
(+)-see. pii. see. aii.

(+)-see. pii. see. aii. (noken, 3α-carbomethoxy-4β-(4-chlorophenyl)-"aine"-methylpyperidine urf see. tii. dii. pii. 31,446
) heey pethidine (eka opioid jyamadhye aine. dii. aar. aay. kriya asatat) aanee aar. tii. aay.-31 sarkhech eka uttejak aushadh aahe, parantu nokenmadhye aar. tii. aay.-31 chya tropen sangadyachya done-carbon pulacha abhav aahe. heey sanyug pratham kokencha paryayi agent mhanoon vikasit karnyat aale hote.
tevhapasoon anek paryayi phenylpyperidine derivativescha shodh lagla aahe, jyamule methylphenidate, maperidine aanee modafinil sarkhya itar samaan renunsah moolbhut noken sanrachaneche sankaran karoon kriyakalap profile aanee sambhavya anuprayoganchya shrenisah derivatives eka mothe kutumb tayar kele jaate. heey sanshodhanache eka mahattvapoorn kshetra aahe, jyavar barech kaam suru aahe aanee dazanbhar naveen sanyuge vikasit kelee gelee aahet, jaree ekahi adyap bajarat aaleli naheet.
noken kutumbat piperidine aadharit koken nakkalinche vividh prakar samavisht aahet. mool sanyug noken heey vyasanadhinatechya upcharasathi kokensathi paryayi aushadh vikasit karnyachya prayatnat vikasit kele gele hote aanee pranyanchya pratikrutinmadhye kokenla paryay mhanoon vaparale jaat asalyache aadhalun aale hote, tarr durupyogachi kshamata lakshaniyaritya qamee hotee.
parshvabhoomi.
kozhikovskyne 1998 madhye chlorines sanyug nondavale asale taree, platidware yachya aadhi sadhya phenylchi nond karnyat aalee hotee.
heey sanyug tayar karnyache naveen marg astitvat asale taree, parshvabhoomi hii ercoline rasayanshastratun udbhavate. eae.jee. see. aine. ess. rasayananchya yaa kshetratun paroxetin ("paxil") aanee phemoxetin dekhil yetat. heey serotonin aadharit avasadarodhi, paxil "aine"-normethylchya babatit dekhil majkuranusar kahee acetylcholinergic aahet.
kozhikovskichya shikavanukinmadhun vyasanadhinatevar upchar karnyasathi aanakhi noken derivatives vikasit kele geleh smith visheshtah sangato qee nokenche butyrophenone analogue eka sakriy agent aahe, tasech pathelimide prakarche alchelamino agents nirdisht karate.
pudhil aadhar eka scale-up prakriya dete jee ercolinever dekhil avalambun asate, jeey vishari aanee aadhich sakriy aushadhopacharayukt meeth aaheh
pieter meltzerne tayar kelele ketanserin analogue sanshleshanachi purnapane vegali paddhat vaparteh jee. ess. keey. 1360707eff. sathee barich varshe aadhi teech prakriya vaparali jaat hotee aanee hii prakriya aadhipasoon aar. tii. aay. dirultropenmadhun dnyat hotee. asha prakare, yaa paddhati aata kalemadhye suprasiddha aahet aanee prarambhik sahitya mhanoon ercolinechya vaparavar avalambun asane aavashyak nahee.
udaharanarth, worner-lambert butler sanshleshan 4-phenylnicotinic aaml prarambhik samagri vaparteh
3 ', 4'-dichloro vakili.
uddhrut qee 3 ', 4'-dichlorophenylne sudharanyachi thyu paddhat aata kalemadhye suprasiddha aahe aanee mothya pramanat paytant keleli aahe.
aushadhashastra.
koken, (-)-cis-cpca aanee (+)-cpca heey dopamine vahkala bandhatat aanee dopamineche sevan rokhatat, undiranmadhye motor kriyakalap uttejit karatat aanee bhedbhav chachanyanmadhye kokencha purnapane paryay banatat. (-)-cis-cpca kinwa (+)-cpca saha purv upchar kelyane undaranmadhye kokenche bhedbhavatmak uttejan vadhate. tathapi, anek farak aahet; piperidine derivatives locomotor uttejak parinam kokendware prerit prabhavanpeksha khoopach qamee aahet aanee undaranvar (-)-cis-cpca kinwa (+)-cpca vaparoon purv upchar kelyane koken prerit aakadi vadhat naheet aanee pratyakshat koken prerit locomotor uttejana qamee hote. (-)-cis-cpca isomerche kokensarkhech balkat karnare parinam asatat, jeey undaranmadhil nishchit-gunottar swayam-prashasana chachanyandvare darshavile gele aahet, parantu (+)-cpca chey doses-pratisad vakr sapat asate aanee tyachpramane (-)-cis-cpca aanee kokenche 'dandatmak pratisad' madhye jawaljawal samaan break point hote (?) swayam-prashasana chachani, (+)-see. pii. see. aii. chaa break point itar konatyahi aushadhachya tulanet qamee hota.
locomotor aanee methamphetamine bhedbhav chachanyanmadhye (+)-see. pii. see. aii. chee samanyatah qamee parinamkarakta, heey done isomerschya detsathi sertchya sapeksh bhinn nivadakatemule houu shakate. mhanjech, jarr serotonin receptor sakriy karane kamal karyakshamatesathi aavashyak asel, tarr (-)-cis-cpca aanee (+)-cpca madheel antar heey nirikshan kelelya aushadhashastratil farkancha hishob karnyat yogdan denari bhoomika bajavu shakate. tii. emm. pii. (methylphenidate) sarkhya catecholamine nivadak aushadhanmadhye yogya durupyogachi kshamata asalyache nondavale gele aahe, tyamule (+)-see. pii. see. aii. majboot swayam-prashasanachya pravruttila qaa aakarshit karat nahee heey mojane sope nahee.
sambhavya spashtikaran asey asoo shakate qee noken pradhanyane Âdat laa bandhato, asha paristhitit too kokenpeksha kahise vegale vagane apekshit asel. kahee prakarcha collinergic prabhav dekhil pratikool asoo shakato. udaharanarth, benztropin analogchi muscarinic kriya tyanchi balkat karanyachi kshamata maryadit karnyasathi olakhali jaate. aayan-vahini kriyakalap haah aanakhi eka ghatak aahe jyacha vapar aushadhashastratil kahee farak spasht karnyasathi keela jaau shakato.
koken aanee yaa piperidine nakkalinmadhil kahee farkansathi sigma receptor kriyakalap dekhil karanibhoot asoo shakatat (aar. matsumoto, ityadi. 2001, (ping aanee tero, 2003 rev). sigma receptors heey koken, methylphenidate, methamphetamine (udaa. guyen, aanee itar. 2005), aanee fencyclidine dekhil yaa majjatantuchya lakshyashi jodalele aahet. yaa receptorchi vadhati samaj alikadech tyachya aushadhashastravar aadharit eka naveen jahirat nondavali gelee.
thodakyat, (+)-see. pii. see. aii. chee kruntakanmadhil halchal vadhavanyasathi kokenpeksha qamee kshamata aanee parinamkarakta aahe. (+)-see. pii. see. aii. heey koken prashikshit pranyanmadhye purnapane kokensarkhe asale taree, keval aanshik methamphetaminesarkhe bhedbhavpurn uttejak parinam nirman karnyat yashasvi hote. (+)-see. pii. see. aii. madhye nishchit aanee pragatishil gunottaradvare moolyankan kelyapramane kokenpeksha qamee balkat karanyachi kshamata aahe 4 undaranmadhil swayam-prashasana chachanya, recess makadanni pushti kelelya tyachya balkat prabhavansah. shivay, (+)-see. pii. see. aii. matra koken-prerit halchalinvar avalambun rahoon virodh karate aanee kokenchya qamee matrechya bhedbhavpurn uttejak prabhavanna ball dete. (+)-see. pii. see. aii., kokenchya ulat, koken-prerit aakadi vadhavat nahee. heey parinam asey soochit karatat qee (+)-see. pii. see. aii. kokenchya kahee vartanukichya krutinchi purnapane nakkal karate, tarr itaranmadhye kamkuvat aanshik agonistsarkhe karya karate, jyat koken-prerit halchalinmadhye vaadh qamee karanyachi aanee undiranmadhye sakaratmak balkat karnara agent mhanoon kaam karanyachi kshamata samavisht aahe. asha prakare, (+)-see. pii. see. aii. chee kokenchya vyasanadhinatechya upcharanmadhye sambhavya upayuktata asoo shakate aanee tee maulyavan aushadhashastriy mahitee dekhil deu shakate, jyamule kokenchya krutichya yantranebaddalchi aapali samaj adhik vadhate, kaaran tee itar sambandhit darry renunpeksha moolbhut farak darshavate.
rasayanshastra.
sanshleshanache marg.
ericoline marg methylecgonidinepasoon suru honanya aar. tii. aay.-31 sarkhach jaato. trudel yogya prakriyesathi payabharani karato, jee nantar ess. see. eff. dware mothya pramanat paytant karnyat aalee hotee.
paytant kelelya paddhati nondavalya gelya
platty aanee clarkchya purvichya aitihasik prayatnanchya tulanet 3 saiddhantik sudharanah 
ester aanee amainmadhye badal.
naveen aine-aanee 3aii-sudharit noken analogchi malika sanshleshit kelee gelee aanee undaranmadhil tyanchya ess. aine. dii. aar. kriyakalap aanee vartanukichya gunadharmansathi tyanchi chachani kelee gelee.
monomine vahatukdaransathi purvanirdharit shakti aanee nivadaktesah legandschee tarksangat rachana yaa lakshyanchya 3 dii sanrachanebaddalachya dnyanachya abhavamule adthala aanate. jyaa prakarananmadhye lakshyit prathinanmadhye bandhanyachya jaagechi 3dii rachana changlya prakare paribhashit keleli nahee, jase qee monoamine vahak prathinanchya babatit aahe, tethe pharmacophore vikasit karnyasathi ligand-aadharit rachana karata yete. mhanjech, aushadhshastriyadrushtya samaan sanyuganchya malikechya sanrachanatmak gunadharmancha abhyas karoon, pharmacophoreshy sambandhit gruhitak tayar kele jaau shakate. bahutek shaktishali tropen-aadharit avarodhak, ink. koka, vahak bandhanyachya jageshi kiman 3 pramukh parasparkriya karatat asey manale jaateh moolbhut nitrogenver eka ionic kinwa etch-bandh parasparkriya, ester gatacha eka dvidhruviy-dvidhruviy kinwa etch-bandh parasparkriya aanee lipophilic bandhanyachya pockets eril gatacha parasparkriya. heey model naveen piperidine-aadharit dett avarodhakchya rachnesathi yashasviritya vaparale gele, jeey utpadan karnyasathi aarthikdrushtya parvadanare aahe.
jaree (+)-see. pii. see. aii. chya inn vivo chayapchayamadhye aine-demethylation, sambandhit mukt aamlasathi chayapachay, serve monoamine vahatukdaranvar sanyug nishkriy karnyasathi samavisht asanyachi shakyata aahe, kadachit 'inn vivo' haah pramukh marg asel. chayapachay kriyandvare chayapachay talhata yete assa tark keela jaat asey qee ester gatala jaiv-isosteric gatane badaloon chayapachay kriyansathi adhik sthir aahe. mageel abhyasanmadhye asey aadhalun aale hote qee auxadiazole jaree kokensarkhe asale taree chayapachay mand gatine hott asalyamule lakshaniyaritya dirgh kalavadhichi kriya darshavate. sarvasadharanpane, sambandhit aine-methyl sanyuganchya tulanet, norpiperidine cert/netwar vadhiv kriyakalap pradarshit kele aanee detwar fakt kirkol badal kele.
koken, ester 1aii, alcohole 2aii aanee norrester 1bii madheel eka manoranjak farak mhanje undaranmadhil gatishil kriyakalap chachanyanmadhye nantarchi done sanyuge kokenpeksha lakshaniyaritya jaast kaal karya karatat. alcohole 2aii aanee auxadiazole 3aii sarkhya sanyuganpasun dirghkal krutee apekshit asali taree, jyat 3α ester gut nasla aahe aanee tyamule chayapachay karane adhik katheen aahe, norrester 1beesaaathii heey apekshit nahee, kaaran 3α ester gut kokenchya ester gatapramane sahajpane hydrolyse keela pahije aanee 1aii. aine-demethylation aanakhi eka parinam mhanje 1beachii prarambhik avasadkari kriya aanee tyanantar vilambit locomotor uttejana, jee gaba receptors kinwa emm. jee. ell. yuu. 5 saha parasparsanvadamule asoo shakate.
3β-badali noken legand rachana.
purvichya abhyasat asey aadhalun aale hote qee 3α-emido aanee 3α-auxadiazoil noken legands, jeey ester karyatmak gatachya tulanet adhik sthirata thevatat aanee tyamule sambhavya upchar mhanoon adhik aakarshak asatat, teey nishkriy aahet. yaa parinamamule asey gruhitak tayar jhaale qee piperidine ringchya 3α-sthitichya jawal asalele dett aanee jaale bandhanyache thikan sankshipt aahe aanee 3-pratisthapit 1,2,4-oxadiazolil gatansarkhe avjad, sterically aucluded paryay samavoon gheu shakat nahee. methylene spacerchya vaparamule parinami yenanya renunvar monoamine vahak bandhaniche sambandh sudhartil assa tark hota.
see2-see3 sanyuge see1 sanyuganpeksha adhik sakriy asanyache eka sambhavya kaaran mhanje see2-see3 legandschya adhik lavchik 3α-parishishtat upasthit asalela dhruviy gut piperidine ringchya jawal asalelya bandhansthalachya pratikool parasparsanvad talhanyas saksham aahe. yach karanastav see2-see3 maliketil upang adhik jawalun, parantu tantotant nahee, adhik sakriy "ss" aadharit legandschya bandhan paddhatichi nakkal karoo shakate aanee kadachit tropen aadharit sanyuganmadhye dekhil hastantarit houu shakate.
see1 aanee see2-see3 maliketil farak adhik changlya prakare samajoon ghenyasathi, sanyuge urja qamee kelee gelee aanee wiin-35,428 varr lavchikpane adhiropit kelee gelee. parinami aachchadan darshavite qee keval see2-see3 legands eka rachana swikaranyas saksham aahet jyamadhye 3α-paryay dhruviy gut wiin 35428 madheel 2β-dhruviy gatachya nikatvarti sthanavar kabja karato.
nokenah gandhak upang.
sanyug 16eae
pharmacophore.
koken aanee phenyltropensathy samanyatah manyataprapt pharmacophore modelmadhye moolbhut nitrogen aanee see-2 paryayatil ester gatache done sthir vidyut parasparkriya aanee see-3 eril gatache eka hydrophobic parasparkriya yancha samavesh hoto. heey model vadgrast tharale aahe kaaran kahee sanyuganmadhye uchch bandhan sambandh aanee marchya pratibandhasathi moolbhut aine kinwa ester gut aavashyak navhata. tyaeivaji, see-2 carbonchya parisarat hydrophobic pockett astitvat thevanyacha prastav thevanyat aala hota. caroll aanee itar.tathapi, nantarchya abhyasat see-2 beeta-sthiteet sthir vidyut parasparsanvadasathi aanakhi purave pradan kele.
dett binding sitesathi prastavit itar modelmadhye 3β-pratisthapit phenyltropen analogsathi resheey fashion binding pockett aanee 3α-pratisthapit piperidine ringpasoon door 5.5-10 chya aaspas pratibandhit shankuchya aakaracha pradesh samavisht aahe. lakshaniy baab mhanje, diameric piperidine-aadharit ester aanee amideschya detmadhye uchch shaktine asey suchavale qee done piperidine units ekatra karnara lavchik linker tyachi abhimukhata samayojit karnyas aanee bandhansthalachya pratikool parasparsanvad talhanyasathi saksham hota. yaa serve puravyanchya olee soochit karatat qee prastavit pharmacophore modelspeksha dett binding site adhik klisht aahe.
dett binding siteche tapasheel ughad karnyachya prayatnat, anek 3 dii-kyusar abhyas kele gele. phenyltropenavar laksh kendrit karananya anek kyusar/compha abhyasanni assa nishkarsh kadhala qee tropen ringchya 3β-pratisthapan aanee phenyl ringchya parra-sthitichya aaspaschya pradeshat vadhaleli nakaratmak sthir vidyut kshamata matsla pratibandhit karnyat uchch shaktila anukool aahe. theek aahe aanee itar. detshee bandhanyat aanee daa rii-uptech rokhanyat tropenchya 3β-pratisthapananchya bhoomikecha abhyas keela. tyanchya compha modelane soochit kele qee 3β-paryayi bandhan sthal heey baryl-aakarache aahe aanee hydrophobic parasparsanvad heey bandhanamadhye pramukh yogdan detat, jeey neuman aanee itaranni nondavalelya 3α-paryayi tropen analogchya abhyasashi susangat aahe. neuman aanee saha-lekhakanni aine-pratisthapit tropensacha dekhil abhyas keela aanee assa nishkarsh kadhala qee aine-pratisthapakacha dates steric parasparkriya haah bandhan sambandhasathi eka pramukh ghatak aahe.