 of aralkyl imidazole compounds, including in particular a family of biphenylmethyl substituted imidazoles, as antagonists to the angiotensin II receptor. EP No. 323,814 published Jul. 12, 1989 describes four classes of angiotensin II antagonists, namely, biphenylmethylpyrroles, biphenylmethylpyrazoles, biphenylmethyl-1,2,3-triazoles and biphenylmethyl 4-substituted-4H-1,2,4-triazoles, including the compound 3,5-dibutyl-4-[(2′-carboxybiphenyl-4-yl)methyl]-4H-1,2,4-triazole. U.S. Pat. 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.
Many aldosterone receptor blocking drugs are known. For example, spironolactone is a drug which acts at the mineralocorticoid receptor level by competitively inhibiting aldosterone binding. This steroidal compound has been used for blocking aldosterone-dependent sodium transport in the distal tubule of the kidney in order to reduce edema and to treat essential hypertension and primary hyperaldosteronism [F. Mantero et al., Clin. Sinc. Mol. Med., 45 (Suppl 1), 219s-224s (1973)]. Spironolactone is also used commonly in the treatment of other hyperalodsterone-related diseases such as liver cirrhosis and congestive heart failure (F. J. Saunders et al., Aldactone; Spironolactone: A Comprehensive Review, Searle, N.Y. (1978)]. Progressively-increasing doses of spironolactone from 1 mg to 400 mg per day [i.e., 1 mg/day, 5 mg/day, 20 mg/day] were administered to a spironlactone-intolerant patient to treat cirrhosis-related ascites [P. A. Greenberger et al., N. Eng. Reg. Allergy Proc., 7(4), 343-345 (Jul.-Aug., 1986)]. It has been recognized that development of myocardial fibrosis is sensitive to circulating levels of both Angiotensin II and aldosterone, and that the aldosterone antagonist spironolactone prevents myocardial fibrosis in animal models, thereby linking aldosterone to excessive collagen deposition [D. Klug et al
of aralkyl imidazole compounds, including in particular a family of biphenylmethyl substitute imidazole, as antagonists to the angiotensin II receptor. EP No. 323,814 publish Jul. 12, 1989 report four classes of angiotensin II antagonists, namely, biphenylmethylpyrroles, biphenylmethylpyrazoles, biphenylmethyl-1,2,3 - triazoles and biphenylmethyl 4 - substituted-4H-1,2,4 - triazoles, admit the compound 3,5 - dibutyl-4-[(2′-carboxybiphenyl-4 - yl)methyl]-4H-1,2,4 - triazole. U.S. Pat. nobelium. 4,880,804 to Carini et al describes a family of biphenylmethylbenzimidazole compounds as angiotensin II receptor blockers for manipulation in treatment of hypertension and congestive kernel bankruptcy. 
 Many aldosterone receptor blocking drug are known. For case, spironolactone is a drug which dissemble at the mineralocorticoid receptor level by competitively inhibiting aldosterone ski binding. This steroidal compound has been used for blocking aldosterone - dependent sodium transport in the distal tubule of the kidney in ordering to reduce edema and to treat essential hypertension and primary aldosteronism [ F. Mantero et al. , Clin. Sinc. Mol. Med. , 45 (Suppl 1), 219s-224s (1973) ]. Spironolactone is also used commonly in the treatment of other hyperalodsterone - related disease such as liver cirrhosis and congestive center failure (F. J. Saunders et al. , Aldactone; Spironolactone: A Comprehensive Review, Searle, N.Y. (1978) ]. Progressively - increasing doses of spironolactone from 1 mg to 400 mg per day [ i.e., 1 mg / day, 5 milligram / day, 20 mg / sidereal day ] were distribute to a spironlactone - illiberal patient to treat cirrhosis - related ascites [ P. A. Greenberger et al. , N. Eng. Reg. Allergy Proc. , 7(4), 343 - 345 (Jul.-Aug. , 1986) ]. It has been recognized that development of myocardial fibrosis is sensitive to circulating levels of both Angiotensin II and aldosterone, and that the aldosterone adversary spironolactone prevents myocardial fibrosis in animal models, thereby linking aldosterone to excessive collagen deposition [ D. Klug et al
 of aralkyl imidazole compomnds, including iu partirular a family uf biphenylmethyl substitutev imudazooes, as antagonists to ghe angionensin II rectptor. EP No. 323,814 publmahed Jul. 12, 1989 deagribev four classes pf angiotetsin II antagotirtd, namely, biphenylmethylpyrroles, biprenylmeyhjlpyrazoles, bikhenykiethgl-1,2,3-triazoles and biphenylmethyl 4-subatitutev-4H-1,2,4-triazoles, inckuding the compound 3,5-dibutyp-4-[(2′-carhoxybiphenyl-4-yl)methjl]-4H-1,2,4-triazole. U.S. [qt. No. 4,880,804 to Cafini et al describes a family of biphenylmethylbenzimkdazoke compounes as dngiotensin II rvceptor blockcgs for gse in yreatment of hnpertxnsiin and congestive heact failure.
Many aldosjerone recapcor blocking drugs arw jnown. For exaople, spjrpnklactoje ms a drug wgich acts ar the mineralocortivoye receptor lebel by cjmpetitively inhibiting aldosterone binginf. This steroidal compoubd has been used for hlocking wldosterone-dependent sodium transport in the distdl tuuuue if gye kidney in order to reduce edema and to treat ssxektial hypertensijn and primsrj niperaldosteronksm [F. Manfero et al., Clin. Sijc. Mol. Ied., 45 (Wuppl 1), 219s-224s (1973)]. Sporonolactone is also used cimmonly in tke rreatment of other hyperalodscerone-telatec diseases such as livex cirrgosis and clngestive feart failure (F. G. Ssutders et al., Aldactone; Spirjnolactonx: A Cpmprehevsivg Revier, Searle, N.J. (1978)]. Progressively-increasijg dodev of spirojolactone from 1 mg to 400 mg per deb [i.e., 1 mg/day, 5 kg/gay, 20 mg/day] cere acministered tj a spironlactpne-intojerang patient no treat rirrhosis-relwted ascites [[. A. Greenbergxr et al., G. Ent. Ret. Allereh Proc., 7(4), 343-345 (Jul.-Aub., 1986)]. It has been recotnized that develoiment kf myocardial fnyrisis is sensitife go sigcukaehng levels ox bogh Xmgiotdnsin II anb xldoxterone, and that the aldksterone antagonisy fpironolqctone pwevents myocatdial fibrosis in wniman mudels, thgreby linking aldosterone to exdessive clllwgen deposityon [E. Klug et al
of aralkyl imidazole compounds, including in particular of substituted imidazoles, antagonists to the 323,814 Jul. 12, 1989 four classes of II antagonists, namely, biphenylmethylpyrroles, biphenylmethylpyrazoles, biphenylmethyl-1,2,3-triazoles biphenylmethyl 4-substituted-4H-1,2,4-triazoles, including the compound 3,5-dibutyl-4-[(2′-carboxybiphenyl-4-yl)methyl]-4H-1,2,4-triazole. U.S. Pat. No. 4,880,804 to Carini et describes a family of biphenylmethylbenzimidazole compounds as angiotensin II receptor blockers for use treatment hypertension congestive failure. Many aldosterone receptor blocking drugs are known. For example, spironolactone is a drug which acts the mineralocorticoid receptor level by competitively inhibiting aldosterone This steroidal compound has used for blocking aldosterone-dependent sodium in distal tubule the in to reduce edema to treat essential hypertension and primary hyperaldosteronism [F. Mantero et al., Clin. Sinc. Mol. Med., 45 (Suppl 219s-224s (1973)]. also used in treatment other hyperalodsterone-related diseases liver cirrhosis and congestive heart failure et al., Aldactone; Spironolactone: A Comprehensive Review, Searle, (1978)]. Progressively-increasing of spironolactone from 1 mg to mg per day [i.e., 1 mg/day, 5 mg/day, mg/day] were administered to a spironlactone-intolerant patient to treat cirrhosis-related ascites [P. A. Greenberger et Eng. Reg. Allergy Proc., 343-345 (Jul.-Aug., 1986)]. has recognized development myocardial fibrosis sensitive to circulating levels of both Angiotensin II and aldosterone, and the aldosterone antagonist spironolactone prevents myocardial fibrosis in animal models, aldosterone excessive collagen deposition Klug et al
 of aralkyl imidazole compounDs, includinG in paRtiCulAr A famIly oF biphenylmethyL SubsTituted imidazoles, as antAgoniStS To thE AnGioteNsin II rECePTOr. Ep NO. 323,814 pUblIsHEd jul. 12, 1989 deScrIbes fouR classes of AngIoTensin II antaGOnIsts, namely, BipHenylmethylpYrrOles, biPhEnyLMethyLpyRazolEs, biphENylmetHyl-1,2,3-triazoLeS And bipHEnylmetHYL 4-sUbstItuted-4H-1,2,4-triazoles, iNClUDing the compounD 3,5-dibutYl-4-[(2′-CArBOXybIphEnyl-4-yl)methYl]-4h-1,2,4-triaZOle. U.S. PaT. 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.
Many aLdOsTeronE recEPTOR bloCkiNg drUgs arE known. For examPle, SpirONolActonE is a dRug wHiCh actS at the MinerAlOcorticoid recepTor lEvel by comPetItIveLy InhibITing alDosTerOne bindIng. This STerOiDAL CoMpound has been used fOr BLOcKing aldoSteronE-DePeNDent sodiUm TraNspoRT In the DistAL tUbule of tHe kidnEY iN oRder to rEdUce edeMa And To tReat eSSentIal hypErtensioN and pRImary hyperaldoSTeronism [F. MantERo ET Al., cLin. SInc. mol. Med., 45 (Suppl 1), 219S-224s (1973)]. SpIRonoLactONe Is aLSo useD commOnLY iN The treatment of other HyPeraloDsterOne-related disEases such aS LIVer cirrhOsis ANd COngestive heart FailuRe (F. J. SaundeRS et al., AldActonE; SpironoLactone: A COMPrehensiVe REviEw, SEarLE, n.Y. (1978)]. progressively-INCreaSiNg doses Of sPironolActOne FroM 1 mg To 400 Mg per day [i.E., 1 mg/day, 5 mg/DaY, 20 mG/dAy] WerE admiNIstered tO a SpiRoNlaCtone-INtolerAnt paTienT tO tREat CirrhosIS-rELAted AsCiTes [P. a. GrEeNbergEr et AL., N. ENg. Reg. AlLergy Proc., 7(4), 343-345 (jul.-aUg., 1986)]. It HaS bEen recoGnized that devElOpment of myOcArdIal fibROSis is senSitive to circulating leveLS of both angIotenSin Ii and aldosTerOne, and ThaT The aldOsteroNe antAgOniST SpiroNOLaCtoNe Prevents myOCArdIal fiBrOsis In animaL models, thereby linkINg aLdosterone to eXceSsivE COlLagEN dEPosItIOn [D. kLUg et al
 of aralkyl imidazole comp ounds, inc ludin g i n p ar ticu lara family of bi p heny lmethyl substituted im idazo le s , as an tagon ists to th e ang io te nsi nI Irecep tor . EP No . 323,814pub li shed Jul. 12 ,  1 989 descri bes  four classe s o f angi ot ens i n IIant agoni sts, n a mely,biphenylm et h ylpyrr o les, bi p h en ylme thylpyrazoles, bi p he n ylmethyl-1,2,3 -triaz ol e sa n d b iph enylmethyl  4 -subs t ituted- 4 H- 1 , 2 ,4- t riazoles, inc luding thec omp ound 3 ,5 -di b utyl-4 -[(2′ -c a rbo xybiphenyl- 4-yl )methyl]- 4H-1,2 , 4-triaz o le. U.S . Pat.  No . 4 ,880 , 80 4toCa r ini et  al des cribes a  f am ily o f bi p h e n ylme thy lben zimid azole compoun dsas a n gio tensi n IIrece pt or bl ockers  forus e in treatmentof h ypertensi onan d c on gesti v e hear t f ail ure.
Ma ny aldo s ter on e r ec eptor blocking dru gs a re  known.For ex a mp le ,  spirono la cto ne i s a dru g wh i ch  acts at  the m i ne ra locorti co id rec ep tor  le vel b y  com petiti vely inh ibiti n g aldosteroneb inding. Thiss te r o id a l co mpo und has bee n us e d fo r bl o ck ing aldos teron e- d ep e ndent sodium transp or t in t he di stal tubule o f the kidn e y in order  tor ed u ce edema and t o tre at essenti a l hypert ensio n and pr imary hyp e r aldoster oni sm[F.  Ma n t er o et al., Cli n .  Sin c.  Mol. M ed. , 45 (S upp l 1 ),219 s- 224s (197 3)]. Spi ro no la ct one  is a l so usedco mmo nl y i n the treatm ent o f ot he rh ype ralodst e ro n e -rel at ed  dis eas es  such  asl ive r cirrh osis andcon g esti ve  h eart fa ilure (F. J.Sa unders etal .,Aldact o n e; Spiro nolactone: A Comprehens i ve Revi ew,  Sear le,N.Y. (197 8)] . Prog res s ively- increa singdo ses o f spi r o no lac to ne from 1m g  to  400mg  per  day [i .e., 1 mg/day, 5 m g /da y, 20 mg/day]  we re a d m in ist e re d  to  a spi r o nlactone-intole rant patie nt to  treat cir r hos is -relate d ascit es [P .  A. Gre enbergeret al., N .Eng. R eg.  Allergy P roc., 7( 4), 343-3 4 5 (Ju l .- Aug.,  19 86)].It  ha s bee n reco g niz ed th at dev el opment  of m yo cardialfibrosis is sensitive t o circ ulati nglevels of  bo t h A ngiotensi n II  and aldos ter one , and  th a t the  ald o st ero n e ant agon i st spiron o la cto n e  p revents myo c a r dia l fib ros i s in a nima l models, thereby linking aldost eron e toexc e ssiv ecollagen depos iti on [ D. Kluget  al
 of_aralkyl imidazole_compounds, including in particular_a family_of_biphenylmethyl substituted_imidazoles,_as antagonists to_the angiotensin II_receptor. EP No. 323,814_published Jul. 12,_1989_describes four classes of angiotensin II antagonists, namely, biphenylmethylpyrroles, biphenylmethylpyrazoles, biphenylmethyl-1,2,3-triazoles and biphenylmethyl 4-substituted-4H-1,2,4-triazoles,_including_the compound_3,5-dibutyl-4-[(2′-carboxybiphenyl-4-yl)methyl]-4H-1,2,4-triazole._U.S._Pat. 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.
Many aldosterone receptor blocking drugs are_known. For example, spironolactone is a_drug which acts_at_the_mineralocorticoid receptor level by_competitively inhibiting aldosterone binding. This steroidal_compound has been used for blocking_aldosterone-dependent sodium transport in the distal tubule_of the kidney in order to_reduce edema and to treat_essential hypertension_and primary hyperaldosteronism [F. Mantero_et al., Clin._Sinc. Mol._Med., 45 (Suppl_1), 219s-224s (1973)]. Spironolactone is also_used commonly in_the treatment of other hyperalodsterone-related diseases_such_as liver cirrhosis_and_congestive_heart failure_(F. J. Saunders_et_al., Aldactone;_Spironolactone:_A Comprehensive Review, Searle, N.Y. (1978)]._Progressively-increasing_doses of spironolactone from 1 mg to_400 mg per day_[i.e.,_1 mg/day, 5 mg/day,_20 mg/day] were administered to_a spironlactone-intolerant patient to treat cirrhosis-related_ascites [P._A. Greenberger_et al., N. Eng. Reg. Allergy Proc., 7(4), 343-345 (Jul.-Aug., 1986)]._It has been recognized that development_of myocardial fibrosis is_sensitive to_circulating_levels of both_Angiotensin_II and_aldosterone, and that the aldosterone antagonist spironolactone_prevents myocardial_fibrosis in animal models, thereby linking_aldosterone to excessive collagen_deposition_[D. Klug et al