrolidine, piperidine, morpholine, thiamorpholine, piperazine or N-methylpiperazine 2,5 dioxo-1-pyrrolidinyl,(3-pyridinylcarbonyl)amino,1,3-dihydro-1,3-dioxo-2H-i soindol-2-yl,1,3-dihydro-2H-isoindol-2-yl,2,4-imidazolinedion-1-yl,2,6-pipe ridinedion-1-yl,2-imidazolyl,2-oxo-1,3-dioxolen-4-yl,piperindin-1-yl,morpho lin-1-yl or piperazin-1-yl, or b) the radical W-R.sup.20 ;
R.sup.20 is alkyl or C(O)R.sup.23 ;
R.sup.21 is phenyl substituted with 1 or 2 R.sup.22 groups;
R.sup.22 is hydrogen, halogen, lower alkyl, lower alkoxy, lower alkylthio, lower alkylsulfonyl, lower alkylcarbonyl, --CF.sub.3, --CN, --NO.sub.2 or --N.sub.3 ;
R.sup.23 is alkyl, cycloalkyl, monocyclic tetrahydrofuran, tetrahydrothiophene, pyrrolidine, piperidine or tetrahydropyran;
R.sup.24 is the residual structure of a standard amino acid, or R.sup.18 and R.sup.24 attached to the same N can cyclize to form a proline residue;
m is 0 to 1;
n is 0 to 3;
p is 1 to 3 when m is 1;
p is 0 to 3 when m is 0;
r is 0 to 2;
s is 0 to 3;
t is 0 to 2;
u is 0 to 3;
v is 0 or 1;
W is 0, S or NR.sup.15 ;
X.sup.1 is O, or NR.sup.15 ;
X.sup.2 is C(O), CR.sup.11 R.sup.11, S, S(O) or S(O).sub.2 ;
X.sup.3 is C(O), CR.sup.11 R.sup.11, S(O).sub.2 or a bond;
X.sup.4 is CH.dbd.CH, CH.sub.2 --Y.sup.1 or Y.sup.1 --CH.sub.2 ;
Y is X.sup.1 or X.sup.2 ;
Y.sup.1 is O, S, S(O).sub.2 or CH.sub.2 ;
Q is --CO.sub.2 R.sup.12, --C(O)NHS(O).sub.2 R.sup.14, --NHS(O).sub.2 R.sup.14, --S(O).sub.2 NHR.sup.15 --C(O)NR.sup.15 R.sup.15, --CO.sub.2 R.sup.17, --C(O)NR.sup.18 R.sup.24, --CH.sub.2 OH, or 1H- or 2H-tetrazol-5-yl;
and the pharmaceutically acceptable salts thereof.

36 more elements

A sodium salt of a compound which is:

3-[N-(p-chlorobenzyl)-3-(t-butylthio)-5-(quinolin-2-ylmethoxy)indol-2-yl]-2 ,2-dimethylpropanoic acid;
3-[N-(p-chlorobenzyl)-3-methyl-5-(quinolin-2-yl-methoxy)indol-2-yl]-2,2-dim ethylpropanoic acid;
3-[N-(p-t-butylthiobenzyl)-3-(t-butylthio)-5-(quinolin-2-ylmethoxy)indol-2- yl]-2,2-dimethylpropanoic acid;
3-[N-(p-chlorobenzyl)-3-(phenylthio)-5-(quinolin-2-ylmethoxy)indol-2-yl]-2, 2-dimethylpropanoic acid;
3-[N-(p-chlorobenzyl)-3-(phenylsulfonyl)-5-(quinolin-2-ylmethoxy)indol-2-yl ]-2,2-dimethyl propanoic acid, N-oxide;
3-[N-(p-chlorobenzyl)-3-(phenylsulfonyl)-5-(quinolin-2-ylmethoxy)indol-2-yl ]-2,2-dimethylpropanoic acid;
3-[N-(p-chlorobenzyl)-3-(phenylsulfinyl)-5-(quinolin-2-ylmethoxy)indol-2-yl ]-2,2-dimethylpropanoic acid;
3-[N-(p-chlorobenzyl)-5-(quinolin-2-ylmethoxy)indol-2-yl]-2,2-dimethylpropa noic acid;
3-[N-(p-chlorobenzyl)-3-benzoyl-5-(quinolin-2-ylmethoxy)indol-2-yl]-2,2-dim ethylpropanoic acid;
3-[N-(p-chlorobenzyl)-3-benzyl-5-(quinolin-2-ylmethoxy)indol-2-yl]-2,2-dime thylpropanoic acid;
3-[N-(p-chlorobenzyl)-3-(3,3-dimethyl-1-oxo-1-butyl)-5-(quinolin-2-ylmethox y)indol-2-yl]-2,2-dimethylpropanoic acid;
2-[N-(p-chlorobenzyl)-3-(t-butylthio)-5-(quinolin-2-ylmethoxy)indol-2-yl]et hoxyethanoic acid;
3-[N-(p-chlorobenzyl)-3-(3,3-dimethyl-1-butyl)-5-(quinolin-2-ylmethoxy)indo l-2-yl]-2,2-dimethylpropanoic acid;
3-[N-(p-chlorobenzyl)-3-(t-butylthio)-5-(quinolin-2-ylmethoxy)indol-2-yl]-2 -methylpropanoic acid;
3-[N-(p-chlorobenzyl)-3-methyl-5-(6,7-dichloroquinolin-2-ylmethoxy)indol-2- yl]-2,2-dimethylpropanoic acid;
3-[N-(p-chlorobenzyl)-3-methyl-5-(7-chloroquinolin-2-ylmethoxy)indol-2-yl]- 2,2-dimethylpropanoic acid;
3-[N-(p-chlorobenzyl)-4-allyl-5-(quinolin-2-ylmethoxy)-3-(t-butylthio)indol -2-yl]-2,2-dimethylpropanoic acid;
3-[N-(p-chlorobenzyl)-4-allyl-5-(quinolin-2-ylmethoxy)indol-2-yl]-2,2-dimet hylpropanoic acid;
3-[N-(p-chlorobenzyl)-6-(quinolin-2-ylmethoxy)-3-(t-butylthio)indol-2-yl]-2 ,2-dimethylpropanoic acid;
3-[N-(p-chlorobenzyl)-4-(quinolin-2-ylmethoxy)-3-(t-butylthio)indol-2-yl]-2 ,2-dimethylpropanoic acid;
3-[N-(p-chlorobenzyl)-7-(quinolin-2-ylmethoxy)-3-(t-butylthio)indol-2-yl]-2 ,2-dimethylpropanoic acid;
2-[2-[N-(p-chlorobenzyl)-3-(t-butylthio)-5-(quinolin-2-ylmethoxy)indol-2-yl ]ethoxy]propanoic acid;
3-[N-(p-chlorobenzyl)-4-(quinolin-2-ylmethoxy)indol-2-yl]-2,2-dimethylpropa noic acid;
3-[N-methyl-3-(p-chlorobenzoyl)-6-(quinolin-2-yl-methoxy)indol-2-yl]-2,2-di methylpropanoic acid,
3-[N-methyl-3-(p-chlorobenzyl)-6-(quinolin-2-yl-methoxy)indol-2-yl]-2,2-dim ethylpropanoic acid,
3-[N-(4-chlorobenzyl)-3-i-propoxy-5-(quinolin-2-ylmethoxy)indol-2-yl]-2,2-d imethylpropanoic acid,
3-[N-(4-chlorobenzyl)-3-(t-butylthio)-5-(quinolin-2-yl-methoxy)indol-2-yl]- 2-ethylpropanoic acid,
3-[N-(4-chlorobenzyl)-3-trifluoroacetyl-5-(quinolin-2-ylmethoxy)-indol-2-yl ]-2,2-dimethylpropanoic acid,
3-[N-(4-chlorobenzyl)-3-(3,3-dimethyl-1-oxo-1-butyl)-5-(quinolin-2-ylmethox y)indol-2-yl]-2-methylpropanoic acid,
3-[3-(3,3-dimethyl-1-oxo-1-butyl-5-(quinolin-2-ylmethoxy)-indol-2-yl]-2,2-d imethylpropanoic acid,
3-[N-(4-triflouromethylbenzyl)-3-(3,3-dimethyl-1-oxo-1-butyl)-5-(quinolin-2 -yl-methoxy)indol-2-yl]-2,2-dimethylpropanoic acid,
3-[N-benzyl-3-(3,3-dimethyl-1-oxo-1-butyl)-5-(quinolin-2-ylmethoxy)-indol-2 -yl]-2,2-dimethylpropanoic acid,
3-[N-(3-methoxybenzyl)-3-(3,3-dimethyl-1-oxo-1-butyl)-5-(quinolin-2-ylmetho xy)indol-2-yl]-2,2-dumethyl-propanoic acid,
3-[N-allyl-3-(3,3-dimethyl-1-oxo-1-butyl)-5-(quinolin-2-ylmethoxy)-indol-2- yl]-2,2-dimethylpropanoic acid,
3-[N-(4-methoxybenzyl)-3-(,3-dimethyl-1-oxo-1-butyl)-5-(quinolin-2-ylmethox y)indol-2-yl]-2,2-dimethylpropanoic acid,
3-[N-methyl-3-(3,3-dimethyl-1-oxo-1-butyl)-5-(quinolin-2-ylmethoxy)indol-2- yl]-2,2-dimethylpropanoic acid,
3-[3-(4-chlorobenzyl)-6-(quinolin-2-ylmethoxy)indol-2-yl]-2,2-dimethylpropa noic acid,
3-[N-(phenylsulfonyl)-3-(4-chlorobenzyl)-6-(quinolin-2-ylmethoxy)indol-2-yl ]-2,2-dimethylpropanoic acid,
3-[N-benzyl-3-(4-chlorobenzyl)-6-(quinolin-2-ylmethoxy)indol-2-yl]-2,2-dime thylpropanoic acid,
3-[N-(4-chlorobenzyl)-3-(t-butylsulfonyl)-5-(quinolin-2-ylmethoxy)indol-2-y l]-2,2-dimethylpropanoic acid,
3-[N-(4-chlorobenzyl)-3-(t-butylsulfinyl)-5-(quinolin-2-ylmethoxy)indol-2-y l]-2,2-dimethylpropanoic acid,
3-[N-allyl-3-(4-chlorobenzyl)-6-(quinolin-2-yl-methoxy)indol-2-yl]-2,2-dime thylpropanoic acid,
3-[N-(n-propyl)-3-(4-chlorobenzyl)-6-(quinolin-2-ylmethoxy)indol-2-yl]-2,2- dimethylpropanoic acid,
3-[N-ethyl-3-(4-chlorobenzyl)-6-(quinolin-2-yl-methoxy)indol-2-yl]-2,2-dime thylpropanoic acid,
3-[N-(4-chlorobenzyl)-3-(4-t-butylbenzoyl)-5-quinolin-2-yl-methoxy)indol-2- yl]-2,2-dimethylpropanoic acid,
3-[N-(4-chlorobenzyl)-3-(4-chlorobenzoyl)-5-(quinolin-2-ylmethoxy)indol-2-y l]-2,2-dimethylpropanoic acid,
3-[N-(4-chlorobenzyl)-3-(1,1-dimethylethyl)-5-(quinolin-2-ylmethoxy)indol-2 -yl]-2,2-dimethylpropanoic acid,
3-[N-(4-chlorobenzyl)-3-acetyl-5-(quinolin-2-ylmethoxy)indol-2-yl]-2,2-dime thylpropanoic acid,
3-[N-(4-chlorobenzyl)-3-cyclopropanecarbonyl-5-(quinolin-2-ylmethoxy)indol- 2-yl]-2,2-dimethylpropanoic acid,
3-[N-(4-chlorobenzyl)-3-(3-cyclopentylpropanoyl)-5-(quinolin-2-ylmethoxy)in dol-2-yl]-2,2-dimethylpropanoic acid,
3-[N-(4-chlorobenzyl)-3-(3-methylbutanoyl)-5-(quinolin-2-yl-methoxy)indol-2 -yl]-2,2-dimethylpropanoic acid,
3-[N-(4-chlorobenzyl)-3-propanoyl-5-(quinolin-2-ylmethoxy)indol-2-yl]-2,2-d imethylpropanoic acid,
3-[N-(4-chlorobenzyl)-3-(2-methylpropanoyl)-5-(quinolin-2-ylmethoxy)indol-2 -yl]-2,2-dimethylpropanoic acid,
3-[N-(4-chlorobenzyl)-3-trimethylacetyl-5-(quinolin-2-ylmethoxy)indol-2-yl] -2,2-dimethylpropanoic acid,
3-[N-(4-chlorobenzyl)-3-phenylacetyl-5-(quinolin-2-ylmethoxy)indol-2-yl]-2, 2-dimethylpropanoic acid,
3-[N-(4-fluorobenzyl)-3-(3,3-dimethyl-1-oxo-1-butyl)-5-(quinolin-2-ylmethox y)indol-2-yl]-2,2-dimethylpropanoic acid,
3-[N-(4-bromobenzyl)-3-(3.3-dimethyl-1-oxo-1-butyl)-5-(quinolin-2-yl-ethoxy )indol-2-yl]-2,2-dimethylpropanoic acid,
3-[N-(4-iodobenzyl)-3-(3,3-dimethyl-1-oxo-1-butyl)-5-(quinolin-2-ylmethoxy) indol-2-yl]-2,2-dimethylpropanoic acid,
3-[N-(4-chlorobenzyl)-3-(1,1-dimethylbutyl)-5-(quinolin-1-ylmethoxy)indol-2 -yl]-2,2-dimethylpropanoic acid,
3-[N-(4-chlorobenzyl)-3-(1,1-dimethylpropyl)-5-(quinolin-2-ylmethoxy)indol- 2-yl]-2,2-dimethylpropanoic acid,
3-[N-(3-fluorobenzyl)-3-(1,1-dimethylethyl)-5-(quinolin-2-ylmethoxy)indol-2 -yl]-2,2-dimethylpropanoic acid,
3-[N-(4-chlorobenzyl)-3-(1-methylethyl)-5-(quinolin-2-ylmethoxy)indol-2-yl] -2,2-dimethylpropanoic acid,
3-[N-(4-chlorobenzyl)-3-cyclopropyl-5-(quinolin-2-ylmethoxy)indol-2-yl]-2,2 -dimethylpropanoic acid,
3-[N-(4-chlorobenzyl)-3-(1-methyl-1-cyclopropyl)-5-(quinolin-2-ylmethoxy)in dol-2-yl]-2,2-dimethylpropanoic acid,
3-[N-(4-chlorobenzyl)-3-cyclopentyl-5-(quinolin-2-ylmethoxy)indol-2-yl]-2,2 -dimethylpropanoic acid,
3-[N-(4-chlorobenzyl)-3-cyclohexyl-5-(quinolin-2-ylmethoxy)indol-2-yl]-2,2- dimethylpropanoic acid,
3-[N-(4-chlorobenzyl)-3-(.alpha.,.alpha.-dimethylbenzyl)-5-(quinolin-2-ylme thoxy)indol-2-yl]-2,2-dimethylpropanoic acid,
3-[N-(4-chlorobenzyl)-3-(4-chloro-.alpha.,.alpha.-dimethylbenzyl)-5-(quinol in-2-ylmethoxy)indol-2-yl]-2,2-dimethylpropanoic acid,
3-[N-(4-chlorobenzyl)-3-(1-adamantyl)-5-(quinolin-2-ylmethoxy)indol-2-yl]-2 ,2-dimethylpropanoic acid,
3-[N-(4-chlorobenzyl)-3-((1-adamantyl)methyl)-5-(quinolin-2-ylmethoxy)indol -2-yl]-2,2-dimethylpropanoic acid,
3-[N-(1,1-dimethylethyl)-3-(4-chlorobenzyl)-6-quinolin-2-ylmethoxy)indol-2- yl]-2,2-dimethylpropanoic acid,
3-[N-(1,1-dimethylpropyl)-3-(4-chlorobenzyl)-6-(quinolin-2-y)methoxy)indol- 2-yl]-2,2-dimethylpropanoic acid,
3-[N-(4-chlorobenzyl)-3-(3,3-dimethyl-1-oxo-1-butyl)-5-(quinolin-2-ylmethox y)indol-2-yl]-2,2-diethylpropanoic acid.

70 more elements

Dependencies are inferred from the claim text.

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Abstract

A compound of the formula I:

##STR23## wherein:
R.sup.1, R.sup.2, R.sup.3, R.sup.4 and R.sup.10 are independently hydrogen, halogen, lower alkyl, lower alkenyl, lower alkynyl, --CF.sub.3, --CN, --NO.sub.2, --N.sub.3, --C(OH)R.sup.11 R.sup.11, --CO.sub.2 R.sup.12, --SR.sup.14, --S(O)R.sup.14, --S(O).sub.2 R.sup.14, --S(O).sub.2 NR.sup.15 R.sup.15, --OR.sup.15, --NR.sup.15 R.sup.15, --C(O)R.sup.16 or --(CH.sub.2).sub.t R.sup.21 ;
R.sup.5 is hydrogen, --CH.sub.3, --CF.sub.3, --C(O)H, X.sup.1 --R.sup.6 or X.sup.2 --R.sup.7 ;
R.sup.6 and R.sup.9 are independently:
alkyl, --(CH.sub.2).sub.u Ph(R.sup.10).sub.2 or --(CH.sub.2).sub.u Th(R.sup.10).sub.2 ;
R.sup.7 is --CF.sub.3 or R.sup.6 ;
R.sup.8 is hydrogen or X.sup.3 --R.sup.9 ;
each R.sup.11 is independently hydrogen or lower alkyl, or two R.sup.11 's on same carbon atom are joined to form a cycloalkyl ring of 3 to 6 carbon atoms;
R.sup.12 is hydrogen, lower alkyl or --CH.sub.2 R.sup.21 ;
R.sup.13 is lower alkyl or --(CH.sub.2).sub.r R.sup.21 ;
R.sup.14 is --CF.sub.3 or R.sup.13 ;
R.sup.15 is hydrogen, --C(O)R.sup.16, R.sup.13, or two R.sup.15 's on the same nitrogen may be joined to form pyrrolidine, piperidine, morpholine, thiamorpholine, piperazine or N-methylpiperazine 2,5 dioxo-1-pyrrolidinyl, (3-pyridinylcarbonyl)amino, 1,3-dihydro-1,3-dioxo-2H-isoindol-2-yl, 1,3-dihydro-2H-isoindol-2-yl, 2,4-imidazolinedion-1-yl, 2,6-piperidinedion-1-yl, 2-imidazolyl, 2-oxo-1,3-dioxolen-4-yl, piperindin-1-yl, morpholin-1-yl or piperazin-1-yl;
R.sup.16 is hydrogen, --CF.sub.3, lower alkyl, lower alkenyl, lower alkynyl or --(CH.sub.2).sub.r R.sup.21 ;
R.sup.17 is --(CH.sub.2).sub.s --C(R.sup.18 R.sup.18)--(CH.sub.2).sub.s --R.sup.19 or --CH.sub.2 C(O)NR.sup.15 R.sup.15 ;
R.sup.18 is hydrogen or lower alkyl;
R.sup.19 is a) pyrrolidine, piperidine, morpholine, thiamorpholine, piperazine or N-methylpiperazine 2,5 dioxo-1-pyrrolidinyl,(3-pyridinylcarbonyl)amino,1,3-dihydro-1,3-dioxo-2H-i soindol-2-yl,1,3-dihydro-2H-isoindol-2-yl,2,4-imidazolinedion-1-yl,2,6-pipe ridinedion-1-yl,2-imidazolyl,2-oxo-1,3-dioxolen-4-yl,piperindin-1-yl,morpho lin-1-yl or piperazin-1-yl, or b) the radical W-R.sup.20 ;
R.sup.20 is alkyl or C(O)R.sup.23 ;
R.sup.21 is phenyl substituted with 1 or 2 R.sup.22 groups;
R.sup.22 is hydrogen, halogen, lower alkyl, lower alkoxy, lower alkylthio, lower alkylsulfonyl, lower alkylcarbonyl, --CF.sub.3, --CN, --NO.sub.2 or --N.sub.3 ;
R.sup.23 is alkyl, cycloalkyl, monocyclic tetrahydrofuran, tetrahydrothiophene, pyrrolidine, piperidine or tetrahydropyran;
R.sup.24 is the residual structure of a standard amino acid, or R.sup.18 and R.sup.24 attached to the same N can cyclize to form a proline residue;
m is 0 to 1;
n is 0 to 3;
p is 1 to 3 when m is 1;
p is 0 to 3 when m is 0;
r is 0 to 2;
s is 0 to 3;
t is 0 to 2;
u is 0 to 3;
v is 0 or 1;
W is 0, S or NR.sup.15 ;
X.sup.1 is O, or NR.sup.15 ;
X.sup.2 is C(O), CR.sup.11 R.sup.11, S, S(O) or S(O).sub.2 ;
X.sup.3 is C(O), CR.sup.11 R.sup.11, S(O).sub.2 or a bond;
X.sup.4 is CH.dbd.CH, CH.sub.2 --Y.sup.1 or Y.sup.1 --CH.sub.2 ;
Y is X.sup.1 or X.sup.2 ;
Y.sup.1 is O, S, S(O).sub.2 or CH.sub.2 ;
Q is --CO.sub.2 R.sup.12, --C(O)NHS(O).sub.2 R.sup.14, --NHS(O).sub.2 R.sup.14, --S(O).sub.2 NHR.sup.15 --C(O)NR.sup.15 R.sup.15, --CO.sub.2 R.sup.17, --C(O)NR.sup.18 R.sup.24, --CH.sub.2 OH, or 1H- or 2H-tetrazol-5-yl;
and the pharmaceutically acceptable salts thereof.

36 more elements