Synthesis of ortho-functionalized 4-aminomethylpyridazines as substrate-like semicarbazide-sensitive amine oxidase inhibitors

Norbert Haider, Iris Hochholdinger, P. Mátyus, Andrea Wobus

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

A series of 4-aminomethylpyridazines and -pyridazin-3(2H)-ones ("diaza-benzylamines"), bearing alkylamino side chains in ortho position relative to the CH2NH2 unit, was synthesized by catalytic hydrogenation of the corresponding nitriles in strongly acidic medium. N-Benzyl protecting groups either at the pyridazinone ring nitrogen or at an exocyclic nitrogen were selectively removed hydrogenolytically or by treatment with a Lewis acid. The new compounds were tested in vitro for semicarbazide-sensitive amine oxidase (SSAO) inhibitory activity and 4-(aminomethyl)-N,Ń-diethylpyridazine-3,5-diamine (22) was found to be the most active representative.

Original languageEnglish
Pages (from-to)964-970
Number of pages7
JournalChemical and Pharmaceutical Bulletin
Volume58
Issue number7
DOIs
Publication statusPublished - 2010

Fingerprint

Amine Oxidase (Copper-Containing)
Benzylamines
Bearings (structural)
Nitrogen
Lewis Acids
Nitriles
Diamines
Hydrogenation
Substrates
In Vitro Techniques

Keywords

  • 4-Aminomethylpyridazine
  • Diaza-benzylamine
  • Selective debenzylation
  • Semicarbazide-sensitive amine oxidase inhibitor
  • Semicarbazide-sensitive amine oxidase/vascular adhesion protein 1

ASJC Scopus subject areas

  • Drug Discovery
  • Chemistry(all)
  • Medicine(all)

Cite this

Synthesis of ortho-functionalized 4-aminomethylpyridazines as substrate-like semicarbazide-sensitive amine oxidase inhibitors. / Haider, Norbert; Hochholdinger, Iris; Mátyus, P.; Wobus, Andrea.

In: Chemical and Pharmaceutical Bulletin, Vol. 58, No. 7, 2010, p. 964-970.

Research output: Contribution to journalArticle

@article{237925a7c83b4292b9b81407f0517519,
title = "Synthesis of ortho-functionalized 4-aminomethylpyridazines as substrate-like semicarbazide-sensitive amine oxidase inhibitors",
abstract = "A series of 4-aminomethylpyridazines and -pyridazin-3(2H)-ones ({"}diaza-benzylamines{"}), bearing alkylamino side chains in ortho position relative to the CH2NH2 unit, was synthesized by catalytic hydrogenation of the corresponding nitriles in strongly acidic medium. N-Benzyl protecting groups either at the pyridazinone ring nitrogen or at an exocyclic nitrogen were selectively removed hydrogenolytically or by treatment with a Lewis acid. The new compounds were tested in vitro for semicarbazide-sensitive amine oxidase (SSAO) inhibitory activity and 4-(aminomethyl)-N,Ń-diethylpyridazine-3,5-diamine (22) was found to be the most active representative.",
keywords = "4-Aminomethylpyridazine, Diaza-benzylamine, Selective debenzylation, Semicarbazide-sensitive amine oxidase inhibitor, Semicarbazide-sensitive amine oxidase/vascular adhesion protein 1",
author = "Norbert Haider and Iris Hochholdinger and P. M{\'a}tyus and Andrea Wobus",
year = "2010",
doi = "10.1248/cpb.58.964",
language = "English",
volume = "58",
pages = "964--970",
journal = "Chemical and Pharmaceutical Bulletin",
issn = "0009-2363",
publisher = "Pharmaceutical Society of Japan",
number = "7",

}

TY - JOUR

T1 - Synthesis of ortho-functionalized 4-aminomethylpyridazines as substrate-like semicarbazide-sensitive amine oxidase inhibitors

AU - Haider, Norbert

AU - Hochholdinger, Iris

AU - Mátyus, P.

AU - Wobus, Andrea

PY - 2010

Y1 - 2010

N2 - A series of 4-aminomethylpyridazines and -pyridazin-3(2H)-ones ("diaza-benzylamines"), bearing alkylamino side chains in ortho position relative to the CH2NH2 unit, was synthesized by catalytic hydrogenation of the corresponding nitriles in strongly acidic medium. N-Benzyl protecting groups either at the pyridazinone ring nitrogen or at an exocyclic nitrogen were selectively removed hydrogenolytically or by treatment with a Lewis acid. The new compounds were tested in vitro for semicarbazide-sensitive amine oxidase (SSAO) inhibitory activity and 4-(aminomethyl)-N,Ń-diethylpyridazine-3,5-diamine (22) was found to be the most active representative.

AB - A series of 4-aminomethylpyridazines and -pyridazin-3(2H)-ones ("diaza-benzylamines"), bearing alkylamino side chains in ortho position relative to the CH2NH2 unit, was synthesized by catalytic hydrogenation of the corresponding nitriles in strongly acidic medium. N-Benzyl protecting groups either at the pyridazinone ring nitrogen or at an exocyclic nitrogen were selectively removed hydrogenolytically or by treatment with a Lewis acid. The new compounds were tested in vitro for semicarbazide-sensitive amine oxidase (SSAO) inhibitory activity and 4-(aminomethyl)-N,Ń-diethylpyridazine-3,5-diamine (22) was found to be the most active representative.

KW - 4-Aminomethylpyridazine

KW - Diaza-benzylamine

KW - Selective debenzylation

KW - Semicarbazide-sensitive amine oxidase inhibitor

KW - Semicarbazide-sensitive amine oxidase/vascular adhesion protein 1

UR - http://www.scopus.com/inward/record.url?scp=77954301471&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77954301471&partnerID=8YFLogxK

U2 - 10.1248/cpb.58.964

DO - 10.1248/cpb.58.964

M3 - Article

VL - 58

SP - 964

EP - 970

JO - Chemical and Pharmaceutical Bulletin

JF - Chemical and Pharmaceutical Bulletin

SN - 0009-2363

IS - 7

ER -