CA2143192A1 - N-arylheteroarylalkyl 1-cycloalkyl-imidazol-2-one compounds for treatment of circulatory disorders - Google Patents

N-arylheteroarylalkyl 1-cycloalkyl-imidazol-2-one compounds for treatment of circulatory disorders

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CA2143192A1
CA2143192A1 CA002143192A CA2143192A CA2143192A1 CA 2143192 A1 CA2143192 A1 CA 2143192A1 CA 002143192 A CA002143192 A CA 002143192A CA 2143192 A CA2143192 A CA 2143192A CA 2143192 A1 CA2143192 A1 CA 2143192A1
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methyl
butyl
phenyl
imidazol
pyridinyl
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French (fr)
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David B. Reitz
Robert E. Manning
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GD Searle LLC
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/12—Antihypertensives

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  • Heart & Thoracic Surgery (AREA)
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Abstract

A class of N-arylheteroarylalkyl 1-cycloalkyl-imidazol-2-one compounds is described for use in treatment of circulatory disorders such as hypertension and congestive heart failure. Compounds of particular interest are angiotension II antagonists of formula (A), wherein A is selected from (a), (b), (c), (d), (e) and (f); wherein each of R1, R2 and R3 is independently selected from hydrido, alkyl, alkoxy, halo, hydroxy, carboxyl, alkoxycarbonyl, formyl and acetyl; wherein R7 is hydrido; R8 is alkyl;
wherein R9 is an acidic group selected from COOH and (g); or a stereoisomer or a tautomer thereof or a pharmaceutically-acceptable salt thereof.

Description

N-A.RYT~ TR~OARYT-AT-~YL l-CYCT~OAL~YL-INTDA~OL-2-ONE
CO~PO~N~S FO~ TR~TM~T OF CIRC~T-ATORY DTSORn~RS

Rel~te~ c~t-on This is a continuation-in-part of U.S.
Application Ser. No. PCT/US92/02439 filed 1 April 1992 which is a continuation-in-part of U.S. Application Ser.
No. 07/681,011 filed 5 April 1991.

Fiel~ Of ~he Tn~nt~on Non-peptidic N-arylheteroarylalkyl imidazol-2-one compounds are described for use in treatment of circulatory disorders such as hypertension and congestive heart failure. Of particular interest are angiotensin II
antagonist compounds provided by a 1-cycloalkyl-imidazol-
2-one having an arylheteroarylmethyl moiety attached at the 3-nitrogen atom of the 1-cycloalkyl-imidazol-2-one.

Backarotlnd of the Tnvent ion The renin-angiotensin system is one of the hormonal mechanisms involved in regulation of 25 pressure/volume homeostasis and in expression of hypertension. Activation of the renin-angiotensin cascade begins with renin secretion from the juxtaglomerular apparatus of the kidney and clllmin~tes in the formation of angiotensin II, the primary active species of this system.
This octapeptide, angiotensin II, is a potent vasocons~rictor agent and also produces other physiological effects such as promoting aldosterone secretion, promoting sodium and fluid retention, inhibiting renin secretion, increasing sympathetic nervous
3, system activity, increasing vasopressin secretion, causing positive cardiac inotropic ef~ect and modulating othe~
~ormonal systems.

WO 94/08989 PCr/US93/056~
2 1 ~ 3 Previous studies have shown that antagonizing angiotensin II at its receptors is a viable approach to inhibit the renin-angiotensin system, given the pivotal 5 role of this octapeptide which mediates the actions of the renin-angiotensin system through interaction with various tissue receptors. There are several known angiotensin II
antagonists, most of which are peptidic in nature. Such peptidic compounds are of limited use due to their lack of o oral bioavailability or their short duration of action.
Also, commercially-available peptidic angiotensin II
antagonists (e.g., Saralasin) have a significant residual agonist activity which further limit their therapeutic application.
Non-peptidic compounds with angiotensin II
antagonist properties are known. For example, the sodium salt of 2-n-butyl-4-chloro-1-(2-chlorobenzyl)imidazole-5-acetic acid has specific competitive angiotensin II
2c antagonist activity as shown in a series of binding experiments, functional assays and in vivo tests [P. C.
Wong et al, J. Pharmacol. FXD. Ther., 247(1), 1-7 (1988)].
Also, the sodium salt of 2-butyl-4-chloro-1-(2-nitrobenzyl)imidazole-5-acetic acid has specific 25 competitive angiotensin II antagonist activity as shown in a series of binding experiments, functional assays and ~
~i~s tests [A. T. Chiu et al, ~llroDe~n J. Phar~n~col., 157, 13-21 (1988)]. A family of 1-benzylimidazole-5-acetate derivatives has been shown to have competitive angiotensin 30 II antagonist properties [A. T. Chiu et al, J. Pharm~col.
FxD. Ther., 25û (3), 867-874 (1989)]. U.S. Patent No.
4,816,463 to Blankey et al describes a family of 4,5,6,7-tetrahydro-lH-imidazo(4,5-c)-tetrahydro-pyridine derivatives useful as antihypertensives, some of which are 35 reported to antagonize the binding o' labelled angiotensin ,II to rat adrenal receptor preparation and thus cause 2 WO 94/08989 PCr/US93/05601 ~ f j ,2~1~3192 significant decrease in mean arterial blood pressure in conscious hypertensive rats. EP No. 253,310, published 20 Januar}~ 1988, describes a series of aralkyl imidazole compounds, including in particular a family of biphenylmethyl substituted imidazoles, as antagonists to the angiotensin II receptor. EP No. 323,8~1 published 12 July 1989 describes four classes of angiotensin II
antagonists, namely, ~iphenylmethylpyrroles, biphenylmethylpyrazoles, biphenylmethyl-1,2,3-triazoles and biphenylmethyl 4-subst tuted-4H-1,2,4-triazoles, including the compound 3,5~-~ibutyl-4-[(2'-carboxybiphenyl-4-yl)methyl]-4H-1,2,4-triazole. U.S. Patent No. 4,880,804 to Carini et al describes a family of biphenylmethylbenzimidazole compounds as angiotensin II
receptor blockers for use in treatment of hypertension and congestive heart failure.

There are several families of known compounds having one or two oxo substituents on a triazole ring.
For example, East German Patent No. 160,447 published 3 August 1983 describes a family of 1,2,4-triazolin-5-one compounds, specifically ~,4-dihydro-4,5-bis(phenylmethyl)-3~-1,2,4-triazol-3-one, for use as herbicides. Belgian Patent No. 806,146 published 16 October 1972 describes a family of triazolinone compounds, including the compound (3-(4-m-chlorophenyl-1-piperazinyl)-propyl)-3,4-diethyl-1,2,4-triazolin-5-one, having tranquilizer, hypotensive and analgesic activities. Belgian Patent No. 631,842 published 28 February 1963 describes a family of 1,2,4-triazolones having hypnotic, tranquilizer, narcotic, sedative and analgetic activities, which includes a class of 4-N-aralkyl-1,2,4-triazol-5-one compounds. EP i~7,180 published 15 June 1978 describes a family of 1,2-disubstituted-4-all~l-1,2,4-triazolidine-3,5-dione compounds having a wide variety of activities, such as i9~
- . ~ 4 antiulcer, bronchodilator, antifertility and cardiovascular-related activities which include antihypertensive, antiarrhythmic, platelet aggregation inhibition and smooth muscle activities. EP #283,310 published 18 March 1987 describes a family of N1-diarylmethyl-N2-aminoalkyl-diaza-heterocyclic derivatives for treating cerebral vascular and ischemic diseases and for protecting against anoxia.

; 214~192 DRSCRIPTION OF T~E lNv~N~TON

A class of N-substituted arylheteroarylalkyl 1-cycloalkyl-imidazol-2-one compounds useful in treating circulatory disorders, particularly cardiovascular disorders, is defined by Formula I:
Q~ ~
,~N--~CH2]--A

wherein Q is a cycloalkyl group having three to about eight ring carbon atoms, and wherein said cycloalkyl yroup may be unsubstituted or substituted on one or more substitutable positions by one or more groups independently selected from hydrido, alkyl, alkoxy, cyano, halo, hydroxy, nitro, amino, alkylamino, carboxyl, alkoxycarbonyl, formyl, oxo, alkylcarbonyl and haloalkylcarbonyl; wherein R7 is selected from hydrido, alkyl, halo, haloalkyl, formyl, carboxyl and alkoxyalkyl;
wherein R8 is selected from alkyl, phenyl, phenylalkyl, cycloalkyl and cycloalkylalkyl; wherein A is an acid-group-substituted pyridinyl-phenyl moiety selected from ~=,~R9 ~=~ R9 ~=~R9 --~N~ ~N~

R9 ~ N

~N> ~N ~d ~ ~ Rg wherein m is a number selected from one to four, inclusive; wherein R9 is an acid~c group selected _rom COOH and W094/08989 PCT/US93/056~

~ . ~ ..

N - N

N
or a stereoisomer or a tautomer thereof or a pharmaceutically-acceptable salt thereof.

Regioisomers of compounds of Formula I are also embraced as part of the invention, particularly those regioisomers formed by various substitutions on nitrogen atoms of the imidazole ring relative to substitutions on the carbon atoms of the imidazole ring. For purposes of o nomenclature, a numbering system for the imidazole ring is shown below for a preferred set of compounds of the invention within Formula I:
o N ~
,~N--[CH2lm- A

wherein each of Q, R7, R8, m and A is as defined above.

Within Formula I, above, Q may be further defined as R~ / ld ~ /
R2 - C H Ib ~ R6 ~C/ i I H

wherein each of R1, R2, R3, R4, R5 and R6 is independently selected from hydrido, alkyl, alkoxy, cyano, halo, hydroxy, nitro, amino, alkylamino, carboxyl, 21~92 alkoxycarbonyl, formyl, alkylcarbonyl and haloalkylcarbonyl; wherein R1 and R2 may further be taken together to form oxo; wherein R3 and R4 may further be taken together to form oxo; wherein R5 and R6 may further be taken together to form oxo; wherein each of d, b and r is a number selected from zero through five, inclusive, and wherein the sum of d+b+r is a number from zero through five, inclusive;

0 Examples of cycloalkyl groups embraced by the Q
group are the following moieties:

Rl~ R1 ~ R1 `~?

cyclopropyl cyclobutyl cyclopentyl Rl ~ R1 ~ and R1 ~ :

cyclohexyl cycloheptyl cyclooctyl wherein each of R1, R2 and R3 is defined above.

Compounds of Formula I would be useful in treating a variety of circulatory disorders and circulatory-related disorders, including cardiovascular disorders, such as hypertension, congestive heart failure and arteriosclerosis, and other disorders such as 2c glaucoma. These compounds would aiso be useful as adjunctive therapies. For example, compounds of Formula may be used in combination with other drugs, such as a aiuretic, to treat hypertension. Also, compounds of Formula I could be used in conjunction with certain surgical procedures. For exampie, these compounds could be used to prevent post-angioplas~y re-stenosis.

W094/08989 PCT/US93/05 ~

2l43l9~8 Compounds of Formula I are therapeutically effective in treatment of cardiovascular disorders by acting as antagonists to, or blockers of, the angiotensin II ~AII) receptor. Compounds of Formula I would be therapeutically effective in treatment of the above-mentioned circulatory and cardiovascular disorders or would be precursors to, or prodrugs of, therapeutically-effective compounds.

Within Formula I there is a first group of lo compounds of more interest as represented by Formula II:
H

R\ ~ Cd R1 H ~I~N~ II

J~R8 wherein each of Rl through R6 is independently selected 15 from hydrido, methyl, ethyl, n-propyl, isopropyl, tert-butyl, methoxy, ethoxy, propoxy, isopropoxy, tert-butoxy, cyano, fluoro, chloro, iodo, bromo, hydroxy, nitro, amino, N-methylamino, N,N-dimethylamino, N-ethylamino, N,N-diethyl ~m; no, carboxyl, methoxycarbonyl, ethoxycarbonyl, formyl, methylcarbonyl, ethylcarbonyl and trifluoromethylcarbonyl; wherein Rl and R2 may further be taken together to form oxo; wherein R3 and R4 may further be taken together to form oxo; wherein R5 and R6 may further be taken together to form oxo; wherein each o- d, b and r is a number selected from zero through five, inclusive, and wherein the sum of d+b+r is a number selected from zero through five, i~clusive; wherein ~.7 is selected from hydrido, methyl, fluoro, chloro, monofluoromethyl, difluoromethyl, ~_ifluoromethyl, formy_, .

g 2 1 ~ 3 1 9 z carboxyl and dimethoxymethyl; wherein R8 is selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl, neopentyl, phenyl, benzyl, phenethyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclopropylmethyl, cyclopropylethyl, cyclobutylmethyl, cyclobutylethyl, cyclopentylmethyl, cyclopentylethyl, cyclohexylmethyl and cyclohexylethyl; wherein A is an acidic-group-substituted pyridinyl-phenyl moiety selected from ~ ' ~N ald ~ ;

wherein R9 is an acidic group selected from COOH and H
N- N
N

or a stereoisomer or a tautomer thereof or a pharmaceutically-acceptable salt thereof.

Within the compounds of Formula II there is a first group of compounds of more interest as represente~
by Formula III:

W094/08989 PCT/US93/0~6 ~
2~3~92 f' ~ - 10 R R~N C - A III

wherein each of Rl, R2 and R3 is independently selected from hydrido, methyl, ethyl, n-propyl, isopropyl, tert-butyl, methoxy, ethoxy, propoxy, isopropoxy, tert-butoxy, cyano, fluoro, chloro, iodo, bromo, hydroxy, nitro, amino, N-methylamino, N,N-dimethylamino, N-ethyl~mi no, N,N-diethylamino, carboxyl, methoxycarbonyl, ethoxycarbonyl, formyl, methylcarbonyl, ethylcarbonyl and lo trifluoromethylcarbonyl; wherein Rl and R2 may further be taken together to form oxo; wherein R7 is selected from hydrido, methyl, fluoro, chloro, monofluoromethyl, difluoromethyl, trifluoromethyl, formyl, carboxyl and dimethoxymethyl; wherein R8 is selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl, neopentyl, phenyl, benzyl, phenethyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclopropylmethyl, cyclopropylethyl, cyclobutylmethyl, cyclobutylethyl, cyclopentylmethyl, 2c cyclopentylethyl, cyclohexylmethyl and cyclohexylethyli wherein A is an acidic-group-substituted pyridinyl-phenyl moiety selected from ~'~`~

~ ~N ald ~N
2s ~ W O 94/08989 PC~r/US93/05601 11 214319~

wherein R9 is an acidic group selected from COOH and N - N

N

or a stereoisomer or a tautomer thereof or a pharmaceutically-acceptable salt thereof.
Within this first group of compounds of Formula III there is a first class of higher-interest compounds of - 10 Formula III(a):

R~ ~7 H--N~N~N

wherein each of R1, R2 and R3 may be independently selected from hydrido, methyl, ethyl, n-propyl, isopropyl, tert-butyl, hydroxy, methoxy, fluoro, chloro, iodo, bromo, carboxyl, formyl, methylcarbonyl and trifluoromethylcarbonyl; wherein R1 and R2 may further be taken together to form oxo; wherein R7 is hydrido; wherein R8 is selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, isopentvl and neopentyl; or a stereoisomer or a tautomer thereof or a pharmaceutically-acceptable salt thereof.

A family of specific compounds of particular interest within Formula III(a) consists of compounds and their stereoisomers and tautomers and the W094/08989 PCT/US93/056~

pharmaceutically-acceptable salts thereof, said compounds consisting of 1-(2-methylcyclo~lu~1)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2 one;
1-(2-ethylcyclopropyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-propylcyclopropyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-lo tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-isopropylcyclopropyl)-4-butyl-1,3-dihydro-3-[[5-[2-tlH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-tertbutylcyclopropyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-methoxycyclopropyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;1-(2-hydroxycyclopropyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazû1-2-one;
1-(2-carboxycyclopropyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-acetylcyclopropyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-oxocyclopropyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl~methyl]-2H-imidazol-~-one;
_-(2,3-dimethylcyclopropyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazoi-~5 2-one;

~W094/08989 PCT/US93/05601 13 2 1 ~ 3 1 9 2 1-(2-ethyl-3-methylcyclopropyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-isopropyl-3-methylcyclo~lo~yl)-4-butyl-1,3-dihydro-3-s [[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-carboxy-3-methylcyclopropyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyljmethyl3-2H-imidazol-2-one;
lo l-(2-acetyl-3-methylcyclopropyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl~-2H-imidazol-2-one;
1-(2-oxo-3-methylcyclo~o~1)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-methyl-3-ethylcyclo~~ 1)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2,3-diethylcyclopropyl)-4-butyl-1,3-dihydro-3-~5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl3methyl]-2H-imidazol-2-one;
1-(2-isopropyl-3-ethylcyclopropyl)-4-butyl-1,3-dihydro-3-[~5-~2-(lH-tetrazol-5-yl~phenyl~-2-pyridinyl]methyl~-2~-imidazol-2-one;
1-(2-carboxy-3-ethylcyclopropyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one, 1-(2-acetyl-3-ethylcyclopropyl)-4-butyl-1,3-dihydro-3-[[5-~2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2~-imidazol-2-one;
1-(2-oxo-3-ethylcyclopropyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl~methyl]-2H-imidazol-2-one;
1-(2-methyl-3-isopropylcyclopropyl)-4-butyl-1,3-dihydro-3-[[5-[2-tlH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2~-imidazol-2-one;

W094/08989 2~ 43 ~9 ~ PCT/US93/056~
,J.

1-(2-ethyl-3-iso~o~ylcyclo~o~1)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2,3-diisopropylcyclopropyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl~phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-carboxy-3-isopropylcyclopropyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
lo 1-(2-acetyl-3-iso~lo~lcyclo~Lo~1)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-oxo-3-isopropylcyclopropyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2,2-dimethylcyclopropyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one; and 1-(2,2-diethylcyclopropyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one.

Within this first group of compounds of Formula III there is a second class of higher-interest compounds 25 of Formula III(b):

~}CH2 ~ n2 III (b) H--N
~N- N R3 wnerein each of R1, R2 and P~3 may be independently 30 selected from hydrido, methyl, ethyl, n-propyl, isopropyl, tert-butyl, hydrox~, methox~-, fluoro, chlors, iodo, bromo, W094/08989 PCT/USg3/05601 ~ 2I ~ 31~2 carboxyl, formyl, methylcarbonyl and trifluoromethylcarbonyl; wherein R1 and R2 may further be taken together to form oxo; wherein R7 is hydrido; wherein R8 is selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl and neopentyl; or a stereoisomer or a tautomer thereof or a pharmaceutically-acceptable salt thereo~.

A family of specific compounds of particular o interest within Formula III(b~ consists of compounds and their stereoisomers and tautomers and the pharmaceutically-acceptable salts thereof, said compounds consisting of 1-(2-methylcyclo~ru~1)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-ethylcyclo~lo~1)-4-butyl-1,3-dihydro-3-~[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinylimethyl]-2H-imidazol-2-one;
1-(2-propylcyclo~lo~yl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyljmethyl]-2H-imidazol-2-one;
1-(2-isopropylcyclopropyl)-4-butyl-1,3-dihydro-3-l~6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-tertbutylcyclopropyl)-4-butyl-1,3-dihydro-3-[[6-~[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-methoxycyclopropyl)-4-butyl-~,3-dihydro-3-[[6-[2~
tetrazol-5-yl)phenyl]-3-pyridinylime hyl]-2H-imidazol-2-onei J
1-(2-hydroxycyclopropyl)-4-butyl-1,3-dihydro-3-[[6-[2~
~ tetrazol-5-yl)phenyl]-3-pyridinyi]me~hyl]-2H-imidazol~-2-one;

W O 94/08989 PC~r/US93/056 ~
2l~3~ 92 16 1-~2-carboxycyClo~lo~yl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-acetylcyclopropyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-
5 tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one; 4 (2-oxocyclopropyl)-4-butyl-l~3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
lo l-(2,3-dimethylcyclopropyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-ethyl-3-methylcyclopropyl)-4-butyl-l~3-dihydro-3-[[6 [2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-isopropyl-3-methylcyclo~yl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-carboxy-3-methylcyclopropyl)-4-butyl-1,3-dihydro-3-[[6-[2-( lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol- 2 -one;
1-(2-acetyl-3-methylcyclopropyl)-4-butyl-1,3-dihydro-3-C[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-oxo-3-methylcYclo~ 1)-4-butyl-1,3-dihydro-3-[[6-~2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
~-(2-methyl-3-ethylcyclopropyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2,3-diethylcyclo~ro~yl)-4-butyl-1,3-dihydro-3-[[6-[2-,lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imiaazol-2-one;
1-(2-isopropyl-3-ethylcyclopropyl)-4-butyl-1,3-dihydro-3-l[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-~midazol-2-one;

~ r 1 q 31 9 2 1-(2-carboxy-3-ethylcyclopropyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
l-~2-acetyl-3-ethylcyclopropyl)-4-butyl-l~3-dihydro-3-[[6 [2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2~-imidazol-2-one;
1-(2-oxo-3-ethylcyclo~lopyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
o 1-(2-methyl-3-isop~oy~lcyclopropyl)-4-butyl-1,3-dihydro-3-~[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl)methyl]-2H-imidazol-2-one;
1-(2-ethyl-3-iso~ro~ylcyclopropyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl~methyl]-2H-imidazol-2-one;
1-(2,3-diiso~lo~ylcyclo~lo~yl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-carboxy-3-isopropylcyclopropyl)-4-butyl-1,3-dihydro-3-[~6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-acetyl-3-isopropylcyclopropyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl)-3-pyridinylimethyl]-2H-imidazol-2-one;
1-(2-oxo-3-isopropylcyclopropyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2,2-dimethylcyclopropyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one; and 1-(2,2-diethylcyclopropyl)-4-butyl-1,3-dihydro-3-[[~-'[2-~lH-tetrazol-5-yl)phenyl~-3-pyridinyl]methyl]-2H-imidazol-= 2-one.

2 1 4~ 18 Within this first group of compounds of Formula III there is a third class of higher-interest compounds of Formula III(c):

H--N

wherein each of R1, R2 and R3 may be independently selected from hydrido, methyl, ethyl, n-propyl, isopropyl, tert-butyl, hydroxy, methoxy, ~luoro, chloro, iodo, bromo, o carboxyl, formyl, methylcarbonyl and trifluoromethylcarbonyl; wherein R1 and R2 may further be taken together to form oxo; wherein R7 is hydrido; wherein R8 is selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, 5 isopentyl and neopentyl; or a stereoisomer or a tautomer thereof or a pharmaceutically-acceptable salt thereof.

A family of specific compounds of particular interest within Formula III(c) consists of compounds and their stereoisomers and tautomers and the pharmaceutically-acceptable salts thereo,, said compounds consisting of 1-(2-methylcyclopropyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl~-2H-imidazol-2-one;1-(2-ethylcyclopropyl)-4-butyl-1,3-dihydro-3-[[4-[3-(~
tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-propylcyclopropyl)-4-butyl-1,3-dihydro-3-[[4-[3-(1~-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol- -one;

~W094/08989 PCT/US93/05601 21~ ~I 92 1-(2-isopropylcyclopropyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2~-imidazol 2-one;
1-(2-tertbutylcyclopropyl)-4-butyl-1,3-dihydro-3-[[4-[3-5 (lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-methoxycyclopropyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
o 1-(2-hydroxycyclopropyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-carboxycyclo~l~yl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-acetylcyclo~o~yl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-oxocyclopropyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2,3-dimethylcyclopropyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
25 1-(2-ethyl-3-methylcyclopropyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl~methyl]-2H-iIrlidazol-2-onei 1-(2-isopropyl-3-methylcyclopropyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-carboxy-3-methylcyclopropyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyljmethyl]-~2H-~ imidazol-2-one;
1-(2-acetyl-3-methylcyclopropyl)-4-butyl-1,3-dihydro-~3-3~ [[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;

W094/08989 PCT/US93/05 ~
~9~

1-(2-oxo-3-methylcyclopropyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-methyl-3-ethylcyclopropyl)-4-butyl-1,3-dihydro-3-[[4-s [3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2,3-diethylcyclopropyl)-4-butyl-1,3-dihydro-3-[[4- [3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
lo 1-(2-isopropyl-3-ethylcyclopropyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-carboxy-3-ethylcyclopropyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-acetyl-3-ethylcyclo~l~yl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-oxo-3-ethylcyclopropyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-methyl-3-isopropylcyclopropyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-ethyl-3-isopropylcyclopropyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2,3-diisopropylcyclopropyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2~:-imidazol-2-one;
1-(2-carboxy-3-isopropylcyclopropyl)-4-butyl-l~3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl~-2~-imidazol-2-one;
1-(2-acetyl-3-isopropylcyclopropyl)-4-butyl-1,3-dihydro-3-3s [[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2~'-imidazol-2-one;

~ ~ - ~

W094/08989 PCT/~S93/05601 2 ~

1-(2-oxo-3-isopropylcyclopropyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-~-yl)phenyl]-2-pyridinyl]methyl]-2~-imidazol-2-one;
1-(2,2-dimethylcyclopropyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-~-yl)phenyl]-2-pyridinyl]methyl]-2~-imidazol-2-one; and 1-(2,2-diethylcyclopropyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl~phenyl]-2-pyridinyl~methyl]-2H-imidazol-2-one.

Within this first group of compounds of Formula III there is a fourth class of higher-interest compounds of Formula III(d):

~ ~ ~2 III(d) `N_N R3 wherein each of R1, R2 and R3 may be independently selected from hydrido, methyl, ethyl, n-propyl, isopropyl, tert-butyl, hydroxy, methoxy, fluoro, chloro, iodo, bromo, 20 carboxyl, formyl, methylcarbonyl and trifluoromethylcarbonyl; wherein R1 and R2 may further be taken together to form oxo; wherein R7 is hydrido; wherein R8 is selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, 2~ isopentyl and neopentyl; or a stereoisomer or a tautomer thereof or a pharmaceutically-acceptable salt thereof.

~ A family of specific compounds of particular interest within Formula III(d) consists of compounds and 3 Q their stereoisomers and tautomers and the W094/08989 9~ PCT/US93/05 ~ . 22 pharmaceutically-acceptable salts thereof, said compounds consisting of 1-(2-methylcyclopropyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2 one;
1-(2-ethylcyclopropyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-propylcyclo~o~yl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-lo tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-isopropylcyclopropyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-tertbutylcyclo~,o~yl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-methoxycyclo~o~yl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2~-imidazol`2-one;l-(2-hydroxycyclopropyl~-4-butyl-l~3-dihydro-3-[[4-[4-(lH
tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-carboxycyclopropyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-2 5 tetrazol-5-yl)phenyl]-3-pyridinyl~methyl]-2H-imidazol-2-one;
1-(2-acetylcyclopropyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-oxocyclopropyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2,3-dimethylcyclopropyl~-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;

23 21 ~ 9 1-(2-ethyl-3-methylcyclopropyl)-4-butyl-1,3-d~ihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-isopropyl-3-methylcyclo~roy~ 4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-carboxy-3-methylcyclopropyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
lo 1-(2-acetyl-3-methylcyclopropyl)-4-butyl-1,3-dihydro-3-[[4-r4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H
imidazol-2-one;
1-(2-oxo-3-methylcyclo~o~yl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-methyl-3-ethylcyclopropyl)-4-butyl-1,3-dihydro-3-~[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2,3-diethylcyclopropyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-isopropyl-3-ethylcyclopropyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-onei 1-(2-carboxy-3-ethylcyclopropyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyljmethyl]-2H-imidazol-2-one;
1-(2-acetyl-3-ethylcyclopropyl)-4-butyl-1,3-dihydro-3-~[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-3 o imidazol-2-one;
1-(2-oxo-3-ethylcyclopropyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-methyl-3-isopropylcyclopropyli-4-butyl-1.3-dihydro-3-~5 [[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinylimethyl]-2H-imidazol-2-one;

1-(2-ethyl-3-isopropylcyclopropyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2,3-diisopropylcyclo~o~1)-4-butyl-1,3-dihydro-3-~[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-carboxy-3-isopropylcyclopropyl)-4-~utyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
o 1-(2-acetyl-3-isopropylcyclopropyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-oxo-3-isopropylcyclopropyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2,2-dimethylcyclopropyl)-4-butyl-1,3-dihydro-3-~[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one; and 1-(2,2-diethylcyclopropyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one.

Within this first group of compounds of Formula .II there is a fifth class of higher-interest compounas of Formula III(e):

N~}~CH2--N/~ R1 H-N I k ~ R2 III(e) ~N-N R3 wherein each of Rl, R2 and R3 may be independently 3 o selected from hydrido, methyl, ethyl, n-propyl, isopropyl, tert-butyl, hydroxy, methoxy, fluoro, chloro, iodo, bromo, _W094/08989 PCT/US93/05601 ~ 21~319~
2~

carboxyl, formyl, methylcarbonyl and trifluoromethylcarbonyl; wherein ~1 and R2 may further be taken together to form oxo; wherein R7 is hydrido; wherein R8 is selected from methyl, ethyl, n-propyl, isopropyl, s n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, - isopentyl and neopentyl; or a stereoisomer or a tautomer thereof or a pharmaceutically-acceptable salt thereof.

A family of specific compounds of particular o interest within Formula III(e) consists of compounds and their stereoisomers and tautomers and the pharmaceutically-acceptable salts thereof, said compounds consisting of 1-(~-methylcyclo~ro~yl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-ethylcyclopropyl)-4-~utyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-propylcyclopropyl)-4-butyl-1,3-dihydro-3-~14-~3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-isopropylcyclopropyl)-4-butyl-1,3-dihydro-3-[[4-~3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-tertbutylcyclopropyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-onei 1-(2-methoxycyclopropyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-3c tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-hydroxycyclopropyl)-4-butyl-1,3-dihydro-3-[[4-[3-(l~-tetrazol-5-yl3phenyl]-4-pyridinyl]me~hyl]-2H-imidazol-2-one;

W094/08989 PCT/US93/056~
~31~ 26 1-(2-carboxycyclopropyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
l-(2-acetylcyclopropyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-oxocyclopropyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
lo 1-(2,3-dimethylcyclopropyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-ethyl-3-methylcyclopropyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-15 imidazol-2-one;
1-(2-isopropyl-3-methylcyclopropyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-carboxy-3-methylcyclo~lu~yl)-4-butyl-1,3-dihydro-3-20 [ [4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-acetyl-3-methylcyclopropyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
25 1- (2-oxo-3-methylcyclopropyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-methyl-3-ethylcyclopropyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyljmethyl]-2H-imidazol-2-one;
1-(2,3-diethylcyclopropyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-isoprûpyl-3-ethylcyclopropyl)-4-butyl-1,3-dihydro-3-35 [[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;

1-(2-carboxy-3-ethylcyclopropyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl~-2H-imidazol-2-one;
1-(2-acetyl-3-ethylcyclopropyl --4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-oxo-3-ethylcyclopropyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
lo 1-(2-methyl-3-isopropylcyclopropyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-ethyl-3-isopropylcyclopropyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2,3-diiso~ lcyclopropyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-carboxy-3-isopropylcyclopropyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
1-t2-acetyl-3-iso~Lo~ylcyclopropyl)-4-butyl-1,3-dihy8ro-3-[[4-[3-(lH-tetrazol-5-yl)phenyll-4-pyridinyl]methyl]-2H-imidazol-2-one;
2~ 1-(2-oxo-3-isopropylcyclopropyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2,2-dimethylcyclopropyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one; and 1-(2,2-diethylcyclopropyl)-4-butyl-1,3-dihyaro-3-[~4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one.

W094/08989 PCT/US93/05 ~

; ~ 28 Within this first group of compounds of Formula III there is a sixth class of higher-interest compounds of Formula III~f):

~ j `N_N R3 wherein each of Rl, R2 and R3 may be independently selected from hydrido, methyl, ethyl, n-propyl, isopropyl, tert-butyl, hydroxy, methoxy, fluoro, chloro, iodo, bromo, o carboxyl, formyl, methylcarbonyl and trifluoromethylcarbonyl; wherein Rl and R2 may further be taken together to form oxo; wherein R7 is hydrido; wherein R8 is selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl and neopentyl; or a stereoisomer or a tautomer thereof or a pharmaceutically-acceptable salt thereof.

A family of specific compounds of particular interest within Formula III(f) consists of compounds and 2c their stereoisomers and tautomers and the pharmaceutically-acceptable salts thereof, said compounds consisting of i-(2-methylcyclopropyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one1-(2-ethylcyclopropyl)-4-butyl-1,3-dihydro-3-[[4-[2~
~etrazol-5-yl)phenyl]-3-pyridinyl~methyl]-2H-imidazol-2-one;
1-(2-propylcyclopropyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-30 tetrazol-5-yl)phenyl]-3-pyridinyl~methYl]-2H-imidazol-2-onei 29 21~31g2 1-(2-isopropylcyclopropyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-tertbutylcyclo~ro~1)-4-butyl-1,3-dihydro-3-~[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-methoxycyclopropyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2 one;
lo 1-(2-hydroxyCyClo~LO~yl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-carboxycyclo~o~yl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2 one;
1-(2-acetylcycl~L~p~l)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-oxocyclopropyl)-4-butyl-1,3-dihydro-3-[[4-[2-tlH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2,3-dimethylcyclopropyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-py-idinyl]methyl3-2H-imidazol-2-one;
1-(2-ethyl-3-methylcyclopropyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-isopropyl-3-methylcyclopropyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl~-3-pyridinyl]methyl]-2H-30 imidazol-2-one;
1-(2-carboxy-3-methylcyclopropyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-acetyl-3-methylcyclopropyl)-4-butyl-1,3-dihydro-3-3 5 [ [ 4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2~-imidazol-2-one;

W094/08989 ~ PCT/US93/05 1-(2-oxo-3-methylcyclopropyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-methyl-3-ethylcyclo~o~l)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2,3-diethylcyclopropyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl~methyl]-2H-imidazol-2-one;
lo l-(2-isopropyl-3-ethylcyclo~L~1)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-carboxy-3-ethylcyclopropyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl~-3-pyridinyl~methyl~-2H-imidazol-2-one;
1-(2-acetyl-3-ethylcyclopropyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl~-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-oxo-3-ethylcyclo~Lo~l)-4-butyl-1,3-dihydro-3-[[4-[2-20 (lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-methyl-3-isopropylcyclopropyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl~methyl]-2H-imidazol-2-one;
25 1-(2-ethyl-3-isopropylcyclopropyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2,3-diisopropylcyclopropyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-carboxy-3-isopropylcyclopropyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-acetyl-3-isopropylcyclopropyl)-4-bu~yl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2~:-imidazol-2-one;

~ W094/08989 PCT/US93/0560]

1-(2-oxo-3-isopropylcyclopropyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2,2-dimethylcyclopropyl)-4-butyl-1,3-dihydro-3-[[4-~2-(lH-tetrazol-S-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one; and 1-(2,2-diethylcyclopropyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one.

Within the compounds of Formula II there is a second group of compounds of more interest as represented by Formula IV:

R2 ~ o R1 ~L~N A IV

wherein each of R1, R2 and R3 is independently selected from hydrido, methyl, ethyl, n-propyl, isopropyl, tert-butyl, methoxy, ethoxy, propoxy, isopropoxy, tert-butoxy, 2c cyano, fluoro, chloro, iodo, bromo, hydroxy, nitro, amino, N-methylamino, M,N-dimethylamino, N-ethylamino, N,N-diethylamino, carboxyl, methoxycarbonyl, ethoxycarbonyl, formyl, methylcarbonyl, ethylcarbonyl and trifluoromethylcarbonyli wherein R1 and R2 may further be taken together to form oxo; wherein R7 is selected from hydrido, methyl, fluoro, chloro, monofluoromethyl, difluoromethyl, trifluoromethyl, formyl, carboxyl and dimethoxymethyl; wherein ~8 is seiected from methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, 3 o tert-butyl, n-pentyl, isopentyl, neopentyl, phenyl, benzyl, phenethyl, cyclopropyl, cyclobutyl, cyclopentyl, W094/08989 2~ PCT/US93/05 0 cyclohexyl, cyclopropylmethyl, cyclopropylethyl, cyclobutylmethyl, cyclobutylethyl, cyclopentylmethyl, cyclopentylethyl, cyclohexylmethyl and cyclohexylethyl;
wherein A is an acidic-group-substituted pyridinyl-phenyl moiety selected from ~ ' ~ ' ~

~ ' ~ N a~ ~ ;

wherein R9 is an acidic group selected from COOH and H
N- N~
~ N~Y

cr a stereoisomer or a tautomer thereof or a pharmaceutically-acceptable salt thereof.
Within this second group of compounds of Formula IV there is a first class of higher-interest compounds of Formuia IV(a):

~N~N R3 wherein each of R1, R2 and R3 may be independently selected from hydrido, methyl, ethyl, n-propyl, isopro?yl, 21~3192 tert-butyl, hydroxy, methoxy, fluoro, chloro, iodo, bromo, carboxyl, formyl, methylcarbonyl and trifluoromethylcarbonyl; wherein Rl and R2 may further be taken together to form oxo; wherein R7 is hydrido; wherein s R8 is selected ~rom methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl and neopentyl; or a stereoisomer or a tautomer thereof or a pharmaceutically-acceptable salt thereof.

o A family of specific compounds of particular interest within Formula IV(a) consists of compounds and their stereoisomers and tautomers and the pharmaceutically-acceptable salts thereof, said compounds consisting of 1-~2-methylcyclobutyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-ethylcyclobutyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-propylcyclobutyl)-4-butyl-1,3-dihydro-3-[r5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-onei 1-(2-isopropylcyclobutyl)-4-butyl-1,3-dihydro-3-[[5-[2-2s (lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-tertbutylcyclobutyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-methoxycyclobutyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
~ 1-(2-hydroxycyclobutyl)-4-butyl-1,3-dihydro-3-[[5-[2-(1~:-tetrazol-5-yl~phenyl]-2-p~ridinyl]methyl]-2H-imidazol-2-3s one;

W094/08989 PCT/US93/05 ~
21431~2 1-(2-carboxycyclobutyl)-4-butyl-1,3-dihydro-3-[r5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-acetylcyclobutyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-oxocyclobutyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
o 1-(2,4-dimethylcyclobutyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-ethyl-4-methylcyclobutyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-isopropyl-4-methylcyclobutyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-carboxy-4-methylcyclobutyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-acetyl-4-methylcyclobutyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-oxo-4-methylcyclobutyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-methyl-4-ethylcyclobutyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2,4-diethylcyclobutyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-isopropyl-4-ethylcyclobutyl)-4-butyl-1,3-dihydro-~-[[5-[2-(lH-tetrazol-5-yl)Phenyl]-2-pyridinyljmethyl]-2~-imiaazol-2-one;

W094/08989 ~ I ~ 3 1 9 2 PCT/US93/0~601 1-(2-carboxy-4-ethylcyclobutyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-acetyl-4-ethylcyclobutyl)-4-butyl-1,3-dihydro-3-t[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-oxo-4-ethylcyclobutyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
o l-(2-methyl-4-iso~o~ylcyclobutyl~-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-ethyl-4-isopropylcyclobutyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2,4-diisopropylcyclobutyl)-4-butyl-1,3-dihydro-3-~[5-~2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-carboxy-4-isopropylcyclobutyl)-4-butyl-1,3-dihydro-3-[l5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H
imidazol-2-one;
1-(2-acetyl-4-isopropylcyclobutyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-oxo-4-isopropylcyclobutyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2,2-dimethylcyclobutyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one; and 1-(2,2-diethylcyclobutyl)-4-butyl-1,3-dihydro-3-l15-,[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl~methyl]-2H-imidazol - 2-one.

W094/08989 PCT/US93/05 ~
2~3 l~

Within this second group of compounds of Formula IV there is a second class of higher-interest compounds of Formula IV(b):

Re~

H- N , ~ ~ n2 IV(b ~N-~N R~

wherein each of Rl, R2 and R3 may be independently selected from hydrido, methyl, ethyl, n-propyl, isopropyl, tert-butyl, hydroxy, methoxy, fluoro, chloro, iodo, bromo, o carboxyl, formyl, methylcarbonyl and trifluoromethylcarbonyl; wherein Rl and R2 may further be taken together to form oxo; wherein R7 is hydrido; wherein R8 is selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl and neopentyl; or a stereoisomer or a tautomer thereof or a pharmaceutically-acceptable salt thereof.

A family of specific compounds of particular interest within Formula IV(b) consists of compounds and their stereoisomers and tautomers and the pharmaceutically-acceptable salts thereof, said compounds consisting of 1-(2-methylcyclobutyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinylimethyl]-2H-imidazol-2-one;l-(2-ethylcyclobutyl)-4-butyl-~3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinylimethyl]-2H-imidazol-2-one;
l-(2-propylcyclobutyl)-4-butyl-l~3-dihydro-3-[[6-[2-~lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;

-. - 21431~

1-(2-isopropylcyclobutyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-tertbutylcyclobutyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-methoxycyclobutyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2 one;
lG 1- ( 2-hydroxycyclobutyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2 one;
1-~2-carboxycyclobutyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;1-(2-acetylcyclobutyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-oxocyclobutyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-20 tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2,4-dimethylcyclobutyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imiaazol-2-one;
1-(2-ethyl-4-methylcyclobutyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-onei 1-(2-isopropyl-4-methylcyclobutyl~-4-butyl-1,3-dihydro-3-[[6-[2-(lH-~etrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-3 G imidazol-2-one;
1-(2-carboxy-4-methylcyclobutyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-~ imidazol-2-one;
1-(2-acetyl-4-methylcyclobutyl)-4-butyl-1,3-dihydro-3-[[6-3 ~ [ 2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;

W094/08989 PCT/US93/05 ~
~3~

1-(2-oxo-4-methylcyclobutyl)-4-butyl-1,3-dihydro-3-[[6-[2-~lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-methyl-4-ethylcyclobutyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2,4-diethylcyclobutyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
lo l-(2-isopropyl-4-ethylcyclobutyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-carboxy-4-ethylcyclobutyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-acetyl-4-ethylcyclobutyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-oxo-4-ethylcyclobutyl)-4-butyl-1,3-dihydro-3-[[6-[2-20 (lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-methyl-3-isopropylcyclobutyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
25 1- (2-ethyl- 3-isopropylcyclobutyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2,4-diisopropylcyclobutyl)-4-butyl-1,3-dihydro-3-[-[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-3Q imidazol-2-one;
1-(2-carboxy-4-isopropylcyclobutyl)-4-butyl-1,3-dihyaro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2~-imidazol-2-one;
1-(2-acetyl-4-isopropylcyclobutyl)-4-butyl-1,3-dihydr~-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2~-imidazol-2-one;

~ W094/08989 2 1 ~ 3 ~ 9 2 PCT/US93/05601 l-(2-oxo-4-isopropylcyclobutyl)-4-butyl-l,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
l-(2,2-dimethylcyclobutyl)-4-butyl-l,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-~ 2-one; and l-(2,2-diethylcyclobutyl)-4-butyl-l,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one.

Within this second group of compounds of Formula IV there is a third class of higher-interest compounds of Formula IV(c):

CH2-N ~ R-H - N ~ ~ R2 IV(c) ~N~N R3 wherein each of Rl, R2 and R3 may be independently selected from hydrido, methyl, ethyl, n-propyl, isopropyl, tert-butyl, hydroxy, methoxy, fluoro, chloro, iodo, bromo, carboxyl, formyl, methylcarbonyl and trifluoromethylcarbonyl; wherein Rl and ~2 may further be taken together to form oxoi wherein R7 is hydridoi wherein R8 is selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, te~t-butyl, n-pentyl, isopentyl and neopentyl; or a stereoisomer or a tautomer thereof or a pharmaceutically-acceptable salt thereof.

A family of specific compounds of particular interest within Formula IV(c) consists of compounds and 3 G their stereoisomers and tautomers and the W094/08989 PCT/US93/056~
' ~,i43~92 pharmaceutically-acceptable salts thereof, said compounds consisting of 1-(2-methylcyclobutyl)-4-butyl-1,3-dihydro-3- r [ 4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2 5 one;
1-(2-ethylcyclobutyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-propylcyclobutyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-lo tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-isopropylcyclobutyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-tertbutylcyclobutyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-methoxycyclobutyl)-4-butyl-1,3-dihydro-3-[t4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;1-(2-hydroxycyclobutyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
i-(2-carboxycyclobutyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
(2-acetylcyclobutyl)-4-butyl-l~3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
~-(2-oxocyclobutyl)-4-butyl-1,3-dihydro-3-[[4-[3-~lH-; tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2,4-dimethylcyclobutyl)-4-butyl-1,3-dihydro-3-[[4-L~-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;

W094/08989 ~ 9 2 PCT/US93/05601 1-(2-ethyl-4-methylcyclobutyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-isopropyl-4-methylcyclobutyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-carboxy-4-methylcyclobutyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
lo l-(2-acetyl-4-methylcyclobutyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-oxo-4-methylcyclobutyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-methyl-4-ethylcyclobutyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2,4-diethylcyclobutyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-isopropyl-4-ethylcyclobutyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-carboxy-4-ethylcyclobutyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-acetyl-4-ethylcyclobutyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-oxo-4-ethylcyclobutyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-~ 2-one;
1-(2-methyl-4-isopropylcyclobutyl)-4-butyl-1,3-dihydro-3-35 [[4-r3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2~-imidazol-2-one;

W094/08989 PCT/US93/056~
,, 21~319~ ~

1-(2-ethyl-4 -iSOyl u~lcyclobutyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2,4-diisopropylcyclobutyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-carboxy-4-isopropylcyclobutyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
o 1-(2-acetyl-4-isoylo~ylcyclobutyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-oxo-4-isopropylcyclobutyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2,2-dimethylcyclobutyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one; and 1-(2,2-diethylcyclobutyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one.

Within this second group of compounds of Formula IV there is a fourth class of higher-interest compounds of Formula IV(d):

H- N N, ~ ~ R2 IV(d) `N_N R~

wherein each of Rl, R2 and R3 may be independently selected from hydrido, methyl, ethyl, n-propyl, isopropyl, tert-butyl, hydroxy, methox~, fluoro, chloro, iodo, bromo, -W094/08989 PC~/US93/05601 ~ ~ ` 2l~3192 carboxyl, formyl, methylcarbonyl and trifluoromethylcarbonyl; wherein R1 and R2 may further be taken together to form oxo; wherein R7 is hydrido; wherein R8 is selec~ed from methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl and neopentyl; or a stereoisomer or a tautomer thereof or a pharmaceutically-acceptable salt thereof.

A family of specific compounds of particular o interest within Formula IV(d) consists of compounds and their stereoisomers and tautomers and the pharmaceutically-acceptable salts thereof, said compounds consisting of 1-(2-methylcyclobutyl)-4-butyl-1,3-dihydro-3-[[4-[4-tlH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-ethylcyclobutyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1- (2-propylcyclobutyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
l-(2-isopropylcyclobutyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-25 2-one;
1-(2-tertbutylcyclobutyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-methoxycyclobutyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-30 tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-hydroxycyclobutyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-~ tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;

2 i ~3 19 ~ 44 1-(2-carboxycyclobutyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2 one;
1-l2-acetylcyclobutyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-oxocyclobutyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
o l-(2,4-dimethylcyclobutyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-ethyl-4-methylcyclobutyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-iso~Lu~yl-4-methylcyclobutyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-carboxy-4-methylcyclobutyl)-4-butyl-1,3-dihydro-3-[ [ 4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-acetyl-4-methylcyclobutyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-oxo-4-methylcyclobutyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-methyl-4-ethylcyclobutyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-30 imidazol-2-one;
1-(2,4-diethylcyclobutyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-isopropyl-4-ethylcyclobutyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2~.-imidazol-2-one;

t ~21~13192 1-(2-carboxy-4-ethylcyclobutyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-acetyl-4-ethylcyclobutyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-oxo-4-ethylcyclobutyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
o 1-(2-methyl-4-iso~Lu~ylcyclobutyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-ethyl-4-iso~Lu~ylcyclobutyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2,4-diis~o~ylcyclobutyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-carboxy-4-isopropylcyclobutyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-acetyl-4-iso~~oyylcyclobutyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-oxo-4-isopropylcyclobutyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2,2-dimethylcyclobutyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one; and 1-(2,2-diethylcyclobutyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-~ 2-one.

~ 46 Within this second group of compounds of Formula IV there is a fifth class of higher-interest compounds of Formula IV(e):

N ~ R8 H - N ~ 2 IV(e) N_N R3 wherein each Of Rl, ~2 and R3 may be independently selected from hydrido, methyl, ethyl, n-propyl, isopropyl, tert-butyl, hydroxy, methoxy, fluoro, chloro, iodo, bromo, lo carboxyl, formyl, methylcarbonyl and trifluoromethylcarbonyl; wherein Rl and R2 may further be taken together to form oxo; wherein R7 is hydrido; wherein R8 is selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl and neopentyl; or a stereoisomer or a tautomer thereof or a pharmaceutically-acceptable salt thereof.

A family of specific compounds of particular interest within Formula IV(e) consists of compounds and 20 their stereoisomers and tautomers and the pharmaceutically-acceptable salts thereof, said compounds consisting of 1-(2-methylcyclobutyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;1-(2-ethylcyclobutyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl~-4-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-propylcyclobutyl)-4-butyl-1,3-dihydro-3-~[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;

-W094/08989 ~ PCT/US93/05601 21~31~

1-(2-isopropylcyclobutyl~-4-butyl-1,3-dihydro-3-[[4-~3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-tertbutylcyclobutyl)-4-butyl-1,3-dihydro-3-[[4-[3-5 (lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-- 2-one;
1-(2-methoxycyclobutyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-onei lo 1-(2-hydroxycyclobutyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-carboxycyclobutyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl~-4-pyridinyl]methyl]-2H-imidazol-2-one;1-(2-acetylcyclobutyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-oxocyclobutyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2,4-dimethylcyclobutyl)-4-butyl-1,3-dihydro-3-~[4-[3-(lH-tetrazol-5-yl)phenyll-4-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-ethyl-4-methylcyclobutyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-isopropyl-4-methylcyclobutyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-carboxy-4-methylcyclobutyl)-4-butyl-1,3-dihydro-3-[[4-[3- lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-acetyl-4-methylcyclobutyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;

094/08989 . PCT/US93/05601 f _, 2 ~ ~ 3 19 æ 48 1-(2-oxo-4-methylcyclobutyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl~phenyl]-4-pyridinyl~methyl]-2H-imidazol-2-one;
1-(2-methyl-4-ethylcyclobutyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2,4-diethylcyclobutyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
lo 1-(2-isopropyl-4-ethylcyclobutyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-carboxy-4-ethylcyclobutyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-acetyl-4-ethylcyclobutyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-oxo-4-ethylcyclobutyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-methyl-4-iso~lo~ylcyclobutyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-ethyl-4-isopropylcyclobutyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2,4-diiso~ro~ylcyclobutyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinylimethyl]-2H-imidazol-2-one;
1-(2-carboxy-4-isopropylcyclobutYl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
l-t2-acetyl-4-isopropylcyclobutyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;

1-(2-oxo-4-isopropylcyclobutyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl~methyl]-2H-imidazol-2-one;
1-(2,2-dimethylcyclobutyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl~-2H-imidazol-2-one; and 1-(2,2-diethylcyclobutyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one.

Within this second group of compounds of Formula IV there is a sixth class of higher-interest compounds of Formula IV(f):

~ ~ R7 `N- N R3 wherein each of R1, R2 and R3 may be independently selected from hydrido, methyl, ethyl, n-propyl, isopropyl, tert-butyl, hydroxy, methoxy, fluoro, chloro, iodo, bromo, - 20 carboxyl, formyl, methylcarbonyl and trifluoromethylcarbonyl; wherein R1 and R2 may further be taken together to form oxo; wherein R7 is hydrido; wherein R8 is selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, 2s isopentyl and neopentyl; or a stereoisomer or a tautomer thereof or a pharmaceutically-acceptable salt thereof.

A family of specific compounds of particular interest within Formula IV(f) consists of compounds and 3 o their stereoisomers and tau~omers and the w094/08989 2 1 4 3 1 9 2 PCT/US93/056~

pharmaceutically-acceptable salts thereof, said compounds consisting of 1-(2-methylcyclobutyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-s one;1-(2-ethylcyclobutyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-propylcyclobutyl)-4-butyl-1,3-dihydro-3-[[4-[2-~lH-10 tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2 one;
1-(2-isopropylcyclobutyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-ore;
1-(2-tertbutylcyclobutyl)-4-butyl-1,3-dihydro-3-[[4-E2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-methoxycyclobutyl)-4-butyl-1,3-dihydro-3-[[4-[2 (lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;1-(2-hydroxycyclobutyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-carboxycyclobutyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-acetylcyclobutyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-oxocyclobutyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2,4-dimethylcyclobutyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl~-3-pyridinyl]methyl]-2H-imidazol-35 2-one;

W 0 94/08989 1~31g2 PC~r/US93/05601 1-(2-ethyl-4-methylcyclobutyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-isopropyl-4-methylcyclobutyl)-4-butyl-1,3-dihydro-3-s [[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-carboxy-4-methylcyclobutyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
lo 1-(2-acetyl-4-methylcyclobutyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl~methyl~-2H-imidazol-2-one;
1-(2-oxo-4-methylcyclobutyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-methyl-4-ethylcyclobutyl)-4-butyl-1,3-dihydro-3-r[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2,4-diethylcyclobutyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-isopropyl-4-ethylcyclobutyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl] -2H-imidazol-2-one;
1-( 2-carboxy-4-ethylcyclobutyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol -2 -one;
1-(2-acetyl-4-ethylcyclobutyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-oxo-4-ethylcyclobutyl)-4-butyl-1,3-dihydro-3-[14-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-methyl-4-isopropylcyclobutyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]met,hyl~ -2H-imidazol -2 -one;

W094/08989 PCT/US93/056~

1-(2-ethyl-4-isopropylcyclobutyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2,4-diisopropylcyclobutyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-carboxy-4-isopropylcyclobutyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl3methyl]-2H-imidazol-2-one;
o 1-(2-acetyl-4-iso~o~lcyclobutyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-oxo-4-isopropylcyclobutyl)-4-butyl-1,3-dihydro-3-[[4-[2-~lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2,2-dimethylcyclobutyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl~methyl]-2H-imidazol-2-one; and 1-(2,2-diethylcyclobutyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one.

2l43l9~2 Within the compounds of Formula II there is a third group of compounds of more interest as represented by Formula V:
~R3 ~I o R--r N--~
R1 J N--CH2--A v R7 --~

wherein each of Rl, R2 and R3 is independently selected from hydrido, methyl, ethyl, n-propyl, isopropyl, tert-butyl, methoxy, ethoxy, propoxy, isopropoxy, tert-butoxy, cyano, fluoro, chloro, iodo, bromo, hydroxy, nitro, amino, N-methyl ~m; no ~ N~N-dimethyl~m; no ~ N-ethyl ~m; no ~ N,N-diethyl Am; no, carboxyl, methoxycarbonyl, ethoxycarbonyl, formyl, methylcarbonyl, ethylcarbonyl and trifluoromethylcarbonyl; wherein Rl and R2 may further be 15 taken together to form oxo; wherein R7 is selected from hydrido, methyl, fluoro, chloro, monofluoromethyl, difluoromethyl, trifluoromethyl, formyl, carboxyl and dimethoxymethyl; wherein R8 is selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-2~ butyl, n-pentyl, isopentyl, neopentyl, phenyl, benzyl, phenethyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclo~Lopylmethyl, cyclopropylethyl, cyclobutylmethyl, cyclobutylethyl, cyclopentylmethyl, cyclopentylethyl, cyclohexylmethyl and cyclohexylethyl;
wherein A is an acidic-group-substituted pyridinyl-phenyl moiety selected from W094/08989 ; PCT/US93/056 2 1 43 1~ ~ 54 ~ ' ~ ' ~

~ ' ~ N a~
wherein R9 is an acidic group selected from COOH and H
N-N

or a stereoisomer or a tautomer thereof or a pharmaceutically-acceptable salt thereof.

Within this third group of compounds of Formula V
there is a first class of higher-interest compounds of Formula V(a):

2-N ~ R

~ N O ) ~ V(a) H N`NN R3--/

wherein each of R1, R2 and R3 may be independently selected from hydrido, methyl, ethyl, n-propyl, isopropyl, tert-butyl, hydroxy, methoxy, fluoro, chloro, iodo, bromo, carboxyl, formyl, methylcarbonyl and trifluoromethylcarbonyl; wherein R1 and R2 may further be taken together to form oxo; wherein R7 is hydrido; wherein R8 is selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, 21~192 ~5 -isopentyl and neopentyl; or a stereoisomer or a tautomer thereof or a pharmaceutically-acceptable salt thereof, A family of specific compounds of particular - 5 interest within Formula V(a) consists of compounds and their stereoisomers and tautomers and the pharmaceutically-acceptable salts thereof, said compounds consisting of 1-(2-methylcyclopentyl)-4-butyl-1,3-dihydro-3-[[5-~2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-ethylcyclopentyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-propylcyclopentyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-isopropylcyclopentyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-tert~utylcyclopentyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-methoxycyclopentyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-hydroxycyclopentyl)-4-butyl-1,3-dihydro-3-[~5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
l-(2-carboxycyclopentyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
l-(2-acetylcyclopentyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl~methyl]-2H-imidazol-2-one;
1-(2-oxocyclopentyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2,4-dimethylcyclopentyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-onei 1-(2-ethyl-5-methylcyclopentyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-isopropyl-5-methylcyclopentyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)Phenyl]-2-pyridinyl]methyl]-2~-imidazol-2-one;

W094/08989 PCT/US93/056~
2~ 56 1-(2-carboxy-5-methylcyclopentyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-acetyl-5-methylcyclopentyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-oxo-5-methylcyclopentyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl~methyl]-2H-imidazol-2-one;
1-(2-methyl-5-ethylcyclopentyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-t2,5-diethylcyclopentyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-isopropyl-5-ethylcyclopentyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-carboxy-5-ethylcyclopentyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-acetyl-5-ethylcyclopentyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-t2-oxo-5-ethylcyclopentyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-onei 1-(2-methyl-5-isopropylcyclopentyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-ethyl-5-iso~o~lcyclopentyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2,5-diisopropylcyclopentyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;

wo 94/0898g 2 1 ~ 3 1 9 2 PCT/US93/05601 . . ~ . ~

1-(2-carboxy-5-isopropylcyclopentyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-acetyl-5-iso~o~ylcyclopentyl)-4-butyl-1,3-dihydro-3-- 5 [[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]- 2H-imidazol-2-one;
~ 1-(2-oxo-5-isopropylcyclopentyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2,2-dimethylcyclopentyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
and 1-(2,2-diethylcyclopentyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one.
Within this third group of coll-~ounds of Formula V
there is a second class of higher-interest compounds of Formula V(b):

~ ~ n2 `N_N R

wherein each of R1, R2 and R3 may be independently selected from hydrido, methyl, ethyl, n-propyl, isopropyl, tert-butyl, hydroxy, methoxy, fluoro, chloro, iodo, bromo, carboxyl, formyl, methylcarbonyl and trifluoromethylcarbonyl; wherein R1 and R2 may further be taken together to form oxo; wherein R7 is hydrido; wherein R8 is selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl and neopentyl; or a stereoisomer or a tautomer thereof or a pharmaceutically-acceptable salt thereof.

W O 94/08989 PC~r/US93/056~
- 2~43~9~ 58 A family of specific compounds of particular interest within Formula V(b) consists o~ compounds and their stereoisomers and tautomers and the pharmaceutically-acceptable salts thereof, said compounds consisting of 1-(2-methylcyclopentyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-ethylcyclopentyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-propylcyclopentyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-isopropylcyclopentyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyllmethyl]-2H-imidazol-2-one;
1-(2-tertbutylcyclopentyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl~methyl]-2H-imidazol-2-one;
1-(2-methoxycyclopentyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-hydroxycyclopentyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinylimethyl]-2H-imidazol-2-one;
1-(2-carboxycyclopentyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyljmethyl]-2H-imidazol-2-one;
1-(2-acetylcyclopentyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
i-(2-oxocyclopentyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-onei 1-(2,4-dimethylcyclopentyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl~methyl]-2H-imidazol-2-one;
1-(2-ethyl-5-methylcyclopentyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-isopropyl-5-methylcyclopentyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-onei 1-(2-carboxy-~-methylcyclopentyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-onei ?,~31~,~

1-(2-acetyl-5-methylcyclopentyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-oxo-5-methylcyclopentyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl~methyl]-2H-imidazol-2-one;
1-(2-methyl-5-ethylcyclopentyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl3methyl]-2H-imidazol-2-one;
1-(2,5-diethylcyclopentyl)-4-~utyl-1,3-dihydro-3-[~6-[2-(lH-tetrazol-5-yl)phenyl3-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-isopropyl-5-ethylcyclopentyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-carboxy-5-ethylcyclopentyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-acetyl-5-ethylcyclopentyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-oxo-5-ethylcyclopentyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-methyl-5-isop~o~ylcyclopentyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl)methyl]-2H-imidazol-2-onei 1-(2-ethyl-5-isopropylcyclopentyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2,5-diisopropylcyclopentyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-carboxy-5-isopropylcyclopentyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;

W O 94/08989 PC~r/US93/056~
f 21431 9~

1-(2-acetyl-5-iso~l~ylcyclopentyl)-4-butyl-1,3-dihydro-3-[[6-[2-~lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-oxo-5-isopropylcyclopentyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2,2-dimethylcyclopentyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
and 1-(2,2-diethylcyclopentyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one.

Within this third group of compounds of Formula v there is a third class of higher-interest compounds of Formula V(C):

~3CH2-~

wherein each of R1, R2 and R3 may be independently selected from hydrido, methyl, ethyl, n-propyl, isopropyl, tert-butyl, hydroxy, methoxy, fluoro, chloro, iodo, bromo, carboxyl, formyl, methylcarbonyl and trifluoromethylcarbonyl; wherein R1 and R2 may further be taken together to form oxo; wherein R7 is hydrido; wherein R8 is selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl and neopentyl; or a stereoisomer or a tautomer thereof or a pharmaceutically-acceptable salt thereof.

A family of specific compounds of particular interest within Formula v(c) consists of compounds and thei~

2l~3192 stereoisomers and tautomers and the pharmaceutically-acceptable salts thereof, said compounds consisting of 1-(2-methylcyclopentyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-ethylcyclopentyl)-4-~utyl-1,3-dihydro-3-l[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-propylcyclopentyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
l-t2-isopropylcyclopentyl)-4-butyl-1,3-dihydro-3-[[4-[3-~lH-tetrazol-5-yl)phenyl]-2-pyridinyl~methyl]-2H-imidazol-2-one;
1-(2-tertbutylcyclopentyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-methoxycyclopentyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-hydroxycyclopentyl)-4-butyl-1,3-dihydro-3-[~4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-carboxycyclopentyl)-4-butyl-1,3-dihydro-3-[~4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-acetylcyclopentyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl~methyl~-2H-imidazol-2-one;
1-(2-oxocyclopentyl)-4-butyl-1,3-dihy~ro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2,4-dimethylcyclopentyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-ethyl-5-methylcyclopentyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-isopropyl-5-methylcyclopentyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-carboxy-5-methylcyclopentyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl~phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-acetyl-5-methylcyclopentyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
-W094/08989 PCT/US93/056~
214319~

1-(2-oxo-5-methylcyclopentyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-methyl-5-ethylcyclopentyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2,5-diethylcyclopentyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-onei 1-(2-isopropyl-5-ethylcyclopentyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-carboxy-5-ethylcyclopentyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-acetyl-5-ethylcyclopentyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-oxo-5-ethylcyclopentyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;1-(2-methyl-5-iso~lo~ylcyclopentyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-ethyl-5-isopropylcyclopentyl)-4-butyl-1,3-dihydro-3-[[4-[3-~lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2,5-diisopropylcyclopentyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-carboxy-5-isopropylcyclopentyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-acetyl-5-iso~lo~ylcyclopentyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;

2~.3~

1-(2-oxo-5-isopropylcyclopentyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2,2-dimethylcyclopentyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
and 1-(2,2-diethylcyclopentyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one.

Within this third group of compounds of Formula V
there is a fourth class of higher-interest compounds of Formula V(d):

CH2-N ~ R-~ O ~ n~ V(d) H--N N 3~/
`NoN R

wherein each of R1, R2 and R3 may be independently selected from hydrido, methyl, eth~l, n-propyl, isopropyl, tert-butyl, hydroxy, methoxy, - uoro, chloro, iodo, bromo, carboxyl, formyl, methylcarbonyl and trifluoromethylcarbonyl; wherein R1 and R2 may further be taken together to for~, oxo; wherein R7 is hydrido; wherein R8 is selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl and neopentyl; or a stereoisomer or a tautomer 2~ thereof or a pharmaceutically-acceptable salt thereof.

A family of specific compounds of particular interest within Formula V(d) consists of compounds and thei~
stereoisomers and tautomers and the pharmaceutically-acceptable salts thereof, said com~Junds consisting of1-(2-methylcyclopentyl)-4-butyl-1,3-dihydro-3-[[4-[4-(1~-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-onei W094/08989 PCT/US93/056~
i ~43~9~

1-~2-ethylcyclopentyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-propylcyclopentyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-isopropylcyclopentyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-tertbutylcyclopentyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-methoxycyclopentyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-hydroxycyclopentyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl~methyl]-2H-imidazol-2-one;
1-(2-carboxycyclopentyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-acetylcyclopentyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-oxocyclopentyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2,4-dimethylcyclopentyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-ethyl-5-methylcyclopentyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-isopropyl-5-methylcyclopentyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
l-(2-carboxy-5-methylcyclopentyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-acetyl-5-methylcyclopentyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
l-(2-oxo-5-methylcyclopentyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;

W094/08989 PCT/US93/0560t ~ 21~319~

1-~2-methyl-5-ethylcyclopentyl)-4-~utyl-1,3-dihydro-3-~[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2,5-diethylcyclopentyl)-4-butyl-1,3-dihydro-3-tt4-[4-(lH-- 5 tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;1-(2-isopropyl-5-ethylcyclopentyl)-4-butyl-1,3-dihydro-3-[[4-- [4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-carboxy-5-ethylcyclopentyl)-4-butyl-1,3-dihydro-3-[t4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl3methyl]-2H-imidazol-2-one;
1-(2-acetyl-5-ethylcyclopentyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-oxo-5-ethylcyclopentyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-methyl-5-iso~Lo~ylcyclopentyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-ethyl-5-isopropylcyclopentyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-~2,5-diisopropylcyclopentyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-carboxy-5-isopropylcyclopentyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-acetyl-5 -iso~L o~ylcyclopentyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-oxo-5-isopropylcyclopentyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2~-imidazol-2-one;

W094/08989 ~3~ PCT/US93/056 ~

1-(2,2-dimethylcyclopentyl)-4-butyl-1,3-dihydro-3-[[4-[4-~lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
and 1-(2,2-diethylcyclopentyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one.

Within this third group of compounds of Formula V
there is a fifth class of higher-interest compounds of Formula V(e):

N ~

N_N R3 ~ n2 V(e) wherein each of R1, R2 and R3 may be independently selected from hydrido, methyl, ethyl, n-propyl, isopropyl, tert-butyl, hydroxy, methoxy, fluoro, chloro, iodo, bromo,carboxyl, formyl, methylcarbonyl and trifluoromethylcarbonyl; wherein R1 and R2 may further be taken together to form oxo; wherein R7 is hydrido; wherein R8 is selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl and neopentyl; or a stereoisomer or a tautomer thereof or a pharmaceutically-acceptable salt thereof.

A family of specific compounds of particular interest within Formula V(e) consists of compounds and their stereoisomers and tautomers and the pharmaceutically-acceptable salts thereof, said compounds consisting of 1-(2-methylcyclopentyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-ethylcyclopentyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;

~ W094/08989 2 1 ~ 3 1 9 2 PCT/US93/05601 1-(2-propylcyclopentyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-isopropylcyclopentyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-tertbutylcyclopentyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-methoxycyclopentyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one 1-(2-hydroxycyclopentyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-carboxycyclopentyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-acetylcyclopentyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl~methyl]-2H-imidazol-2-one 1-(2-oxocyclopentyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-onei 1-(2,4-dimethylcyclopentyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-onei 1-(2-ethyl-5-methylcyclopentyl)-4-butyl-1,3-dihydro-3~[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-onei 1-(2-isopropyl-5-methylcyclopentyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl)methyl]-2H-imidazol-2-onei 1-~2-carboxy-5-methylcyclopentyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-onei 1-(2-acetyl-5-methylcyclopentyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-onei 1-(2-oxo-5-methylcyclopentyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)~:lenyl]-4-pyridinyl]methyl]-2H-imidazol-2-onei ~-(2-methyl-5-ethylcyclopentyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-onei W094/08989 2 1 4 3 1 9 2 PCT/US93/056 ~

1-(2,5-diethylcyclopentyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-onei 1-(2-isopropyl-5-ethylcyclopentyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-carboxy-5-ethylcyclopentyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-acetyl-5-ethylcyclopentyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl~-4-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-oxo-5-ethylcyclopentyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-methyl-5-iso~lo~lcyclopentyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl3methyl]-2H-imidazol-2-one;
1-(2-ethyl-5-isoy~o~lcyclopentyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2,5-diisopropylcyclopentyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-carboxy-5-isopropylcyclopentyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-acetyl-5-isopropylcyclopentyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-oxo-5-isopropylcyclopentyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol- -2-one;
1-(2,2-dimethylcyclopentyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
and 1-(2,2-diethylcyclopentyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one.

~W094/08989 PCT/US93/05601 Within this third group of compounds of Formula v there is a sixth class of higher-interest compounds of Formula V(f):

~ O ~ V(f) wherein each of R1, R2 and R3 may be independently selected from hydrido, methyl, ethyl, n-propyl, isopropyl, tert-butyl, hydroxy, methoxy, fluoro, chloro, iodo, bromo,carboxyl, formyl, methylcarbonyl and trifluoromethylcarbonyl; wherein R1 and R2 may further be taken together to form oxo; wherein ~7 is hydrido; wherein R8 is selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl and neopentyl; or a stereoisomer or a tautomer thereof or a pharmaceutically-acceptable salt thereof.

A family of specific compounds of particular interest within Formula V(f) consists of compounds and their stereoisomers and tautomers and the pharmaceutically-acceptable salts thereof, said compounds consisting of 1-(2-methylcyclopentyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-ethylcyclopentyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl3methyl]-2H-imidazol-2-one;
1-(2-propylcyclopentyl)-4-butyl-1,3-dihydro-3-[[4-[2-~lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-~2-isopropylcyclopentyl)-4-butyl-1,3-dihydro-3-[[4-[2-~lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-~2-tertbutylcyclopentyl)-4-butvl-1,3-dihydro-3-l[4-[2-~lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;

W094/08989 PCT/US93/056~
21~31~

1-(2-methoxycyclopentyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one 1-(2-hydroxycyclopentyl)-4-butyl-1,3-dihydro-3-[[4-[2-~lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-carboxycyclopentyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-acetylcyclopentyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-oxocyclopentyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-10 tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2,4-dimethylcyclopentyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-ethyl-5-methylcyclopentyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;1-(2-isopropyl-5-methylcyclopentyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-carboxy-5-methylcyclopentyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-acetyl-5-methylcyclopentyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-oxo-5-methylcyclopentyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-methyl-5-ethylcyclopentyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;1-(2,5-diethylcyclopentyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-isopropyl-5-ethylcyclopentyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;

~ 21g3192 1-(2-carboxy-5-ethylcyclopentyl)-4-buty~ 3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-acetyl-5-ethylcyclopentyl)-4-butyl-1,3-dihydro-3-[[4-[2-~ 5 (lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-oxo-5-ethylcyclopentyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-methyl-5-isopropylcyclopentyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-ethyl-5-isopropylcyclopentyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2,5-diis~ lcyclopentyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-carboxy-5-isopropylcyclopentyl)-4-butyl-1,3-dihydro-3-20 [[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-acetyl-5-isopropylcyclopentyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
25 1-(2-oxo-5-isopropylcyclopentyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2,2-dimethylcyclopentyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
and 1-(2,2-diethylcyclopentyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyljmethyl]-2H-imidazol-2-one.

Within the compounds of Formula II there is a fourt~ group of compounds of more interest as represented bv Formula VI:

W094/08989 PCT/US93/05 ~

2143~2 72 n~
R1 ~_ N--CH2 A VI

R7 t' wherein each of Rl, R2 and R3 is independently selected from hydrido, methyl, ethyl, n-propyl, isopropyl, tert-S butyl, methoxy, ethoxy, propoxy, isopropoxy, tert-butoxy, cyano, fluoro, chloro, iodo, bromo, hydroxy, nitro, amino, N-methylamino, N,N-dimethylamino, N-ethyl~m; no, N,N-diethylamino, carboxyl, methoxycarbonyl, ethoxycarbonyl, formyl, methylcarbonyl, ethylcarbonyl and trifluoromethylcarbonyl; wherein Rl and R2 may further be taken together to form oxo; wherein R7 is selected from hydrido, methyl, fluoro, chloro, monofluoromethyl, difluoromethyl, trifluoromethyl, formyl, carboxyl and dimethoxymethyl; wherein R8 is selected from methyl, ethyl, n-propyl, iS0~2 o~l, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl, neopentyl, phenyl, benzyl, phenethyl, CYC1O~LO~Y1~ cyclobutyl, cyclopentyl, cyclohexyl, cyclopropylmethyl, cyclopropylethyl, cyclobutylmethyl, cyclobutylethyl, cyclopentylmethyl, cyclopentylethyl, cyclohexylmethyl and cyclohexylethyl;
wherein A is an acidic-group-substituted pyridinyl-phenyl moiety selected from ~ ' ~N ald wherein R9 is an acidic group selected from COOH and 21~3192 H

1/ N ;

or a stereoisomer or a tautomer thereof or a pharmaceutically-acceptable salt thereof.

Within this fourth group of compounds of Formula VI there is a first class of higher-interest compounds of Formula VI(a):
R8` R7 CH2--N~/ R1 ~ N XR2 VI(a) H N N R3--~

wherein each of R1, R2 and R3 may be independently selected from hydrido, methyl, ethyl, n-propyl, isopropyl, tert-butyl, hydroxy, methoxy, fluoro, chloro, iodo, bromo, carboxyl, formyl, methylcarbonyl and trifluoromethylcarbonyl; wherein R1 and R2 may further be taken together to form oxo; wherein R7 is hydrido; wherein ~8 is selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl and neopentyl; or a stereoisomer or a tautomer thereof or a pharmaceutically-acceptable salt thereof.

family of specific compounds of particular interest within Formula VI(a) consists of compounds and their 2~ stereoisomers and tautomers and the pharmaceutically-acceptable salts thereof, said compounds consisting of 1-~2-methylcyclohexyl)-4-butyl-1,3-dihydro-3-[ r 5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H- imidazol-2-one;

W094/08989 PCT/US93/056~
1' .~ i .
~ 1 4 3 1 ~ 2 74 1-(2-ethylcyclohexyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl~methyl]-2H-imidazol-2-one;
1-(2-propylcyclohexyl)-4-bUtyl-1,3-dihydro-3-[t5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-isopropylcyclohexyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-tertbutylcyclohexyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-methoxycyclohexyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-hydroxycyclohexyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-carboxycyclohexyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-acetylcyclohexyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl3-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-oxocyclohexyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2,6-dimethylcyclohexyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl).phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-ethyl-6-methylcyclohexyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-te~razol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-isopropyl-6-methylcyclohexyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-carboxy-6-methylcyclohexyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-acetyl-6-methylcyclohexyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-oxo-6-methylcyclohexyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-,-one;

21~3~

1-(2-methyl-6-ethylcyclohexyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-onei 1-(2,6-diethylcyclohexyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-- 5 tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-isopropyl-6-ethylcyclohexyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-carboxy-6-ethylcyclohexyl)-4-butyl-1,3-dihydro-3-[~5-[2-(lH-tetrazol-5-yl)phenyl~-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-acetyl-6-ethylcyclohexyl)-4-butyl-1,3-dihydro-3-[E5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-oxo-6-ethylcyclohexyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-methyl-6-is~ro~lcyclohexyl)-4-butyl-1,3-dihydro-3-[r5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-ethyl-6-iso~Lo~lcyclohexyl)-4-butyl-1,3-dihydro-3-~5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2~-imidazol-2-one;
1-(2,6-diisopropylcyclohexyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-carboxy-6-isopropylcyclohexyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-acetyl-6-iso~o~ylcyclohexyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-oxo-6-isopropylcyclohexyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
35 1-(2~2-dimethylcyclohexyl)-4-butyl-l~3-dihydro-3-[~s-~2-( tetrazol-5-yl)phenyl]-2-pyridinyl~methyl]-2H-imidazol-2-one;
and W094/08989 -21 4 3 I 9 ~ PCT/US93/05 ~

1-(2,2-diethylcyclohexyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one.

Within this fourth group of compounds of Formula VI there is a second class of higher-interest compounds of Formula VI(b):

~ CH2- ~ R~ vI(b) wherein each of Rl, R2 and R3 may be independently selected from hydrido, methyl, ethyl, n-propyl, isopropyl, tert-butyl, hydroxy, methoxy, fluoro, chloro, iodo, bromo, carboxyl, formyl, methylcarbonyl and trifluoromethylcarbonyl; wherein Rl and R2 may further be taken together to form oxo; wherein R7 is hydrido; wherein R8 is selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl and neopentyl; or a stereoisomer or a tautomer thereof or a pharmaceutically-acceptable salt thereof.
A family of specific compounds of particular interest within Formula VI(b) consists of compounds and their stereoisomers and tautomers and the pharmaceutically-acceptable salts thereof, said compounds consisting of 1-(2-methylcyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-ethylcyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-propylcyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinylimethyl]-2H-imidazol-2-one;
1-(2-isopropylcyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1~-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one W094/08989 PCT/US93/0560~
21 ~ 31 92 1-~2-tertbutylcyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-methoxycyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-hydroxycyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
~ 1-(2-carboxycyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-acetylcyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-oxocyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2,6-dimethylcyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-~2-ethyl-6-methylcyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-isopropyl-6-methylcyclohexyl)-4-butyl-1,3-dihydro-3-~[6-[2-(lH-tetrazol-~-yl)phenyl]-3-pyridinyl)methyl]-2H-imidazol-2-one;
l-t2-carboxy-6-methylcyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-onei 1-(2-acetyl-6-methylcyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-oxo-6-methylcyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-methyl-6-ethylcyclohexyl)-4-butyl-1,3-dihydro-3-[~6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2,6-diethylcyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-iso~lo~yl-6-ethylcyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;

W094/08989 PCT/US93/056~
214~192 1-~2-carboxy-6-ethylcyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-acetyl-6-ethylcyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-oxo-6-ethylcyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-onei 1-(2-methyl-6-isoulo~ylcyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-ethyl-6-iso~ulu,uylcyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2,6-diiso~lo,uylcyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-carboxy-6-iso,uro,uylcyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-acetyl-6-isopropylcyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-oxo-6-isopropylcyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-~lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2,2-dimethylcyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
and 1-(2,2-diethylcyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one.

Within this fourth group of compounds of Formula ~ there is a third class of higher-interest compounds of Formula VI(c):

~ W094/08989 PCT/US93/05601 21~3192 Rs ~ R7 VI~c) N_N R3 ~

wherein each of R1, R2 and R3 may be independently selected from hydrido, methyl, ethyl, n-propyl, isopropyl, tert-butyl, hydroxy, methoxy, fluoro, chloro, iodo, bromo,carboxyl, formyl, methylcarbonyl and trifluoromethylcarbonyl; wherein R1 and ~2 may further be taken together to form oxo; wherein R7 is hydrido; wherein R8 is selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl and neopentyl; or a stereoisomer or a tautomer thereof or a pharmaceutically-acceptable salt thereof.

A family of specific compounds of particular interest within Formula VI(c) consists of compounds and their stereoisomers and tautomers and the pharmaceutically-acceptable salts thereof, said compounds consisting of 1-(2-methylcyclohexyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-ethylcyclohexyl)-4-butyl-1,3-dihydro-3-[[4-[3-tlH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-propylcyclohexyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinylimethyl]-2H-imidazol-2-one;
1-(2-isopropylcyclohexyl)-4-butyl-1,3-dihydro-3-[[4- r 3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
-(2-tertbutylcyclohexyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
- 1-(2-methoxycyclohexyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl~-2H-imidazol-2-one;
1-(2-hydroxycyclohexyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;

2 ~ ~3 ~ 9 2 8 1-(2-carboxycyclohexyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-acetylcyclohexyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-oxocyclohexyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2,6-dimethylcyclohexyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-ethyl-6-methylcyclohexyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-iso~Lu~1-6-methylcyclohexyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-carboxy-6-methylcyclohexyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl~methyl]-2H-imidazol-2-one;
1-(2-acetyl-6-methylcyclohexyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;1-(2-oxo-6-methylcyclohexyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-methyl-6-ethylcyclohexyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2,6-diethylcyclohexyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-isopropyl-6-ethylcyclohexyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-carboxy-6-ethylcyclohexyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-acetyl-6-ethylcyclohexyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazû1-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;

~ W094/08989 81 2 1 4 3 1 9 2 PCT/Us93/0s601 l-(2-oxo-6-ethylcyclohexyl)-4-butyl-l~3-dihydro-3-[[4-[3-(lH
tetrazol-5-yl)phenyl]-2-pyridinyl3methyl]-2H-imidazol-2-one;
l-(2-methyl-6-isopropylcyclohexyl)-4-butyl-l,3-dihydro-3-[[4-~3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-- 5 2-one;
l-(2-ethyl-6-iso~Lo~lcyclohexyl)-4-butyl-l,3-dihydro-3-[~4-3-(lH-tetrazol-~-yl)phenyl~-2-pyridinyl]methyl]-2H-imidazol-2-one;
l-(2,6-diiso~Lo~lcyclohexyl)-4-butyl-l,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl~methyl]-2H-imidazol-2-one;
l-(2-carboxy-6-iso~lo~ylcyclohexyl)-4-butyl-l,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
15 l-(2-acetyl-6-iso~rop~lcyclohexyl)-4-butyl-l,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
l-(2-oxo-6-isopropylcyclohexyl)-4-butyl-l,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
l-(2,2-dimethylcyclohexyl)-4-butyl-l,3-dihydro-3-[[4-[3- ~lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl~-2H-imidazol-2-one;
and l-(2,2-diethylcyclohexyl)-4-butyl-l,3-dihydro-3-[14-13-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one.

Within this fourth group of compounds of Formula VI there is a fourth class of higher-interest compounds of Formula VI(d):

VI(d) H N. N R3 W094/08989 PCT/US93/056~
2~3~9~

wherein each of Rl, R2 and R3 may be independently selected from hydrido, methyl, ethyl, n-propyl, isopropyl, tert-butyl, hydroxy, methoxy, fluoro, chloro, iodo, bromo, carboxyl, formyl, methylcarbonyl and trifluoromethylcarbonyl; wherein Rl and R2 may further be taken together to form oxo; wherein R7 is hydrido; wherein R8 is selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl and neopentyl; or a stereoisomer or a tautomer thereof or a pharmaceutically-acceptable salt thereof.

A family of specific compounds of particular interest within Formula VI(d) consists of compounds and their stereoisomers and tautomers and the pharmaceutically-acceptable salts thereof, said compounds consisting of1-(2-methylcyclohexyl)-4-butyl-1,3-dihydro-3-t[4-[4-(1~-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-ethylcyclohexyl)-4-butyl-1,3-dihydro-3-~[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-propylcyclohexyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-isopropylcyclohexyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl~methyl]-2H-imidazol-2-one;
1-(2-tertbutylcyclohexyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one 1-(2-methoxycyclohexyl)-4-butyl-1,3-dihydro-3-r[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-hydroxycyclohexyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one 1-(2-carboxycyclohexyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl~methyl]-2H-imidazol-2-one;
1-(2-acetylcyclohexyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-oxocyclohexyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-onei 1-(2,6-dimethylCyCloheXyl)-4-bUtyl-1,3-dihydro-3-[[4-[~-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-onei W094/08989 2 1 ~ 31 9 2 PCT/US93/0560l 1-(2-ethyl-6-methylcyclohexyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-isopropyl-6-methylcyclohexyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl~-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-carboxy-6-methylcyclohexyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyljmethyl]-2H-imidazol-2-one;
1-(2-acetyl-6-methylcyclohexyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-oxo-6-methylcyclohexyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;1-(2-methyl-6-ethylcyclohexyl)-4-butyl-1,3-dihydro-3-~[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2,6-diethylcyclohexyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-isopropyl-6-ethylcyclohexyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-carboxy-6-ethylcyclohexyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-acetyl-6-ethylcyclohexyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-oxo-6-ethylcyclohexyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-methyl-6-isopropylcyclohexyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-onei 1-(2-ethyl-6-isoy~o~ylcyclohexyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imida 2-one;

W094/08989 PCT/US93/056~

1-(2,6-diiso~lo~lcyclohexyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-carboxy-6-iso~Lo~lcyclohexyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-acetyl-6-iso~o~lcyclohexyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-oxo-6-iso~o~lcyclohexyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl3methyl]-2H-imidazol-2-one;
1-~2,2-dimethylcyclohexyl)-4-butyl-1,3-dihydro-3-[[4-[4-(1~-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
and 1-(2,2-diethylcyclohexyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one.

Within this fourth group of compounds of Formula VI there is a fifth class of higher-interest compounds of Formula VI(e):

N ~ C~2 ~ ~2 VI(e) wherein each of Rl, R2 and R3 may be independently selected from hydrido, methyl, ethyl, n-propyl, isopropyl, tert-butyl, hydroxy, methoxy, fluoro, chloro, iodo, bromo, carboxyl, formyl, methylcarbonyl and trifluoromethylcarbonyl; wherein Rl and R2 may further be taken together to form oxo; wherein R7 is hydrido; wherein R8 is selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, W094/08989 21 ~ 3t 92 isopentyl and neopentyl; or a stereoisomer or a tautomer thereof or a pharmaceutically-acceptable salt thereof.

A family of specific compounds of particular - 5 interest within Formula VI(e) consists of compounds and their stereoisomers and tautomers and the pharmaceutically-~ acceptable salts thereof, said compounds consisting of 1-(2-methylcyclohexyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-~-yl)phenyl]-4-pyridinyl~methyl~-2H-imidazol-2-one;
1-~2-ethylcyclohexyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-propylcyclohexyl)-4-butyl-1,3-dihydro-3-[[4-[3-~lH-tetrazol-5-yl~phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-isopropylcyclohexyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-tertbutylcyclohexyl)-4-butyl-1,3-dihydro-3-t[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-methoxycyclohexyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-hydroxycyclohexyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinylimethyl]-2H-imidazol-2-one;
1-(2-carboxycyclohexyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl~-4-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-acetylcyclohexyl)-4-bUtyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-oxocyclohexyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2,6-dimethylcyclohexyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-ethyl-6-methylcyclohexyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-isopropyl-6-methylcyclohexyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;

W094/08989 . PCT/US93/056~
21~3I9~ 86 1-(2-carboxy-6-methylcyclohexyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl~-4-pyridinyljmethyl]-2H-imidazol-2-one;
1-(2-acetyl-6-methylcyclohexyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-oxo-6-methylcyclohexyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-methyl-6-ethylcyclohexyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2,6-diethylcyclohexyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-isopropyl-6-ethylcyclohexyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-carboxy-6-ethylcyclohexyl)-4-butyl-1,3-dihydro-3-[[4-~3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;1-(2-acetyl-6-ethylcyclohexyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl~-2H-imidazol-2-one;
1-~2-oxo-6-ethylcyclohexyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl~-2H-imidazol-2-one;
1-(2-methyl-6-iso~lo~ylcyclohexyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl~-4-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-ethyl-6-iso~ro~lcyclohexyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl~-2H-imidazol-2-one;
1-(2,6-diiso~Lo~lcyclohexyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-carboxy-6-iso~o~lcyclohexyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;

1-(2-acetyl-6-isopropylcyclohexyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-oxo-6-iso~lo~lcyclohexyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
~ 1-(2,2-dimethylcyclohexyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
and l-(2~2-diethylcyclohexyl)-4-buty~ 3-dihydro-3-~[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one.

Within this fourth group of compounds of Formula VI there is a sixth class of higher-interest compounds of Formula VI(f):

~ CH2 ~ R2 VI(f) H N. z N R3 wherein each of Rl, R2 and R3 may be independently selected from hydrido, methyl, ethyl, n-propyl, isopropyl, tert-butyl, hydroxy, methoxy, fluoro, chloro, iodo, bromo, carboxyl, formyl, methylcarbonyl and trifluoromethylcarbonyl; wherein Rl and R2 may further be taken together to form oxoi wherein R7 is hydrido; whereinR8 is selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl and neopentyl; or a stereoisomer or a tautomer thereof or a pharmaceutically-acceptable salt thereof.
A family of specific compounds of particular interest within Formula VI(f) consists of compounds and their W094/08989 PCT/US93/056~

2I~3I ~2 88 stereoisomers and tautomers and the pharmaceutically-acceptable salts thereof, said compounds consisting of 1-(2-methylcyclohexyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-ethylcyclohexyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyllmethyl]-2H-imidazol-2-one;
1-(2-propylcyclohexyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-iso~Lo~lcyclohexyl)-4-butyl-1,3-dihydro-3-[[4-~2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-tertbutylcyclohexyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-methoxycyclohexyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-hydroxycyclohexyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-carboxycyclohexyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-acetylcyclohexyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-oxocyclohexyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2,6-dimethylcyclohexyl)-4-butyl-1,3-dihydro-3-[[4-[2-tlH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-ethyl-6-methylcyclohexyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-isopropyl-6-methylcyclohexyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-carboxy-6-methylcyclohexyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-acetyl-6-methylcyclohexyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;

~ 21~31~

1-(2-oxo-6-methylcyclohexyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-methyl-6-ethylcyclohexyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
~ 1-~2,6-diethylcyclohexyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-~2-isopropyl-6-ethylcyclohexyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-carboxy-6-ethylcyclohexyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-acetyl-6-ethylcyclohexyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl3methyl]-2H-imidazol-2-one;
1-(2-oxo-6-ethylcyclohexyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-methyl-6-iso~lo~lcyclohexyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
l-t2-ethyl-6-isopropylcyclohexyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2,6-diisopropylcyclohexyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-carboxy-6-iso~o~lcyclohexyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2- acetyl-6-iso~oyylcyclohexyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-oxo-6-isopropylcyclohexyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;

W094/08989 PCT/US93/056~
:21~L31~2 go 1-(2,2-dimethylcyclohexyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl~methyl]-2H-imidazol-2-one;
and 1-(2,2-diethylcyclohexyl)-4-butyl-1,3-dihydro-3-[[4-t2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one.

Within the compounds of Formula II there is a fifth group of compounds of more interest as represented by Formula VII:

~_R3 R Rl~N - A VII
R

wherein each of R1, R2 and R3 is independently selected from hydrido, methyl, ethyl, n-propyl, iso~ro~l, tert-butyl, methoxy, ethoxy, propoxy, isopropoxy, tert-butoxy, cyano, fluoro, chloro, iodo, bromo, hydroxy, nitro, amino, N-methyl ~m; no, N,N-dimethylamino, N-ethyl ~m; no, N,N-diethyl ~m; no, carboxyl, methoxycarbonyl, ethoxycarbonyl, formyl, methylcarbonyl, ethylcarbonyl and trifluoromethylcarbonyl; wherein R1 and R2 may further be taken together to form oxo; wherein R7 is selected from hydrido, methyl, fluoro, chloro, monofluoromethyl, difluoromethyl, trifluoromethyl, formyl, carboxyl and dimethoxymethyl; wherein R8 is selected from methyl, ethyl, n-propyl, iso~o~yl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl, neopentyl, phenyl, benzyl, phenethyl, cyclo~lo~yl, cyclobutyl, cyclopentyl, cyclohexyl, cyclo~o~ylmethyl, cyclo~Lo~ylethyl, cyclobutylmethyl, cyclobutylethyl, cyclopentylmethyl, cyclopentylethyl, cyclohexylmethyl and cyclohexylethyl;
wherein A is an acidic-group-substituted pyridinyl-phenyl moiety selected from 2l~3l92 ~ ~ ~ N a~ ~ ;
wherein R9 is an acidic group selected from COOH and .

N- ~
~ ~N
N

or a stereoisomer or a tautomer thereof or a pharmaceutically-accept--f.ble salt thereof.

Within this fifth group of compounds of Formula VII there is a first class of higher-interest compounds of Formula VII(a):

N ~ ~ n~ VII(a) 1~
wherein each of Rl, R2 and R3 may be independently selected from hydrido, methyl, ethyl, n-propyl, iSO~l o~yl, tert-butyl, hydroxy, methoxy, fluoro, chloro, iodo, bromo, carboxyl, formyl, methylcarbonyl and trifluoromethylcarbonyl; wherein Rl and R2 may further be taken together to form oxo; wherein R7 is hydrido; wherein R8 is selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, W094/08989 PCT/US93/056~

" , ., isopentyl and neopentyl; or a stereoisomer or a tautomer thereof or a pharmaceutically-acceptable salt thereof.

A family of specific compounds of particular interest within Formula VII(a) consists of compounds and their stereoisomers and tautomers and the pharmaceutically-acceptable salts thereof, said compounds consisting of 1-(2-methylcycloheptyl)-4-butyl-1,3-dihydro-3-~[5-~2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-ethylcycloheptyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-propylcycloheptyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-isopropylcycloheptyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-tertbutylcycloheptyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-methoxycycloheptyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-hydroxycycloheptyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-carboxycycloheptyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-acetylcycloheptyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-oxocycloheptyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2,7-dimethylcycloheptyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-~-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-ethyl-7-methylcycloheptyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-isopropyl-7-methylcycloheptyl)-4-butyl-1,3-dihydro-3-[[5-[2-tlH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;

~ 21~3192 1-(2-carboxy-7-methylcycloheptyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-acetyl-7-methylcycloheptyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-oxo-7-methylcycloheptyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-methyl-7-ethylcycloheptyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2,7-diethylcycloheptyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-isopropyl-7-ethylcycloheptyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-carboxy-7-ethylcycloheptyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-acetyl-7-ethylcycloheptyl)-4-butyl-1,3-dihydro-3-~[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-oxo-7-ethylcycloheptyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl3methyl]-2H-imidazol-2-one;
1-(2-methyl-7-iso~o~ylcycloheptyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-ethyl-7-iso~ro~ylcycloheptyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2,7-diiso~Lo~ylcycloheptyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;

W094/08989 , ~ PCT/US93/056 2 1 ~3 19 2 94 1-(2-carboxy-7-iso~Lo~lcycloheptyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-acetyl-7-isu~Lo~lcycloheptyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-oxo-7-isopropylcycloheptyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2,2-dimethylcycloheptyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
and - 1-(2,2-diethylcycloheptyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl3methyl]-2H-imidazol-2-one.
Within this fifth group of compounds of Formula VII there is a second class of higher-interest compounds of Formula VII(b):
R~ 7 ~ ) ~ n2 VII(b) H- N I R3~
`NoN '~' wherein each of R1, R2 and R3 may be independently selected from hydrido, methyl, ethyl, n-propyl, isopropyl, tert-butyl, hydroxy, methoxy, fluoro, chloro, iodo, bromo, carboxyl, formyl, methylcarbonyl and trifluoromethylcarbonyl; wherein R1 and R2 may furthe~ be taken together to form oxo; wherein R7 is hydridoi wherein R8 is selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl and neopentyl; or a stereoisomer or a tautomer thereof or a pharmaceutically-acceptable salt thereof.

~ 2143192 A family of specific compounds of particular interest within Formula VIItb) consists of compounds and their stereoisomers and tautomers and the pharmaceutically-acceptable salts thereof, said compounds consisting of l-(2-methylcycloheptyl)-4-butyl-l,3-dihydro-3-[~6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl~methyl]-2H-imidazol-2-one;
l-(2-ethylcycloheptyl)-4-butyl-l,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
l-(2-propylcycloheptyl)-4-butyl-l,3-dihydro-3-~[6-~2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
l-(2-isopropylcycloheptyl)-4-butyl-l,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl~-3-pyridinyl]methyl]-2H-imidazol-2-one;
l-(2-tertbutylcycloheptyl)-4-butyl-l,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
lS l-(2-methoxycycloheptyl)-4-butyl-l,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
l-(2-hydroxycycloheptyl)-4-butyl-l,3-dihydro-3-~16-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
l-(2-carboxycycloheptyl)-4-butyl-l,3-dihydro-3-[[6-[2-,(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
l-~2-acetylcycloheptyl)-4-butyl-l,3-dihydro-3-[[6-[2-( lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
l-(2-oxocycloheptyl)-4-butyl-l,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
l-(2,7-dimethylcycloheptyl)-4-butyl-l,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
l-(2-ethyl-7-methylcycloheptyl)-4-butyl-l,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
l-(2-isopropyl-7-methylcycloheptyl)-4-butyl-l,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2~-imidazol-2-one;
1-(2-carboxy-7-methylcycloheptyl)-4-butyl-l,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;

W094/08989 2 1 ~ 3 1 9 2 PCT/US93/056~

1-(2-acetyl-7-methylcycloheptyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-oxo-7-methylcycloheptyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-methyl-7-ethylcycloheptyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2,7-diethylcycloheptyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-isopropyl-7-ethylcycloheptyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-carboxy-7-ethylcycloheptyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-acetyl-7-ethylcycloheptyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-oxo-7-ethylcycloheptyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-onei 1-(2-methyl-7-isopropylcycloheptyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
l-(2-ethyl-7-isopropylcycloheptyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2,7-diisopropylcycloheptyl)-4-butyl-1,3-dihydro-3-[[6-[2-(l~-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-onei ~-(2-carboxy-7-isopropylcycloheptyl)-4-butyl-1,3-dihydro-3-[~6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;

~ W094/~8989 2 i ~ 3 1 9 2 PCT/US93/05601 1-(2-acetyl-7-is~ro~ylcycloheptyl)-4-butyl-1,3-dihydro-3-E[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl~methyl]-2H
imidazol-2-one;
1-(2-oxo-7-isopropylcycloheptyl)-4-butyl-1,3-dihydro-3-[[6-- 5 ~2-(lH-tetra~ol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2,2-dimethyl.cycloheptyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
and 1-(2,2-diethylcycloheptyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one.

Within this fifth group of compounds of Formula VII there is a third class of higher-interest compounds of Formula VII(c):

~CH2--N~ Rl H - ~ N, ~ ~ n2 VII(c) wherein each of R1, R2 and R3 may be independently selected from hydrido, methyl, ethyl, n-propyl, iso~o~1, tert-butyl, hydroxy, methoxy, fluoro, chloro, iodo, bromo, carboxyl, formyl, methylcarbonyl and trifluoromethylcarbonyl; wherein R1 and R2 may further be taken together to form oxo; wherein R7 is hydrido; wherein R8 is selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl and neopentyl; or a stereoisomer or a tautomer thereof or a pharmaceutically-acceptable salt thereof.

A family of specific compounds of particular interest within Formula VII(c) consists of compounds and W094/08989 PCT/US93/056~
21~3~9~

their stereoisomers and tautomers and the pharmaceutically-acceptable salts thereof, said compounds consisting of 1-(2-methylcycloheptyl)-4-butyl-1,3-dihydro-3-[[4-[3-tlH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-ethylcycloheptyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl~methyl]-2H-imidazol-2-one;
1-(2-propylcycloheptyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-isopropylcycloheptyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-tertbutylcycloheptyl)-4-butyl-1,3-dihydro-3-[[4-[3-tlH-tetrazol-5-yl)phenyl]-2-pyridinyl~methyl]-2H-imidazol-2-one;
1-(2-methoxycycloheptyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyllmethyl]-2H-imidazol-2-one;
1-(2-hydroxycycloheptyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl~-2-pyridinyl]methyl]-2H-im;~ol-2-one;
1-(2-carboxycycloheptyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-acetylcycloheptyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-oxocycloheptyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2,7-dimethylcycloheptyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-ethyl-7-methylcycloheptyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-iso~o~1-7-methylcycloheptyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-carboxy-7-methylcycloheptyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-acetyl-7-methylcycloheptyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;

W094/08989 ' ~ 2 1~ 3 1 ~ 2 1-(2-oxo-7-methylcycloheptyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-methyl-7-ethylcycloheptyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2,7-diethylcycloheptyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-isopropyl-7-ethylcycloheptyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-carboxy-7-ethylcycloheptyl)-4-butyl-1,3-dihydro-3-[[4-- [3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl3-2H-imidazol-2-one;
1-(2-acetyl-7-ethylcycloheptyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-oxo-7-ethylcycloheptyl)-4-butyl-1,3-dihydro-3-[~4-~3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-methyl-7-isoy~o~ylcycloheptyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-ethyl-7-isopropylcycloheptyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyljmethyl]-2H-imidazol-2-one;
1-(2,7-diisopropylcycloheptyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-ylJphenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-carboxy-7-isopropylcycloheptyl)-4-butyl-1,3-dihydro-3-[[4-~3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-acetyl-7-isopropylcycloheptyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2~-imidazol-2-one;

W094/08989 PCT/US93/056~
2I~3192 1-(2-oxo-7-isopropylcycloheptyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2,2-dimethylcycloheptyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
and 1-(2,2-diethylcycloheptyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one.

Within this fifth group of compounds of Formula VII there is a fourth class of higher-interest compounds of Formula VII(d):

~ n2 VII(d wherein each of Rl, R2 and R3 may be independently selected from hydrido, methyl, ethyl, n-propyl, isopropyl, tert-butyl, hydroxy, methoxy, fluoro, chloro, iodo, bromo, carboxyl, formyl, methylcarbonyl and trifluoromethylcarbonyl; wherein Rl and R2 may further be taken together to form oxo; wherein R7 is hydrido; wherein R8 is selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl and neopentyl; or a stereoisomer or a tautomer thereof or a pharmaceutically-acceptable salt thereof.

A family of specific compounds of particular interest within Formula VII(d) consists of compounds and their stereoisomers and tautomers and the pharmaceutically-acceptable salts thereof, said compounds consisting of1-(2-methylcycloheptyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;

' 'i .. ~ .. .
lol 21 ~31 92 1-(2-ethylcycloheptyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2~-imidazol-2-one;
1-(2-propylcycloheptyl)-4-butyl-1,3-dihydro-3-~[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-isopropylcycloheptyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
~ 1-(2-tertbutylcycloheptyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-methoxycycloheptyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-hydroxycycloheptyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-carboxycycloheptyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-acetylcycloheptyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
l-t2-oxocycloheptyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2,7-dimethylcycloheptyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-ethyl-7-methylcycloheptyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-isopropyl-7-methylcycloheptyl)-4-butyl-1,3-dihydro-3-[[4-l4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-carboxy-7-methylcycloheptyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-acetyl-7-methylcycloheptyl)-4-butyl-1,3-dihydro-3-[[4-~4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-oxo-7-methylcycloheptyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imiàazol-2-one;

W094/08989 PCT/US93/0~6~
214319~ 102 1-(2-methyl-7-ethylcycloheptyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl3methyl]-2H-imidazol-2-one;
1-(2,7-diethylcycloheptyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-isu~o~1-7-ethylcycloheptyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-carboxy-7-ethylcycloheptyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-acetyl-7-ethylcycloheptyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-oxo-7-ethylcycloheptyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-methyl-7-isopropylcycloheptyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-ethyl-7-isopropylcycloheptyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2,7-diisopropylcycloheptyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-carboxy-7-isopropylcycloheptyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-acetyl-7-iso~ro~ylcycloheptyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]m~thyl]-2H-imidazol-2-one;
1-(2-oxo-7-isopropylcycloheptyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imiaazol-2-one;

~ W094/08989 2 1 ~ 3 1 9 2 PCT/US93/05601 ; ~ !, ;` 1 11 ~'}

1-(2,2-dimethylcycloheptyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl3methyl]-2H-imidazol-2-one;
and 1-(2,2-diethylcycloheptyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one.

Within this fifth group of compounds of Formula VII there is a fifth class of higher-interest c~ ounds of Formula VII(e):

R~

N~}CH2--N~l/ R
H ~N~NI ~ ~ n2 VII(e) wherein each of R1, R2 and R3 may be independently selected from hydrido, methyl, ethyl, n-propyl, isopropyl, tert-butyl, hydroxy, methoxy, fluoro, chloro, iodo, bromo, carboxyl, formyl, methylcarbonyl and trifluoromethylcarbonyl; wherein R1 and R2 may further be taken together to form oxo; wherein R7 is hydrido; wherein R8 is selected from methyl, ethyl, n-propyl, iso~u~
n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl and neopentyl; or a stereoisomer or a tautomer thereof or a pharmaceutically-acceptable salt thereof.

A family of specific compounds of particular interest within Formula VII(e) consists of compounds and their stereoisomers and tautomers and the pharmaceutically-acceptable salts thereof, said compounds consisting of 1-(2-methylcycloheptyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pYridinYl]methyl]-2H-imidazol-2-one;
1-(2-ethylcycloheptyl)-4-butyl-l~3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;

W094/08989 PCT/US93/05 ~
. , . ~.
`2i4319~ 104 1-(2-propylcycloheptyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-isopropylcycloheptyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-tertbutylcycloheptyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-methoxycycloheptyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-hydroxycycloheptyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
l-t2-carboxycycloheptyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
- 1-(2-acetylcycloheptyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-oxocycloheptyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2,7-dimethylcycloheptyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-ethyl-7-methylcycloheptyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-isopropyl-7-methylcycloheptyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-carboxy-7-methylcycloheptyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-acetyl-7-methylcycloheptyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-oxo-7-methylcycloheptyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-methyl-7-ethylcycloheptyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;

21~3192 1-(2,7-diethylcycloheptyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-isopropyl-7-ethylcycloheptyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-carboxy-7-ethylcycloheptyl)-4-butyl-1,3-dihydro-3-[[4-r3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-acetyl-7-ethylcycloheptyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-oxo-7-ethylcycloheptyl)-4-butyl-1,3-dihydro-3-[[4-[3-- (lH-tetrazol-~-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-methyl-7-iso~ ylcycloheptyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-ethyl-7-iso~Lo~lcycloheptyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2,7-diiso~o~lcycloheptyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-onei 1-(2-carboxy-7-iso~ro~lcycloheptyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-acetyl-7-isop~oyylcycloheptyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-oxo-7-isopropylcycloheptyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2,2-dimethylcycloheptyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
and 1-~2,2-diethylcycloheptyl)-4-butyl-1,3-dihydro-3-[[4-[3-(1~-tetrazol-5-yl)Phenyl~-4-pyridinyl]methyl]-2H-imidazol-2-one.

W094/08989 PCT/US93/05 ~
21~13i~

Within this fifth group of compounds of Formula VII there is a sixth class of higher-interest compounds of Formula VII(f):

~ CH2- N ~ n~ VII~f) wherein each of R1, R2 and R3 may be independently selected from hydrido, methyl, ethyl, n-propyl, iso~Lo~yl, tert-butyl, hydroxy, methoxy, fluoro, chloro, iodo, bromo,carboxyl, formyl, methylcarbonyl and trifluoromethylcarbonyl; wherein R1 and R2 may further be taken together to form oxo; wherein R7 is hydrido; wherein R8 is selected from methyl, ethyl, n-propyl, isopropy~l, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl and neopentyl; or a stereoisomer or a tautomer thereof or a pharmaceutically-acceptable salt thereof.

A family of specific compounds of particular interest within Formula VII(f) consists of compounds and their stereoisomers and tautomers and the pharmaceutically-acceptable salts thereof, said compounds consisting of 1-(2-methylcycloheptyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-ethylcycloheptyl)-4-butyl-1,3-dihydro-3-~[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-propylcycloheptyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-onei 1-(2-isopropylcycloheptyl)-4-butyl-1,3-dihydro-3-[[4-[2-~lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-onei 1-(2-tertbutylcycloheptyl)-4-butyl-1,3-dihydro-3-[[4-[2-(l~-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-onei 21~31,9~

1-~2-methoxycycloheptyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-hydroxycycloheptyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-carboxycycloheptyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one 1-(2-acetylcycloheptyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-oxocycloheptyl)-4-~utyl-1,3-dihydro-3-[[4-[2-(lH-10 tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2,7-dimethylcycloheptyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-ethyl-7-methylcyclohepeyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-iso~lo~yl-7-methylcycloheptyl)-4-butyl-1,3-dihydro-3-[[4-t2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-carboxy-7-methylcycloheptyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-acetyl-7-methylcycloheptyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-oxo-7-methylcycloheptyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-methyl-7-ethylcycloheptyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2,7-diethylcycloheptyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-isopropyl-7-ethylcycloheptyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;

W094/08989 PCT/~S93/056~

~143192 108 1-(2-carboxy-7-ethylCYcloheptyl)-4-buty~ 3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-acetyl-7-ethylcycloheptyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl3methyl]-2H-imidazol-2-one;
1-(2-oxo-7-ethylcycloheptyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-methyl-7-iso~o~ylcycloheptyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-ethyl-7-isopropylcycloheptyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl~methyl]-2H-imidazol-2-one;
1-(2,7-diisopropylcycloheptyl)-4-butyl-1,3-dihydro-3-~[4-E2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-carboxy-7-isopropylcycloheptyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-acetyl-7-isopropylcycloheptyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-onei 1-(2-oxo-7-isopropylcycloheptyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2,2-dimethylcycloheptyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
and 1-(2,2-diethylcycloheptyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one.

Within the compounds Formula II there is an sixth group of compounds of more interest as represented by Formula VIII:

~ W094/08989 2 1 4 3 1 9 ~ PCT/US93/05601 l~N - A VIII

wherein each of R1, R2 and R3 is independently selected from hydrido, methyl, ethyl, n-propyl, isopropyl, tert-butyl, methoxy, ethoxy, propoxy, isopropoxy, tert-butoxy, cyano, fluoro, chloro, iodo, bromo, hydroxy, nitro, amino, N-methylamino, N,N-dimethylamino, N-ethylamino, N,N-diethylamino, carboxyl, methoxycarbonyl, ethoxycarbonyl, formyl, methylcarbonyl, ethylcarbonyl and trifluoromethylcarbonyl; wherein R1 and R2 may further be taken together to form oxo; wherein R7 is selected from hydrido, methyl, fluoro, chloro, monofluoromethyl, difluoromethyl, trifluoromethyl, formyl, carboxyl and dimethoxymethyl; wherein R8 is selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl, neopentyl, phenyl, benzyl, phenethyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclopropylmethyl, cyclopropylethyl, cyclobutylmethyl, cyclobutylethyl, cyclopentylmethyl, cyclopentylethyl, cyclohexylmethyl and cyclohexylethyl;
wherein A is an acidic-group-substituted pyridinyl-phenyl moiety selected from ~ ' ~ N a~
- wherein ~9 is an acidic group selected from COOH an-W094J08989 PC~/US93/056~
~-21~31;9~ llo N-~ N~

or a stereoisomer or a tautomer thereof or a pharmaceutically-acceptable salt thereof.

Within this sixth group of compounds of Formula VIII there is a first class of higher-interest compounds of Formula VIII(a):
R8` R7 -- R R
H - N . R~ VIII(a) `N--N ~J

wherein each of Rl, R2 and R3 may be independently selected from hydrido, methyl, ethyl, n-propyl, isopropyl, tert-butyl, hydroxy, methoxy, fluoro, chloro, iodo, bromo,carboxyl, formyl, methylcarbonyi and trifluoromethylcarbonyl; wherein Rl and ~2 may further be taken together to form oxo; wherein P.7 is hydrido; wherein R8 is selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl and neopentyl; or a s~ereoisomer or a tautomer thereof or a pharmaceutically-acceptable salt thereof.

A family of specifi- compounds of particular 2~ interest within Formula VIII(a consists o- compounds and their stereoisomers and tautomers and the pharmaceu~ically-acceptable salts thereof, said compounds consisting o_ W094l~8989 PCT/US93/05601 21~3192 1-(2-methylcyclooctyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-ethylcyclooctyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-propylcyclooctyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-isopropylcyclooctyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-tertbutylcyclooctyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-methoxycyclooctyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-hydroxycyclooctyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-t2-carboxycyclooctyl)-4-butyl-1,3-dihydro-3-[[5-~2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-acetylcyclooctyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-oxocyclooctyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2,8-dimethylcyclooctyl)-4-butyl-1, 3 -dihydro-3-~[5-[2-( lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-ethyl-8-methylcyclooctyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl~methyl]-2H-imidazol-~-one;
1-(2-isopropyl-8-methylcyclooctyli-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-carboxy-8-methylcyclooctyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-acetyl-8-methylcyclooctyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-oxo-8-methylcyclooctyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imiaazol-~-one;

W094/08989 PCT/US93/056 ~

2i4319~ 112 1-(2-methyl-8-ethylcyclooctyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinylJmethyl]-2H-imidazol-2-one;
1-(2,8-diethylcyclooctyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-onei 1-(2-isopropyl-8-ethylcyclooctyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-carboxy-8-ethylcyclooctyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-acetyl-8-ethylcyclooctyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imiaazol-2-one;
1-(2-oxo-8-ethylcyclooctyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-methyl-8-isoyLuyylcyclooctyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-ethyl-8 isopropylcyciooctyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2,8-diisopropylcyclooctyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imiaazol-2-one;
1-(2-carboxy-8-isopropylcyclooctyl)-4-butyl-1,3-dihyaro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-acetyl-8-isopropylcyclooctyl)-4-butyl-1,3-dihyd-o-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2~-imidazol-2-one;
1-~2-oxo-8-isopropylcyclo~ctyl)-4-butyl-1,3-dihydro-~-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyli-2H-imidazol-^-one;
1-(2,2-dimethylcyclooctyl)-4-butyl-1,3-dihydro-3-[[5-~2-(~
tetrazol-5-yl)phenyl]-2-pyriainyl]methyl]-2H-imidazcl-2-or.ei and 2I ~3I92 1-(2,2-diethylcyclooctyl)-4-butyl-1,3-dihydro-3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one.

Within this sixth yroup of compounds of Formula 5 VIII there is a second class of higher-interest compounds o~
Formula VIIIlb):
R8` R7 ~43 CH2--N~/
\ R1 R2 ~N R3 ~ VIII(b~
H--N ~ ~ , ` N--- N

wherein each of R1, R2 and R3 may be independently selected from hydrido, methyl, ethyl, n-propyl, isopropyl, tert-butyl, hydroxy, methoxy, fluoro, chloro, iodo, bromo, carboxyl, formyl, methylcarbonyl and trifluoromethylcarbonyl; wherein R1 and R2 may further be taken together to form oxo; wherein R7 is hydrido; wherein R8 is selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobuty', tert-butyl, n-pentyl, isopentyl and neopentyl; or a stereoisomer or a tautomer thereof or a pharmaceutically-acceptable salt thereof.
A family of specific compounds of particular interest within Formula VIII(b) consists of compounds and their stereoisomers and tautomers and the pharmaceutically-acceptable salts thereof, said compounds consisting of 2~ 1-(2-methylcyclooctyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1~-tetrazol-5-yl)phenyl]-3-pyridinyljmethyl]-2H-imidazol-2-one;
l-t2-ethylcyclooctyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1~-te~razol-5-yl)phenyl]-3-pyridinyl]methyl]-2~-imidazol-2-one;
1-(2-propylcyclooctyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1~-3C tetrazol-5-yl)phenyl]-3-pyridinyl]metnyl]-2~-imidazol-2-one;

W094/08989 PCT/US93/056~

1-(2-isopropylcyclooctyl)-4-butyl-1,3-dihydro-3-[[6- r 2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one 1-(2-tertbutylcyclooctyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-methoxycyclooctyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-hydroxycyclooctyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one 1-(2-carboxycyclooctyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-acetylcyclooctyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-oxocyclooctyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2,8-dimethylcyclooctyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-ethyl-8-methylcyclooctyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-isopropyl-8-methylcyclooctyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-carboxy-8-methylcyclooctyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-acetyl-8-methylcyclooctyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-oxo-8-methylcyclooctyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one 1-(2-methyl-8-ethylcyclooctyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2,8-diethylcyclooctyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;

W094/08989 PCT/US93/0~601 115 ~ 9~
1-(2-isopropyl-8-ethylcyclooctyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-carboxy-8-ethylcyclooctyl)-4-butyl-1,3-dihydro-3-[[6-[2-- 5 (lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-acetyl-8-ethylcyclooctyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-ylJphenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
10 1-(2-oxo-8-ethylcyclooctyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2 one;
1-(2-methyl-8-iso~ro~ylcyclooctyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
15 1-(2-ethyl-8-iso~ ylcyclooctyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2,8-diisopropylcyclooctyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-carboxy-8-isopropylcyclooctyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-~2-acetyl-8-isopropylcyclooctyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
l-(2-oxo-8-isopropylcyclooctyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
l-(2,2-dimethylcyclooctyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
and 1-(2,2-diethylcyclooctyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1~;-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazoi-2-one.

W094/08989 PCT/US93/056~
, 21~3192 116 Within this sixth group of compounds of Formula VIII there is a third class of higher-interest compounds of Formula VIII(c):
Rs ~ R7 R R
H - N ~ R3~ VIII(c) `N--N ~J

wherein each of R1, R2 and R3 may be independently selected from hydrido, methyl, ethyl, n-propyl, isopropyl, tert-butyl, hydroxy, methoxy, fluoro, chloro, iodo, bromo, carboxyl, formyl, methylcarbonyl and trifluoromethylcarbonyl; wherein R1 and R2 may further be taken together to form oxo; wherein R7 is hydrido; wherein R8 is selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl and neopentyl; or a stereoisomer or a tautomer thereof or a pharmaceutically-acceptable salt thereof.

A family of specific compounds of particular interest within Formula VIII(c) consists of compounds and their stereoisomers and tautomers and the pharmaceutically-acceptable salts thereof, said compounds consisting of 1-(2-methylcyclooctyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-ethylcyclooctyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-propylcyclooctyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-isopropylcyclooctyl)-4-butyi-1,3-dihydro-3-[[4-~3~
tetrazol-5-yl)phenyl]-2-pyridinyl~methyl]-2H-imidazol-2-one;
1-(2-tertbutylcyclooctyl)-4-butyl-1,3-dihydro-3-[[4-[3-(1:~-tetrazol-5-yl)phenyi]-2-pyridinyl~me~hyl]-2H-imidazoi-2-onei 214319~

1-(2-methoxycyclooctyl)-4-butyl-1,3-dih~dro-L3~[~4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-hydroxycyclooctyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
- 5 1-(2-carboxycyclooctyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-acetylcyclooctyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-oxocyclooctyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2,8-dimethylcyclooctyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-ethyl-8-methylcyclooctyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;1-(2-isopropyl-8-methylcyclooctyl)-4-butyl-1,3-dihydro-3-[[4- .
[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-carboxy-8-methylcyclooctyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-acetyl-8-methylcyclooctyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-oxo-8-methylcyclooctyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-methyl-8-ethylcyclooctyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2,8-diethylcyclooctyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-isopropyl-8-ethylcyclooctyl)-4-butyl-1,3-dihydro-3-[[ G -[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl,-2H-imi~azol-2-one;

A`21 43~ 92 a~oxy-8-ethylcyclooctyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-acetyl-8-ethylcyclooctyl)-4-butyl-1,3-dihydro-3-[[4-[3-~lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-oxo-8-ethylcyclooctyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-onei 1-(2-methyl-8-iso~Lo~ylcyclooctyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-ethyl-8-isopropylcyclooctyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2,8-diisopropylcyclooctyl)-4-~utyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-carboxy-8-iso~o~lcyclooctyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-onei 1-(2-acetyl-8-iso~Lo~ylcyclooctyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-onei 1-(2-oxo-8-isopropylcyclooctyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl~phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-onei 1-(2,2-dimethylcyclooctyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one;
and 1-(2,2-diethylcyclooctyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-one.

Within this sixth group of compounds of Formul2 VIII there is a fourth class of higner-interest compounas o~
3~ Formula VIII(d):

~ 21~3192 R8~R7 ~3 ~ R

H - N ~ R3~ VIII(d) 'N N ~_J

wherein each of Rl, R2 and R3 may be independently selected from hydrido, methyl, ethyl, n-propyl, iSb~r G~l, tert-butyl, hydroxy, methoxy, fluoro, chloro, iodo, bromo,carboxyl, formyl, methylcarbonyl and trifluoromethylcarbonyl; wherein Rl and R2 may further be taken together to form oxo; wherein R7 is hydrido; wherein R8 is selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl and neopentyl; or a stereoisomer or a tautomer thereof or a pharmaceutically-acceptable salt thereof.

A family of specific compounds of particular l_ interest within Formula VIII (d) consists of compounds and their stereoisomers and tautomers and the pharmaceuticaliy-acceptable salts thereof, said compounds consisting of l-(2-methylcyclooctyl)-4-butyl-l,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
l-(2-ethylcyclooctyl)-4-butyl-l,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one l-(2-propylcyclooctyl)-4-butyl-l,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
l-(2-isopropylcyclooctyl)-4-butyl-l,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
l-(2-tertbutylcyclooctyl)-4-butyl-l,3-dihydro-3-[[4-[4~
tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
l-(2-methoxycyclooctyl)-4-butyl-l,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
3C l-(2-hydroxycyclooctyl)-4-butyl-l,3-dihydro-3-[[4-[4-(l~:-tetrazol-5-yl)phenyl]-3-pyridinYl]methyl]-2H-imidazol-2-one;

W O 94/08989 PC~r/US93/05601 21431~9~

l-(2-carboxycyclooctyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-acetylcyclooctyl)-4-butyl-1,3-dihydro-3-[[4-[4-~lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-oxocyclooctyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2,8-dimethylcyclooctyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-ethyl-8-methylcyclooctyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-isopropyl-8-methylcyclooctyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-carboxy-8-methylcyclooctyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-acetyl-8-methylcyclooctyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;1-(2-oxo-8-methylcyclooctyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
l-(2-methyl-8-ethylcyclooctyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
l-(2,8-diethylcyclooctyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-isopropyl-8-ethylcyclooctyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
l-(2-carboxy-8-ethylcyclooctyl~-4-butyl-1,3-dihydro-<-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imiaazol-2-one;
1-~2-acetyl-8-ethylcyclooctyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imiaazoi-~-one;

W094l08989 PCT/US93/05601 21~31~92 1-(2-oxo-8-ethylcyclooctyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-onei 1-(2-methyl-8-isopropylcyclooctyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl~-3-pyridinyljmethyl]-2H-imidazol-2-one;
1-(2-ethyl-8-isopropylcyclooctyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2,8-diisopropylcyclooctyl)-4-butyl-1,3-dihydro-3-[[4-[4-10 (lH-tetrazol-5-yl)phenyl]-3-p~Tridinyl]methyl]-2H-imidazol-2-one;
1-(2-carboxy-8-iso~o~ylcyclooctyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl~methyl]-2H-imidazol-2-one;
1-(2-acetyl-8-isopropylcyclooctyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-oxo-8-isopropylcyclooctyl)-4-butyl-1,3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2,2-dimethylcyclooctyl)-4-butyl-1,3-dihydro-3-[[4-[4-(1~-tetrazol-5-yl)phenyl~-3-pyridinyl]methyl]-2H-imidazol-2-one;
and l-(2~2-diethylcyclooctyl)-4-butyl-l~3-dihydro-3-[[4-[4-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one.

Within this sixth group of compounds of Formula VIII there is a fifth class of higher-interest compounds of Formula VIII(ej:

N ~ CH2- N

H - N N ~3~ V~ e~
~N--N l J

wherein each of Rl, R2 and R3 may be independently selected from hydrido, methyl, ethyl, n-propyl, isopropyl, tert-butyl, hydroxy, methoxy, fluoro, chloro, iodo, bromo, carboxyl, formyl, methylcarbonyl and trifluoromethylcarbonyl; wherein Rl and R2 may further be taken together to form oxo; wherein R7 is hydrido; wherein R8 is selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl and neopentyl; or a stereoisomer or a tautomer thereof or a pharmaceutically-acceptable salt thereof.

A family of specific compounds of particular interest within Formula VIII(e) consists of compounds and their stereoisomers and tautomers and the pharmaceutically-acceptable salts thereof, said compounds consisting of 1-(2-methylcyclooctyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
l-(2-ethylcyclooctyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-propylcyclooctyl)-4-butyl-l~3-dihydro-3-E[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-isopropylcyclooctyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-iimidiazol-2-one;
1-(2-tertbutylcyclooctyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-methoxycyclooctyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-hydroxycyclooctyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-carboxycyclooctyl)-4-butyl-1,3-dihydro-3-[[4-[3- (lr:-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-acetylcyclooctyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methylj-2H-imidazol-2-one;
1-~2-oxocyclooctyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;

W094/08989 21 q 3 1 9~

1-(2,8-dimethylcyclooctyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-ethyl-8-methylcyclooctyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;1-(2-isopropyl-8-methylcyclooctyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-carboxy-8-methylcyclooctyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-acetyl-8-methylcyclooctyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-oxo-8-methylcyclooctyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-methyl-8-ethylcyclooctyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2,8-diethylcyclooctyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-isopropyl-8-ethylcyclooctyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-carboxy-8-ethylcyclooctyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-acetyl-8-ethylcyclooctyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-oxo-8-ethylcyclooc~yl)-4-butyl-1,3-dihydro-3-[[4-[3-(1~:-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-methyl-8-isopropylcyclooctyl)-4-butyl-1,3-dihydro-3-[[~-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;

21~31~2 ~

1-(2-ethyl-8-isopropylcyclooctyl)-4-butyl-1,3-dihydro-3-[[4-[3-~lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2,8-diisopropylcyclooctyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-carboxy-8-isopropylcyclooctyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-acetyl-8-isopropylcyclooctyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-oxo-8-isopropylcyclooctyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2,2-dimethylcyclooctyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one;
and 1-(2,2-diethylcyclooctyl)-4-butyl-1,3-dihydro-3-[[4-[3-(lH-tetrazol-5-yl)phenyl]-4-pyridinyl]methyl]-2H-imidazol-2-one.

Within this sixth group of compounds of Formula VIII there is a sixth class of higher-interest compounds of Formula VIII(f):
R8` R7 ~3 CH2--N~l/
N=< ~-- \ R1 R2 ~ N R3~ VIII(f) `N--N

/

wherein each of P~-, R2 and R3 may be inaependently sele~e~
from hydrido, methyl, ethyl, n-propyl, iso~Lo~i~l, tert-buty', hydroxy, methoxy, fluoro, chloro, iodo, brom^,carboxyl, formyl, methylcarbonyl and ~ W094/08989 2 1 4 3 1 9 2 PCT/Usg3/0560l trifluoromethylcarbonyl; wherein R1 and R2 may further be taken together to form oxo; wherein R7 is hydrido; wherein R8 is selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl and neopentyl; or a stereoisomer or a tautomer thereof or a pharmaceutically-acceptable salt thereof.

A family of specific compounds of particular interest within Formula VIII(f) consists of compounds and their stereoisomers and tautomers and the pharmaceutically-acceptable salts thereof, said compounds consisting of 1-(2-methylcyclooctyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl~methyl~-2H-imidazol-2-one;
1-(2-ethylcyClooctyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-propylcyclooctyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-isopropylcyclooctyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidaz~ol-2-one;
1-(2-tertbutylcyclooctyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-~-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-methoxycyclooctyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl3methyl]-2H-imidazol-2-one;
1-(2-hydroxycyclooctyl)-4-butyl-1,3-dihydro-3-[[4-~2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-carboxycyclooctyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-acetylcyclooctyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-oxocyclooctyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-~-yl)phenyl]-3-pyridinyl]me hyl]-2H-imidazol-2-one;
1-(2,8-dimethylcyclooctyl)-4-butyl-1,3-dihydro-3-[[4-[2~
tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-ethyl-8-methylcyclooctyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl)-3-pyridinyl]methyl]-2H-imidazol-2-one;

W094/08989 PCT/US93/056~
,, . ~

2 1 43 1 g 2 126 1-(2-isopropyl-8-methylcyclooctyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-carboxy-8-methylcyclooctyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-acetyl-8-methylcyclooctyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-oxo-8-methylcyclooctyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-methyl-8-ethylcyclooctyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl~methyl]-2H-imidazol-2-one;1-(2,8-diethylcyclooctyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-isopropyl-8-ethylcyclooctyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-carboxy-8-ethylcyclooctyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-onei 1-(2-acetyl-8-ethylcyclooctyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-oxo-8-ethylcyclooctyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-methyl-8-isopropylcyclooctyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-ethyl-8-isopropylcyclooctyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2,8-diiso~lo~lcyclooctyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;

~ W094/08989 21 ~31 92 PCT/US93/05601 1-(2-carboxy-8-isopropylcyclooctyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-acetyl-8-isopropylcyclooctyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazDl-2-one;
1-(2-oxo-8-isopropylcyclooctyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2,2-dimethylcyclooctyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl3methyl]-2H-imidazol-2-one;
and i-(2,2-diethylcyclooctyl)-4-butyl-1,3-dihydro-3-[[4-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl3methyl]-2H-imidazol-2-one.

W094/08989 PCT/US93/056~1 219L319~ ~

The term '~hydrido~ denotes a single hydrogen atom (H). This hydrido group may be attached, for example, to an oxygen atom to form a hydroxyl group; or, as another example, one hydrido group may be attached to a carbon atom to form a ~ Cll--- group; or, as another example, two hydrido groups may be attached to a carbon atom to form a -CH~- group. Where the term "alkyl~ is used, either alone or within other terms such as Uhaloalkyl~, the term '~alkyl'~
embraces linear or branched radicals having one to about twenty carbon atoms or, preferably, one to about twelve carbon atoms. More preferred alkyl radicals are '~lower alkyl" radicals having one to about ten carbon atoms. Most preferred are lower alkyl radicals having one to abou~ five carbon atoms. The term ucycloalkyl~ embraces cyclic radicals having three to about ten ring carbon atoms, preferably three to about six carbon atoms, such as cycloyLo~yl, cyclobutyl, cyclopentyl and cyclohexyl. The term "haloalkyl" embraces radicals wherein any one or more of the alkyl carbon atoms is substituted with one or more halo groups, preferably selected from bromo, chloro and fluoro. Specifically embraced by the term "haloalkyl~ are monohaloalkyl, dihaloalkyl and polyhaloalkyl groups. A
monohaloalkyl group, for example, may have either a bromo, a chloro, or a fluoro atom within the group. Dihaloalkyl and polyhaloalkyl groups may be substituted with two or more of the same halo groups, or may have a combination of different halo groups. A dihaloalkyl group, for example, may have two fluoro atoms, such as difluoromethyl and difluorobutyl groups, or two chloro atoms, such as a dichloromethyl group, or one fluoro atom and one chloro atom, such as a fluoro-chloromethyl group. Examples cf a polyhaloalkyl are trifluoromethyl, 1,1-difluoroethyl, 2,2,2-trifluoroethyl, perfluoroethyl and 2,2,3,3-tetrafluoropropyl groups. The term ~difluoroalkyl~
embraces alkyl groups having two fluoro atoms substituted on any one or two of the alkyl group carbon atoms. ThG
terms ~'alkoxy" and "alkoxyalkyl~ embrace linear or branched 21~31'92 oXy-containing radicals each having alkyl portions of one to about ten carbon atoms, such as methoxy group. The term ~alkoxyalkyl" also embraces alkyl radicals having two or more alkoxy groups attached to the alkyl radical, that is, to form monoalkoxyalkyl and dialkoxyalkyl groups. The llalkoxy" or "alkoxyalkyl" radicals may be further substi-tuted with one or more halo atoms, such as fluoro, chloro or bromo, to provide haloalkoxy or haloalkoxyalkyl groups.
The terms ~benzyl" and uphenylmethyl~ are interchangeable.
For any of the foregoing defined radicals, preferred radicals are those cont~nins from one to about ten carbon atoms.

Specific examples of alkyl groups are methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl, methylbutyl, dimethylbutyl and neopentyl.

Compounds of Formula I have been found to inhibit the action of angiotensin II in m~mm~l S. Angiotensin II is a potent vasoconstrictor and participates in the formation of aldosterone which regulates sodium and water balance in m~mm~l S . Thus, compounds of Formula I are therapeutically useful in methods for treating hypertension by administering to a hypertensive patient a therapeutically-effective amount of a compound of Formula I. The phrase ~hypertensive patient" means, in this context, a m~mm~l ian subject suffering from or afflicted by the effects of hypertension or susceptible to a hypertensive condition if not treated to prevent or control such hypertension.

Also included in the family of compounds c r Formula I are isomeric forms including diastereoisomers and tne pharmaceutically-acceptable salts thereo_. The term ~pharmaceutically-acceptable salts~ embraces salts commonly used to form alkali metal salts and to form addition salts of free acids or free bases. The nature of the salt is not W O 94/08989 PC~r/US93/056 ~

critical, provided that it is pharmaceutically-acceptable.
Suitable pharmaceutically-acceptable acid addition salts of compounds of Formula I may be prepared from an inorganic acid or from an organic acid. Examples of such inorganic acids are hydrochloric, hydrobromic, hydroiodic, nitric, carbonic, sulfuric and phosphoric acid. Appropriate organic acids may be selected from aliphatic, cycloaliphatic, aromatic, araliphatic, heterocyclic, carboxylic and sulfonic classes of organic acids, example of which are formic, acetic, propionic, succinic, glycolic, gluconic, lactic, malic, tartaric, citric, ascorbic, glucuronic, maleic, fumaric, pyruvic, aspartic, glutamic, benzoic, anthranilic, p-hydroxybenzoic, salicyclic, phenylacetic, m~n~elic, ~mhon;c (pamoic), methansulfonic, ethanesulfonic, 2-hydroxyethanesulfonic, pantothenic, benzenesulfonic, toluenesulfonic, sulfanilic, mesylic, cyclohexyl ~mi nosulfonic, stearic, algenic, ~-hydroxybutyric, malonic, galactaric and galacturonic acid. Suitable pharmaceutically-acceptable base addition salts of compounds of Formula I include metallic salts made from aluminium, calcium, lithium, magnesium, potassium, sodium and zinc or organic salts made from N,N'-dibenzylethylenediamine, chloroprocaine, choline, diethanolamine, ethylenediamine, meglumine (N-methylgluca-mine) and procaine. All of these salts may be prepared hyconventional means from thecorresponding compound of Formula I by reacting, for example, the appropriate acid or base with the compound of Formula I.

W094/08989 PCT/US93~0S601 ~ 21~319~

~ner~l svnthet~c ProceAures The compounds of the invention can be synthesized according to the following procedures of Schemes I-XXXI, wherein the R substituents are as defined for Formula I, above, except where further noted.
Scheme I

CO2H 1 SOCl2 , ~ ~CH3 1. n-BuLi, THF, -78 C
2. B(OCH3)3 3. H30+

Il /C(CH3)3 Q--C-N

B(OH)2 [R9 = CON(CH3)C(CH3)3]

W094/08989 PCT/US93/056~
21431~2 Synthetic Scheme I shows the preparation of the boronic acid 1 where R9 equals N-tertbutyl-N-methylcarboxamide. In step 1, benzoic acid is treated with thionyl chloride to give the correspo~i ng acid chloride which is subsequently reacted wi~h N-tertbutyl-N-methylamine to give N-tertbutyl-N-methylbenzamide. In step 2, the amide is ortho-metalated and subsequently reacted with trimethyl borate. The free boronic acid 1 is produced on hydroylsis.

21~l3192 Scheme II

(H9C4)35nCl,NaN3 ~N~,N~N

Cl-C(C6HS)3. N(C~HS)3 N--N` 1. n-BuLi, THF~ -78 /=< N--N
~N 2. B(OCH3)3 ~N~N
C(C6Hs)3 C(C6Hs)3 rR9 = CN4c(c6~5)3]

W094/08989 PCT/US93/056~
21~19~

Synthetic Scheme II shows the preparation of the boronic acid 1 where R9 equals N-triphenylmethyl-lH-tetrazole. In step 1, 2-bromobenzonitrile (Aldrich) is reacted with tributyltin azide to give the corresponding tetrazole. In step 2, the tetrazole is reacted with triphenylmethyl chloride in the presence of triethylamine to give the protected bromophenyltetrazole. In step 3, halogen-metal interchange with n-butyllithium generates the corresponding ortho-lithiated species which is reacted with trimethyl borate. The free boronic acid 1 is produced on hydrolysis.

WO 94/08989 PCI`JUS93/05601 21dS319~

Scheme III

O R8 o (CH3)3C-O-C-I - lC--C--OH

I

1. cl-co-ocE~2cH(cH3)2 N(C2HS)3, CH2Cl2, 0 2&H3 H--N

O R8 o ,CH3 (CH3)3C-O-C-N-C--G--N ~
l l O-CH3 R7-Li o R8 o Il l 11 - (CH3)3C-O-C-N-C--C--R7 H H

2 1 ~ 31 ~ ~ 136 Synthetic Scheme III shows the preparation of N-Boc-amino ketones 2 (or aldehydes when R7 = H) from the corresponding N-Boc-amino acides ~. In step 1, the amino acid 3 is reacted with isobutyl chloroformate in the presence of triethylamine and subsequently with N,O-dimethylhydroxylamine to give the corresponding N-methoxy-N-methylamide ~. In step 2, the amide ~ is reacted with an organolithium reagent R7-Li (or lithium aluminum hydride (LAH) when R7 = H) to give the desired ketone 2 (or aldehyde when R7 = H).

WO 94/08989 PCl/US93/05601 21~3192 Scheme IV

METHOD A:

o R8 ;~ R8 o (CH3)3C-O-C-N-C-- I N~ 3 TPA ~ TFA:H2N-C--~ N~
l l 0-CH3 CH2C12 ¦ 0-CH3 ~N-C=0 ( 7 ), N(C2H5)3, CHC13 Rl ~Ct~ ,R5 , C H Cb R6 0 R8 o R2 I H 1. R7-Li ~ 1 ,CH3 R ' ~ ~N-C-N-C--C--N
,3~Cr 2. H30+ H H H 0-CH3 % ~ 9 ~ 138 Synthetic Scheme IV shows the preparation of imidazol-2-ones ~ from the corresponding amides ~ via Method A. In step 1, the protected amide 4 (prepared in Scheme III) is reacted with trifluoroacetic acid (TFA) to give the TFA salt 6 of the free amine. In step 2, the salt
6 is reacted with the appropriate isocyanate l in the presence of triethylamine to give the urea 8. In step 3, the urea 8 is reacted with an organolithium reagent R7-Li (or lithium alnm;nllm hydride (LAH) when R7 = H) and subsequently cyclized to the imidazole-2-one 5 on treatment with dilute acid during the work-up procedure.

Scheme V

METHOD B:

O R8 o (CH3)3C-O-C-I -C--I--R7 HCl, tlioY~ne R8 o HCI:H2N-C--C--R7 Q-N=C=O, CHC13 R, ~ Cd~, Rs R2,C H Cb--R6 R7 ~`~ R3 1, H

R8 N ~ O R

W094/08989 PCT/US93/OS6~
, . ~
21~319~ 140 Synthetic Scheme V shows the preparation of imidazol-2-ones 5 from the correspo~i n~ N-Boc-protected amino ketones 2 (or aldehydes when R7 = ~) via Method B.
In step 1, the carbonyl compound ~ (prepared in Scheme III) is reacted with anhydrous hydrogen chloride in dioxane to give the HCl salt 9. In step 2, the salt 9 is reacted with the appropriate isocyanate 7 in chloroform to give the imidazol-2-one 5 directly.

~ WO 94/08989 2 1 4 3 1 ~ ~ Pcr/US93/0560l Scheme VI

METHOD C:

o R8 o o R8 R7 (CH3)3C-o-8-lN- I--C--R7 C H2 T OH ,~ 2 ~(CH3)3C-O-C-I -C~~
H H H H

TFA. CH2CI2 8 R8 7 Q-N=C=O l8 R7 ~N-C-N-C ~~. TFA:H2N-C ¦--~
H H H ~, N(C2H5)3, CHCl3 1 O~

6NHCl, 60 H

,C/ I Cb--R~

C/ H

H

W O 94/08989 P~r/US93/056 ~

21~3192 142 Synthetic Scheme VI shows the preparation of imidazol-2-ones 5 from the corresponding N-Boc-protected amino ketones ~ (or aldehydes when R7 = H) via Method C.
In step 1, the carbonyl compound 2 (prepared in Scheme III) is reacted with 2,2-dimethyl-1,3-propandiol to give the cyclic ketal lQ. In step 2, the ketal lQ is reacted with TFA to give the TFA salt 11 of the free amine. In step 3, the salt 11 is reacted with the a~-o~riate isocyanate 7 in the presence of triethylamine to give the urea ketal 1~-In step 4, the urea ketal 1~ is reacted with 6N
hydrochloric acid at 60C to give the desired imidazol-2-one ~ directly.

~WO 94/08989 2 1 4 3 1 9 ~ PCI/US93/05601 Scheme VII

CH3 CH3 CH2-Br ~r Br2 ~ I NBS ~N
AlCl3, ~ I~J CC14, ~
Br Br KMnO4 ~Br N

1. Cl-CO-OCH,CH(CH3)2 N(C2H5)3, CH2Cl2, 0 C
'~. HN(CH3)0CH3 3. LAEI

CHO
~N

Br 2 1 4 ~ ~ 9 2 144 Synthetic Scheme VII shows the preparation of 2-bromomethyl-5-bromopyridine (1~ and 5-bromo-2-pyridinecarboxaldehyde (1~) from 2-picoline (Aldrich). In step 1, 2-picoline is reacted with bromine in the presence of a large excess of alnminllm chloride at elevated temperatures to give 5-bromo-2-picoline (1~). In step 2a, 1~ is reacted with NBS to give the 2-pyridinylmethyl bromide 1~ In step 2b, the intermediate 1~ is treated with potassium permanganate to give the correspo~in~
picolinic acid 1~. In step 3b, the acid 1~ is first converted to its N-methoxy-N-methylamide and subsequently reduced with LAH to provide 5-bromo-2-pyridinecarboxaldehyde (1~)-WO 94/08989 PCT~/US93/0560]
21~3192 145 : ~
Scheme VIII

CH3 CH3 CH2-Br Br2 ~ NBS
~N NaNO2 HBr, l~NCCl4, /~ bi~N
NH2 Br Br KMnO4 ~N
Br 1. Cl-CO-OCH2CHCH3)2 N(C2Hs)3, CH2Cl2, 0 C
2. HN(CH3)0CH3 3. LAH

CHO

~N
Br W094/08989. PCT/US93/056~

21431~2 146 Synthetic Scheme VIII shows the preparation of 2-bromo-5-bromomethylpyridine (17) and 2-bromo-5-pyridinecarboxaldehyde (1~) from 2-amino-5-picoline (Aldrich). In step 1, 2-amino-5-picoline is reacted with bromine in the presence of hydrobromic acid and sodium nitrite at 0C to give 2-bromo-5-picoline (1~) In step 2a, 19 is reacted with NBS to give the 3-pyridinylmethyl bromide 17. In step 2b, the intermediate 1~ is treated with potassium permanganate to give the corresponding nicotinic acid ~Q. In step 3b, the acid 20 is first converted to its N-methoxy-N-methylamide and subsequently reduced with LAH to provide 2-bromo-5-pyridinecarboxaldehyde (1~) ~WO 94/08989 2 1 4 3 1 9 ~Cr/US93/05601 Scheme IX

R3 o N(c2Hs)3~ R5 o TFA H N ¦ 11,CH3 CH,Cl ~ M~SO H~ l ll CH3 Br NaBH4 H I N~ ~ O-N=C=O (7) $ N ~ I N~CH3 1 R7 Li Br 2. H30~

R~ /Cd~ ~Rs R2~C R Ib_ HR6 ~ C/ H

Br W094/08989 PCT/US93/056~

2143~9~ 148 Synthetic Scheme IX shows the preparation of (4-bromobenzyl)imidazol-2-ones ~1 from the TFA salt of the amino amide 6 (prepared in Scheme III). In step 1, the TFA
salt ~ is allowed to react with the 4-bromobenzaldehyde in the presence of triethylamine and anhydrous magnesium sulfate to give the imine 2~. In step 2, the imine ~ is allowed to react with sodium borohydride to give the substituted benzylamine ~. In step 3, the benzylamine is allowed to react with the appropriate isocyanate 7 to give the substituted benzylurea ~. In step 4, the urea 24 is first allowed to react with an organolithium reagent R7-Li (or lithium aluminum hydride (LAH) when R = H) and subsequently with dilute aqueous acid to give the desired 3-t4-bromobenzyl)imidazol-2-ones.

~WO 94/08989 2 1 4 3 1 9 ~ PCI/US93/05601 Scheme X

R8 o N(C2H5)3~ R8 o 11 ~CH3CH2C12, MgS04 H~ ,CH3 TFA:H2N--C--C--N 14 ~ H 26 Br NaBH4 ~H2N 28 ~N 27 b~ 1. R7-Li Br Br 2. H30+

Rl jCd~ ~Rs R2 H Ib_ R6 R _H
~ N 1 3~ Cr R8--~'N~O R4 cH2 2 5 1~ N
1~1 Br 21 ~ 31 9 2 150 Synthetic Scheme X shows the preparation of 3-(5-bromo-2-pyridinylmethyl)imidazol-2-ones ~ from the TFA salt of the amino amide 6 (prepared in Scheme III). In step 1, the TFA salt 6 is allowed to react with the 5-bromo-2-pyridinylaldehyde 14 (prepared in Scheme VII) in the presence of triethylamine and anhydrous magnesium sulfate to give the imine ~. In step 2, the imine ~ is allowed to react with sodium borohydride to give the substituted benzylamine ~. In step 3, the benzylamine is allowed to react with the appropriate isocyanate 7 to give the substituted benzylurea ~. In step 4, the urea 28 is first allowed to react with an organolithium reagent R7-Li (or lithium aluminum hydride (LAH) when R' ~ H) and subsequently with dilute aqueous acid to give the desired 3-(5-bromo-2-pyridinylmethyl)imidazol-2-ones ~.

~0 94/08989 PCr/US93/05601 2~q3192 Scheme XI

TFAH N_O 1I N CH3 C~2CI_.MgSO4 ; `C= N C_B_N:

NaBH4 O R8 o ~ R8 o Q-N-B- N- C_ 1I N 3 ~Q-l~-c=o (7)CH2--N- C_ 1I N
H I H ~CH3 CH~CI2 ~ H H O-CH3 CH2 3 2 r ~ 31 1~ ~ N
~,N Br 1. R7-Li Br 2- H30' H
R~ /Cd~ ,Rs R2, C R3 1 H
~ ,~ C H

cH2 2 9 ~N
Br W094/08989 PCT/US93/05 ~
21~31~2 Synthetic Scheme xI shows the preparation of 3-(2-bromo-5-pyridinylmethyl)imidazol-2-ones 29 from the TFA salt of the amino amide ~ (prepared in Scheme III). In step 1, the TFA salt ~ is allowed to react with 2-bromo-5-pyridinylaldehyde 18 tprepared in Scheme VIII) in thepresence of triethylamine and anhydrous magnesium sulfate to give the imine ~. In step 2, the imine 3D is allowed to react with sodium borohydride to give the substituted benzylamine ~1- In step 3, the benzylamine 31 is allowed to react with the appropriate isocyanate 7 to give the substituted benzylurea ~. In step 4, the urea ~ is first allowed to react with an organolithium reagent R7-Li (or lithium alllminllm hydride tLAH) when R7 - H) and subsequently with dilute aqueous acid to give the desired 3-~2-bromo-5-pyridinylmethyl)imidazol-2-ones ~.

~10 94/08989 214 319 2 PCr/US93/05601 Scheme XII 'c~ Id~c' i, H R7 R3 ¦--H
~ 1/ ~ 1. base, DMF r Clt2 R3 N~O I 2. Br~CH2Br Br 1. base, DMF
2. 13 \1. base,DMF
\ 2. 17 H

~C H i~` r} \ i,.H

CH2 2 ~; ~

[~N ~ N

Br 2~431~2 Synthetic Scheme XII shows the preparation of 3-(4-bromobenzyl)imidazol-2-ones ~1, 3-(5-bromo-2-pyridinylmethyl)imidazol-2-ones ~, and 3-(2-bromo-5-pyridinylmethyl)imidazol-2-ones ~ from the parent imidazol-2-ones ~ (prepared in Scheme IV, Scheme V, or Scheme VI). The imidazol-2-one 5 is first treated with a base, such as potassium t-butoxide, and subsequently with the alkylating agent 4-bromobenzyl bromide, 1~ (prepared in Scheme VII), and 17 (prepared in Scheme VIII) to give 3-(4-bromobenzyl) imidazol-2-ones ~1, 3-(5-bromo-2-pyridinylmethyl)imidazol-2-ones ~, and 3-(2-bromo-5-pyridinylmethyl)imidazol-2-ones ~, respectively.

WO 94/08989 3~ 9~ PCI/US93/05601 Scheme XIII

R2~ C H b R6 R~~ ~Cc~ ~Rs , ~ C/ H

R,~ N~\C~ ~H Sl~;r~L . coupling ' CH2 R3 N )~ O R4 ~ N
cH2 25 ~

~N ~ R9 Br W094/08989 PCT/US93/05 ~

Synthetic Scheme XIII shows the preparation of 3-[ r 5- [ 2-(lH-tetrazol-5-yl3phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-ones ~0 from the boronic acid 1 (prepared in Scheme I and Scheme II) and the bromoimidazol-2-one coupling reagent ~ (prepared in Scheme X and Scheme XII).
The boronic acid 1 is reacted with the bromoimidazol-2-one coupling reagent ~ in the presence of a palladium zero catalyst via a Snieckus coupling [see M. J. Sharp and V.
Snieckus, Tetr~he~ron T.ett., 5997(1985)] to give the angiotensin II antagonists ~Q of this invention.

~WO 94/08989 2 1 ~ 3 1 9 2 PCr/Us93/o56ol Scheme XIV

Rl~ ~ Cd~ ~ R~

R2~ C I, H

R2~ H Cit--R3 R8--~ R

~ N IR~ C~ Snieckus coupli~ CH2 R8--~N~O R4 ~N O~ R9 Br 31 W094/08989 PCT/US93/05 ~
~,~ 43~

Synthetic Scheme XIV shows the preparation of 3-[[6-[2-(lH-tetrzol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-ones ~1 from the boronic acid 1 (prepared in Scheme I and Scheme II) and the bromoimidazol-2-one coupling reagent ~ (prepared in Scheme XI and Scheme XII).
The boronic acid 1 is reacted with the bromoimidazol-2-one coupling reagent 2~ in the presence of a palladium zero catalyst via a Snieckus coupling [see M. ~. Sharp and V. Snieckus, Tetr~he~ron T.ett., 5997(1985)] to give the angiotensin II antagonists ~1 of this invention.

WO 94/08989 2 1 ~ 3 1 9 ~ PCr/US93/05601 Scheme XV

R~ ~Cd~ ,Rs R2 H Ib RE

R2~C i~R6 TEIF,7~C ~ --I~H

~ \ H 2. B(0CH3)3 R8 ~N~0 1 3- H30+

B(OH)2 ~ 32 Br W094/08989 PCT/US93/05 ~
21~31~

Synthetic Scheme xv shows the preparation of the imidazol-2-one boronic acid coupling reagents 32 from the correspon~ing 3-(4-bromobenzyl)imidazol-2-ones 21 (prepared in Scheme IX and Scheme XII). Halogen-metal interchange generates the corresponding lithiated species from ~1 which is reacted with trimethyl borate. The free imidazol-2-one boronic acid coupling reagents ~ are produced on acid hydrolysis.

W O 94/68989 2 1 ~ 3 1 9 2 P~r/US93/05601 Scheme XVI

CO H
N

1. soC12 2. HN(CH3)C(CH3)3 ., Il ~C(CH3)3 C-N
rd~ CH3 ~N

1. sec-BuLi, TMEDA, THF, -78 C
2. (CH3)~Si-Cl 3. Br2, AcOH

Il ~C(CH3)3 11 ~C(CH3)3 Br~CH3 [R9 = CON(CH3)C(CH3)3] [R9 = CON(CH3)C(CH3)3]

W094/08989 PCT/US93/05 ~

21~3192 162 Synthetic Scheme XVI shows the preparation of the 4-bromopyridine coupling reagent ~ [R9 =
CON(CH3)C(CH3) 3 ] and the 2-bromopyridine coupling reagent 34 [R9 - CON(CH3)C(CH3)3] from nicotinic acid. In step 1, N-tertbuty-N-methylnicotinamide is prepared from nicotinoyl chloride and N-tertbutyl-N-methyl~m; ne. In step 2, ortho-metalalion with sec-butyllithium gives a mixture of regioanions which are reacted with trimethylsilyl chloride;
subsequent conversion to the corresponding bromides on treatment with bromine in acetic acid and separation of the regioisomers by chromatography provides ~ and ~.

WO 94/08989 21 ~ 31 92 PCr/US93/05601 Scheme XVII

~H

1. SOc~2 2. HN(CH3)C(CH3)3 ~C(CH3)3 ~-N
~CH3 1. sec-BuLi,TMEDA,THF,-78C
2. (CH3)3S}-Cl 3. Br2, AcOH

Il ~C(CH3)3 C-N
Br~3~CH3 3 ~ lR9 = CON(CH3)C(CH3~3]

~ 3~92 164 Synthetic Scheme XVII shows the preparation of the 3-bromopyridine coupling reagent ~
[R9 = CON(CH3)C(CH3)3] from isonicotinic acid. In step 1, N-tertbutyl-N-methylisoniCotinamide is prepared from isonicotinoyl chloride and N-tertbutyl-N-methylamine. In step 2, reaction with sec-butyllithium gives the ortho-lithiated species which is reacted with trimethylsilyl chloride and subsequently converted to the corresponding bromide 35 on treatment with bromine in acetic acid.

W094/08989 2 L 43 l~ PCr/US93/05601 Scheme XVIII

~N

1. SOCl2 2. HN(CH3)C(CH3)3 ~C(CH3)3 ~-N
~J~ ~CH3 1. sec-BuLi, TMEDA, THF, -78 C
2. (CH3)3Si-Cl 3. Br2, AcOH

Il ~C(CH3)3 C-N
Br~s ~ ~CH3 36 rR9 = CON(CH3)C(CH3)3]
-W094/08989 PCT/US93/05 ~

2~3~9~ 166 Synthetic Scheme XVIII shows the preparation of the 3-bromopyridine coupling reagent 36 [R9 = CON(CH3)C(CH3)3] from picolinic acid. In step 1, N-tertbutyl-N-methylpicolinamide is prepared from picolinoyl chloride and N-tertbutyl-N-methylamine. In step 2, reaction with sec-butyllithium gives the ortho-lithiated species which is reacted with trimethylsilyl chloride and subsequently converted to the corresponding bromide 36 on treatment with bromine in acetic acid.

21~319~

Scheme XIX

,C~Hd`C'b R6 RR N~O R

~37 ~,N ~
Smdcus Couphng R2~ C H Cl b R R2 ' C H Cl b R R2 C H Cl D R
R7 J~R3 C--H R7 J~R3 C--H R7 J~R3 C--H
R8 N~O R4 R8 N~O R4 R8 N~O R4' [~3 Snickus Coupling ~3 Smckus Coupling ~N~R9 B(3H2)2 I~R9 4 0 Snickus Coupling 3 8 C' d` C' R6 R7 J~ R3 Cr~ H
R8 N~O R4 '~ R9 N

SUB~; 111 ~JTE S~EET

W094/08989 PCT/US93/05 ~
~1~31~ 168 Synthetic Scheme XIX shows the preparation of 3-(pyridinylbenzyl)imidazol-2-ones 37, 38, 39 and 40 from the common imidazol-2-one boronic acids ~ (Scheme XV) and .
the corresponding bromo coupling reagents 36 (Scheme XVIII), ~ (Scheme XVI, ~ (Scheme XVII), and 34 (Scheme XVI), respectively. The boronic acids ~ are reacted with the bromo coupling reagents ~ and ~ in the presence of a palladium zero catalyst via a Snieckus coupling [see M. J. Sharp and V. Snieckus, Tetrahedron Lett., 5997 (1985)] to give the angiotensin II antagonists 37, 38, ~ and 40, respectively, of this invention.

WO 94/08989 PCr/US93/05601 21~3~ 9~

Scheme XX

Il ~C(CH3)3 . R--C-a A O AcOH ' R--C-a 43 CH3 44 CH3 oo C 4~ CH3 1. KOH, A
2. H30+

O O
R--CN ~ CCl 50 C R--C-NH2 ,1. (COC~)2R--C-OH
~7 46 4 (CH3)3SnN3 xylene, N--N
R 1~ N ,N

H

W094/08989 PCT/US93/05 ~

~9 170 Synthetic Scheme XX shows the preparation of carboxylic acid analogs ~1 and lH-tetrazole analogs ~ from analogs which have R5 = CON(CH3)C(CH3)3. In step 1, the N-tertbutyl-N-methylamide analog ~ is reacted with trifluoroacetic acid at reflux to give the N-methylamide 44. In step 2, the N-methylamide ~ is reacted with sodium nitrite in acetic anhydride/acetic acid at 0C to give the correspo~;n~ N-methyl-N-nitrosoamide g~. In step 3, the N-methyl-N-nitrosoamide ~ is hydrolyzed in base to give the corresponding carboxylic acid angiotensin II
antagonists of this invention. In step 4, the acid analog ~1 is reacted with oxalyl chloride and subsequently with anhydrous AmmQnia to give the primary amide 46. In step 5, the amide 46 is reacted with triphenylphosphine in carbon tetrachloride at 50C to give the correspo~ing nitrile 47.
In step 6, the nitrile 47 is reacted with trimethyltin azide in xylene at reflux to provide the lH-tetrazole angiotensin II antagonists of this invention.

~WO 94/08989 l721 !~ 31 92 Pcr/US93/05601 Scheme XXI

Br2, ~ , b~Br 49 \ / 50 \ sec-BuLi TMEDA /n-BuLi \~F,-78 C ~/THF, -78 C

Li Z;nCl2 , ZnCI

R9 = CO2R, CN, CN 4C(C6H5)3, or CN4H

2 143 1~2 Synthetic Scheme XXI shows the preparation of the organozinc reagent ~ from the appropriate benzoic acid analog ~. In step 1, the analog ~ is brominated with bromine in the presence of a suitable catalyst, e.g., iron, to give the 2-bromo analog ~Q. In step 2, the 2-bromo analog ~Q was converted to the organolithium reagent 51 by reaction with n-butyllithium in THF at -78C, a process known as halogen-metal interchange.
Alternatively, the organolithium reagent ~1 can be generated directly by the reaction of 49 with an alkyllithium reagent in the presence or absence of a suitable complexing agent in THF at -78C, e.g., sec-butyllithium/TMEDA (N,N,N',N'-tetramethyl-ethylenediamine). In step 3, the organolithium reagent 51 was treated with anhydrous zinc chloride at -78C and subsequently allowed to warm to ambient temperature.
The organozinc reagent ~ was generated and used in .

~WO 94/08989 2 1 ~ 3 1 9 ~ Pcr/US93/05601 Scheme x x l l .~ni~rh~ccol~rling CJN R~

Br Ne;~ichi (~ollrlir~

NBS, AIBN
CCl4, CH3 CH2Br ¢NI ¢NI

1, .S~;rrL .~ Coupling or 48, Negishi Coupling CH3 CH2Br ~N NBS, AIBN ~N
CC14, A T
R9 ~ R9 ~i3 W094/08989 I PCT/US93/05 ~
21431~ 174 Synthetic Scheme XXII shows the preparation of the 2-pyridinyl alkylating reagent ~ and the 3-pyridinyl alkylating 53 from 1~ (Scheme VII) and 1~
(Scheme VIII), respectively. In step 1, 1~ and 12 were coupled with 1 using Snieckus conditions (Scheme XIII) or g~ using Negishi conditions [see E. Negishi, A. O.
King, and N. Okukado, J. Or~. Ch~m., ~, 1821 (1977)] to give ~ and ~, respectively. In step 2, the coupled biaryl compounds ~ and ~ were brominated using NBS/AIBN to give the 2-pyridinyl alkylating reagent ~
and the 3-pyridinyl alkylating reagent ~, respectively.

~WO 94/08989 21 1 31 9 Z rcr/us93/os6 Scheme X2~111 H R~ ~Cd~ ~R
R\ ~Gd~ ~R R2' I H Ib_R6 R2 C I lCb--R5 1. base R7 NJ~R~C~~H
J~R3 C _H 2. ~2 R~;~O R

R3 N o R4 CH2 H ~; ~N

~ R9 1. base 2 ~i3 R~ ~Cd~ ~R

~ R3 C _ H

R5 N o R4 ~N

21431~2 Synthetic Scheme XXIII shows the preparation of 3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-ones ~Q (R5=CN4H) and 3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-ones ~1 (R5=CN4H) from the parent imidazol-2-ones ~ (prepared in Scheme IV, Scheme V, or Scheme VI).
The imidazol-2-one 5 was first treated with a base, such as potassium t-butoxide, and subsequently with the alkylating reagent ~ or ~ (Scheme XXII) to give 3-[[5-[2-(lH-tetrazol-5-yl)phenyl]-2-pyridinyl]methyl]-2H-imidazol-2-ones 30 (R5=CN4H) and 3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-ones ~1 (R5=CN4H), respectively.

Scheme XXl~l 1 Mg O(~Hs) ~ 78C
Br 3. H30+ B(OH)2 Synthetic Scheme XXIV shows the preparation of 4-methylphenylboronic acid (~) from 4-bromotoluene. In step l, the Grignard reagent was generated by the reaction of 4-bromotoluene with metallic magnesium in ether at reflux. In step 2, a THF solution of trimethoxyborane was cooled to -78 C and slowly treated with the Grignard reagent. In step 3, the boronic ester was hydrolyzed with a~ueous hydrochloric acid to give 4-methylphenylboronic acid ~

WO 94/08989 PCT~/US93/05~
21~31~2 178 Scheme XXV

NH2 Br Br N~CH3 Br2, E~r N~ 3KMnO4 N~CO2H
W oo c, NaNO2 W ~J

BH3, THF

Br Br Br N ~CH=N-OH NH_OH N ~ Swern N ~CH20H
IW IW oxi~l~tion ~J

Ac,O, ~

Br CH3 CH2-Br N~ Coupling , ~ CC14, ~ ~

64 NJ~CN N~CN

6~ 57 W094/08989 PCT/US93/~601 179 21 ~ 31 92 Synthetic Scheme XXV shows the 8-step preparation of the alkylating reagent 2-(4-bromomethylphenyl)-3-cyanopyridine (57) from 2-amino-3-picoline ~) (Aldrich). In step l, the aminopicoline 58 was converted to the bromopicoline ~ by reaction with bromine, concentrated hydrobromic acid, and sodium nitrite at 0C. In step 2, the picoline ~ was oxidized with KMNO4 to give the corresponding carboxylic acid ~Q.
In step 3, the acid 60 was reduced to the alcohol ~1 with borane/THF. In step 4, the alcohol ~1 was oxidized to the aldelyde 62 under Swern conditions or by using MnO2. In step 5, the aldehyde ~ was reacted with hydroxylamine to give the oxime ~. In step 6, the oxime was converted to 2-bromo-3-cyanopyridine (~) with acetic anhydride at reflux. In step 7, the nitrile ~
was coupled with 4-methylphenylboronic acid (~) (Scheme XXIV) usiny Snieckus conditions (Scheme XIII) to give 3-cyano-2-(4-methylphenyl)pyridine (~). In step 8, ~ was brominated with NBS/AIBN in carbon tetrachloride at reflux to give the desired alkylating reagent 57.

3~9~ 180 Scheme XXVI

Br Br ~ Br2, /~ ~ KMnO4 ~CO2H
NH2SO4, S03 N~ N~

1. (COC1)2 2. NH3 Br Br fi~ ~ P205~ ~ ~CONH2 N N

SniçrL~llc COup]i~lg CH3 CH2-Br ¢I NBS, AIBN
N~ C~ C

181 21~3i9~

Synthetic Scheme XXVI shows the 6-step preparation of the alkylating reagent 3-(4-bromomethylphenyl)-4-cyanopyridine (66) from 4-picoline (67) (Aldrich). In step 1, 4-picoline was brominated with bromine in fuming sulfuric acid at high temperatures to give 3-bromo-4-picoline (~). In step 2, the picoline ~ was oxidized to the corresponding carboxylic acid 69 with KMnO4. In step 3, the acid 69 was first converted to its acid chloride with oxalyl chloride and subsequently treated with condensed ~mo~ia to give the amide 70. In step 4, the amide 70 was converted to 3-bromo-4-cyanopyridine (ll) by treatment with P2Os at high temperatures. In step 5, the nitrile 71 was coupled with 4-methylphenylboronic acid (~) (Scheme XXIV) using Snieckus conditions (Scheme XIII) to give 4-cyano-3-(4-methylphenyl)pyridine ~72). In step 6, 72 was brominated with NBS/AIBN in carbon tetrachloride at reflux to give the desired alkylating reagent 66.

2~31~ 182 `--Scheme XXVII

Br Br Br 2 DMF ¢~ ¢~

[ b~N~C, CH3 CH2C12.

¢I Br ¢~CN Snier~ls Coupling ¢~CN

NBS, AIBN, CCl4, CH2-Br [¢
~CN

183 21 ~31 92 Synthetic Scheme XXVII shows the 5-step preparation of the alkylating reagent 4-(4-bromomethylphenyl)-3-cyanopyridine (73) from 4-bromopyridine (74) (Aldrich). In step l, the ortho-bromo carbanion was generated with LDA in THF at -78 C and reacted with anhydrous DMF to give 4-bromo-3-carboxaldehyde l~- In step 2, the aldehyde 75 was reacted with hydroxylamine to give the oxime 76. In step 3, the oxime 76 was dehydrated with l,l -carbonyldiimidazole in methylene chloride at reflux to give 4-bromo-3-cyanopyridine (77). In step 4, the nitrile 77 was coupled with 4-methylphenylboronic acid (56) (Scheme XXIV) using Snieckus conditions (Scheme XIII) to give 3-cyano-4-(4-methylphenyl)pridine (78).
In step 5, 78 was brominated with NBS/AIBN in carbon tetrachloride at reflux to give the desired alkylating reagent 73.

2143i~Z Scheme XXVIII

Br Br N AcOH. A `o (CH3)3SiCN, N(C2H5)3 CH3 CH3CN, g, Sniecbls Coupling ~CN

NBS, AIBN, CC14, A

CH2-Br ~,CN

-~ 185 21 ~ 31 g2 Synthetic Scheme XXVIII shows the 4-step preparation of the alkylating reagent 2-cyano-3-(4-b~o~llolllethylphenyl)pyridine ~79) from 3-bromopyridine (80) tAldrich). In step l, the pyridine 80 was reacted with hydrogen peroxide in acetic acid at reflux to give the pyridine N-oxide ~l. In step 2, the N-oxide ~1 was converted to 3-bromo-2-cyanopyridine (~) by reaction with trimethysilylcyanide and triethyl anine in acetonitrile at reflux. In step 3, the nitrile ~ was coupled with 4-methylphenylboronic acid ~) (Scheme XXIV) using Snieckus conditions (Scheme XIII) to give 2-cyano-3-(4-methylphenyl) pyridine (~). In step 4, ~
was brominated with NBS/AIBN in carbon tetrachloride at reflux to gi~e the desired alkylating reagent 79.

WO 94/08989 PCI`/US93/05601 2~d~3~92 -186-Scheme XXIX

R ~ R ~C,--H NJ~ ^

~CH2 R8~N~o R4 ~\1. base 1. base 79 2.~ ~ R9 Rl ' R5 R~ J~ R, ~C--H

R9 N o R4 ~ ~ d~ ~ ~ 2. ~R1~ Cd ~R5 R2--C I Cl b_R6 R2-Cl H I b~R6 R7J~ R~C,--H ~ NJ~C

~339 ~34 N~ R9 N~ R9 SUB~ 11 l ~JTE SHEET

_ 187 ~3 ~X~

Synthetic Scheme XXIX shows the preparation of 1,4,5-trisubstituted-1,3-dihydro-3-[[4-(2-cyano-3-pyridinyl)phenyl]methyl]-2H-imidazol-2-ones 37 (R5=CN), 1,4,5-trisubstituted-1,3-dihydro-3-[[4-(3-cyano-4-pyridinyl)phenyl]methyl]-2H-imidazol-2-ones 38 (R5=CN), 1,4,5-trisubstituted-1,3-dihydro-3-[[4-(4-cyano-3-pyridinyl)phenyl]methyl]-2H-imidazol-2-ones 39 (R5=CN), and 1,4,5-trisubstituted-1,3,-dihydro-3-[[4-(3-cyano-2-pyridinyl)phenyl]methyl]-2H-imidazol-2-ones gO (R5=CN) from the parent 1,4,5-trisubstituted-1,3-dihydro-2H-imidazol-2-ones 5 (prepared in Scheme IV, Scheme V, or Scheme VI). The imidazol-2-one ~ was first treated with a base, such as potassium ~-butoxide, and subsequently with the alkylating reagents 79 (Scheme XXVIII), 73 (Scheme XXVII), ~ (Scheme XXVI), and 57 (Scheme XXV) to give the alkylated products 37 (R5=CN), ~ (R5=CN, (R5=CN), and ~Q (R5=CN), respectively.

Scheme XXX

9-BBN ~ BR2 diglyme, 50 1. H2NOSO2H
diglyme, 50 2. HCI

H H 1.1,1'-carbonyl-~\N~N ~ sl~ ~
N--CH~ ~ CH2C12. (H5C2)3N C~IIINH3CI

8 OCH3 DAMP, 1. LAH, THF
ether, 0 2. KHSO4 (aq) 3. CHCI3, TFA (cat), N

H

189 ~1 ~ 3~ ~2 Synthetic Scheme XXX shows the steriospecific synthesis of the parent 2H-imidazol-2-one ~ (Q=2a, 6~-dimethyl-l~-cyclohexyl; R7=H; R8=butyl) from commercially available l,3-dimethylcyclohexene (Wiley Organics). In Step l, the olefin was reacted with 9-borabicyclo [3.3.l] nonane (9-BBN) in diglyme to give the 2a, 6~-dimethyl-l~-cyclohexylborane adduct. In Step 2, the borane adduct was reacted with hydroxylamine-O-sulfonic acid to give the corresponding amine with retention of steriochemistry. In Step 3, the amine was treated with l,l'-carbonyldiimidazole (CDI) to generate the acylimidazole ; n s; tll which was subsequently reacted with the aminoamide ~ (Scheme IV) to give the corresponding urea ~. In Step 4, the ureaamide 8 was reduced with the LAH to the corresponding ureaaldelyde, which partially cyclized to the 2H-imidazol-2-one (Q=2a,6~-dimethyl-l~-cyclohexyl; R7=H; R8=butyl) on aqueous potassium bisulfate workup. The cyclization was completed by stirring the crude material in chloroform at reflux for 3h in the presence of a catalytic amount of trifluoroacetic acid (TFA).

WO 94/08989 PCI`/US93/05~
lso 2i431~ Scheme XXXI

HCO2C2Hs ~bJ BuSH ~b~s THF
2. CH31 N-OH o o 'b HONH3CI ~ KOH (aq) ~S~
NaOAc, H20 I~J diethylene ~J
glycol"~

LAH, ether 'b 1. CDI, 1. LAH, THF, 2. 6 ~V 2. CHCI3, ,~
,H TFA(cat), ~ ~N
~N~N~ N O
O C,~=O H

l9l ~l ~31 92 Synthetic Scheme XXXI shows the synthesis of the parent 2H-imidazol-2-one 5 (Q=2,2-dimethylcyclohexyl; R7=H;
R8=butyl) as a mixture of diastereomers from commercially available 2-methylcyclohexanone (Aldrich). In Step l, the hydroxyeneone was prepared by the reaction of ethyl formate with the anion generated by sodium methoxide. In Step 2, the hydroxyeneone was converted to the corresponding butylthioeneone by reaction with n-butylmercaptan in the presence of acid. In Step 3, the regiospecific anion at the 2-position was generated with potassium tert-butoxide and reacted with methyliodide to give the corresponding 2,2-dimethyl analog. In Step 4, the protecting group was removed with aqueos potassium hydroxide to give 2,2-dimethylcyclohexanone. In Step 5, reaction with hydroxyamine hydrochloride in the presence of sodium acetate gave the oxime. In Step 6, the oxime was reduced with LAH to give 2,2-dimethylcyclohe~l~;ne as a mixture of diastereomers.
In Step 7, the amine was treated with CDI to generate the acylimidazole i n si tu which was subsequently reacted with the aminoamide 6 (Scheme IV) to give the corresponding urea ~. In Step 8, the ureaamide ~ was reduced with LAH to the corresEs.~ding ureaaldelyde which was cyclized by stirring in chloroform at reflux for 3h in the presence of a catalytic amount of TFA.

W094/08989 PCT/US93/OS60l 214~ 31~2 The following Examples contain detailed descriptions of the method of preparation of compounds of Formula I. These detailed descriptions fall within the scope of, and serve to exemplify, the above described General Synthetic Procedures which form part of the invention. These detailed descriptions are presented for illustrative purposes only and are not intended as a restriction on the scope of the invention. All parts are by weight and temperatures are in degrees Centigrade, 1o unless otherwise indicated.
- hx~mple 1 N~O
~O

N--N

~N
l-c~clopentyl-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-~ yl)phenyl~-3-pyridinyllmethyl] -2H-imidazol-2-one Ste~ 1: PreD~r~tion cf 1-cvclo~entyl-4-hlltyl-1,3~ y~ro-2H-;m;~zol-2-one.

Following General Synthetic Schemes III and IV, 1-cyclopentyl-4-butyl-1,3-dihydro-2H-imidazol-2-one was prepared: NMR (CDCl3) ~ 0.91 (t, ~=8 Hz, 3H), 1.29-1.42 (m, 2H), 1.48-1.85 ~m, lOH), 1.98-2.12 (m, 2H), 2.47 (tc, J=8 2~ and 1 Hz, 2H), 4.44-4.57 (m, lH), 5.88 (t, ~=1 Hz, lH), 10.22 (br s, lH); Ms (FAB) m/e (rel intensity) 209 (100), 141 (43); HRMS. Calc'd for M+H: 209.1654. Found: 209.1656.

.

193 21~3192 Ste~ 2: PrenAr~t;on of l-cyclo~ntvl-4-hlltyl-1 3-~i~y~ro-3-rr6-~2-(l~-tetr~zol-5-vl)~h~nvll-3-Dvr;~invllmethyll-2H
i m; ~zol -2-one.

Following General Synthetic Schemes XII and XIV
or XXIII, the imidazol-2-one from Step 1 was converted to l-cyclopentyl-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl~methyl]-2H-imidazol-2-one as a lo colorless solid: NMR (CDC13) ~ 0.88 (t, ~=7 Hz, 3H), 1.30-1.40 (m, 2H), 1.41-1.52 (m, 2H), 1.56-1.86 (m, 6H), 2.02-2.14 (m, 2H), 2.27 (t, ~=7 Hz, 2H), 4.55 (m, ~=7 Hz, lH), 4.97 (s, 2H), 5.98 (s, lH), 7.27 (d, J=8 Hz, lH), 7.44-7.54 (m, 3H), 7.62 (dd, J=8 and 2 Hz, lH), 7.98-8.05 (m, lH), 8.48 (d, J=2 Hz, lH); MS (FAB) m/e (rel intensity) 444 (100), 416 (12), 401 (6), 387 (4), 233 (13), 209 (22), 194 (12), 180 (25); HRMS. Calc'd for M+H: 444.2512. Found:
4~4.2518.

~ 194 F,x~mple 2 N~ .
--~N ~

N--N

~N

l-cyclohexyl-4-butyl-1,3-dihydro-3-[16-t2-(lH-tetrazol-5-yl)phen,yl]-3-pyridinyllmeth~1]-2H-imidazol-2-one SteD 1: Pre~r~t;on of l-cvclohexvl-4-hutvl-1,3-d;hvdro-2H-i m; ~zol-2-one.

~ollowing General Synthetic Schemes III and IV, 1-cyclohexyl-4-butyl-1,3-dihydro-2H-imidazol-2-one was prepared: NMR (CDC13) ~ 0.91 (t, J=7 Hz, 3H), 1.05-1.24 (m, 2H), 1.26-1.46 (m, 4H), 1.47-1.58 (m, 2H), 1.63-1.76 (m, 2H), 1.78-1.96 (m, 4H), 2.36 (td, J=8 and 1 Hz, 2H), 3.87-lo 4.00 (m, lH), 5.89 (t, ~=1 Hz, lH), 9.82 (br s, lH); MS
(FAB) m/e (rel intensity) 223 (100), 141 (53); HRMS. Calcld for M+H: 223.1810. Found: 223.1738.

SteD 2: PreD~r~t;on of 1-cvclohexvl-4-hutvl-1,3-~;~v~ro-3-~6-~2-(lH-te~r~zol-5-Yl)Dhenvll-3-Dvridin~llmethvll-2H
i mi d~zol-2-one.

Following General Synthetic Schemes XII and XIV
or XXIII, the imidazol-2-one from Step 1 was converted to 1-cyclohexyl-4-butyl-1,3-dihydro-3-[~6-~2-(lH-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one as a colorless solid: mp 202-203 C (dec); NMR (CDC13) ~ 0.89 (t, ~=8 Hz, 3H), 1.08-1.24 (m, 2H), 1.26-1.54 (m, 7H), 1.66-1.76 (m, lH), 1.77-2.00 (m, 4H), 2.28 (t, ~=8 Hz, 2H), 3.95-4.07 (m, lH), 4.97 (s, 2H), 6.00 (s, lH), 7.32 (d, J=8 Hz, lH), 7.45-7.55 ~m, 3H), 7.69 (dd, J=8 and 2 Hz, lH), 7.96-8.04 (m, lH), 8.47 (d, ~=2 Hz, lH); MS (FAB) m/e (rel intensity) 458 (56), 430 (19), 237 (19), 208 (100), 194 (36), 180 (76); HRMS. Calc'd for M+H: 458.2668. Found:
458.2732.

43~9~
F,x~mple 3 --N ~
C~2 N--N

~ N

1-(2a,6a-1 ,B-c~clohexyl)-4-but~1-1,3-dihydro-3-[16-[2-(lH-tetrazol-~-yl)phen~ -3-pyridinyllmethyl~-2H-imidazol-2-one Ste~ 1: PreD~r~tion of 1-(2a.6a-dimethvl-1B-cyc~ohexvl)-4-hlltv~ 3-~ihv~ro-2H-imi~zol-2-one.
Following Synthetic Scheme XXX, 1-~2a,6a-dimethyl-1~-cyclohexyl)-4-butyl-1,3-dihydro-2H-imidazol-2-one was prepared: NMR (CDCl3) ~ 0.78 (d, J=7 Hz, 6H), 0.90 (t, ~=7 Hz, 3H), 1.08-1.26 (m, 2H), 1.26-1.40 (m, 3H), 1.46-1.59 (m, 4H), 1.66-1.85 (m, 3H), 2.37 (t, ~=7 Hz, 2H), 3.35 (t, o J=11 Hz, lH), 5.48 (s, lH), 9.80 (br s, lH); MS (FAB) m/e (rel intensity) 251 (100), 141 (58).

SteD 2: PreD~r~tion of 1-(2a.6-~imethvl-1~-cvclohexvl)-4-hutvl-l~3-~ihv~ro-3-~6-~2-(lH-tetr~zol-5-vl)Dhenvll-3 Dvri~i~vllmet~vll-2H-imi~zol-2-one.
Following Synthetic Schemes XXII and XXIII, the imidazol-2-one from Step 1 was converted to 1-(2a,6a-dimethy~
cyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(lH-tetrazol-~-yl)phenyl]-3-pyridinyl~methyl]-2H-imidazol-2-one as a colorless solid: NMR (CDC13) ~ 0.77 (d, ~=7 Hz, 6H), 0.88 197 2 1 ~ 3 1 ~ 2 (t, ~=7 Hz, 3H), 1.06-1.39 (m, 5H), 1.41-1.63 (m, 4H), 1.65-1.86 (m, 3H), 2.27 (t, ~=7 Hz, 2H), 3.41 (br t, ~=11 Hz, lH), 5.00 (s, 2H), 5.90 (s, lH); 7.16(d, ~=8 Hz, lH),
7.42-7.48 (m, 3H), 7.52 (dd, ~=8 and 2 Hz, lH), 7.86-7.91 S (m, lH), 8.38 (d, J=2 Hz, lH); MS (FAB) m/e (rel intensity) 486 (100), 458 (21), 443 (6), 429 (6), 237 (15), 209 (47), 194 (20), 180 (51); HRMS. ~alc~d for M+H: 486.2918. Found:
486.2918.

WO 94/08989 Pcr/us93/0560 F,x~mple 4 O

~, N

~ N
~J H

1-(2,2-dimethylcyclohes~1)-4-butyl-1,3-dihydro-3-[~6-[2-(lH-tetrazol-5-yl)phenyl~-3-pyridinyl~methyl]-2H-imidazol-2-one Ste~ 1: PreD~r~tion of 1-(2 2-~imethvlcvclohexyl)-4-hutv~ 3-~ihv~ro-~H-imi~zol-2-one.
Following Synthetic Scheme XXXI, 1-(2,2-dimethylcyclohexyl)-4-butyl-1,3-dihydro-2H-imidazol-2-one was prepared: NMR (CDC13) ~ 0.91 (t, ~=7 Hz, 3H), 0.93 (s, 6H), 1.21-1.87 (m, 12H), 2.35 (t, ~=8 Hz, 2H), 3.59 (dd, lo ~=13 and 4 Hz, lH), 5.80-5.85 (m, lH), 10.2 (s, lH).

Step 2: Pre~r~tion of 1-t~.2-~imeth~vlcyclohexy1)-4-hUtyl-l 3-~ihv~ro-3-rr6-r2-(1~-tetr~zol-5-vl)~henvll-3-~vri~invllmethvll-2H-i mi ~ zol-2-one.
Following Synthetic Schemes XXII and XXIII, the imidazol-2-one from Step 1 was converted to 1-~2,2-dimethylcyclohexyl)-4-butyl-l~3-dihydro-3-[[6-[2-(lH-tetrazol-5-yl)phenyl]-3-pyridinylimethyl]-2H-imidazol-2-one as a colorless solid: NMR (CDCl3) ~ 0.79 (s, 3H), 0.82 (t, J=7 Hz, 3H), 0.89 (s, 3H), 1.20-1.50 (~, lOH), 1.69-1.95 199 214319;~

(m, 2H), 2.23 (t, J=7 Hz, 2H), 3.77 (dd, J=14 and 3 Hz, lH), 7.78 (d, J=15 Hz, lH), 7.83 (d, J=15 Hz, lH), 6.23 (s, lH), 7.40 (d, ~=8 Hz, lH), 7.53 (dd, ~=8 and 2 Hz, lH), 7.58-7.78 (m, 4H), 8.20 (d, J=2 Hz, lH); MS (FAB) m/e (rel 5 intensity) 486 (47), 458 (32), 243 (26), 209 (100), 180 (78), 141 (40); HRMS. Calc~d for M~H: 486.2981. Found:
486.2979.

WO 94/08989 PCr/US93/056 ~I~3192 RIoT~oGIrAT~ VAT~JATION

Assay A: ~naiot~n~in TI R;n~inc~ Activ;tv Compounds of the invention were tested for ability to bind to the smooth muscle angiotensin II
receptor using a rat uterine membrane preparation.
Angiotensin II (AII ) was purchased from Peninsula Labs.
5I-angiotensin II (specific activity of 2200 Ci/mmol) was 0 purchased from Du Pont-New England Nuclear. Other chemicals were obtained from Sigma Chemical Co. This assay was carried out according to the method of Douglas et al [~ntlocr;nol oc~v, 106, 120-124 (1980)]. Rat uterine membranes were prepared from fresh tissue. All procedures were carried out at 4C. Uteri were stripped of fat and homogenized in phosphate-buffered saline at pH 7.4 cont~ining 5 mM EDTA . The homogenate was centrifuged at 1500 x g for 20 min., and the supernatant was recentrifuged at 100,000 x g for 60 min. The pellet was resuspended in buffer consisting of 2 mM EDTA and 50 mM Tris-HCl (pH 7.5) to a final protein concentration of 4 mg/ml. Assay tubes were charged with 0.25 ml of a solution contAining 5 mM
MgCi2, 2 mM EDTA, 0.5% bovine serum albumin, 50 mM Tris-HCl, pH 7.5 and 125I-AII (approximately 105 cpm) in the absence or in the presence of unlabelled ligand. The reaction was initiated by the addition of membrane protein and the mixture was incubated at 25C for 60 min. The incubation was terminated with ice-cold 50 mM Tris-HCl (pH
7.5) and the mixture was filtered to separate membrane-3~ bound labelled peptide from the free ligand. The incubation tube and filter were washed with ice-cold buffer. Filters were assayed for radioactivity in a Micromedic gamma counter. Nonspecific binding was defined as binding in the presence of 10 ~LM of unlabelled AII. Specific binding was 3~ calculated as total binding minus nonspecific binding. Th~

~ W094/08989 PCT/US93/05601 201 ' receptor binding affinity of an AII antagonist compound was indicated by the concentration (ICso) of the tested AII
antagonist which gi~es 50~ displacement of the total specifically bound 125I-AII from the high affinity AII
receptor. Binding data were analyzed by a nonlinear least-squares curve fitting program. Results are reported in Table I.

A~s~y B: Tn V;tro V~c~ r ~mnoth ~llscle-Res~o~e for ATI

The compounds of the in~ention were tested for antagonist activity in rabbit aortic rings. Male New ZeAl~n~ white rabbits (2-2.5 kg) were sacrificed using an o~erdose of pentobarbital and exsanguinated ~ia the carotid arteries. The thoracic aorta was removed, cleaned of adherent fat and connective tissue and then cut into 3-mm ring segments. The endothelium was removed from the rings by gently sliding a rolled-up piece of filter paper into 20 the vessel lumen. The rings were then mounted in a water-jacketed tissue bath, maintained at 37C, between moveable and fixed ends of a stainless steel wire with the moveable end attached to an FT03 Grass transducer coupled to a Model 7D Grass Polygraph for recording isometric force responses.
25 The bath was filled with 20 ml of oxygenated (95% oxygen/5%
carbon dioxide) Krebs solution of the following composition (mM): 130 NaCl, 15 NaHC03, 15 KCl, 1.2 Na~2P04, 1.2 MgS04, 2.5 CaC12, and 11.4 glucose. The preparations were equilibrated for one hour before approximately one gram of - 30 passive tension was placed on the rings. Angiotensin II
concentration-response curves were then recorded (3 X 10-1 to 1 X 10-3 M). Each concentration of AII was allowed to elicit its maximal contraction, and then AII was washed out repeatedly for 30 minutes before rechallenging with a 3s higher concentration of AII. Aorta rings were exposed to W094/08989 PCT/US93/056~

21~3i~2 202 the test antagonist at 10-5 M for 5 minutes before challenging with AII. Adjacent segments of the same aorta ring were used for all concentration-response curves in the presence or absence of the test antagonist. The s effectiveness of the test compound was expressed in terms cf PA2 values and were calculated according to H.O. Schild ~sr. J. PhAr~Acol~ Ch~m~ther.~ ~,189-206 (1947)]. The PA2 value is the concentration of the antagonist which increases the ECso value for AII by a factor of two. Each o test antagonist was evaluated in aorta rings from two rabbits. Results are reported in Table I.

A~s~y C: Tn V;vo Tntr~ tr;c Pressor A~sav Res~on~e for All ~nt~onists Male Sprague-Dawley rats weighing 225-300 grams were anesthetized with methohexital (30 mg/kg, i.p.) and catheters were implanted into the femoral artery and vein.
The catheters were tunneled subcutaneously to exit dorsally, posterior to the head and between the scapulae.
The catheters were filled with heparin (1000 units/ml of saline). The rats were returned to their cage and allowed regular rat chow and water ~ lihitl~m. After full recovery from surgery (3-4 days), rats were placed in Lucite holders and the arterial line was connected to a pressure transducer. Arterial pressure was recorded on a Gould polygraph (mmHg). Angiotensin II was administered as a 30 ng/kg bolus via the venous catheter delivered in a 50 ~1 volume with a 0.2 ml saline flush. The pressor response in m.m Hg was measured by the difference from pre-injection arterial pressure to the maximum pressure achieved. The AII injection was repeated every 10 minutes until three consecutive injections yielded responses within 4 mmHg or each other. These three responses were then averaged and represented the control response to AII. The test compound was suspended in 0.5~ methylcellulose in water and was ~mi n; stered by gavage. The volume administered was 2 ml/kg body weight. The st~n~rd dose was 3 mg/kg.
Angiotensin II bolus injections were given at 30, 45, 60, 7S, 120, 150, and 180 minutes after gavage. The pressor response to AII was measured at each time point. The rats were then returned to their cage for future testing. A
mi n i mnm of 3 days was allowed between tests. Percent lo inhibition was calculated for each time point following gavage by the following formula: [(Control Response -Response at time point)/Control Response] X 100. Results a e shown in Table I.

WO 94/08989 PCI/US93/05~j~

T~RT T` I
In Vitro And In Vivo Anaiot~n~in II
Activitv of ~mno~lnds of the Invention Test 1Assay A 2Assay B 3Assay C
Compound ICso (nM) pA2Dose: 3 mg/kg (i.a.) F~Amnle # Inh;hitio~ (%) ~ration (min . ) 1 S09.04/8.6050 >180 2 209.14/9.lS40 >180 3 4.9 NC 70 >180 4 3.6 NT NT --lA~say A: Angiotensin II Receptor Binding Activity 2Assay B: In Vitro Vascular Smooth Muscle Response 3Assay C: In Vivo Pressor Response (all test compounds A~ini~tered intragastrically at 3 mg/kg).
NT= Not Tested NC = Non-competitive antagonist ~ W094/08989 PCT/US93/05601 ,,, 21~3192 Also embraced within this invention is a class of pharmaceutical compositions comprising one or more compounds of Formula I in association with one or more non-toxic, pharmaceutically acceptable carriers and/or diluents and/or adjuvants (collectively referred to herein as "carrier" mater.~ls) and, if desired, other active ingredients. The compounds of the present invention may be ~mi ni stered by any suitable route, preferably in the form of a pharmaceutical composition adapted to such a route, lo and in a dose effective for the treatment intended.
Therapeutically effective doses of the compounds of the present invention required to prevent or arrest the progress of the medical condition are readily ascertained by one of ordinary s~ill in the art. The compounds and composition may, for example, be ~dm;nistered intra-vascularly, intraperitoneally, subcutaneously, intra-muscularly or topically.

For oral A~ministration, the pharmaceutical 20 composition may be in the form of, for example, a tablet, capsule, suspension or liquid. The pharmaceutical composition is preferably made in the form of a dosage unit containing a particular amount of the active ingredient.
Examples of such dosage units are tablets or capsules.
These may with advantage contain an amount of active ingredient from about 1 to 250 mg, preferably from about 25 to 150 mg. A suitable daily dose for a mammal may vary widely depending on the condition of the patient and other factors. However, a dose of from about 0.1 to 3000 mg/kg 30 body weight, particularly from about 1 to 100 mg/kg body weight, may be appropriate.

The active ingredient may also be administered by injection as a composition wherein, for example, saline, 3, dextrose or water may be used as a suitable carrier. ~

2 1 ~ 3 1 9 2 206 suitable daily dose is from about 0.1 to 100 mg/kg body weight injected per day in multiple doses depending on the disease being treated. A preferred daily dose would be from about 1 to 30 mgJkg body weight. Compounds indicated for prophylactic therapy will preferably be ~mi n; stered in a daily dose generally in a range from about 0.1 mg to about 100 mg per kilogram of body weight per day. A more preferred dosage will be a range from about 1 mg to about 100 mg per kilogram of body weight. Most preferred is a o dosage in a range from about 1 to about 50 mg per kilogram of body weight per day. A suitable dose can be A~mi ni stered, in multiple sub-doses per day. These sub-doses may be ~mini stered in unit dosage forms. Typically, a dose or sub-dose may contain from about 1 mg to about 100 mg of active compound per unit dosage form. A more preferred dosage will contain from about 2 mg to about 50 mg of active compound per unit dosage form. Most preferred is a dosage form containing from about 3 mg to about 25 mg of active compound per unit dose.
The dosage regimen for treating a disease condition with the compounds and/or compositions of this invention is selected in accordance with a variety of factors, including the type, age, weight, sex and medical condition of the patient, the severity of the disease, the route of administration, and the particular compound employed, and thus may vary widely.

For therapeutic purposes, the compounds of this invention are ordinarily combined with one or more adjuvants appropriate to the indicated route of administration. If administered E~ ~, the compounds may be admixed with lactose, sucrose, starch powder, cellulose esters of alkanoic acids, cellulose alkyl esters, talc, ~, stearic acid, magnesium stearate, magnesium oxide, sodium W094/08989 PCT/US93/0 ~1 .

2143 1~ 207 and calcium salts of phosphoric and sulfuric acids, gelatin, acacia gum, sodium alginate, polyvinylpyrrolidone, and/or polyvinyl alcohol, and then tableted or encapsulated for convenient ~m; ni stration. Such capsules or tablets may contain a controlled-release formulation as may be provided in a dispersion of active compound in hydroxypropylmethyl cellulose. Formulations for parenteral A~m;nistration may be in the form of a~ueous or non-aqueous isotonic sterile injection solutions or suspensions. These solutions and suspensions may be prepared from sterile powders or granules having one or more of the carriers or diluents mentioned for use in the formulations for oral administration. The compounds may be dissolved in water, polyethylene glycol, propylene glycol, ethanol, corn oil, cottonseed oil, peanut oil, sesame oil, benzyl alcohol, sodium chloride, and/or various buffers. Other adjuvants and modes of ~min;stration are well and widely known in the pharmaceutical art.

2c Although this invention has been described with respect to specific embodiments, the details of these embodiments are not to be construed as limitations.

Claims (30)

What Is Claimed Is:
1. A compound of Formula I:

I

wherein Q is a cycloalkyl group having three to about eight ring carbon atoms, and wherein said cycloalkyl group may be unsubstituted or substituted on one or more substitutable positions by one or more groups independently selected from hydrido, alkyl, alkoxy, cyano, halo, hydroxy, nitro, amino, alkylamino, carboxyl, alkoxycarbonyl, formyl, oxo, alkylcarbonyl and haloalkylcarbonyl; wherein R7 is selected from hydrido, alkyl, halo, haloalkyl, formyl, carboxyl and alkoxyalkyl; wherein R8 is selected from alkyl, phenyl, phenylalkyl, cycloalkyl and cycloalkylalkyl; wherein m is a number selected from one to four, inclusive; wherein A is an acid-group-substituted pyridinyl-phenyl moiety selected from , , , and ;

wherein R9 is an acidic group selected from COOH and ;

or a stereoisomer or a tautomer thereof or a pharmaceutically-acceptable salt thereof.
2. A compound of Claim 1 wherein Q is wherein each of R1, R2, R3, R4, R5 and R6 is independently selected from hydrido, alkyl, alkoxy, cyano, halo, hydroxy, nitro, amino, alkylamino, carboxyl, alkoxycarbonyl, formyl, alkylcarbonyl and haloalkylcarbonyl; wherein R1 and R2 may further be taken together to form oxo; wherein R3 and R4 may further be taken together to form oxo; wherein R5 and R6 may further be taken together to form oxo; wherein each of d, b and r is a number selected from zero through five, inclusive, and wherein the sum of d+b+r is a number from zero through five, inclusive.
3. Compound of Claim 2 wherein Q is selected from , , , and wherein each of R1, R2 and R3 is independently selected from hydrido, alkyl, alkoxy, cyano, halo, hydroxy, nitro, amino, alkylamino, carboxyl, alkoxycarbonyl, formyl, alkylcarbonyl and haloalkylcarbonyl; and wherein R1 and R2 may further be taken together to form oxo.
4. Compound of Claim 1 of Formula II:

II

wherein each of R1 through R6 is independently selected from hydrido, methyl, ethyl, n-propyl, isopropyl, tert-butyl, methoxy, ethoxy, propoxy, isopropoxy, tert-butoxy, cyano, fluoro, chloro, iodo, bromo, hydroxy, nitro, amino, N-methylamino, N,N-dimethylamino, N-ethylamino, N,N-diethylamino, carboxyl, methoxycarbonyl, ethoxycarbonyl, formyl, methylcarbonyl, ethylcarbonyl and trifluoromethylcarbonyl; wherein R1 and R2 may further be taken together to form oxo; wherein R3 and R4 may further be taken together to form oxo; wherein R5 and R6 may further be taken together to form oxo; wherein each of d, b and r is a number selected from zero through five, inclusive, and wherein the sum of d+b+r is a number selected from zero through five, inclusive; wherein R7 is selected from hydrido, methyl, fluoro, chloro, monofluoromethyl, difluoromethyl, trifluoromethyl, formyl, carboxyl and dimethoxymethyl;
wherein R8 is selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl, neopentyl, phenyl, benzyl, phenethyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclopropylmethyl, cyclopropylethyl, cyclobutylmethyl, cyclobutylethyl, cyclopentylmethyl, cyclopentylethyl, cyclohexylmethyl and cyclohexylethyl; wherein A is an acidic-group-substituted pyridinyl-phenyl moiety selected from , , , and ;

wherein R9 is an acidic group selected from COOH and ;

or a stereoisomer or a tautomer thereof or a pharmaceutically-acceptable salt thereof.
5. Compound of Claim 4 of Formula V:

V

wherein each of R1, R2 and R3 is independently selected from hydrido, methyl, ethyl, n-propyl, isopropyl, tert-butyl, methoxy, ethoxy, propoxy, isopropoxy, tert-butoxy, cyano, fluoro, chloro, iodo, bromo, hydroxy, nitro, amino, N-methylamino, N,N-dimethylamino, N-ethylamino, N,N-diethylamino, carboxyl, methoxycarbonyl, ethoxycarbonyl, formyl, methylcarbonyl, ethylcarbonyl and trifluoromethylcarbonyl; wherein R1 and R2 may further be taken together to form oxo; wherein R7 is selected from hydrido, methyl, fluoro, chloro, monofluoromethyl, difluoromethyl, trifluoromethyl, formyl, carboxyl and dimethoxymethyl; wherein R8 is selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl, neopentyl, phenyl, benzyl, phenethyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclopropylmethyl, cyclopropylethyl, cyclobutylmethyl, cyclobutylethyl, cyclopentylmethyl, cyclopentylethyl, cyclohexylmethyl and cyclohexylethyl;
wherein A is an acidic-group-substituted pyridinyl-phenyl moiety selected from , , , and ;

wherein R9 is an acidic group selected from COOH and ;

or a stereoisomer or a tautomer thereof or a pharmaceutically-acceptable salt thereof.
6. Compound of Claim 5 of Formula V(b):

V(b) wherein each of R1, R2 and R3 may be independently selected from hydrido, methyl, ethyl, n-propyl, isopropyl, tert-butyl, hydroxy, methoxy, fluoro, chloro, iodo, bromo, carboxyl, formyl, methylcarbonyl and trifluoromethylcarbonyl; wherein R1 and R2 may further be taken together to form oxo; wherein R7 is hydrido; wherein R8 is selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl and neopentyl; or a stereoisomer or a tautomer thereof or a pharmaceutically-acceptable salt thereof.
7. Compound of Claim 6 selected from compounds and their stereoisomers and tautomers and the pharmaceutically-acceptable salts thereof, said compounds consisting of 1-(2-methylcyclopentyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-ethylcyclopentyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-propylcyclopentyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-isopropylcyclopentyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-tertbutylcyclopentyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-methoxycyclopentyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;

1-(2-hydroxycyclopentyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-carboxycyclopentyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-acetylcyclopentyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one 1-(2-oxocyclopentyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-methyl-5-methyl-cyclopentyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-ethyl-5-methyl-cyclopentyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-isopropyl-5-methyl-cyclopentyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-carboxy-5-methyl-cyclopentyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-acetyl-5-methyl-cyclopentyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-oxo-5-methyl-cyclopentyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-methyl-5-ethyl-cyclopentyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-ethyl-5-ethyl-cyclopentyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-isopropyl-5-ethyl-cyclopentyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;

1-(2-carboxy-5-ethyl-cyclopentyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-acetyl-5-ethyl-cyclopentyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-oxo-5-ethyl-cyclopentyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-methyl-5-isopropyl-cyclopentyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-ethyl-5-isopropyl-cyclopentyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-isopropyl-5-isopropyl-cyclopentyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-carboxy-5-isopropyl-cyclopentyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-acetyl-5-isopropyl-cyclopentyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-oxo-5-isopropyl-cyclopentyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2,2-dimethylcyclopentyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
and 1-(2,2-diethylcyclopentyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one.
8. Compound of Claim 7 which is 1-cyclopentyl-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one or a pharmaceutically-acceptable salt thereof.
9. Compound of Claim 4 of Formula VI:

VI

wherein each of R1, R2 and R3 is independently selected from hydrido, methyl, ethyl, n-propyl, isopropyl, tert-butyl, methoxy, ethoxy, propoxy, isopropoxy, tert-butoxy, cyano, fluoro, chloro, iodo, bromo, hydroxy, nitro, amino, N-methylamino, N,N-dimethylamino, N-ethylamino, N,N-diethylamino, carboxyl, methoxycarbonyl, ethoxycarbonyl, formyl, methylcarbonyl, ethylcarbonyl and trifluoromethylcarbonyl; wherein R1 and R2 may further be taken together to form oxo; wherein R7 is selected from hydrido, methyl, fluoro, chloro, monofluoromethyl, difluoromethyl, trifluoromethyl, formyl, carboxyl and dimethoxymethyl; wherein R8 is selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl, neopentyl, phenyl, benzyl, phenethyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclopropylmethyl, cyclopropylethyl, cyclobutylmethyl, cyclobutylethyl, cyclopentylmethyl, cyclopentylethyl, cyclohexylmethyl and cyclohexylethyl;
wherein A is an acidic-group-substituted pyridinyl-phenyl moiety selected from , , , and ;

wherein R9 is an acidic group selected from COOH and ;

or a stereoisomer or a tautomer thereof or a pharmaceutically-acceptable salt thereof.
10. Compound of Claim 9 of Formula VI(b):

VI(b) wherein each of R1, R2 and R3 may be independently selected from hydrido, methyl, ethyl, n-propyl, isopropyl, tert-butyl, hydroxy, methoxy, fluoro, chloro, iodo, bromo, carboxyl, formyl, methylcarbonyl and trifluoromethylcarbonyl; wherein R1 and R2 may further be taken together to form oxo; wherein R7 is hydrido; wherein R8 is selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl and neopentyl; or a stereoisomer or a tautomer thereof or a pharmaceutically-acceptable salt thereof.
11. Compound of Claim 10 selected from compounds and their stereoisomers and tautomers and the pharmaceutically-acceptable salts thereof, said compounds consisting of 1-(2-methylcyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-ethylcyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-propylcyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-isopropylcyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-tertbutylcyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-methoxycyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-hydroxycyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-carboxycyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-acetylcyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-oxocyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-methyl-6-methyl-cyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-ethyl-6-methyl-cyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-isopropyl-6-methyl-cyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-carboxy-6-methyl-cyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;

1-(2-acetyl-6-methyl-cyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-oxo-6-methyl-cyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-methyl-6-ethyl-cyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-ethyl-6-ethyl-cyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-isopropyl-6-ethyl-cyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-carboxy-6-ethyl-cyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-acetyl-6-ethyl-cyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-oxo-6-ethyl-cyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-methyl-6-isopropyl-cyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-ethyl-6-isopropyl-cyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-isopropyl-6-isopropyl-cyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-carboxy-6-isopropyl-cyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;

1-(2-acetyl-6-isopropyl-cyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-oxo-6-isopropyl-cyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;

1-(2,2-dimethylcyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
and 1-(2,2-diethylcyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one.
12. Compound of Claim 11 which is 1-cyclohexyl-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one or a pharmaceutically-acceptable salt thereof.
13. Compound of Claim 11 which is 1-(2.alpha.,6.alpha.-1.beta.-cyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one or a pharmaceutically-acceptable salt thereof.
14. Compound of Claim 11 which is 1(2,2-dimethylcyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl-3-pyridinyl]methyl]-2H-imidazol-2-one or a pharmaceutically-acceptable salt thereof.
15. A pharmaceutical composition comprising a therapeutically-effective amount of an angiotensin II
antagonist compound and a pharmaceutically-acceptable carrier or diluent, said antagonist compound selected from a family of compounds of Formula VI:

VI

wherein each of R1, R2 and R3 is independently selected from hydrido, methyl, ethyl, n-propyl, isopropyl, tert-butyl, methoxy, ethoxy, propoxy, isopropoxy, tert-butoxy, cyano, fluoro, chloro, iodo, bromo, hydroxy, nitro, amino, N-methylamino, N,N-dimethylamino, N-ethylamino, N,N-diethylamino, carboxyl, methoxycarbonyl, ethoxycarbonyl, formyl, methylcarbonyl, ethylcarbonyl and trifluoromethylcarbonyl; wherein R1 and R2 may further be taken together to form oxo; wherein R7 is selected from hydrido, methyl, fluoro, chloro, monofluoromethyl, difluoromethyl, trifluoromethyl, formyl, carboxyl and dimethoxymethyl; wherein R8 is selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl, neopentyl, phenyl, benzyl, phenethyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclopropylmethyl, cyclopropylethyl, cyclobutylmetllyl, cyclobutylethyl, cyclopentylmethyl, cyclopentylethyl, cyclohexylmethyl and cyclohexylethyl;
wherein A is an acidic-group-substituted pyridinyl-phenyl moiety selected from , , , and ;

wherein R9 is an acidic group selected from COOH and ;

or a stereoisomer or a tautomer thereof or a pharmaceutically-acceptable salt thereof.
16. The composition of Claim 15 wherein said antagonist compound is of Formula VI(b):

VI(b) wherein each of R1, R2 and R3 may be independently selected from hydrido, methyl, ethyl, n-propyl, isopropyl, tert-butyl, hydroxy, methoxy, fluoro, chloro, iodo, bromo, carboxyl, formyl, methylcarbonyl and trifluoromethylcarbonyl; wherein R1 and R2 may further be taken together to form oxo; wherein R7 is hydrido; wherein R8 is selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl and neopentyl; or a stereoisomer or a tautomer thereof or a pharmaceutically-acceptable salt thereof.
17. The composition of Claim 16 wherein said antagonist compound is selected from compounds and their stereoisomers and tautomers and the pharmaceutically-acceptable salts thereof, said compounds consisting of 1-(2-methylcyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-ethylcyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;

1-(2-propylcyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-isopropylcyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-tertbutylcyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-methoxycyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-hydroxycyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-carboxycyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-acetylcyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-oxocyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-methyl-6-methyl-cyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-ethyl-6-methyl-cyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-isopropyl-6-methyl-cyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-carboxy-6-methyl-cyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-acetyl-6-methyl-cyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-oxo-6-methyl-cyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-methyl-6-ethyl-cyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;

1-(2-ethyl-6-ethyl-cyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-isopropyl-6-ethyl-cyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-carboxy-6-ethyl-cyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-acetyl-6-ethyl-cyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-oxo-6-ethyl-cyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-methyl-6-isopropyl-cyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-ethyl-6-isopropyl-cyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-isopropyl-6-isopropyl-cyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-carboxy-6-isopropyl-cyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-acetyl-6-isopropyl-cyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-oxo-6-isopropyl-cyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2,2-dimethylcyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
and 1-(2,2-diethylcyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one.
18. The composition of Claim 17 wherein said antagonist compound is 1-cyclohexyl-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one or a pharmaceutically-acceptable salt thereof.
19. The composition of Claim 17 wherein said antagonist compound is 1-(2.alpha.,6.alpha.-1.beta.-cyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one or a pharmaceutically-acceptable salt thereof.
20. The composition of Claim 17 wherein said antagonist compound is 1(2,2-dimethylcyclohexyl)-4-butyl-1,3-dihydro-3-[[6-t2-(1H-tetrazol-5-yl)phenyl-3-pyridinyl]methyl]-2H-imidazol-2-one or a pharmaceutically-acceptable salt thereof.
21. A therapeutic method for treating a circulatory disorder or a circulatory-related disorder, said method comprising administering to a subject susceptible to or afflicted with such disorder a therapeutically-effective amount of an active compound of Formula VI:

VI

wherein each of R1, R2 and R3 is independently selected from hydrido, methyl, ethyl, n-propyl, isopropyl, tert-butyl, methoxy, ethoxy, propoxy, isopropoxy, tert-butoxy, cyano, fluoro, chloro, iodo, bromo, hydroxy, nitro, amino, N-methylamino, N,N-dimethylamino, N-ethylamino, N,N-diethylamino, carboxyl, methoxycarbonyl, ethoxycarbonyl, formyl, methylcarbonyl, ethylcarbonyl and trifluoromethylcarbonyl; wherein R1 and R2 may further be taken together to form oxo; wherein R7 is selected from hydrido, methyl, fluoro, chloro, monofluoromethyl, difluoromethyl, trifluoromethyl, formyl, carboxyl and dimethoxymethyl; wherein R8 is selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl, neopentyl, phenyl, benzyl, phenethyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclopropylmethyl, cyclopropylethyl, cyclobutylmethyl, cyclobutylethyl, cyclopentylmethyl, cyclopentylethyl, cyclohexylmethyl and cyclohexylethyl;
wherein A is an acidic-group-substituted pyridinyl-phenyl moiety selected from , , , and ;

wherein R9 is an acidic group selected from COOH and ;

or a stereoisomer or a tautomer thereof or a pharmaceutically-acceptable salt thereof.
22. The method of Claim 21 wherein said active compound is of Formula VI(b):

VI(b) wherein each of R1, R2 and R3 may be independently selected from hydrido, methyl, ethyl, n-propyl, isopropyl, tert-butyl, hydroxy, methoxy, fluoro, chloro, iodo, bromo, carboxyl, formyl, methylcarbonyl and trifluoromethylcarbonyl; wherein R1 and R2 may further be taken together to form oxo; wherein R7 is hydrido; wherein R8 is selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl and neopentyl; or a stereoisomer or a tautomer thereof or a pharmaceutically-acceptable salt thereof.
23. The method of Claim 22 wherein said compound is selected from compounds and their stereoisomers and tautomers and the pharmaceutically-acceptable salts thereof, said compounds consisting of 1-(2-methylcyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-ethylcyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-propylcyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-isopropylcyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-tertbutylcyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-methoxycyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;

1-(2-hydroxycyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-carboxycyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-acetylcyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-oxocyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-methyl-6-methyl-cyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-ethyl-6-methyl-cyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-isopropyl-6-methyl-cyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-carboxy-6-methyl-cyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-acetyl-6-methyl-cyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-oxo-6-methyl-cyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-methyl-6-ethyl-cyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-ethyl-6-ethyl-cyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-isopropyl-6-ethyl-cyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;

1-(2-carboxy-6-ethyl-cyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-acetyl-6-ethyl-cyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-oxo-6-ethyl-cyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-methyl-6-isopropyl-cyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-ethyl-6-isopropyl-cyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-isopropyl-6-isopropyl-cyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-carboxy-6-isopropyl-cyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-acetyl-6-isopropyl-cyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2-oxo-6-isopropyl-cyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
1-(2,2-dimethylcyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one;
and 1-(2,2-diethylcyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one.
24. The method of Claim 23 wherein said compound is 1-cyclohexy1-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one or a tautomer thereof or a pharmaceutically-acceptable salt thereof.
25. The method of Claim 23 wherein said compound is 1-(2.alpha.,6.alpha.-1.beta.-cyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl]-3-pyridinyl]methyl]-2H-imidazol-2-one or a pharmaceutically-acceptable salt thereof.
26. The method of Claim 23 wherein said compound is 1(2,2-dimethylcyclohexyl)-4-butyl-1,3-dihydro-3-[[6-[2-(1H-tetrazol-5-yl)phenyl-3-pyridinyl]methyl]-2H-imidazol-2-one or a pharmaceutically-acceptable salt thereof.
27. The method of Claim 21 wherein said circulatory disorder is a cardiovascular disorder.
28. The method of Claim 27 wherein said cardiovascular disorder is hypertension.
29. The method of Claim 27 wherein said cardiovascular disorder is congestive heart failure.
30. The method of Claim 21 wherein said circulatory-related disorder is glaucoma.
CA002143192A 1992-10-13 1993-06-16 N-arylheteroarylalkyl 1-cycloalkyl-imidazol-2-one compounds for treatment of circulatory disorders Abandoned CA2143192A1 (en)

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