133081-27-3

Basic information

• Product Name: SHNH
• Synonyms: SHNH;SUCCINIMIDYL 2-HYDRAZINONICOTINATE HYDROCHLORIDE;SUCCINIMIDYL HYDRAZINIUMNICOTINATE HYDROCHLORIDE;HYDRALINK(TM) SHNH REAGENT;HYDRALINK SHNH REAGENT;succinimidyl 6-hydrazinonicotinate;Succinimidyl-Hynic hydrochloride;s-HYNIC
• CAS NO: 133081-27-3
• Molecular Formula: C₁₀H₁₀N₄O₄*ClH
• Molecular Weight: 286.67
• Mol File: 133081-27-3.mol
• Article Data: 1

Chemical Properties

• Boiling Point: 491.3 °C at 760 mmHg
• Flash Point: 250.9 °C
• Appearance: /
• Vapor Pressure: 8.49E-10mmHg at 25°C
• CAS DataBase Reference: SHNH(CAS DataBase Reference)
• NIST Chemistry Reference: SHNH(133081-27-3)
• EPA Substance Registry System: SHNH(133081-27-3)

Safety Data

• Hazardous Substances Data: 133081-27-3(Hazardous Substances Data)

Usage

Chemical Properties

Colourless to slightly grey solid

InChI:InChI=1/C10H10N4O4.ClH/c11-13-7-2-1-6(5-12-7)10(17)18-14-8(15)3-4-9(14)16;/h1-2,5H,3-4,11H2,(H,12,13);1H

Synthetic route

6-Chloro-3-pyridinecarboxylic acid (5326-23-8) → succinimidyl 6-hydrazinopyridine-3-carboxylate hydrochloride (133081-27-3)

Conditions	Yield
Multi-step reaction with 4 steps 1: hydrazine hydrate / 4 h / 100 °C 2: triethylamine / N,N-dimethyl-formamide / 16 h / 20 °C 3: dicyclohexyl-carbodiimide / N,N-dimethyl-formamide / 20 °C 4: hydrogenchloride / 1,4-dioxane / 4 h / 20 °C / Inert atmosphere; Sealed tube View Scheme

6-hydrazinylnicotinic acid (133081-24-0) → succinimidyl 6-hydrazinopyridine-3-carboxylate hydrochloride (133081-27-3)

Conditions	Yield
Multi-step reaction with 3 steps 1: triethylamine / N,N-dimethyl-formamide / 16 h / 20 °C 2: dicyclohexyl-carbodiimide / N,N-dimethyl-formamide / 20 °C 3: hydrogenchloride / 1,4-dioxane / 4 h / 20 °C / Inert atmosphere; Sealed tube View Scheme

6-({[(tert-butoxy)carbonyl]amino}amino)pyridine-3-carboxylic acid (133081-25-1) → succinimidyl 6-hydrazinopyridine-3-carboxylate hydrochloride (133081-27-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: dicyclohexyl-carbodiimide / N,N-dimethyl-formamide / 20 °C 2: hydrogenchloride / 1,4-dioxane / 4 h / 20 °C / Inert atmosphere; Sealed tube View Scheme

2-(N'-tert-butoxycarbonylhydrazino)pyridine-5-carboxylic acid 2,5-dioxopyrrolidin-1-yl ester (133081-26-2) → succinimidyl 6-hydrazinopyridine-3-carboxylate hydrochloride (133081-27-3)

Conditions	Yield
With hydrogenchloride In 1,4-dioxane at 20℃; for 4h; Inert atmosphere; Sealed tube;	42 mg

succinimidyl 6-hydrazinopyridine-3-carboxylate hydrochloride (133081-27-3) + N,N'-(5-(4-aminobutoxy)-1,3-phenylene)bis(methylene)bis(1-(pyridin-2-yl)-N-(pyridin-2-ylmethyl)methanamine) (819066-98-3) → C42H46N10O2 (1313597-09-9)

Conditions	Yield
With N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid In N,N-dimethyl-formamide; acetonitrile at 20℃; for 1.5h; Darkness;	10.3%

succinimidyl 6-hydrazinopyridine-3-carboxylate hydrochloride (133081-27-3) + C38H61Cl2N13O8S2 → C44H66Cl2N16O9S2

Conditions	Yield
In N,N-dimethyl-formamide at 20℃; for 12h;

Upstream product

• 133081-26-2 2-(N'-tert-butoxycarbonylhydrazino)pyridine-5-carboxylic acid 2,5-dioxopyrrolidin-1-yl ester 
• 133081-25-1 6-({[(tert-butoxy)carbonyl]amino}amino)pyridine-3-carboxylic acid 
• 133081-24-0 6-hydrazinylnicotinic acid 
• 5326-23-8 6-Chloro-3-pyridinecarboxylic acid 

Downstream Products

• 1313597-09-9 C₄₂H₄₆N₁₀O₂ 

Relevant articles and documents

99mTc-labeled NGR-chlorambucil conjugate, 99mTc-HYNIC-CLB-c(NGR) for targeted chemotherapy and molecular imaging

Targeted delivery of chemotherapeutic drug at the tumor site enhances the efficacy with minimum systemic exposure. Towards this, drugs conjugated with peptides having affinity towards a particular molecular target are recognized as affective agents for targeted chemotherapy. Thus, in the present study, tumor-homing asparagine-glycine-arginine (NGR) peptide ligand was conjugated to DNA alkylating nitrogen mustard, chlorambucil (CLB). The peptide-drug conjugate (PDC), CLB-c(NGR), was radiolabeled with 99mTc-HYNIC core to trace its pharmacokinetics and biodistribution pattern. In vitro cell-binding studies of 99mTc-HYNIC-CLB-c(NGR) were conducted in murine melanoma B16F10 cells. The cytotoxicity studies conducted by incubation of the peptide/drug/PDC with B16F10 cells demonstrated enhanced cytotoxic effect of PDC in comparison to either the peptide or the drug alone. In vivo biodistribution studies in C57BL6 mice bearing melanoma tumor showed maximum tumor uptake at 30?minutes pi (2.45?±?0.28% ID/g), which reduced to 0.77?±?0.1% ID /g at 3?hours pi. The radiotracer being hydrophilic cleared rapidly from the heart, lungs, liver, and muscle. The tumor-to-blood and tumor-to-muscle ratios improved with time. This study opens avenues for conjugation of other targeting peptides with the drug CLB for enhanced toxicity at the diseased site.