This "J147" drug being developed and tested by the Salk Institute could be an extremely important breakthrough. According to a recent RAND study, Alzheimer's disease is already one of the most expensive diseases,(See this article). With the upcoming aging baby boomers (us), the disease could bankrupt our medical care system. If a simple drug could help reverse brain damage due to Alzheimer's disease, it could help mitigate that impact. The J147 drug is an extract of curcumin -- the spice in curry. See this article Alzheimer’s drug candidate reverses disease in mice Page 1 of 2 | UTSanDiego.com:
The drug has already been in development for 6 years of preclinical studies at Salk. The lead author of the study is Marguerite Prior, a research associate in Dave Schubert's laboratory. Schubert is the head of Salk's cellular neurobiology laboratory.
David Schubert has apparently talked to drug companies and they are not interested in pursuing further development of the drug, and right now he needs only $1.5M to start the initial human trials -- and apparently can't get the funding. I can see why the big pharmaceuticals might not be interested since it would be difficult to patent a naturally occurring spice, so there would not be much profit margin in producing the drug. http://www.utsandiego.com/news/2013/may/15/tp-potential-alzheimers-drug-reverses-disease-in/
Since currently there really is no real cure, and the drugs that are prescribed only slow down the process slightly, it reduces the value of even screening for the disease. Why find out if you've got it, if there's nothing that can be done about it? http://www.utsandiego.com/news/2012/dec/03/alzheimers-dilemma/
Article in Science2.0
Alzheimer's Research Journal about J147
Make your own J147:
The synthesis of J147 has been carried out using simple chemistry as described in our
previous paper by condensation of 3-methoxybenzaldehyde and (2, 4-dimethylphenyl)
hydrazine hydrochloride in EtOH at room temperature, followed by acetylation using
trifluoroacetic anhydride and triethylamine in CH2Cl2 gave J147 (Scheme 1). Donepezil has
been synthesized with 99% purity according to the literature procedure published in Organic
Process Research & Development 2008, 12:731-735 (Scheme 2).
Synthesis of (E)-N-(2,4-dimethylphenyl)-2,2,2-trifluoro-N'-(3methoxybenzyli-dene)
acetohydrazide (J147) {2nd Level Heading}
A mixture of 3-methoxybenzaldehyde (50 g, 367.64 mmol) and (2, 4-dimethylphenyl)
hydrazine hydrochloride (63.23 g, 367.64 mmol) in EtOH (50 mL) was stirred at room
temperature for 1 h, the obtained solid was filtered off, washed with ethanol and dried under
vacuum to afford hydrazone hydrochloride 1 (95.94 g) in 90% yield as a light brown solid.
This unstable hydrazone (50 g, 172.41 mmol) was dissolved in CH2Cl2 (50 ml), Et3N (57.56
mL, 413.79 mmol) followed by (CF3CO)2O (28.77 mL, 206.89 mmol), was added at 0°C and
the mixture was stirred at room temperature for 1 h. Reaction mixture was diluted with aq.
sat. NaHCO3 solution (500 mL), extracted with CH2Cl2 (2 x 500 mL), dried (Na2SO4) and
evaporated, resulting solid was recrystalized from ethanol to give J147 (49.11 g, 81%) as a
white solid: mp 70 to 72°C; LCMS purity 98%; 1H NMR (CDCl3, 500 MHz) δ ppm 2.10 (s,
3H), 2.42 (s, 3H), 3.82 (s, 3H), 6.98 (dd, J = 8.5, 2.0 Hz, 1H), 7.07 (d, J = 7.5 Hz, 1H), 7.14
(d, J = 8.0 Hz, 1H), 7.28 (m, 3H). MS (ESI): m/z calcd for C18H17F3N2O2 ((M + H) +)
351.1314; found 351.1366 ((M + H) +).
The drug has already been in development for 6 years of preclinical studies at Salk. The lead author of the study is Marguerite Prior, a research associate in Dave Schubert's laboratory. Schubert is the head of Salk's cellular neurobiology laboratory.
David Schubert has apparently talked to drug companies and they are not interested in pursuing further development of the drug, and right now he needs only $1.5M to start the initial human trials -- and apparently can't get the funding. I can see why the big pharmaceuticals might not be interested since it would be difficult to patent a naturally occurring spice, so there would not be much profit margin in producing the drug. http://www.utsandiego.com/news/2013/may/15/tp-potential-alzheimers-drug-reverses-disease-in/
Since currently there really is no real cure, and the drugs that are prescribed only slow down the process slightly, it reduces the value of even screening for the disease. Why find out if you've got it, if there's nothing that can be done about it? http://www.utsandiego.com/news/2012/dec/03/alzheimers-dilemma/
Article in Science2.0
Alzheimer's Research Journal about J147
Make your own J147:
The synthesis of J147 has been carried out using simple chemistry as described in our
previous paper by condensation of 3-methoxybenzaldehyde and (2, 4-dimethylphenyl)
hydrazine hydrochloride in EtOH at room temperature, followed by acetylation using
trifluoroacetic anhydride and triethylamine in CH2Cl2 gave J147 (Scheme 1). Donepezil has
been synthesized with 99% purity according to the literature procedure published in Organic
Process Research & Development 2008, 12:731-735 (Scheme 2).
Synthesis of (E)-N-(2,4-dimethylphenyl)-2,2,2-trifluoro-N'-(3methoxybenzyli-dene)
acetohydrazide (J147) {2nd Level Heading}
A mixture of 3-methoxybenzaldehyde (50 g, 367.64 mmol) and (2, 4-dimethylphenyl)
hydrazine hydrochloride (63.23 g, 367.64 mmol) in EtOH (50 mL) was stirred at room
temperature for 1 h, the obtained solid was filtered off, washed with ethanol and dried under
vacuum to afford hydrazone hydrochloride 1 (95.94 g) in 90% yield as a light brown solid.
This unstable hydrazone (50 g, 172.41 mmol) was dissolved in CH2Cl2 (50 ml), Et3N (57.56
mL, 413.79 mmol) followed by (CF3CO)2O (28.77 mL, 206.89 mmol), was added at 0°C and
the mixture was stirred at room temperature for 1 h. Reaction mixture was diluted with aq.
sat. NaHCO3 solution (500 mL), extracted with CH2Cl2 (2 x 500 mL), dried (Na2SO4) and
evaporated, resulting solid was recrystalized from ethanol to give J147 (49.11 g, 81%) as a
white solid: mp 70 to 72°C; LCMS purity 98%; 1H NMR (CDCl3, 500 MHz) δ ppm 2.10 (s,
3H), 2.42 (s, 3H), 3.82 (s, 3H), 6.98 (dd, J = 8.5, 2.0 Hz, 1H), 7.07 (d, J = 7.5 Hz, 1H), 7.14
(d, J = 8.0 Hz, 1H), 7.28 (m, 3H). MS (ESI): m/z calcd for C18H17F3N2O2 ((M + H) +)
351.1314; found 351.1366 ((M + H) +).
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