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| Names | |||
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| IUPAC name 2-Aminoguanidine | |||
Other names
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| Identifiers | |||
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3D model (JSmol) | |||
| ChEMBL | |||
| ChemSpider |
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| ECHA InfoCard | 100.001.076 | ||
| KEGG | |||
| UNII | |||
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| Properties | |||
| CH6N4 | |||
| Molar mass | 74.085 g/mol | ||
| Density | 1.72 g/ml | ||
| Boiling point | 261 °C (502 °F; 534 K) | ||
| logP | −1.475 | ||
| Related compounds | |||
Related compounds | Guanidine | ||
Except where otherwise noted, data are given for materials in theirstandard state (at 25 °C [77 °F], 100 kPa). | |||
Aminoguanidine is the chemical compound with the formulaNH2C(=NH)NHNH2. It is a versatile synthetic intermediate.[1]
Aminoguanidine was studied as an investigationaldrug for the treatment ofdiabetic nephropathy, under thenonproprietary namePimagedine. It is no longer under development as a drug.[2] Pimagedine functions as aninhibitor ofdiamine oxidase andnitric oxide synthase. It acts to reduce levels ofadvanced glycation end products (AGEs) through interacting with3-deoxyglucosone,glyoxal,methylglyoxal, and related dicarbonyls. These reactive species are converted to less reactive heterocycles by this condensation reaction.
The industrial synthesis uses the reaction betweencyanamide andhydrazine in aqueous solution.[1]
The compound can also be obtained from the reduction ofnitroguanidine withzinc inacetic acid.[3]
Aminoguanidine is a colorless solid that is soluble in water and ethanol. It is basic, producing salts when reacted with organic acids. As established by manycrystallographic studies, protonation of aminoguanidine occurs at the imino nitrogen.[4] With formic acid, condensation occurs, leading to cyclization to give3-amino-1,2,4-triazole.[1]
The compound reacts withnitrous acid in acidic medium to give5-aminotetrazole via the intermediate guanylazide.[1] At neutral pH, the reaction leads totetrazene.[5]Diazotization inacetic acid yields 1,3-di-(tetrazolyl)-triazene.[1]
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.[6] In 1987, Alteon acquired a license to intellectual property relating to AGE inhibition from Rockefeller University.[7] In 1989, Alteon and Marion Merrell Dow Inc (MMD) entered into a joint development program for pimagedine.[8] In 1992, Alteon licensed a patent from Rockefeller University relating to the use of pimagedine to inhibit AGE formation.[7] In 1995, Hoechst AG (now Sanofi-Aventis) acquired MMD and subsequently terminated its agreement with Alteon, which led Alteon to stop clinical trials, which caused some controversy.[8] In 1997, Alteon and Genentech announced a collaboration under which Genentech would fund development of pimagedine and would have the rights to sell the drug if it would be approved.[9]
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.[10] 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."[11] In February, 1999, Genentech ended its collaboration with Alteon to develop pimagedine.[12] 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.[13] Alteon's 2000, 2001, 2002 annual reports indicated that it was not running any clinical trials on pimagedine but was seeking co-development partners.[14][15][16] Alteon's 2003 and subsequent annual reports did not mention that Alteon was seeking partners for pimagedine,[17] 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.[citation needed]
