Medicinska hemija — разлика између измена

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Medicinska hemija ili farmaceutska hemija je disciplina na raskršću hemije, farmakologije, i biologije koja obuhvata dizajn, sintezu i razvoj farmaceutiskih lekova. Medicinska hemija se bavi identifikacijom, sintezom i razvojem novih hemijskih entiteta podesnih za terapeutsku upotrebu. Ona takođe obuhvata izučavanje postojećih lekova, njihovih bioloških osovina, i njihovih kvantitativnih odnosa strukture i aktivnosti (QSAR).^[1]^[2]^[3]^[4] Medicinska hemija je visoko interdisciplinarna nauka koja kombinuje organsku hemiju sa biohemijom, računarskom hemijom, farmakologijom, farmakognozijom, molekularnom biologijom, statistikom, i fizičkom hemijom.

Jedinjenja koja se koriste kao lekovi su prvenstveno organska jedinjenja, koja mogu da budu mali organski molekuli (e.g., atorvastatin, fluticasone, clopidogrel) i biopolimeri (infliximab, erythropoietin, insulin glargine), the latter of which are most often medicinal preparations of proteins (natural and recombinant antibodies, hormones etc). Međutim, i za neorganska jedinjenja i jedinjenja koja sadrže metale je nađeno da mogu da budu korisni lekovi. Na primer, cisplatin serija kompleksa koji sadrže platinu se koristi u tretmanu raka, i litijum bazirani medikamenti imaju dugu tradiciju u lečenju niza mentalnih oboljenja. The discipline of Medicinal Inorganic Chemistry investigates the role of metals in medicine (metallotherapeutics), which involves the study and treatment of diseases and health conditions associated with inorganic metals in biological systems. There are several metallotherapeutics approved for the treatment of cancer (e.g., contain Pt, Ru, Gd, Ti, Ge, V, and Ga), antimicrobials (e.g., Ag, Cu, and Ru), diabetes (e.g., V and Cr), broad-spectrum antibiotic (e.g., Bi), bipolar disorder (e.g., Li).^[5]^[6] Other areas of study include: metallomics, genomics, proteomics, diagnostic agents (e.g., MRI: Gd, Mn; X-ray: Ba, I) and radiopharmaceuticals (e.g., ^99mTc for diagnostics, ¹⁸⁶Re for therapeutics).

In particular, medicinal chemistry in its most common practice—focusing on small organic molecules—encompasses synthetic organic chemistry and aspects of natural products and computational chemistry in close combination with chemical biology, enzymology and structural biology, together aiming at the discovery and development of new therapeutic agents. Practically speaking, it involves chemical aspects of identification, and then systematic, thorough synthetic alteration of new chemical entities to make them suitable for therapeutic use. It includes synthetic and computational aspects of the study of existing drugs and agents in development in relation to their bioactivities (biological activities and properties), i.e., understanding their structure–activity relationships (SAR). Pharmaceutical chemistry is focused on quality aspects of medicines and aims to assure fitness for purpose of medicinal products.^[7]

Proces razvoja lekova

Otkrivanje

Otkrivanje je identifikacija novih aktivnih jedinjenja, koja se često nazivaju „pogoci“. Oni se tipično nalaze testiranjem velikog broja jedinjenja (kolekcija jedinjenja) za željene biološke osobine.^[8] Dok postoje brojni pristupi identifikaciji pogodataka, neke od najuspešnijih tehnika su zasnovane na hemijskoj i biološkoj intuiciji koja je razvijena tokom godina rigoroznog hemijsko-biološkog treninga. Inicijalna pozitivna jedinjenja mogu da potiču od nalaženja novih vidova primene postojećih agenasa u novim patološkim procesima,^[9] i od zapažanja bioloških dejstava novih ili postojećih prirodnih produkata, kao što su biljke,^[10] životinje, ili gljive.^[11] Pogoci mogu takođe da dolaze iz sintetičkih hemijskih kolekcija, kao što su kolekcije kreirane putem kombinatorne hemije, ili istorijskih kolekcija hemijskih jedinjenja, koje se masovno testiraju za aktivnost na određenom biološkom cilju.

Optimizacija

Sledeći stupanj u razvoju lekova su dalje hemijske modifikacije s ciljem poboljšanja bioloških, ADME i fiziko-hemijskih osobina date kolekcije jedinjenja. Hemijske modifikacije mogu da poboljšaju prepoznavanje i geometriju vezivanja (farmakofore) kandidata, njihov afinitet i farmakokinetiku, ili njihovu reaktivnost i stabilnost ka metaboličkoj degradacije. Brojni metodi se koriste za kvalitativno i kvantitativno predviđanje metaboličke stabilnosti^[12], kao i niza drugih ADMET osobina. Modeli kvantitativnih odnosa strukture i aktivnosti (QSAR) zajedno sa farmakofornom analizom pomažu nalaženje vodećih jedinjenja, koja pokazuju najveću potentnost i selektivnost, imaju najbolje farmakokinetičke osobine i najmanju toksičnost.

Razvoj

Završni stupanj se sastoji od pripreme vodećih jedinjenja za upotrebu u kliničkim ispitivanjima. Razvoj obuhvata optimizaciju sintetičkog pristupa za proizvodnju većih količina materijala, i pripremu podesne formulacije leka.

Reference

^ Thomas L. Lemke; David A. Williams, ур. (2007). Foye's Principles of Medicinal Chemistry (6. изд.). Baltimore: Lippincott Willams & Wilkins. ISBN 0781768799.
^ Hardman JG, Limbird LE, Gilman AG (2001). Goodman & Gilman's The Pharmacological Basis of Therapeutics (10. изд.). New York: McGraw-Hill. ISBN 0071354697. doi:10.1036/0071422803.
^ Davis A, Ward SE, ур. (2015). Handbook of Medicinal Chemistry: Principles and Practice. Royal Society of Chemistry. ISBN 978-1-78262-419-6. doi:10.1039/9781782621836.
^ Barret R (2018). Medicinal Chemistry: Fundamentals. London: Elsevier. ISBN 978-1-78548-288-5.
^ Hanif M, Yang X, Tinoco AD, Plażuk D (2020-05-28). „Editorial: New Strategies in Design and Synthesis of Inorganic Pharmaceuticals”. Frontiers in Chemistry. 8: 453. Bibcode:2020FrCh....8..453H. PMID 32548093. doi:10.3389/fchem.2020.00453 .
^ Anthony EJ, Bolitho EM, Bridgewater HE, Carter OW, Donnelly JM, Imberti C, et al. (новембар 2020). „Metallodrugs are unique: opportunities and challenges of discovery and development”. Chemical Science. 11 (48): 12888—12917. doi:10.1039/D0SC04082G.
^ Roughley SD, Jordan AM (мај 2011). „The medicinal chemist's toolbox: an analysis of reactions used in the pursuit of drug candidates”. Journal of Medicinal Chemistry. 54 (10): 3451—3479. PMID 21504168. doi:10.1021/jm200187y.
^ Hughes, Jp; Rees, S; Kalindjian, Sb; Philpott, Kl (1. 3. 2011). „Principles of early drug discovery”. British Journal of Pharmacology (на језику: енглески). 162 (6): 1239—1249. ISSN 1476-5381. PMC 3058157 . PMID 21091654. doi:10.1111/j.1476-5381.2010.01127.x.
^ Johnston, Kelly L.; Ford, Louise; Umareddy, Indira; Townson, Simon; Specht, Sabine; Pfarr, Kenneth; Hoerauf, Achim; Altmeyer, Ralf; Taylor, Mark J. (1. 12. 2014). „Repurposing of approved drugs from the human pharmacopoeia to target Wolbachia endosymbionts of onchocerciasis and lymphatic filariasis”. International Journal for Parasitology: Drugs and Drug Resistance. Includes articles from two meetings: "Anthelmintics: From Discovery to Resistance", pp. 218--315, and "Global Challenges for New Drug Discovery Against Tropical Parasitic Diseases", pp. 316--357. 4 (3): 278—286. PMC 4266796 . PMID 25516838. doi:10.1016/j.ijpddr.2014.09.001.
^ Cragg, Gordon M.; Newman, David J. (1. 6. 2013). „Natural products: A continuing source of novel drug leads”. Biochimica et Biophysica Acta (BBA) - General Subjects. 1830 (6): 3670—3695. PMC 3672862 . PMID 23428572. doi:10.1016/j.bbagen.2013.02.008.
^ Harvey, Alan L. (1. 10. 2008). „Natural products in drug discovery”. Drug Discovery Today. 13 (19–20): 894—901. PMID 18691670. doi:10.1016/j.drudis.2008.07.004.
^ Smith, J.; Stein, V. (2009). „SPORCalc: A development of a database analysis that provides putative metabolic enzyme reactions for ligand-based drug design”. Computational Biology and Chemistry. 33 (2): 149—159. PMID 19157988. doi:10.1016/j.compbiolchem.2008.11.002.

Literatura

D. Radulović, S. Vladimirov, Farmaceutska hemija I deo, Farmaceutski fakultet, Beograd, 2005.
S. Vladimirov, D. Živanov-Stakić, Farmaceutska hemija II deo, Farmaceutski fakultet, Beograd, 2006.
John M. Beale; John Block, ур. (2010). Wilson and Gisvold's Textbook of Organic Medicinal and Pharmaceutical Chemistry (Twelfth изд.). London, Philadelphia, New York,: Lippincott Williams & Wilkins. ISBN 978-0-7817-7929-6.
Watson, David G. (2005). Pharmaceutical Analysis: A Textbook for Pharmacy Students and Pharmaceutical Chemists (second изд.). Edinburg: Churchill Livingstone. ISBN 978-0-443-07445-5.
Foreman, John C.; Johansen, Torben; Gibb, Alasdair J. (2009). Textbook of Receptor Pharmacology, Second Edition. CRC Press. ISBN 9781439887578.
Brunton, Laurence (2011). Brunton, L. L.; Chabner, Bruce; Knollmann, Björn C., ур. Goodman and Gilman's The Pharmacological Basis of Therapeutics (12 изд.). New York: McGraw-Hill. ISBN 978-0-07-162442-8.
Whalen, Karen (2014). Lippincott Illustrated Reviews: Pharmacology.
Takács-Novák, K.; Avdeef, A. (август 1996). „Interlaboratory study of log P determination by shake-flask and potentiometric methods”. Journal of Pharmaceutical and Biomedical Analysis. 14 (11): 1405—13. PMID 8877846. doi:10.1016/0731-7085(96)01773-6.
Luch A, ур. (2009). Molecular, clinical and environmental toxicology. Springer. стр. 20. ISBN 978-3-7643-8335-0. Архивирано из оригинала 6. 8. 2020. г. Приступљено 21. 7. 2020.
Brater DC, Daly WJ (мај 2000). „Clinical pharmacology in the Middle Ages: principles that presage the 21st century”. Clinical Pharmacology and Therapeutics. 67 (5): 447—50. PMID 10824622. S2CID 45980791. doi:10.1067/mcp.2000.106465.
Hollinger, Mannfred A. (2003). Introduction to pharmacology. CRC Press. стр. 4. ISBN 0-415-28033-8. Архивирано из оригинала 17. 4. 2021. г. Приступљено 27. 6. 2015.
Rang HP (јануар 2006). „The receptor concept: pharmacology's big idea”. British Journal of Pharmacology. 147 Suppl 1 (S1): S9—16. PMC 1760743 . PMID 16402126. doi:10.1038/sj.bjp.0706457.
Maehle AH, Prüll CR, Halliwell RF (август 2002). „The emergence of the drug receptor theory”. Nature Reviews. Drug Discovery. 1 (8): 637—41. PMID 12402503. S2CID 205479063. doi:10.1038/nrd875.
Rang HP, Dale MM, Ritter JM, Flower RJ (2007). Pharmacology. China: Elsevier. ISBN 978-0-443-06911-6.
Masood N. Khan; John W. Findlay, ур. (2009). Ligand-binding assays development, validation, and implementation in the drug development arena. Hoboken, N.J.: John Wiley & Sons. ISBN 978-0470541494.
„Psychopharmacology | Psychology Today International”. www.psychologytoday.com. Архивирано из оригинала 24. 2. 2022. г. Приступљено 2020-07-23.
„What is Psychopharmacology”. ascpp.org. 29. 11. 2012. Архивирано из оригинала 23. 7. 2020. г. Приступљено 2020-07-23.
Gomez A, Ingelman-Sundberg M (април 2009). „Pharmacoepigenetics: its role in interindividual differences in drug response”. Clinical Pharmacology and Therapeutics. 85 (4): 426—30. PMID 19242404. S2CID 39131071. doi:10.1038/clpt.2009.2.
„What is Clinical Pharmacology?”. ascpt.org. Архивирано из оригинала 31. 10. 2021. г. Приступљено 31. 10. 2021.
„Posology, Factors Influencing Dose, Calculation of Doses”. pharmamad.com. 23. 1. 2019. Архивирано из оригинала 31. 10. 2021. г. Приступљено 31. 10. 2021.
„The Science of Pharmacology & Toxicology”. Faculty of Medicine, University of Toronto. Архивирано из оригинала 16. 7. 2019. г. Приступљено 16. 7. 2019.

Spoljašnje veze

„Medicinska hemija”. Приступљено 14. 4. 2011.
Američko hemijsko društvo, odeljenje medicinske hemije
Evropska federacija za medicinsku hemiju
Vodič za razvoj lekova
Pregled medicinske hemije

Naučni časopisi

[Foye-1] Thomas L. Lemke; David A. Williams, ур. (2007). Foye's Principles of Medicinal Chemistry (6. изд.). Baltimore: Lippincott Willams & Wilkins. ISBN 0781768799.

[Goodman_Gilman-2] Hardman JG, Limbird LE, Gilman AG (2001). Goodman & Gilman's The Pharmacological Basis of Therapeutics (10. изд.). New York: McGraw-Hill. ISBN 0071354697. doi:10.1036/0071422803.

[3] Davis A, Ward SE, ур. (2015). Handbook of Medicinal Chemistry: Principles and Practice. Royal Society of Chemistry. ISBN 978-1-78262-419-6. doi:10.1039/9781782621836.

[4] Barret R (2018). Medicinal Chemistry: Fundamentals. London: Elsevier. ISBN 978-1-78548-288-5.

[5] Hanif M, Yang X, Tinoco AD, Plażuk D (2020-05-28). „Editorial: New Strategies in Design and Synthesis of Inorganic Pharmaceuticals”. Frontiers in Chemistry. 8: 453. Bibcode:2020FrCh....8..453H. PMID 32548093. doi:10.3389/fchem.2020.00453 .

[6] Anthony EJ, Bolitho EM, Bridgewater HE, Carter OW, Donnelly JM, Imberti C, et al. (новембар 2020). „Metallodrugs are unique: opportunities and challenges of discovery and development”. Chemical Science. 11 (48): 12888—12917. doi:10.1039/D0SC04082G.

[JMC-7] Roughley SD, Jordan AM (мај 2011). „The medicinal chemist's toolbox: an analysis of reactions used in the pursuit of drug candidates”. Journal of Medicinal Chemistry. 54 (10): 3451—3479. PMID 21504168. doi:10.1021/jm200187y.

[8] Hughes, Jp; Rees, S; Kalindjian, Sb; Philpott, Kl (1. 3. 2011). „Principles of early drug discovery”. British Journal of Pharmacology (на језику: енглески). 162 (6): 1239—1249. ISSN 1476-5381. PMC 3058157 . PMID 21091654. doi:10.1111/j.1476-5381.2010.01127.x.

[9] Johnston, Kelly L.; Ford, Louise; Umareddy, Indira; Townson, Simon; Specht, Sabine; Pfarr, Kenneth; Hoerauf, Achim; Altmeyer, Ralf; Taylor, Mark J. (1. 12. 2014). „Repurposing of approved drugs from the human pharmacopoeia to target Wolbachia endosymbionts of onchocerciasis and lymphatic filariasis”. International Journal for Parasitology: Drugs and Drug Resistance. Includes articles from two meetings: "Anthelmintics: From Discovery to Resistance", pp. 218--315, and "Global Challenges for New Drug Discovery Against Tropical Parasitic Diseases", pp. 316--357. 4 (3): 278—286. PMC 4266796 . PMID 25516838. doi:10.1016/j.ijpddr.2014.09.001.

[10] Cragg, Gordon M.; Newman, David J. (1. 6. 2013). „Natural products: A continuing source of novel drug leads”. Biochimica et Biophysica Acta (BBA) - General Subjects. 1830 (6): 3670—3695. PMC 3672862 . PMID 23428572. doi:10.1016/j.bbagen.2013.02.008.

[11] Harvey, Alan L. (1. 10. 2008). „Natural products in drug discovery”. Drug Discovery Today. 13 (19–20): 894—901. PMID 18691670. doi:10.1016/j.drudis.2008.07.004.

[12] Smith, J.; Stein, V. (2009). „SPORCalc: A development of a database analysis that provides putative metabolic enzyme reactions for ligand-based drug design”. Computational Biology and Chemistry. 33 (2): 149—159. PMID 19157988. doi:10.1016/j.compbiolchem.2008.11.002.

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+{{Short description|Naučna grana hemija}}
-'''Medicinska hemija''' ili ''farmaceutska hemija'' je disciplina na raskršću [[hemija|hemije]], [[farmakologija|farmakologije]], i [[биологија|biologije]] koja obuhvata [[dizajn leka|dizajn]], [[organska sinteza|sintezu]] i razvoj [[Farmacija|farmaceutiskih]] [[lek]]ova. Medicinska hemija se bavi identifikacijom, sintezom i razvojem [[novi hemijske entitet|novih hemijskih entiteta]] podesnih za terapeutsku upotrebu. Ona takođe obuhvata izučavanje postojećih lekova, njihovih bioloških osovina, i njihovih [[kvantitativni odnos strukture i aktivnosti|kvantitativnih odnosa strukture i aktivnosti]] (-{QSAR}-).<ref name="Foye">{{FoyePrinciplesMedChem6th}}</ref><ref name="Goodman_Gilman">{{GoodmanGilman10th}}</ref>
+[[File:Bzr_pm.png|thumb|[[Pharmacophore|Farmakoforski]] model mesta vezivanja [[benzodiazepine|benzodiazepina]] u [[GABAA receptor]]u|250px]]
+'''Medicinska hemija''' ili ''farmaceutska hemija'' je disciplina na raskršću [[hemija|hemije]], [[farmakologija|farmakologije]], i [[биологија|biologije]] koja obuhvata [[dizajn leka|dizajn]], [[organska sinteza|sintezu]] i razvoj [[Farmacija|farmaceutiskih]] [[lek]]ova. Medicinska hemija se bavi identifikacijom, sintezom i razvojem [[novi hemijske entitet|novih hemijskih entiteta]] podesnih za terapeutsku upotrebu. Ona takođe obuhvata izučavanje postojećih lekova, njihovih bioloških osovina, i njihovih [[kvantitativni odnos strukture i aktivnosti|kvantitativnih odnosa strukture i aktivnosti]] (-{QSAR}-).<ref name="Foye">{{FoyePrinciplesMedChem6th}}</ref><ref name="Goodman_Gilman">{{GoodmanGilman10th}}</ref><ref>{{cite book|title=Handbook of Medicinal Chemistry: Principles and Practice | veditors = Davis A, Ward SE |doi=10.1039/9781782621836|isbn=978-1-78262-419-6|year=2015|publisher=Royal Society of Chemistry}}</ref><ref>{{cite book|title=Medicinal Chemistry: Fundamentals| vauthors = Barret R |location=London|year=2018|isbn=978-1-78548-288-5|publisher=Elsevier}}</ref> Medicinska hemija je visoko interdisciplinarna nauka koja kombinuje [[organska hemija|organsku hemiju]] sa [[biohemija|biohemijom]], [[računarska hemija|računarskom hemijom]], [[farmakologija|farmakologijom]], [[Farmakognozija|farmakognozijom]], [[molekularna biologija|molekularnom biologijom]], [[statistika|statistikom]], i [[fizička hemija|fizičkom hemijom]].
-Jedinjenja koja se koriste kao lekovi su prvenstveno [[Organsko jedinjenje|organska jedinjenja]], koja mogu da budu [[mali molekul|mali organski molekuli]] i [[biopolimer]]i. Međutim, i za neorganska jedinjenja i jedinjenja koja sadrže metale je nađeno da mogu da budu korisni lekovi. Na primer, [[cisplatin]] serija kompleksa koji sadrže [[platina|platinu]] se koristi u tretmanu raka, i [[litijum]] bazirani medikamenti imaju dugu tradiciju u lečenju niza mentalnih oboljenja.
+{{rut}}
+Jedinjenja koja se koriste kao lekovi su prvenstveno [[Organsko jedinjenje|organska jedinjenja]], koja mogu da budu [[mali molekul|mali organski molekuli]] (e.g., [[atorvastatin]], [[fluticasone]], [[clopidogrel]]) i [[biopolimer]]i ([[infliximab]], [[erythropoietin]], [[insulin glargine]]), the latter of which are most often medicinal preparations of proteins (natural and [[Recombinant DNA|recombinant]] [[antibodies]], [[hormones]] etc). Međutim, i za neorganska jedinjenja i jedinjenja koja sadrže metale je nađeno da mogu da budu korisni lekovi. Na primer, [[cisplatin]] serija kompleksa koji sadrže [[platina|platinu]] se koristi u tretmanu raka, i [[litijum]] bazirani medikamenti imaju dugu tradiciju u lečenju niza mentalnih oboljenja. The discipline of Medicinal Inorganic Chemistry investigates the role of [[metals in medicine]] ([[metallotherapeutics]]), which involves the study and treatment of diseases and health conditions associated with inorganic metals in biological systems.  There are several metallotherapeutics approved for the treatment of cancer (e.g., contain Pt, Ru, Gd, Ti, Ge, V, and Ga), antimicrobials (e.g., Ag, Cu, and Ru), diabetes (e.g., V and Cr), broad-spectrum antibiotic (e.g., Bi), bipolar disorder (e.g., Li).<ref>{{cite journal | vauthors = Hanif M, Yang X, Tinoco AD, Plażuk D | title = Editorial: New Strategies in Design and Synthesis of Inorganic Pharmaceuticals | journal = Frontiers in Chemistry | volume = 8 | pages = 453 | date = 2020-05-28 | pmid = 32548093 | doi = 10.3389/fchem.2020.00453 | pmc = | bibcode = 2020FrCh....8..453H | doi-access = free }}</ref><ref>{{cite journal | vauthors = Anthony EJ, Bolitho EM, Bridgewater HE, Carter OW, Donnelly JM, Imberti C, Lant EC, Lermyte F, Needham RJ, Palau M, Sadler PJ, Shi H, Wang FX, Zhang WY, Zhang Z | display-authors = 6 | title = Metallodrugs are unique: opportunities and challenges of discovery and development | journal = Chemical Science | volume = 11 | issue = 48 | pages = 12888–12917 | date = November 2020 | pmid = | pmc = | doi = 10.1039/D0SC04082G }}</ref>  Other areas of study include: [[metallomics]], [[genomics]], [[proteomics]], [[Medical test|diagnostic agents]] (e.g., MRI: Gd, Mn; X-ray: Ba, I) and [[Radiopharmaceutical|radiopharmaceuticals]] (e.g., <sup>99m</sup>Tc for diagnostics, <sup>186</sup>Re for therapeutics).
+In particular, medicinal chemistry in its most common practice—focusing on small organic molecules—encompasses [[synthetic organic chemistry]] and aspects of natural products and [[computational chemistry]] in close combination with [[chemical biology]], [[enzymology]] and [[structural biology]], together aiming at the discovery and development of new therapeutic agents.  Practically speaking, it involves chemical aspects of identification, and then systematic, thorough synthetic alteration of [[new chemical entity|new chemical entities]] to make them suitable for therapeutic use. It includes synthetic and computational aspects of the study of existing drugs and agents in development in relation to their bioactivities (biological activities and properties), i.e., understanding their [[structure–activity relationship]]s (SAR). Pharmaceutical chemistry is focused on quality aspects of medicines and aims to assure fitness for purpose of medicinal products.<ref name=JMC>{{cite journal | vauthors = Roughley SD, Jordan AM | title = The medicinal chemist's toolbox: an analysis of reactions used in the pursuit of drug candidates | journal = Journal of Medicinal Chemistry | volume = 54 | issue = 10 | pages = 3451–3479 | date = May 2011 | pmid = 21504168 | doi = 10.1021/jm200187y }}</ref>
-Medicinska hemija je visoko interdisciplinarna nauka koja kombinuje [[organska hemija|organsku hemiju]] sa [[biohemija|biohemijom]], [[računarska hemija|računarskom hemijom]], [[farmakologija|farmakologijom]], [[Farmakognozija|farmakognozijom]], [[molekularna biologija|molekularnom biologijom]], [[statistika|statistikom]], i [[fizička hemija|fizičkom hemijom]].
 == Proces razvoja lekova ==
@@ Ред 16: / Ред 19: @@
 == Reference ==
-{{reflist|2}}
+{{reflist|}}
 == Literatura ==
-{{refbegin|2}}
+{{refbegin|30em}}
 * D. Radulović, S. Vladimirov, Farmaceutska hemija I deo, Farmaceutski fakultet, Beograd, 2005.
 * S. Vladimirov, D. Živanov-Stakić, Farmaceutska hemija II deo, Farmaceutski fakultet, Beograd, 2006.
 * {{Cite book|ref=harv|title=Wilson and Gisvold's Textbook of Organic Medicinal and Pharmaceutical Chemistry |editor1=John M. Beale |editor2=John Block |publisher=Lippincott Williams & Wilkins |edition=Twelfth |location=London, Philadelphia, New York, |year=2010 |isbn=978-0-7817-7929-6|pages=}}
 * {{Cite book|ref=harv|title=Pharmaceutical Analysis: A Textbook for Pharmacy Students and Pharmaceutical Chemists |url=https://archive.org/details/pharmaceuticalan0000wats_f5h6|edition=second |last=Watson|first=David G.|publisher = Churchill Livingstone |location=Edinburg |year=2005 |isbn=978-0-443-07445-5|pages=}}
+* {{cite book|url=https://books.google.com/books?id=Y9bsUpefYW0C&pg=PA51|title=Textbook of Receptor Pharmacology, Second Edition|last1=Foreman|first1=John C.|last2=Johansen|first2=Torben|last3=Gibb|first3=Alasdair J. |publisher=CRC Press|year=2009|isbn=9781439887578}}
+* {{cite book|title=[[Goodman and Gilman's The Pharmacological Basis of Therapeutics]] |edition=12 |year=2011|first1=Laurence |last1=Brunton |editor1-last=Brunton |editor1-first=L. L. |editor2-last=Chabner |editor2-first=Bruce |editor3-last=Knollmann |editor3-first=Björn C. |isbn=978-0-07-162442-8|location=New York |publisher=McGraw-Hill }}
+* {{cite book|title=Lippincott Illustrated Reviews: Pharmacology|first1=Karen|last1=Whalen |year=2014}}
+* {{cite journal | pmid =8877846 |title = Interlaboratory study of log P determination by shake-flask and potentiometric methods | volume=14 | issue=11 | date=Aug 1996 | pages=1405–13|last1 = Takács-Novák |first1 = K. |last2 = Avdeef |first2 = A. |journal = Journal of Pharmaceutical and Biomedical Analysis |doi = 10.1016/0731-7085(96)01773-6 }}
+* {{cite book |url = https://books.google.com/books?id=MtOiLVWBn8cC&pg=PA20 |page = 20 |title = Molecular, clinical and environmental toxicology |veditors = Luch A |publisher = Springer |year = 2009 |isbn = 978-3-7643-8335-0 |access-date = 21 July 2020 |archive-date = 6 August 2020 |archive-url = https://web.archive.org/web/20200806043108/https://books.google.com/books?id=MtOiLVWBn8cC&pg=PA20 |url-status = live }}
+* {{cite journal | vauthors = Brater DC, Daly WJ | title = Clinical pharmacology in the Middle Ages: principles that presage the 21st century | journal = Clinical Pharmacology and Therapeutics | volume = 67 | issue = 5 | pages = 447–50 | date = May 2000 | pmid = 10824622 | doi = 10.1067/mcp.2000.106465 | s2cid = 45980791 }}
+* {{cite book | first = Mannfred A. | last = Hollinger | date = 2003 | url = https://books.google.com/books?id=bx-WfLwrVH8C&pg=PA4 | title = Introduction to pharmacology | publisher = [[CRC Press]] | page = 4 | isbn = 0-415-28033-8 | access-date = 27 June 2015 | archive-date = 17 April 2021 | archive-url = https://web.archive.org/web/20210417050725/https://books.google.com/books?id=bx-WfLwrVH8C&pg=PA4 | url-status = live }}
+* {{cite journal | vauthors = Rang HP | title = The receptor concept: pharmacology's big idea | journal = British Journal of Pharmacology | volume = 147 Suppl 1 | issue = S1 | pages = S9-16 | date = January 2006 | pmid = 16402126 | pmc = 1760743 | doi = 10.1038/sj.bjp.0706457 }}
+* {{cite journal | vauthors = Maehle AH, Prüll CR, Halliwell RF | s2cid = 205479063 | title = The emergence of the drug receptor theory | journal = Nature Reviews. Drug Discovery | volume = 1 | issue = 8 | pages = 637–41 | date = August 2002 | pmid = 12402503 | doi = 10.1038/nrd875 }}
+* {{cite book|title=Pharmacology| vauthors = Rang HP, Dale MM, Ritter JM, Flower RJ |publisher=[[Elsevier]]|year=2007|isbn=978-0-443-06911-6|location=[[China]]}}
+* {{cite book|title=Ligand-binding assays development, validation, and implementation in the drug development arena|year=2009|publisher=John Wiley & Sons|location=Hoboken, N.J.|isbn=978-0470541494|editor1=Masood N. Khan |editor2=John W. Findlay }}
+* {{Cite web|title=Psychopharmacology {{!}} Psychology Today International|url=https://www.psychologytoday.com/intl/basics/psychopharmacology|access-date=2020-07-23|website=www.psychologytoday.com|archive-date=24 February 2022|archive-url=https://web.archive.org/web/20220224115628/https://www.psychologytoday.com/intl/basics/psychopharmacology|url-status=live}}
+* {{Cite web|title=What is Psychopharmacology|url=https://ascpp.org/resources/information-for-patients/what-is-psychopharmacology/|access-date=2020-07-23|website=ascpp.org|date=29 November 2012 |archive-date=23 July 2020|archive-url=https://web.archive.org/web/20200723100542/https://ascpp.org/resources/information-for-patients/what-is-psychopharmacology/|url-status=live}}
+* {{cite journal | vauthors = Gomez A, Ingelman-Sundberg M | title = Pharmacoepigenetics: its role in interindividual differences in drug response | journal = Clinical Pharmacology and Therapeutics | volume = 85 | issue = 4 | pages = 426–30 | date = April 2009 | pmid = 19242404 | doi = 10.1038/clpt.2009.2 | s2cid = 39131071 }}
+* {{cite web|url=https://www.ascpt.org/Resources/Knowledge-Center/What-is-Clinical-Pharmacology|title=What is Clinical Pharmacology?|website=ascpt.org|accessdate=31 October 2021|archive-date=31 October 2021|archive-url=https://web.archive.org/web/20211031021835/https://www.ascpt.org/Resources/Knowledge-Center/What-is-Clinical-Pharmacology|url-status=live}}
+* {{cite web|url=https://www.pharmamad.com/posology/|title=Posology, Factors Influencing Dose, Calculation of Doses|date=23 January 2019|accessdate=31 October 2021|website=pharmamad.com|archive-date=31 October 2021|archive-url=https://web.archive.org/web/20211031021837/https://www.pharmamad.com/posology/|url-status=live}}
+* {{cite web|url=https://www.pharmtox.utoronto.ca/science-pharmacology-toxicology|title=The Science of Pharmacology & Toxicology|publisher=Faculty of Medicine, University of Toronto|access-date=July 16, 2019|archive-date=16 July 2019|archive-url=https://web.archive.org/web/20190716151155/https://www.pharmtox.utoronto.ca/science-pharmacology-toxicology|url-status=live}}
 {{refend}}
 == Spoljašnje veze ==
 {{Commonscat|Medicinal chemistry}}
-{{refbegin|2}}
+{{refbegin|30em}}
 * {{cite web|url=http://portal.acs.org/portal/acs/corg/content?_nfpb=true&_pageLabel=PP_ARTICLEMAIN&node_id=1188&content_id=CTP_003395&use_sec=true&sec_url_var=region1&__uuid=71801b29-ed10-4d25-be75-65cd35c6d433 | title = Medicinska hemija |date=| format = | work = | publisher = | language = | archiveurl = | archivedate=| quote = | accessdate=14. 4. 2011.}}
 * [http://www.acsmedchem.org/ Američko hemijsko društvo, odeljenje medicinske hemije]

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