645-65-8

Usage

Uses

Used in Pharmaceutical Industry:
Imidazole-4-acetic acid is used as a therapeutic agent for its anti-inflammatory and immunomodulatory properties, targeting the treatment of inflammation and autoimmune diseases. Its unique structure allows it to modulate immune responses and reduce inflammation, making it a promising candidate for pharmaceutical development.
Used in Organic Chemistry:
Imidazole-4-acetic acid is used as a valuable intermediate in the synthesis of various pharmaceutical compounds. Its functional groups enable it to participate in a wide range of chemical reactions, contributing to the development of new drugs and chemical products.
Used in Research Settings:
Imidazole-4-acetic acid is used as a research tool to study its potential applications and mechanisms of action in biological systems. Its role in metabolic pathways and interaction with other biomolecules provide insights into its therapeutic potential and possible side effects, aiding in the optimization of its use in medicine and other applications.

InChI:InChI=1/C5H6N2O2/c8-5(9)1-4-2-6-3-7-4/h2-3H,1H2,(H,6,7)(H,8,9)

Synthetic route

4-cyanomethylimidazole (18502-05-1) → 2-(1H-imidazol-4-yl)acetic acid (645-65-8)

Conditions	Yield
With ethanol; sodium
With sodium hydroxide; water
With hydrogenchloride; water

α-oxy-β--propionic acid → 2-(1H-imidazol-4-yl)acetic acid (645-65-8)

Conditions	Yield
With barium permanganate; sulfuric acid

2-(1H-imidazol-4-yl)ethanol (872-82-2) + water (7732-18-5) → 2-(1H-imidazol-4-yl)acetic acid (645-65-8)

Conditions	Yield
UV-Licht.Irradiation;

urocanic Acid (3465-72-3) → 2-(1H-imidazol-4-yl)acetic acid (645-65-8) + 4(5)formylimidazole (3034-50-2) + imidazole-4-carboxylic acid (1072-84-0) + (Z)-urocanic acid (7699-35-6)

Conditions	Yield
With dihydrogen peroxide pH=7.2; Product distribution / selectivity; aqueous phosphate buffer; UV-irradiation;

urocanic Acid (3465-72-3) → 2-(1H-imidazol-4-yl)acetic acid (645-65-8) + 4(5)formylimidazole (3034-50-2) + imidazole-4-carboxylic acid (1072-84-0)

Conditions	Yield
With dihydrogen peroxide pH=7.2; Product distribution / selectivity; Fenton Oxidation; aqueous phosphate buffer;
With dihydrogen peroxide In water pH=7.2; Product distribution / selectivity; Fenton Oxidation;

methanol (67-56-1) + 2-(1H-imidazol-4-yl)acetic acid (645-65-8) → (1H-imidazol-4-yl)-acetic acid methyl ester (4200-46-8)

Conditions	Yield
With thionyl chloride for 4h; Reflux;	99%
With hydrogenchloride Heating;
With hydrogenchloride
With thionyl chloride at 70℃;

methanol (67-56-1) + 2-(1H-imidazol-4-yl)acetic acid (645-65-8) → methyl 2-(1H-imidazol-4-yl)acetate hydrochloride (51718-80-0)

Conditions	Yield
With hydrogenchloride In 1,4-dioxane at 60℃;	98%
With thionyl chloride for 4h; Heating / reflux;

2-(1H-imidazol-4-yl)acetic acid (645-65-8) + (1S,2S)-2,3-dihydro-1'-(((2-amino-7,7-dimethylbicyclo<2.2.1>hept-1-yl)methyl)sulfonyl)spiro(1H-indene-1,4'-piperidine) (142643-14-9) → (1S,2S)-2,3-dihydro-1'-(((7,7-dimethyl-2-((4-imidazolylacetyl)amino)bicyclo<2.2.1>hept-1-yl)methyl)sulfonyl)spiro(1H-indene-1,4'-piperidine)

Conditions	Yield
With N-(3-dimethylaminopropyl)-N-ethylcarbodiimide; 1-hydroxybenzotriazol-hydrate; triethylamine In N,N-dimethyl-formamide at 25℃; for 18h;	92%

ethanol (64-17-5) + 2-(1H-imidazol-4-yl)acetic acid (645-65-8) → (1H-imidazol-4-yl)-acetic acid ethyl ester (28782-45-8)

Conditions	Yield
With sulfuric acid	90%
With acetyl chloride for 5h;

2-(1H-imidazol-4-yl)acetic acid (645-65-8) + 2,4-Dinitrofluorobenzene (70-34-8) → [1-(2,4-dinitrophenyl)-1H-imidazol-4-yl]acetic acid (153527-31-2)

Conditions	Yield
With sodium hydrogencarbonate In N,N-dimethyl-formamide	72%

C20H30N2O2 + 2-(1H-imidazol-4-yl)acetic acid (645-65-8) → N-(cyclopentylmethyl)-2-(1H-imidazol-4-yl)-N-{1-(4-methylphenyl)-2-oxo-2-[(tetrahydrofuran-2-ylmethyl)amino]ethyl}acetamide

Conditions	Yield
Stage #1: 2-(1H-imidazol-4-yl)acetic acid With 1-chloro-1-(dimethylamino)-2-methyl-1-propene In dichloromethane at 20℃; for 1h; Stage #2: C20H30N2O2 With triethylamine In dichloromethane at 20℃;	70%

(S)-1-(2-aminoacetyl)pyrrolidine-2-carbonitrile 4-methylbenzenesulfonate (1428264-81-6) + 2-(1H-imidazol-4-yl)acetic acid (645-65-8) → (S)-N-(2-(2-cyanopyrrolidin-1-yl)-2-oxoethyl)-2-(1H-imidazol-4-yl)acetamide (1448440-90-1)

Conditions	Yield
Stage #1: 2-(1H-imidazol-4-yl)acetic acid With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In N,N-dimethyl-formamide for 0.25h; Stage #2: (S)-1-(2-aminoacetyl)pyrrolidine-2-carbonitrile 4-methylbenzenesulfonate In N,N-dimethyl-formamide at 20℃;	66%

1,8-diaminooctan (373-44-4) + 2-(1H-imidazol-4-yl)acetic acid (645-65-8) → N-(8-(2-(1H-imidazol-4-yl)acetamido)octyl)-2-(1H-imidazol-5-yl)acetamide

Conditions	Yield
With (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In dichloromethane at 0 - 20℃; for 12h;	65%

2-(1H-imidazol-4-yl)acetic acid (645-65-8) + 3,5-bis-trifluoromethylbenzylamine (85068-29-7) → C14H11F6N3O

Conditions	Yield
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In water; N,N-dimethyl-formamide	62%

4-cyano-1H-imidazole-2-carboxylic acid (2-cyclohex-1-enyl-4-piperidin-4-yl-phenyl)-amide trifluoroacetic acid salt + 2-(1H-imidazol-4-yl)acetic acid (645-65-8) → 4-cyano-1H-imidazole-2-carboxylic acid {2-cyclohex-1-enyl-4-[1-(2-1H-imidazol-4-yl-acetyl)piperidin-4-yl]phenyl}amide trifluoroacetic acid salt

Conditions	Yield
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 25℃; for 10h;	60%

di-tert-butyl dicarbonate (24424-99-5) + 2-(1H-imidazol-4-yl)acetic acid (645-65-8) → 4-carboxymethyl-imidazole-1-carboxylic acid tert-butyl ester (112856-43-6)

Conditions	Yield
With dmap; triethylamine In tetrahydrofuran; water at 0 - 20℃;	54%

C35H38N4O3 + 2-(1H-imidazol-4-yl)acetic acid (645-65-8) → C54H50N6O8

Conditions	Yield
With benzotriazol-1-ol; O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 20℃; for 6h;	38%

2-(1H-imidazol-4-yl)acetic acid (645-65-8) + 6-nitro-1,4-benzoxazine (28226-22-4) → C13H12N4O4 (928118-22-3)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine; HATU In N,N-dimethyl-formamide at 20 - 25℃;	38%

C43H44N4O5 (702692-02-2) + 2-(1H-imidazol-4-yl)acetic acid (645-65-8) → C48H48N6O6

Conditions	Yield
With benzotriazol-1-ol; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In tetrahydrofuran for 6h;	38%

2-(1H-imidazol-4-yl)acetic acid (645-65-8) + 4-(2-((5-chloro-2-propoxybenzyl)amino)ethyl)-N-(prop-2-yn-1-yl)benzenesulfon-amide → N-(5-chloro-2-propoxybenzyl)-2-(1H-imidazol-4-yl)-N-(4-(N-(prop-2-yn-1-yl)sulfamo-yl)phenethyl)acetamide

Conditions	Yield
Stage #1: 2-(1H-imidazol-4-yl)acetic acid With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 0.5h; Inert atmosphere; Stage #2: 4-(2-((5-chloro-2-propoxybenzyl)amino)ethyl)-N-(prop-2-yn-1-yl)benzenesulfon-amide With triethylamine In dichloromethane at 20℃; for 3h; Inert atmosphere;	35%

3-{4-[(3R)-piperidin-3-ylamino]pyrimidin-2-yl}imidazo[1,2-a]pyridine-6-carbonitrile (1313006-17-5) + 2-(1H-imidazol-4-yl)acetic acid (645-65-8) → 3-(4-{[(3R)-1-(1H-imidazol-4-ylacetyl)piperidin-3-yl]amino}pyrimidin-2-yl)imidazo[1,2-a]pyridine-6-carbonitrile (1313007-40-7)

Conditions	Yield
Stage #1: 2-(1H-imidazol-4-yl)acetic acid With triethylamine; 1,1'-carbonyldiimidazole In N,N-dimethyl-formamide at 20℃; for 0.333333h; Stage #2: 3-{4-[(3R)-piperidin-3-ylamino]pyrimidin-2-yl}imidazo[1,2-a]pyridine-6-carbonitrile In N,N-dimethyl-formamide	32%
Stage #1: 2-(1H-imidazol-4-yl)acetic acid With triethylamine; 1,1'-carbonyldiimidazole In N,N-dimethyl-formamide at 20℃; for 0.333333h; Stage #2: 3-{4-[(3R)-piperidin-3-ylamino]pyrimidin-2-yl}imidazo[1,2-a]pyridine-6-carbonitrile	32%

ethyl 5-amino-3-(4-chlorophenyl)-4-cyanothiophene-2-carboxylate (1322757-73-2) + 2-(1H-imidazol-4-yl)acetic acid (645-65-8) → ethyl 5-(2-(1H-imidazol-4-yl)acetamido)-3-(4-chlorophenyl)-4-cyanothiophene-2-carboxylate

Conditions	Yield
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In N,N-dimethyl-formamide at 20℃; for 120h; Inert atmosphere;	30%

2-(1H-imidazol-4-yl)acetic acid (645-65-8) + (2S,3S)-3-methyl-2-methylaminopentanoic acid benzyl ester → (2S,3S)-2-[(2-1H-imidazol-4-ylacetyl)methylamino]-3-methylpentanoic acid benzyl ester

Conditions	Yield
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; for 16h;	27.4%

2-(1H-imidazol-4-yl)acetic acid (645-65-8) + dimethyl sulfate (77-78-1) → zwitterionic zooanemonin (584-91-8)

dimethyl 3-aminophthalate (34529-06-1) + 2-(1H-imidazol-4-yl)acetic acid (645-65-8) → dimethyl 3-<<2-(4-carboxymethyl)imidazolyl>azo>phthalate (141344-44-7)

Conditions	Yield
With hydrogenchloride; sodium carbonate; sodium nitrite 2.) 4 deg C, 30 min; Multistep reaction;

2-(methoxycarbonyl)-6-aminobenzoic acid (103259-06-9) + 2-(1H-imidazol-4-yl)acetic acid (645-65-8) → methyl 2-carboxy-3-<<2-(4-carboxymethyl)imidazolyl>azo>benzoate (141344-48-1)

Conditions	Yield
With hydrogenchloride; sodium carbonate; sodium nitrite 2.) 4 deg C, 30 min; Multistep reaction;

2-(1H-imidazol-4-yl)acetic acid (645-65-8) + 3-amino-2-(methoxycarbonyl)benzoic acid (113579-20-7) → methyl 2-carboxy-6-<<2-(4-carboxymethyl)imidazolyl>azo>benzoate (141344-43-6)

Conditions	Yield
With hydrogenchloride; sodium carbonate; sodium nitrite 2.) 4 deg C, 30 min; Multistep reaction;

2-(1H-imidazol-4-yl)acetic acid (645-65-8) + 3-Amino-N,N-dimethyl-phthalamic acid methyl ester → N,N-dimethyl-2-carbomethoxy-6-<<2-(4-carboxymethyl)imidazolyl>azo>benzamide (141344-46-9)

Conditions	Yield
With hydrogenchloride; sodium carbonate; sodium nitrite 2.) 4 deg C, 30 min; Multistep reaction;

2-(1H-imidazol-4-yl)acetic acid (645-65-8) + 2-amino-5-<3,5-bis(trifluoromethyl)phenyl>-1-(3-indolyl)-3-pentanone hydrochloride → N-[(S)-4-(3,5-Bis-trifluoromethyl-phenyl)-1-(1H-indol-3-ylmethyl)-2-oxo-butyl]-2-(1H-imidazol-4-yl)-acetamide

Conditions	Yield
With triethylamine; 1,1'-carbonyldiimidazole 1.) DMF, CH2Cl2, 2.) DMF, CH2Cl2; Multistep reaction;

2-(1H-imidazol-4-yl)acetic acid (645-65-8) + chloroformic acid ethyl ester (541-41-3) → 4-(2-Ethoxycarbonyloxy-2-oxo-ethyl)-imidazole-1-carboxylic acid ethyl ester

Conditions	Yield
With triethylamine In dichloromethane at 0 - 5℃; for 0.25h;

Upstream product

• 18502-05-1 4-cyanomethylimidazole 
• 872-82-2 2-(1H-imidazol-4-yl)ethanol 
• 7732-18-5 water 
• 3465-72-3 urocanic Acid 
• 18502-05-1 2-(1H-imidazol-5-yl)acetonitrile 

Downstream Products

• 584-91-8 zooanemonin 
• 4200-46-8 (1H-imidazol-4-yl)-acetic acid methyl ester 
• 141344-44-7 dimethyl 3-<<2-(4-carboxymethyl)imidazolyl>azo>phthalate 
• 141344-48-1 methyl 2-carboxy-3-<<2-(4-carboxymethyl)imidazolyl>azo>benzoate 
• 153527-31-2 [1-(2,4-dinitrophenyl)-1H-imidazol-4-yl]acetic acid 
• 141344-43-6 methyl 2-carboxy-6-<<2-(4-carboxymethyl)imidazolyl>azo>benzoate 
• 141344-46-9 N,N-dimethyl-2-carbomethoxy-6-<<2-(4-carboxymethyl)imidazolyl>azo>benzamide 
• 151094-26-7 3-Amino-2-(1-trityl-1H-imidazol-4-yl)-butyric acid methyl ester 
• 153527-32-3 1-(2,4-dinitrophenyl)-imidazole 4-acetic acid N-hydroxysuccinimide ester 
• 153527-33-4 N-[2-(9-{(2R,4S,5R)-5-[Bis-(4-methoxy-phenyl)-phenyl-methoxymethyl]-4-hydroxy-tetrahydro-furan-2-yl}-6-oxo-6,9-dihydro-1H-purin-2-ylamino)-ethyl]-2-[1-(2,4-dinitro-phenyl)-1H-imidazol-4-yl]-acetamide 
• 153527-35-6 N-(2-{9-{(2R,4S,5R)-5-[Bis-(4-methoxy-phenyl)-phenyl-methoxymethyl]-4-hydroxy-tetrahydro-furan-2-yl}-6-[2-(4-nitro-phenyl)-ethoxy]-9H-purin-2-ylamino}-ethyl)-2-[1-(2,4-dinitro-phenyl)-1H-imidazol-4-yl]-acetamide 
• 110295-89-1 methyl 2-<azo>imidazole-4(5)-acetate 
• 141344-45-8 N,N-dimethyl-2-carboxy-6-<<2-(4-carboxymethyl)imidazolyl>azo>benzamide 
• 51718-80-0 methyl 2-(1H-imidazol-4-yl)acetate hydrochloride 

Relevant academic research and scientific papers

PHARMACEUTICAL AND COSMETIC COMPOSITIONS COMPRISING UROCANIC ACID DERIVATIVES AS RADICAL SCAVENGERS OR ANTIOXIDANTS

Upon exposure to UVB, the epidermal component trans-urocanic acid is not only photoisomerized into cis-urocanic acid, but will also, at least in part, be photooxidized into urocanic acid oxidation products. We hypothesized that urocanic acid oxidation products can mimic UV-induced systemic immunosuppression comparable to the suppressive properties already established for cis-urocanic acid. A crude mixture of urocanic acid oxidation products showed a significant suppression of the sensitization phase of the systemic contact hypersensitivity response to picryl chloride. Three of the urocanic acid oxidation products were selected for this study: imidazole-4-carboxylic acid, imidazole-4-carboxaldehyde and imidazole-4-acetic acid. Effects on the sensitization-, elicitation- and post-elicitation phase of contact hypersensitivity to picryl chloride in BALB/c mice were studied and compared to the effects of cis-urocanic acid. Imidazole-4-carboxaldehyde was equally effective at suppressing the sensitization phase as cis-urocanic acid. The triplet combination of the imidazoles showed more pronounced suppression than that induced by cis-urocanic acid. The most effective compounds for the suppression of the elicitation phase appeared to be imidazole-4-acetic acid and cis-urocanic acid. Significant suppression of the post-elicitation phase was only obtained with the triplet combination of imidazole-4-carboxaldehyde, imidazole-4-carboxylic acid and imidazole-4-acetic acid, which combination appeared to be effective at all three tested phases, Because these three urocanic acid oxidation products are present in UVB-exposed human stratum corneum, these compounds may play a role in UVB-induced immunosuppression.

Highly potent geminal bisphosphonates. From pamidronate disodium (Aredia) to zoledronic acid (Zometa)

Bisphosphonates (BPs) are pyrophosphate analogues in which the oxygen in P-O-P has been replaced by a carbon, resulting in a metabolically stable P-C-P structure. Pamidronate (1b, Novartis), a second-generation BP, was the starting point for extensive SAR studies. Small changes of the structure of pamidronate lead to marked improvements of the inhibition of osteoclastic resorption potency. Alendronate (1c, MSD), with an extra methylene group in the N-alkyl chain, and olpadronate (1h, Gador), the N,N-dimethyl analogue, are about 10 times more potent than pamidronate. Extending one of the N-methyl groups of olpadronate to a pentyl substituent leads to ibandronate (1k, Roche, Boehringer-Mannheim), which is the most potent close analogue of pamidronate. Even slightly better antiresorptive potency is achieved with derivatives having a phenyl group linked via a short aliphatic tether of three to four atoms to nitrogen, the second substituent being preferentially a methyl group (e.g., 4g, 4j, 5d, or 5r). The most potent BPs are found in the series containing a heteroaromatic moiety (with at least one nitrogen atom), which is linked via a single methylene group to the geminal bisphosphonate unit. Zoledronic acid (6i), the most potent derivative, has an ED50 of 0.07 mg/kg in the TPTX in vivo assay after sc administration. It not only shows by far the highest therapeutic ratio when comparing resorption inhibition with undesired inhibition of bone mineralization but also exhibits superior renal tolerability. Zoledronic acid (6i) has thus been selected for clinical development under the registered trade name Zometa. The results of the clinical trials indicate that low doses are both efficacious and safe for the treatment of tumor-induced hypercalcemia, Paget's disease of bone, osteolytic metastases, and postmenopausal osteoporosis.