항 파킨슨씨 약물 Anti-Parkinson Drug

파킨슨씨병 의 날 4월 11일

Substansia Nigra (흑질)

History of Parkinson’s Disease Parkinon’s small but famous publication, "Essay on the Shaking Palsy", appeared in 1817, 7 years before his death in 1824.

Epidemiology Average incidence is 20 per 100,000 in North America 1 Million affected in the United States 50,000 new cases per year Cost estimated to exceed $5.6 Billion annually

Four Typical Signs of Parkinsonism Diagnostic Features Four Cardinal Signs Tremor Rigidity Akinesia and bradykinesia Postural instability Four Typical Signs of Parkinsonism

Reduction of inhibitory Dopaminergic Neron Parkinson’s Disease Reduction of inhibitory Dopaminergic Neron Imbalance of Ach & DA Pakinson Syndrome

Positron-Emission Tomography

Antiparkinson’s Drug Treatment for Parkinson’s disease Pakinson syndrome Dopamine receptor agonist DA Synthesis MAO-B inhibitor Anti-Muscarinic agent

Parkinson’s disease 예방

담배와 파킨슨씨병

Drug Interaction

Structure of Drug for Parkinson’s Disease

Why L-Dopa instead of DA? If dopamine is too polar to cross the BBB, how can L-DOPA cross it?

Trojan horse Approach for Carrier Protein Recognized as amino acid by carrier protein

The Effect of Carbidopa on the metabolism of L-Dopa

The Action of Selegiline in the metabolism of Dopamine

The mechanism of Entacaone as Anti-parkinsonism

Muscarine Antagonist ☞ Chemical Name: 3-(1-Piperidyl)-1-cyclohexyl-1-phenyl-1-propanol HCl a-Cyclphexyl-a-phenyl-1-piperidinepropanol HCl ☞ Trade Name: 트리헥산 정 (태극), 염산트리헥시딜 정 (장우), Artane® (Lederle) 24

Retrosynthesis of Trihexylphenidyl

Muscarine Antagonist ☞ Chemical Name: :1-(Bicyclo[2.2.1]hept-5-en-2-yl-1-phenyl-3-phenyl-3-(piperidin- 1-yl)propan-1-ol HCl :a-(2-Norbonenyl)-a-pheny-1-piperidinepropanol HCl ☞ Trade Name: 아톨 정 (유나이티드), 염산비페리덴 정 (풍림), Akineton® (Abbot)

Muscarine Antagonist

Mannich Reaction

Dopamine Agonist ☞ Chemical Name: :(S)-2-Amino-3-(3,4-dihydroxyphenyl)propanic acid ☞ Trade Name: 레보다 서방정 (산도스), 스다레보 필름코팅 정 (노바티스), 씨네메트/씨알정 (MSD), 콤비도파 서방정(노바티스) Stalevo® (a mixture of L-DOPA, carbidopa, entacapone, Orion

Side Effect of levodopa

Drug Interactions

Why L-Dopa, not Dopamine ? Not cross the BBB Cross the BBB In Brain

Retro synthesis of L-DOPA L-Tyrosine

L-DOPA

Regiochemistry of Bayer-Villiger-Oxidation

Retrosyntheis of L-DOPA(II)

L-DOPA (Dopamine Agonist)

Carbidopa ☞ Chemical Name: :(S)-3-(3,4-dihydroxyphenyl)-2-hydrazinyl-2-methylpropanoic acid ☞ Trade Name: : Stalevo® (a mixture of L-DOPA, carbidopa, entacapone, Orion

Levodopa & Carbidopa Nausea and Vomiting

Retrosynthesis of Carbidopa

Dopamine Agonist

Dopamine Agonist

Dopamine Agonist

Dopamine Agonist Ropinirole ☞ Chemical Name: 4-[2-(Dipropylamino)ethyl-1,3-dihydro-2H-indol-2-one ☞ Trade Name: : RopiniroleHCl: 뉴큅 정 (유한), 로큅 정 (대웅), 로피맥스 전 (고려), 파로킨 정 (현대), 도파로핀(일동), 로킨스 정(신풍). 리큅피디 정 (글라고스미스클라인) : Ropinirole: 리큅 정 (글락소스미스클라인, ropinirole), Requip (GSK)

Retrosynthesis of ropinirole OH

Synthesis of Ropinirole Dopamine Agonist Synthesis of Ropinirole

selegiline (R)-N-methyl-N-(1-phenylpropan-2-yn)-1-amine 유멕스 정(사노피-아벤티스 코리아), 아오비 정(초당), Eldepryl(Somerset)

Retrosynthesis of Selegiline

Synthesis of Selegiline Dopamine Agonist Synthesis of Selegiline

Asymmetric Synthesis of Selegiline Dopamine Agonist Asymmetric Synthesis of Selegiline

Entacapone Dopamine Agonist ☞ Chemical Name: (E)-2-cyano-N,N-diethyl-3-(3,4-dihydroxy-5-nitrophenyl)-propenamide ☞ Trade Name: : 콤탄 정 (노바티스), 스타레보 필름코팅 정 (L-DOPA 및 Carbidopa 와 복합제, 노바티 스), Comtan® (Orion)

Retrosynthesis of Entacapone

Synthesis of Entacapone Dopamine Agonist Synthesis of Entacapone