Pimagedine

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Pimagedine
Skeletal formula of a pimagedine
Spacefill model of a pimagedine
Names
IUPAC name
2-Aminoguanidine
Other names
  • Aminoguanidine
  • Guanyl hydrazine
  • Hydrazinecarboximidamide
  • Imino semicarbazide
  • Monoaminoguanidine
Identifiers
3D model (JSmol)
ChemSpider
ECHA InfoCard 100.001.076
KEGG
UNII
Properties
CH6N4
Molar mass 74.085 g/mol
Density 1.72 g/ml
Boiling point 261 °C (502 °F; 534 K)
log P −1.475
Related compounds
Related compounds
Guanidine
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Infobox references

Pimagedine, also known as aminoguanidine, is an investigational drug for the treatment of diabetic nephropathy that is no longer under development as a drug.[1] Pimagedine is a diamine oxidase and nitric oxide synthase inhibitor. It acts to reduce levels of advanced glycation end products (AGEs) through interacting with 3-deoxyglucosone.

Development as a potential drug[edit]

Pimagedine was under development as a drug for kidney diseases by the pharmaceutical company Alteon (now known Synvista Therapeutics Inc.) that was founded in 1986.[2]

In 1987, Alteon acquired a license to intellectual property relating to AGE inhibition from Rockefeller University.[3]


In 1989, Alteon and Marion Merrell Dow Inc (MMD) entered into a joint development program for pimagedine.[4]

In 1992, Alteon licensed a patent from Rockefeller University relating to the use of pimagedine to inhibit AGE formation.[3]

In 1995, Hoechst AG (now sanofi-aventis) acquired MMD and subsequently terminated its agreement with Alteon, which led Alteon to stop of all clinical trials due to lack of funds, which caused some controversy.[4]

In 1997, Alteon and Genentech announced a collaboration agreement under which Genentech would fund development of pimagedine and would have the rights to sell the drug if it would be approved.[5]

In March 1998, Alteon announced that it had been advised that it should discontinue its Phase III trial of pimagedine in non-insulin-dependent (type II) diabetes patients with overt nephropathy, after the trial's external safety monitoring committee found an increased risk of side effects in the treatment group.[6]

In November 1998, Alteon announced that its Phase III trial for pimagedine as a treatment for end stage renal disease had failed to prove efficacy, which led Carl Gordon, a leading biotech analyst, to say: "It looks like pimagedine is probably finished."[7]

In February, 1999, Genentech ended its collaboration with Alteon to develop pimagedine.[8]

In April 1999 Alteon announced that it would cease development of pimagedine as a treatment for end stage renal disease but might consider continuing development in type 1 diabetic patients with overt nephropathy or progressive kidney disease.[9]

Alteon's 2000, 2001, 2002 annual reports indicated that it was not running any clinical trials on pimagedine but was seeking co-development partners.[10][11][12] Alteon's 2003 and subsequent annual reports did not mention that Alteon was seeking partners for pimagenine,[13] which indicated that efforts to interest other companies and investors had failed and which signaled that commercial efforts to develop pimagedine as a drug were indeed finished.

References[edit]

  1. ^ W Kline Bolton, Emaad Abdel-Rahman (2002). "Pimagedine: a novel therapy for diabetic nephropathy". Expert Opinion on Investigational Drugs. 11 (4): 565–574. PMID 11922864. doi:10.1517/13543784.11.4.565. 
  2. ^ Synvista Therapeutics Inc. Biocentury. Retrieved August 17, 2017.
  3. ^ a b "Alteon 10-K For the fiscal year ended December 31, 1996". Alteon via SEC Edgar. March 27, 1997. 
  4. ^ a b Harry Keen; JH Fukker; G Menzinger (July 19, 1997). "Early closure of European Pimagedine trial". The Lancet. PlumX Metrics. 350 (9072): 214–215. doi:10.1016/S0140-6736(97)26029-0. 
  5. ^ Barbara Marsh (January 3, 1998). "Biotech's New Watchword: Partnership". Los Angeles Times. Retrieved August 17, 2017. 
  6. ^ "Alteon May Drop Pimagedine In NIDDM". The Pharma Letter. March 19, 1998. Retrieved August 17, 2017. 
  7. ^ "Alteon Shares Plummet On Poor Pimagedine Test Results". San Diego Source. November 16, 1998. Retrieved August 17, 2017. 
  8. ^ http://business.globe24h.com/sec/001/06/060000/0000060271.shtml[dead link]
  9. ^ "Alteon's pimagedine fails primary endpoint". The Pharma Letter. April 12, 1999. Retrieved August 17, 2017. 
  10. ^ https://www.sec.gov/Archives/edgar/data/878903/0000893220-00-000381.txt
  11. ^ https://www.sec.gov/Archives/edgar/data/878903/000089322001000240/0000893220-01-000240.txt
  12. ^ https://www.sec.gov/Archives/edgar/data/878903/000089322002000222/0000893220-02-000222.txt
  13. ^ https://www.sec.gov/Archives/edgar/data/878903/000089322003000272/0000893220-03-000272.txt