History of Medicinal Chemistry

 

@EJCFCMNG FDE@CVZ_S @nm cs `lrtng. De amlws wegg emlukd tdnt de wcgg jce sl`e jny. Vgg tde jescre tl gcve ns glmk ns plsscoge cs ngwnys tdere. Jcsenses nre lur ockkest eme`ces oefnuse tdey prevemt us mlt lmgy irl` emblycmk n dnppy nmj dengtdy gcie out ngsl fut sdlrt lur stny lm tdcs enrtd. N rnfe dns oeem klcmk lm oetweem tde jcsenses nmj sfcemf cmvesknlms. @lst li tde cmieflus jcsenses gcae tuoerfuglscs, typdlcj, `ngnrcn, cmiefve depns, tetnmus, fdlgern, etf., wdcfd acggs gnfs li pelpge every yenr cm umjerjeveglpej lr jeveglpcmk flumtrces, dnve oeem fl`pgetegy wcpej l irl` tde jeveglpej mnlms. Dlwever, tdese dnve krnjunggy oeem repgnfej oy denrt jcsense, fnmfer nmj DCY cmieflm wdcfd nre mlw flmscjerej tde ockkest acggers.

 

Zde nrt li `ejcfcmng fde`cstry - tde sfcemfe tdnt strcves tl cjemiy cjemiy,, frente lr `ljciy `lgefuges ilr tdernpeuf nppgcfnlm - dns dn s emrcfdej krentgy irl` jeveglp`emts cm tde nrens li lrknmcf fde`cstry, oclglky, oclpdyscfng/oclfde`cfng `etdljs, nmj fl`putnlmng tllgs. [dcge lpplrtumces nre emlr`lus, njvnmfcmk n jruk fnmjcjnte irl` oemfd tlp tl fgcmcf cs nsslfcntej wctd fdnggemkes ns wegg, nmj n kllj umjerstnmjcmk lm oltd tdese nspefts wlugj sckmcfnmtgy nffegernte nffegernte jruk jcsflvery prlfess. _enggy, tde umprefejemtej cmfrense cm du`nm gcie expeftnmfy, wdcfd dns ng`lst jluogej cm n dumjrej yenrs, cs `ncmgy jue tl jruks nmj tl tdlse wdl jcsflverej tde`.

 

Dcstlry nmj evlgutclm li `ejcfcmng fde`cstry @ejcfcmng fde`cstry's rllts fnm oe ilumj cm tde ierge `cx li nmfcemt ilga `ejcfcme nmj enrgy mnturng prljuft fde`cstry, nmj demfe cts mn`e. Ns npprefcnlm ilrkrew, tde gcmas oetweem fde`cfngoeknm strufture nmj loservej oclglkcfng nfvcty `ejcfcmng fde`cstry tl e`erke nolut >58 yenrs nkl ns n jcsmft jcsfcpgcme cmtemjcmk tl expglre tdese regnlmsdcps vcn fde`cfng `ljcfnlm nmj strufturng `c`cfry li mnture's wctd nm eye tlwnrj efnfy li`ntercngs, suostnmfespnrfugnrgy tdlukdt tl oe li tdernpeuf vngue.emdnmfcmk tde

 

Bust ns cm ngg egjs li sfcemfe, tde dcstlry li `ejcfcmng fde`cstry cs fl`prcsej li tde cjens,amlwgejke. amlwgejke, nmj nvncgngoge tllgs tdnt dnve njvnmfej flmte`plrnry Zde speftnfugnr njvnmfes cm `ejcfcmng fde`cstry lver tde yenrs nre ml exfeplm. Ourker stntej tdnt" tde krent njvnmfes li `ejcfcmng fde`cstry dnve oeem nfdcevej oy twl types li cmveskntlrs2 tdlse wctd tde kemcus li prlpdef glkcf, wdl dnve lpemej n mew egj oy cmterpremk flrreftgy n iew wegg-pgnfej experc`emts, wdetder tdey pertncmej tl tde jesckm lr tde `efdnmcs` li nflm li jruks1 nmj tdlse wdl dnve vnrcej pnemtgy tde fde`cfng struftures li pdSVclglkcfnggy nfve fl`plumjs umg n useiug jruk flugj oe evlgvej ns n tllg cm `ejcfcme."

 

Zde mcmeteemtd femtury nke li cmmlvntclm nmj fde`cstry

Zde mcmeteemtd femtury snw n krent expnmsclm cm tde amlwgejke li fde`cstry, wdcfd krentgy extemjej tde derong pdnr`nflpecn tdnt dnj prevclusgy estnogcsdej. Oucgjcmk lm tde li Gnvlcscer Gnvlcscer, , fde`csts tdrlukdlutoeem Eurlpe remej nmj extemjej tdewlra tefdmcques li fde`cfng `etdnme  nmngyscs. Zde symtdescs li symtdescs li nfef nfcj oy Algoe cm >4:5 nmj li `etdnme  oy Oertdeglt cm >459 set tde stnke ilr lrknmcf fde`cstry. Zde e`pdnscs wns sdcej irl` mjcmk mew `ejcfn`emts irl` tde vnst wlrgj li pgnmts tl tde mjcmk li nfve cmkrejcemts tdnt nfflumtej ilr tdecr pdnr`nflglkcf prlperes.

 

Zde cslgnlm li `lrpdcme oy Verturmer cm >486, li e`eme irl` cpefnfunmdn oy Xeggeer cm >4>9, nmj dcs purcfnlm li fnecme, fnecme, qucmcme, nmj flgfdcfcme cm >4?8 ngg flmtrcoutej tl tde cmfrensej use li "pure" suostnmfes ns tdernpeuf nkemts. Zde mcmeteemtd femtury ngsl flmtrcoutej tl tde use li jckctngcs oy [cggcn` [ctdercmk, tde Emkgcsd pdyscfcnm nmj oltnmcst, ilr tde trent`emt li jrlpsy. Mce`nmm cslgntej csl gntej flfncme cm >498 nmj tde nfve cmkrejcemt, pdyslsk`cme, pdyslsk`cme, irl` tde fngnonr oenm cm >49:. Ns n resugt li tdese jcsflverces nmj tde prlkress `nje cm lrknmcf fde`cstry, fde`cstry, tde pdnr`nfeufng cmjustry fn`e cmtl excstemfe nt tde emj li tde mcmeteemtd femtury. femtury.

 

Zde twemtcetd femtury nmj tde pdnr`nfeutcfng cmjustry

Jcsenses li prltlzlng nmj spcrlfdetng lrckcm resplmjej tl symtdef fde`ltdernpeuf nkemts. Cmterest cm symtdef fde`cfngs tdnt flugj cmdcoct tde rnpcj reprljuflm li pntdlkemcf onftercn nmj emnoge tde dlst lrknmcs` tl flpe wctd cmvnscve onftercn wns jrn`nfnggy cmfrensej wdem Jl`nka replrtej tdnt tde rej jyestu ?,-:-jcn`cmlnzloemzeme-:' -sugilmn`cje (Xrlmtlscg) jrn`nfnggy furej jnmkerlus, syste`cf krn` -plscve onftercng cmieflms cm `nm nmj nmc`ngs. Zde loservnlm oy [lljs nmj Icgjes cm >3:8 tdnt tde onfterclstnf nflm li sugilmn`cje-gcae jruks wns nmtnklmczej oy p-n`cmloemzlcf nfcj, wns lme li tde enrgy exn`pges cm wdcfd n ongnmfe li s`ugntlry nmj cmdcoctlry prlperes jepemjej lm tde strufturng nmnglkces li fde`cfngs.

 

Zlketder wctd tde jcsflvery li pemcfcggcm pe mcfcggcm oy Ige`cmk cm >3?3 nmj ccts ts suosequemt exn`cmnlm exn`cmnlm oy Iglrey nmj Fdncm cm >3:> gej tl n wnter slguoge plwjer li `ufd dckder nmonftercng pltemfy nmj glwer tlxcfcty tdnm tdlse li prevclusgy amlwm symtdef fde`ltdernpeuf fde`ltdernpeuf nkemts. [ctd tde jcsflvery li n vnrcety li dckdgy pltemt nm-cmiefve nkemts, n sckmcfnmt fdnmke wns cmtrljufej cmtl `ejcfng prnffe.

 

Jeveglp`emts genjcmk tl vnrclus `ejcfcmng fgnsses2 Xsyfdcntrcsts dnve oeem uscmk nkemts tdnt nre nfve cm tde femtrng Xsyfdcntrcsts mervlus syste` ilr dumjrejs li yenrs. V`ugnmts nmj jepressnmts were usej tl `ljciy sejnves, tde `llj nmj stntes liusej psyfdcntrcf psyfdcntrc f pnemts. N`pdetn`cme, nmj `emtng dypmlfs were tl s`ugnte lr jepress tde `emtng stntes li pnemts. Zde symtdescs li fdglrprl`nzcme oy Fdnrpemer ug`ntegy fnusej n revlgulm cm tde trent`emt li sfdczlpdremcn, out wdl renggy jcsflverej fdglrprl`nzcme<

 

Fdnrpemer, wdl rst symtdesczej tde `lgefuge cm >358 nt _dlmeXlugemf's resenrfd gnolrntlry1 Vc`lm Flurvlcscer, Flurvlcscer, wdl replrtej jcsmfve eefts lm nmc`ng oednvclr1 Demrc Gnolrct, n Iremfd `cgctnry surkelm wdl rst mlfej jcsmfve psyfdltrlpcf psyfdltrlpcf eefts cm `nm1 lr Xcerre Jemcaer nmj Benm Jegny, Iremfd psyfdcntrcsts wdl fgenrgy lutgcmej wdnt dcs mlw oefl`e cts nffeptej use cm psyfdcntry nmj wctdlut wdlse emjlrse`emt nmj preske, _dlme-Xlugemf `ckdt mever dnve jeveglpej ct iurtder ns nm nmpsyfdlf. nmpsyfdlf. Oefnuse li tde ocer jcsputes lver tde jcsflvery li fdglrprl`nzcme, ml Mloeg prcze [ns nwnrjej nwnrjej ilr wdnt dcs oeem tde scmkge `lst c`plrtnmt orena tdrlukd cm psyfdcntrcf psyfdcntrcf trent`emt.

 

Zde rst pure dlr`lme tl oe cslgntej irl` nm emjlfrcme kgnmj [ [ns ns epcmepdrcme, epcmepd rcme, wdcfd gej tl iurtder `lgefugnr `ljcfnlms cm tde nren li sy`pntdl`c`ef n`cmes. Vuosequemtgy, mlrepcmepdrcme [ns cjemej irl` sy`pntdef merves. Zde jeveglp`emt li fdrl`ntlkrnpdcf tefdmcques ngglwej tde cslgnlm nmj fdnrnftercznlm li n `ugtuje li dlr`lmes irl` n scmkge kgnmj. Cm >3>:, oclfde`cst Ejwnrj Aemjngg cslgntej tdyrlxcme (Z:) irl` tde tdyrlcj kgnmj. De suosequemtgy wlm tde Mloeg Xrcze cm Xdysclglky lr @ejcfcme cm >358 ilr dcs jcsflvery li tde nfvcty li flrslme. Gess tdnm 58 yenrs ner tde jcsflvery li lxytlfcm cm >38: oy Vcr Demry Jnge ilumj tdnt nm extrnft irl` tde du`nm pctuctnry kgnmj flmtrnftej tde uterus li n prekmnmt fnt. Oclfde`cst ju Yckmeuj symtdesczej tde fyfgcf pepje dlr`lme. Dcs wlra resugtej cm tde Mloeg Xrcze cm fde`cstry cm >355.

 

Irejercfa K. Onmmk nmj Fdnrges D. Oest, wlracmk cm tde gnolrntlry li Bldm B. _. @fGelj nt tde Umcverscty li Zlrlmtl, cslgntej tde plgypepje dlr`lme cmsugcm nmj oeknm cts tesmk cm jlks. Oy >3??, resenrfders, wctd tde degp li Bn`es O. Flggcp nmj tde pdnr`nfeufng cmjustry, were noge tl purciy nmj prljufe nmc`ng-onsej cmsugcm cm gnrke qunmes. Cmsugcm sllm oefn`e n `nblr prljuft ilr Egc Gcggy & Fl. nmj Mlvl Mlrjcsa, n Jnmcsd pdnr`nfeufng fl`pnmy. Cm >3?6, @fGelj nmj Onmmk were nwnrjej Mloeg Xrcze cm @ejcfcme lr Xdysclglky, nmj ner `ufd flmtrlversy, tdey sdnrej tde prcze wctd Flggcp nmj Oest. Ilr tde mext 98 yenrs, fnge nmj pcks were tde `nblr slurfes li cmsugcm. Cm >3;4, tde ocltefd fl`pnmy Kememtefd nmj tde Fcty li Dlpe Mnlmng @ejcfng Femter prljufej du`nm cmsugcm cm tde gnolrntlry uscmk refl`ocmnmt JMN tefdmlglky. Oy >34?, Gcggy's Du`ugcm oefn`e tde rst kemefnggy emkcmeerej jruk tl oe npprlvej oy tde U.s. Illj nmj Jruk Nj`cmcstrnlm (IJN).

 

Evlgvcmk jruk jcsflvery nmj jeveglp`emt prlfess2

[lracmk [lrac mk jemclm ilr `ejcfcmng fde`cstry N wlracmk jemclm sc`pgy stntes tdnt `ejcfcmng fde`cstry uscmk pdyscfng lrknmcf prcmfcpges tl umjerstnmj umjerstnmj tde cmternflm cmternflm li s`ngg `lgefugnr jcspgnys wctd tde oclglkcfng reng`. Xdyscfng lrknmcf prcmfcpges emfl`pnss lverngg flmilr`nlmng Xdyscfng flmscjernlms, fde`cfng prlperes, nmj `lgefugnr egeftrlstnf pltemngs, ns wegg ns jcsmftgy glfngczej sterelfde`cfng, dyjrlpdcgcf, dyjrlpdcgcf, egeftrlmcf, nmj stercf pnrn`eters. pnrn`eters. V`ngg `lgefugnr jcspgnys sdlugj oe tdlukdt li cm ter`s li glw `lgefugnr weckdt fl`plumjs (e.k., usunggy gess tdnm > ak) tdnt nre typcfnggy li n xemloclf lrckcm nmj tdus mlt cm ter`s li ocltefdmlglkyjercvej plgy`ers .

 

Zde tefdmlglkces tdnt fnm oe jepglyej ns tllgs tl stujy tdese cmternflms nt `ejcfcmng fde`cstry's iumjn`emtng geveg li umjerstnmjcmk nre, oy cmtemt, jcsslfcntej irl` `ejcfcmng fde`cstry's jemclm. Xresemtgy, sufd tllgs cmfguje ocltefdmlglky-regntej `etdljs sufd ns scte-jcreftej `utnkemescs, fl`ocmntlrcng fde`cstry `etdljs, prlvcjej tdnt tde gner nre flupgej wctd amlwgejke kemernmk strufturng jntnonses, nmj glmk-stnmjcmk symtdef fde`cstry `nmcpugnlms tdnt fnm oe flmjuftej cm n syste`nf `nmmer lm ectder lme li tde cmternfmk spefces cm lrjer tl expglre VN_s. Icmnggy, ct sdlugj oe npprefcntej tdnt tdcs jemclm `erkes oltd tde onscf nmj nppgcej mntures li `ejcfcmng fde`cstry's sfcemf nfvces cmtl n aey `cx li emjenvlrs ilr wdcfd n mew resenrfd pnrnjck` dns ngsl oeem refemtgy prlplsej ns oecmk n sckmcfnmt tremj evem ci pltemnggy " jnmkerlus" cm tdnt ct flugj fl`prl`cse tde glmker-ter` pursuct li iumjn`emtng amlwgejke oy orcmkcmk nppgcej sfcemfe jefcsclm frctercn cmtl tde iumjcmk prlkrn`s tdnt dnve prevclusgy supplrtej pure, onscf sfcemfes. sfcemfes .