Related compounds | Molar mass 74.085 g/mol | |
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Pimagedine, also known as aminoguanidine, is an investigational drug for the treatment of diabetic nephropathy that is no longer under development as a drug. 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.
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Development as a potential drug
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.
In 1987, Alteon acquired a license to intellectual property relating to AGE inhibition from Rockefeller University.
In 1989, Alteon and Marion Merrell Dow Inc (MMD) entered into a joint development program for pimagedine.
In 1992, Alteon licensed a patent from Rockefeller University relating to the use of pimagedine to inhibit AGE formation.
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.
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.
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.
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."
In February, 1999, Genentech ended its collaboration with Alteon to develop pimagedine.
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.
Alteon's 2000, 2001, 2002 annual reports indicated that it was not running any clinical trials on pimagedine but was seeking co-development partners. Alteon's 2003 and subsequent annual reports did not mention that Alteon was seeking partners for pimagenine, 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.
Uses for other aminoguanidines
Aminoguanidines and their derivatives are also being developed for energetic material applications. Thorough combustion of aminoguanidines can produce voluminous non-toxic gases, at moderate temperatures, with a minimum of smoke or dust. This characteristic favors application to explosive gas generators for automotive airbags, and solid-rocket propellants that generate high thrust per kilogram, while emitting minimal visible smoke or infrared radiation (useful militarily as well as to reduce environmental impact). Aminoguanidines can also be used as precursors for the synthesis of tetrazole-based energetic materials and drugs.