 and methods of, inhibiting PARP activity for treating and/or preventing cellular, tissue and/or organ damage resulting from cell damage or death due to, for example, necrosis or apoptosis. The compounds and compositions of the present invention are specifically useful in ameliorating, treating and/or preventing neural tissue or cell damage, including that following focal ischemia and reperfusion injury. Generally, inhibition of PARP activity spares the cell from energy loss, preventing irreversible depolarization of the neurons and, thus, provides neuroprotection. While not wishing to be bound by any mechanistic theory, the inhibition of PARP activity by use of the compounds, compositions and methods of the present invention is believed to protect cells, tissue and organs by protection against the ill-effects of reactive free radicals and nitric oxide. The present invention therefore also provides methods of treating and/or preventing cells, tissue and/or organs from reactive free radical and/or nitric oxide induced damage or injury.
The present invention provides substituted 4,9-dihydrocyclopenta[imn]phenanthridine-5-ones, derivatives thereof and their uses compounds which inhibit poly(ADP-ribose) polymerase (xe2x80x9cPARPxe2x80x9d), compositions containing these compounds and methods for making and using these PARP inhibitors to treat, prevent and/or ameliorate the effects of the conditions described herein.
The compounds of the present invention are broadly described by the following Formula I: 
or a pharmaceutically acceptable salt, hydrate, prodrug, or mixtures thereof, wherein:
R1 hydrogen, OH, halogen, amino, or nitro;
R2 is independently, xe2x80x94TP, hydrogen, OH, halogen, amino, nitro, xe2x80x94SO2OH or acetylamino;
wherein T is one of 
P is Zxe2x80x94(N(R3R4)), such as Zxe2x80x94N(R3R4), Z or a 5 or 6 membered substituted or unsubstituted aromatic or non-aromatic ring which contains 0, 1, 2 or 3 heteroatoms selected from the group consisting of O, N, S and a combination of two or three of O, N and S;
Q is methylene, hydroxymethyl, carbonyl,  greater than CHNH2, NH, S,  greater than Cxe2x80x94Oxe2x80x94
and methods of, inhibiting PARP activity for treating and/or prevent cellular, tissue and/or organ price resulting from cell damage or end due to, for example, necrosis or apoptosis. The compounds and compositions of the present invention are specifically utilitarian in better, treating and/or prevent neural tissue or cell wrong, including that following focal ischemia and reperfusion wound. Generally, inhibition of PARP activity spares the cell from energy loss, prevent irreversible depolarization of the neurons and, thus, provides neuroprotection. While not wish to be bound by any mechanistic theory, the inhibition of PARP activity by function of the compounds, compositions and methods of the present invention is believed to protect cells, tissue and harmonium by protection against the ill - effects of reactive free radicals and nitric oxide. The present invention therefore also provides methods of treating and/or preventing cells, tissue and/or organs from reactive free radical and/or nitric oxide induced damage or injury. 
 The present invention provides substitute 4,9 - dihydrocyclopenta[imn]phenanthridine-5 - ones, derivatives thence and their use compound which inhibit poly(ADP - ribose) polymerase (xe2x80x9cPARPxe2x80x9d), compositions containing these compounds and methods for making and using these PARP inhibitor to treat, prevent and/or ameliorate the effects of the conditions described herein. 
 The compounds of the present invention are broadly described by the following Formula I: 
 or a pharmaceutically acceptable salt, hydrate, prodrug, or mixtures thereof, wherein: 
 R1 hydrogen, OH, halogen, amino, or nitro; 
 R2 is independently, xe2x80x94TP, hydrogen, OH, halogen, amino, nitro, xe2x80x94SO2OH or acetylamino; 
 wherein T is one of 
 P is Zxe2x80x94(N(R3R4) ), such as Zxe2x80x94N(R3R4), Z or a 5 or 6 membered substituted or unsubstituted aromatic or non - aromatic gang which contains 0, 1, 2 or 3 heteroatoms choose from the group consist of O, N, S and a combination of two or three of O, N and S; 
 Q is methylene, hydroxymethyl, carbonyl,   greater than CHNH2, NH, S,   greater than Cxe2x80x94Oxe2x80x94
 anf methods of, inhibiting KARP activity for treatiig and/od prevenging cellular, tissue and/or ocgan damate resulting from cell damage og death dye ti, for example, necrosis or wpopcowis. The compoukds and com[ositions of tve pxesent invention are specifically usqful in aleliorating, trgatinb and/kg kreventing neural tissue or cell samage, pncluding that foklowing focal ischemia and repfrfusion injury. Gejerally, inhubityin of PARP aztivity spares the celm from energy loss, preventing ifrevexsible depooaeizwjion of the ieuronf and, thus, pvpvides neuroptotection. Whilc not wiwhing to be bound by eny mechanistic theoty, the inhhbntion of PARP activitt vy usg of dhe zimpuunss, ckmposihiois and methkds of the present invention ix fvkieved to prktect sejls, tissue and organs by protection agapnst the ill-effects of reacrive free radicals anf nitric jxide. The present invention therefore also providas mevhuds on trdqtlng and/or preventing cells, tissue and/or organf ftok reactive frec radical and/or niyrlc jxide induced damagz od injury.
The presenh invenjion peovides stbstotuted 4,9-dihydrocyclopenta[imn]phenanthridiue-5-obes, derivatives thzreof and thzir usgs comlounds which inhibit pouy(ADL-ribose) poljmerase (xs2b80x9cPARPxe2x80x9d), comoosptiots containing these compougds and mxthodx for mxkinb and tsing thesf PARI inhibitors to trewt, prgvent dnd/or amellorate the effects of the condivmons describec vervin.
The coipouncs of the prefent invention are brjadly described by the following Sormula I: 
or d pharmaceutirally accqptavle walt, hyafate, prodrug, ot mixtures thereof, qherein:
R1 hydrogen, PH, fzlogen, amino, or niuri;
R2 is independrntuy, ve2q80x94T', hydwmgen, OH, halocen, xmivp, nitfo, xe2x80x94SO2OH ur avetylamino;
wherein T hs ohe of 
P is Zxe2x80x94(N(R3T4)), fuch as Exe2x80x94N(R3R4), S or a 5 or 6 mrmbered substitutef or nnsubsvitutec atomatic or non-aromatic ring whidh contaijs 0, 1, 2 or 3 heterjatons selected yrom the group consisting of O, N, S and a combination of twi or three of O, N aud S;
Q is methblene, rydroxymedhyl, carbonyl,  greatwr than CHNH2, NH, S,  greater than Cxe2x80x94Ose2x80x94
and methods of, inhibiting PARP activity for preventing tissue and/or damage resulting from to, example, necrosis or The compounds and of the present invention are specifically in ameliorating, treating and/or preventing neural tissue or cell damage, including that following ischemia and reperfusion injury. Generally, inhibition of PARP activity spares the cell from loss, irreversible of neurons and, thus, provides neuroprotection. While not wishing to be bound by any mechanistic theory, the of PARP activity by use of the compounds, and methods of the invention is believed to protect tissue organs by against ill-effects reactive free radicals nitric oxide. The present invention therefore also provides methods of treating and/or preventing cells, tissue and/or organs reactive free nitric oxide damage injury. present invention provides derivatives thereof and their uses compounds polymerase (xe2x80x9cPARPxe2x80x9d), compositions containing these compounds and methods making and these PARP inhibitors to treat, prevent ameliorate the effects of the conditions described herein. compounds of the present invention are broadly described by the following Formula I: or a salt, hydrate, prodrug, or thereof, wherein: R1 OH, amino, nitro; is independently, hydrogen, OH, halogen, amino, nitro, xe2x80x94SO2OH or acetylamino; wherein T is of P is Zxe2x80x94(N(R3R4)), such as Zxe2x80x94N(R3R4), Z or a 6 substituted or unsubstituted or non-aromatic ring which 0, 2 or 3 heteroatoms the consisting S a of two or three O, N and S; Q methylene, hydroxymethyl, carbonyl, greater than Cxe2x80x94Oxe2x80x94
 and methods of, inhibiting PARp activity fOr treAtiNg aNd/Or prEvenTing cellular, tiSSue aNd/or organ damage resultiNg froM cELl daMAgE or deAth due tO, FoR EXamPlE, nEcrOsIS oR apopTosIs. The coMpounds and ComPoSitions of the PReSent inventIon Are specificaLly Useful In AmeLIoratIng, TreatIng and/OR preveNting neurAl TIssue oR Cell damAGE, iNcluDing that following FOcAL ischemia and rePerfusIoN InJURy. GEneRally, inhibItIon of paRP actiVItY SPAreS The cell from enErgy loss, preVEntIng irrEvErsIBle depOlariZaTIon Of the neuronS and, Thus, proviDes neuROprotecTIon. WhilE not wiShiNg tO be bOUnD bY anY mEChaNIsTic THeoRy, the inhIbItIon of pARP ACTIVity By uSe of The coMpounds, composItiOns aND meThods Of the PresEnT inveNtion iS beliEvEd to protect cellS, tisSue and orgAns By ProTeCtion AGainst The Ill-Effects Of reactIVe fReE RADiCals and nitric oxide. thE PReSent inveNtion tHErEfORe also prOvIdeS metHODs of tReatINg And/or preVentinG CeLlS, tissue AnD/or orgAnS frOm rEactiVE freE radicAl and/or nItric OXide induced damAGe or injury.
The PReSENt INvenTioN provides suBstiTUted 4,9-DihyDRoCycLOpentA[imn]pHeNAnTHridine-5-ones, derivatiVeS thereOf and Their uses compOunds which INHIbit poly(aDP-rIBoSE) polymerase (xe2x80X9cPARpxe2x80x9d), compOSitions cOntaiNing thesE compoundS ANd methodS foR maKinG anD USiNg these PARP inHIBitoRs To treat, PreVent and/Or aMelIorAte ThE effects oF the condItIoNs DeScrIbed hERein.
The cOmPouNdS of The prESent inVentiOn arE bRoADly DescribED bY THe foLlOwIng FOrmUlA I: 
or a PharMAceUticallY acceptabLe sALt, hyDrAtE, prodruG, or mixtures thErEof, wherein:
r1 hYdrOgen, OH, HALogen, amiNo, or nitro;
R2 is independentLY, xe2x80x94TP, HydRogen, oH, haLogen, aminO, niTro, xe2x80X94SO2oh or aceTylamiNo;
wheReIn T IS One of 
p IS ZXe2x80X94(N(r3R4)), such as ZxE2X80X94N(R3r4), Z or a 5 Or 6 MembEred subStituted or unsubstiTUteD aromatic or noN-arOmatIC RiNg wHIcH ConTaINs 0, 1, 2 oR 3 HEteroatoms selecTed from the GrOUp Consisting OF O, N, s aNd a combInation Of two OR three oF O, N and S;
Q iS methylenE, hYdroXYMetHyl, carbonyL,  greater Than CHNH2, Nh, s,  greaTEr Than CXe2x80X94Oxe2x80x94
 and methods of, inhibitin g PARP act ivity  fo r t re atin g an d/or preventin g  cel lular, tissue and/or o rganda m ager es ultin g fromc el l dam ag eorde a th  dueto,  for ex ample, nec ros is  or apoptosi s .The compou nds  and composi tio ns ofth e p r esent  in venti on are specif ically us ef u l in a m eliorat i n g,  tre ating and/or prev e nt i ng neural tiss ue orce l ld a mag e,includingth at fo l lowingf oc a l isc h emia and repe rfusion inj u ry.  Gener al ly, inhibi tionof PAR P activityspar es the ce ll fro m  energy loss, p revent ing  ir reve r si bl e d ep o lar i za tio n  of  the neu ro ns  and,  thu s , p rovi des  neu ropro tection. Whil e n ot w i shi ng to  be b ound  b y any  mecha nisti ctheory, the inh ibit ion of PA RPac tiv it y byu se ofthe  co mpounds , compo s iti on s a nd  methods of the pr es e n tinventio n is b e li ev e d to pro te ctcell s ,  tiss ue a n dorgans b y prot e ct io n again st  the i ll -ef fec ts of reac tive f ree radi calsa nd nitric oxid e . The present in v e nt i on t her efore alsoprov i desmeth o ds  of treat ing a nd / or preventing cells, t is sue an d/ororgans from r eactive fr e e radicaland/ o rn itric oxide in duced  damage or injury.The p resent i nventionp r ovides s ubs tit ute d 4 , 9 -d ihydrocyclope n t a[im n] phenant hri dine-5- one s,der iva ti ves there of and t he ir  u se s c ompou n ds which  i nhi bi t p oly(A D P-ribo se) p olym er as e  (x e2x80x9 c PA R P xe2x 80 x9 d),com po sitio ns c o nta ining t hese comp oun d s an dme thods f or making and  u sing these  P ARP  inhib i t ors to t reat, prevent and/or am e liorate  th e eff ects  of the c ond itions  de s cribed  herei n.
Th ecom p o undso f  t hepr esent inve n t ion  arebr oadl y descr ibed by the follow i ngFormula I: 
o r a  pha r m ac eut i ca l lyac c ept a b le salt, hydrat e, prodrug ,o rmixtures t h ere of , where in:
R1hydro g en, OH,  halogen,  amino, o rnitr o ; 
R2  is indepe ndently,  xe2x80x9 4 TP, h y dr ogen,  OH , halo ge n,amino , nitr o , x e2x80 x94SO2 OH  or ac etyla mi no;
wher ein T is one of 
P is Z xe2x80 x94(N (R3 R4)), suc h a s  Zx e2x80x94N (R3R 4), Z or a  5or6 mem ber e d sub stit u te d o r  unsu bsti t uted arom a ti c o r no n-aromaticr i n g w hichcon t ains 0 , 1,  2 or 3 heteroato m s selected fro m th e gro upc onsi st ing of O, N, S  an da combinat io n of two or  three o fO , N a nd S;Q is m ethylen e ,  h y droxym ethy l,carbonyl,   g re a ter tha nCH N H2, NH , S,  greate r than Cxe2 x 8 0x94Oxe2x80x94
 and_methods of,_inhibiting PARP activity for_treating and/or_preventing_cellular, tissue_and/or_organ damage resulting_from cell damage_or death due to,_for example, necrosis_or_apoptosis. The compounds and compositions of the present invention are specifically useful in ameliorating,_treating_and/or preventing_neural_tissue_or cell damage, including that_following focal ischemia and reperfusion_injury. Generally,_inhibition of PARP activity spares the cell from_energy_loss, preventing irreversible_depolarization of the neurons and, thus, provides neuroprotection. While_not wishing to be bound by_any mechanistic theory,_the_inhibition_of PARP activity by_use of the compounds, compositions and_methods of the present invention is_believed to protect cells, tissue and organs_by protection against the ill-effects of_reactive free radicals and nitric_oxide. The_present invention therefore also provides_methods of treating_and/or preventing_cells, tissue and/or_organs from reactive free radical and/or_nitric oxide induced_damage or injury.
The present invention provides_substituted_4,9-dihydrocyclopenta[imn]phenanthridine-5-ones, derivatives thereof_and_their_uses compounds_which inhibit poly(ADP-ribose)_polymerase_(xe2x80x9cPARPxe2x80x9d), compositions_containing_these compounds and methods for making_and_using these PARP inhibitors to treat, prevent_and/or ameliorate the effects_of_the conditions described herein.
The_compounds of the present invention_are broadly described by the following_Formula I:_
or a_pharmaceutically acceptable salt, hydrate, prodrug, or mixtures thereof, wherein:
R1 hydrogen, OH,_halogen, amino, or nitro;
R2 is independently,_xe2x80x94TP, hydrogen, OH, halogen,_amino, nitro,_xe2x80x94SO2OH_or acetylamino;
wherein T_is_one of_
P is Zxe2x80x94(N(R3R4)), such as Zxe2x80x94N(R3R4), Z_or a_5 or 6 membered substituted or_unsubstituted aromatic or non-aromatic_ring_which contains 0, 1, 2 or_3 heteroatoms selected from the group_consisting of O, N, S_and_a_combination of two or three_of O, N and S;
Q is_methylene, hydroxymethyl, carbonyl,_ greater than CHNH2, NH, S, _greater_than Cxe2x80x94Oxe2x80x94