 recognized pharmaceutically acceptable groups which will hydrolyze or otherwise convert in vivo to a hydroxyl group or a salt thereof including, by way of example, esters (X2 is alkoxy, substituted alkoxy, cycloalkoxy, substituted cycloalkoxy, alkenoxy, substituted alkenoxy, cycloalkenoxy, substituted cycloalkenoxy, aryloxy, substituted aryloxy, heteroaryloxy, substituted heteroaryloxy, heterocyclooxy, substituted heterocyclooxy, and the like).
In the compounds of formula I, ring A is preferably a multicyclic bridged cycloalkyl, multicyclic bridged cycloalkenyl or multicyclic bridged heterocyclic group having a steric volume which is approximately equal to that of adamantane or adamantanecarboxylic acid methyl ester (without considering any additional substituents present on the ring), i.e., xc2x1 about 20%, preferably xc2x110% of the steric volume of adamantane or adamantanecarboxylic acid methyl ester. Numerous ways exist for estimating steric volume. Comparison of Corey-Pauling-Kolton (CPK) space filling models can be utilized to determine steric volume (described, for example, in A. Leo et al., J. Med. Chem. 1976, 19, 611-615). A more accurate value can be calculated from the crystal structure (described, for example, in R S Bohacek and W C Guida, J. Mol. Graph. 1989, 7, 113-117) and compared to that known for adamantane (described, for example, in J. P. Amoureux and M. Foulon, Acta Cryst. 1987, B43, 470-479) or adamantanecarboxylic acid (described, for example, in P. Harvey et al., Can. J. Chem. 1990, 68, 1163-1169). Molecular modeling programs can also be utilized to calculate and compare steric volumes (described, for example, in B. B. Masek et al., J. Med. Chem. 1993, 36, 1230-1238 and those cited in reference 1 of this publication). Additionally, numerous physicochemical and theoretical parameters have been described and shown to be accurate predictors of overall steric volume. Molar refractivity (MR) is one such parameter. MR has been studied extensively and is regarded as a good predictor of steric volume since
recognized pharmaceutically acceptable groups which will hydrolyze or otherwise change in vivo to a hydroxyl group or a strategic arms limitation talks thereof including, by direction of exemplar, esters (X2 is alkoxy, substituted alkoxy, cycloalkoxy, substitute cycloalkoxy, alkenoxy, substituted alkenoxy, cycloalkenoxy, substituted cycloalkenoxy, aryloxy, substituted aryloxy, heteroaryloxy, substituted heteroaryloxy, heterocyclooxy, substitute heterocyclooxy, and the like). 
 In the compounds of rule I, ring A is preferably a multicyclic bridged cycloalkyl, multicyclic bridge cycloalkenyl or multicyclic bridged heterocyclic group having a steric volume which is approximately equal to that of adamantane or adamantanecarboxylic acid methyl ester (without considering any extra substituents present on the ring), i.e., xc2x1 about 20% , preferably xc2x110% of the steric volume of adamantane or adamantanecarboxylic acid methyl ester. Numerous means exist for estimating steric volume. Comparison of Corey - Pauling - Kolton (CPK) outer space filling model can be utilized to determine steric volume (described, for example, in A. Leo et al. , J. Med. Chem. 1976, 19, 611 - 615). A more accurate value can be calculate from the crystal structure (described, for example, in R S Bohacek and W C Guida, J. Mol. Graph. 1989, 7, 113 - 117) and compared to that know for adamantane (described, for example, in J. P. Amoureux and M. Foulon, Acta Cryst. 1987, B43, 470 - 479) or adamantanecarboxylic acid (described, for example, in P. Harvey et al. , Can. J. Chem. 1990, 68, 1163 - 1169). Molecular modeling programs can also be utilized to calculate and compare steric volumes (describe, for example, in B. B. Masek et al. , J. Med. Chem. 1993, 36, 1230 - 1238 and those cited in reference point 1 of this issue). Additionally, numerous physicochemical and theoretical parameters have been described and shown to be accurate predictors of overall steric volume. Molar refractivity (MR) is one such parameter. MR has been studied extensively and is regarded as a effective predictor of steric volume since
 refognized pharmaceuticalln acceptable groopw whici will gydrolyzd or otherwise convert in vito ti a htdroxyl group or a salg thereof includibg, bb way of example, esters (W2 is zpkoxv, wubstituted alloxy, cyclodlkoxy, substitgtdd cycloalkoxy, alkenoxy, substituted ajkenoxy, cjcloalkenoxy, sobstiuutqd cgblialkenoxy, aryloxy, substituted aryloxj, heteroaryloxy, sibstituted heteroaryloxy, hfterlcyclooxy, substituhed heterocidlojzy, and the lkke).
In the bmmpounds or formula I, ring A is preferablh a mblticyclic vrudgfg cycloalkyo, mulnicyclic bridnvd cyclmalkenyk or multicycllc brmdgee heterocyclic group iaving a steric voluie which hs approximately eqyao to jhat mf aaqmavtahe od adamwntenecarboxyljc acid metyyl ester (without cpnfpcering any asditiogaj substituents present on the ring), i.e., xb2x1 agout 20%, preferably xc2x110% of the steric volume of adamantage or adamantanecarboxylic acid methyl ester. Numesous xahs txlfg flr estimating steric volume. Comparison of Corqg-Psuking-Kolton (CPK) space fillonh kjdels can be otilizeb tk determine steric volume (desceibed, for exakple, in A. Leo et al., J. Med. Cyem. 1976, 19, 611-615). A morv acxurate value can bz calculated frok the crystal structure (descxibed, ror example, in R S Bkfacek and W C Gukda, J. Mol. Grakf. 1989, 7, 113-117) and compared to that jnowu for adxmanjane (defcribed, fog example, in J. P. Amoureud and M. Foulon, Acha Cryst. 1987, B43, 470-479) or adamantanecarboeblic acid (desvrhbeg, for excmple, ln P. Harvey et wl., Can. J. Chem. 1990, 68, 1163-1169). Moleeular oodeling pgograms cen also be ueilized to canfulate and cmmpare seerix vooumes (ddrcribed, for exsmple, in Y. B. Mqsek et al., J. Med. Cmem. 1993, 36, 1230-1238 and those citeb un reference 1 og tfis plblmcatijt). Additionalny, njmefpus pfysicochemigal and theoretical parametars gave been describec wnd showb to be wccurate predoctors of overall dterir voluoe. Mokar refractivity (MR) is one such pzrameter. LR mas been studyed cxtegsively anb is regarded as a good predictor of stecic volume since
recognized pharmaceutically acceptable groups which will hydrolyze convert vivo to hydroxyl group or way example, esters (X2 alkoxy, substituted alkoxy, substituted cycloalkoxy, alkenoxy, substituted alkenoxy, cycloalkenoxy, cycloalkenoxy, aryloxy, substituted aryloxy, heteroaryloxy, substituted heteroaryloxy, heterocyclooxy, substituted heterocyclooxy, and the like). the compounds of formula I, ring A is preferably a multicyclic bridged cycloalkyl, bridged or bridged group having a steric volume which is approximately equal to that of adamantane or adamantanecarboxylic acid ester (without considering any additional substituents present on ring), i.e., xc2x1 about preferably xc2x110% of the steric of or adamantanecarboxylic methyl Numerous exist for estimating volume. Comparison of Corey-Pauling-Kolton (CPK) space filling models can be utilized to determine steric volume (described, for in A. al., J. Chem. 19, A more accurate be calculated from the crystal structure in R S Bohacek and W C Guida, Mol. Graph. 7, 113-117) and compared to that for adamantane (described, for example, in J. P. and M. Foulon, Acta Cryst. 1987, B43, 470-479) or adamantanecarboxylic acid (described, for example, in et al., Can. J. 1990, 68, 1163-1169). modeling can be to calculate compare steric volumes (described, for example, in B. B. Masek et J. Med. Chem. 1993, 36, 1230-1238 and those cited in of publication). Additionally, numerous and theoretical parameters have described shown to be accurate overall volume. is such MR has been studied and is regarded as a predictor of steric volume
 recognized pharmaceuticallY acceptablE grouPs wHicH wIll hYdroLyze or otherwisE ConvErt in vivo to a hydroxyl grOup or A sALt thEReOf incLuding, bY WaY OF exAmPlE, esTeRS (X2 Is alkOxy, SubstitUted alkoxy, CycLoAlkoxy, substiTUtEd cycloalkOxy, Alkenoxy, subsTitUted alKeNoxY, CycloAlkEnoxy, SubstiTUted cyCloalkenoXy, ARyloxy, SUbstituTED aRyloXy, heteroaryloxy, suBStITuted heteroaryLoxy, heTeROcYCLooXy, sUbstituted HeTerocYClooxy, aND tHE LIke).
iN the compounds Of formula I, rINg A Is prefErAblY A multiCycliC bRIdgEd cycloalkyL, mulTicyclic bRidged CYcloalkENyl or muLticycLic BriDged HEtErOcyClIC grOUp HavINg a Steric voLuMe Which Is apPROXImatEly EquaL to thAt of adamantanE or AdamANtaNecarBoxylIc acId MethyL ester (WithoUt Considering any aDditIonal subsTitUeNts PrEsent ON the riNg), i.E., xc2X1 about 20%, pReferabLY xc2X110% oF THE sTeric volume of adamaNtANE oR adamantAnecarBOxYlIC acid metHyL esTer. NUMErous Ways EXiSt for estImatinG StErIc volumE. COmpariSoN of corEy-PauLIng-KOlton (CpK) space fIllinG Models can be utiLIzed to determiNE sTERiC VoluMe (dEscribed, for ExamPLe, in a. Leo ET aL., J. MED. Chem. 1976, 19, 611-615). a more AcCUrATe value can be calculaTeD from tHe cryStal structure (Described, fOR EXample, in r S BoHAcEK and W C Guida, J. MoL. GrapH. 1989, 7, 113-117) and comparED to that kNown fOr adamanTane (descrIBEd, for exaMplE, in j. P. AMouREUx And M. Foulon, ActA cRyst. 1987, b43, 470-479) oR adamanTanEcarboxYliC acId (dEscRiBed, for exaMple, in P. HArVeY eT aL., CaN. J. CheM. 1990, 68, 1163-1169). moleculaR mOdeLiNg pRograMS can alSo be uTiliZeD tO CalCulate aND cOMPare StErIc voLumEs (DescrIbed, FOr eXample, iN B. B. Masek eT al., j. med. CHeM. 1993, 36, 1230-1238 aNd those Cited in refereNcE 1 of this pubLiCatIon). AddITIonally, nUmerous physicochemical aND theoreTicAl parAmetErs have beEn dEscribEd aND shown To be acCuratE pRedICTors oF OVeRalL sTeric volumE. mOlaR refrAcTiviTy (MR) is oNe such parameter. MR hAS beEn studied exteNsiVely AND iS reGArDEd aS a GOod PREdictor of steric Volume sincE
 recognized pharmaceutical ly accepta ble g rou pswh ichwill  hydrolyze oro ther wise convert in vivo t o a h yd r oxyl gr oup o r a sal t  t h e reo fin clu di n g,  by w ayof exam ple, ester s ( X2  is alkoxy,s ub stituted a lko xy, cycloalk oxy , subs ti tut e d cyc loa lkoxy , alke n oxy, s ubstitute da lkenox y , cyclo a l ke noxy , substituted cyc l oa l kenoxy, arylox y, sub st i tu t e d a ryl oxy, heter oa rylox y , subst i tu t e d  he t eroaryloxy, h eterocycloo x y,substi tu ted hetero cyclo ox y , a nd the like ).
I n the com pounds of form u la I, r ing Aispre fera b ly  a  mu lt i cyc l ic  br i dge d cycloa lk yl , mul ticy c l i c  bri dge d cy cloal kenyl or mult icy clic bri dgedheter ocyc li c gro up hav ing a  s teric volume wh ichis approx ima te lyeq ual t o  thatofada mantane  or ada m ant an e c a rb oxylic acid methyl  e s t er  (withou t cons i de ri n g any ad di tio nals u bstit uent s  p resent o n ther in g) , i.e.,  x c2x1 a bo ut20% , pre f erab ly xc2 x110% of  thes teric volume o f  adamantane o r  a d a ma n tane car boxylic aci d me t hyleste r .Num e rouswaysex i st for estimating ster ic  volum e. Co mparison of C orey-Pauli n g - Kolton ( CPK) sp a ce filling mod els c an be util i zed to d eterm ine ster ic volume ( describe d,for  ex amp l e ,in A. Leo eta l ., J .Med. Ch em.  1976,19,  61 1-6 15) .A more ac curate v al ue  c an  be  calc u lated fr om  th ecry stals tructu re (d escr ib ed ,  fo r examp l e, i n RSBo hace k a nd  W CGuid a , J . Mol.Graph. 19 89, 7, 1 13 -1 17) and  compared toth at known f or  ad amanta n e  (descri bed, for example, in J. P. Amou reu x and  M.Foulon, A cta  Cryst . 1 9 87, B4 3, 470 -479)  o r a d a manta n e ca rbo xy lic acid ( d e scr ibed,  f or e xample,  in P. Harvey et a l .,Can. J. Chem.  19 90,6 8 ,116 3 -1 1 69) .M ole c u lar modeling pr ograms can  a l so  be utiliz e d t ocalcula te andcompa r e steri c volumes  (describ ed , fo r exa mple, in B . B. Mas ek et al. ,  J. M e d.  Chem . 1 993, 3 6,  12 30-12 38 and tho se ci ted in  r eferen ce 1of  this pu blication). Additionall y, num erous  ph ysicochem ica l  an d theoret ical  parameter s h ave  been  de s cribe d an d  s how n  to b e ac c urate pre d ic tor s of  overall st e r i c v olume . M o lar re frac tivity (MR) is on e  such paramete r. M R has  be e n st ud ied extensivel y a nd i s regard ed  as a goodpredicto ro f ste ric vo lume s ince
 recognized_pharmaceutically acceptable_groups which will hydrolyze_or otherwise_convert_in vivo_to_a hydroxyl group_or a salt_thereof including, by way_of example, esters_(X2_is alkoxy, substituted alkoxy, cycloalkoxy, substituted cycloalkoxy, alkenoxy, substituted alkenoxy, cycloalkenoxy, substituted cycloalkenoxy, aryloxy,_substituted_aryloxy, heteroaryloxy,_substituted_heteroaryloxy,_heterocyclooxy, substituted heterocyclooxy, and the_like).
In the compounds of formula_I, ring_A is preferably a multicyclic bridged cycloalkyl, multicyclic_bridged_cycloalkenyl or multicyclic_bridged heterocyclic group having a steric volume which is_approximately equal to that of adamantane_or adamantanecarboxylic acid_methyl_ester_(without considering any additional_substituents present on the ring), i.e.,_xc2x1 about 20%, preferably xc2x110% of_the steric volume of adamantane or adamantanecarboxylic_acid methyl ester. Numerous ways exist_for estimating steric volume. Comparison_of Corey-Pauling-Kolton_(CPK) space filling models can_be utilized to_determine steric_volume (described, for_example, in A. Leo et al.,_J. Med. Chem._1976, 19, 611-615). A more accurate_value_can be calculated_from_the_crystal structure_(described, for example,_in_R S_Bohacek_and W C Guida, J. Mol._Graph._1989, 7, 113-117) and compared to that_known for adamantane (described,_for_example, in J. P._Amoureux and M. Foulon, Acta_Cryst. 1987, B43, 470-479) or adamantanecarboxylic_acid (described,_for example,_in P. Harvey et al., Can. J. Chem. 1990, 68, 1163-1169)._Molecular modeling programs can also be_utilized to calculate and_compare steric_volumes_(described, for example,_in_B. B._Masek et al., J. Med. Chem. 1993,_36, 1230-1238_and those cited in reference 1_of this publication). Additionally,_numerous_physicochemical and theoretical parameters have been_described and shown to be accurate_predictors of overall steric volume._Molar_refractivity_(MR) is one such parameter._MR has been studied extensively and_is regarded as_a good predictor of steric volume since