1254073-77-2

Upstream product

• 723286-80-4 3-bromo-5,6-dihydro-8H-[1,2,4]triazolo[4,3-a]pyrazine-7-carboxylic acid tert-butyl ester 
• 17997-47-6 2-tri-n-butylstannylpyridine 
• 76003-29-7 4-(t-butyloxycarbonyl)piperazin-2-one 

Downstream Products

• 1338372-21-6 [1,1′-biphenyl]-4-yl(3-(pyridin-2-yl)-5,6-dihydro-[1,2,4]triazolo-[4,3-a]pyrazin-7(8H)-yl)methanone 
• 1338372-16-9 (4-fluorophenyl)(3-(pyridin-2-yl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)methanone 
• 1338372-18-1 (3-(4-chlorophenyl)-1H-pyrazol-5-yl)(3-(pyridin-2-yl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)methanone 
• 1338372-36-3 (3-(pyridin-2-yl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)(4-(thiophen-2-yl)phenyl)methanone 
• 1159522-34-5 3-(2-pyridyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine 

Relevant academic research and scientific papers

Discovery and Optimization of Novel Antagonists to the Human Neurokinin-3 Receptor for the Treatment of Sex-Hormone Disorders (Part I)

Neurokinin-3 receptor (NK3R) has recently emerged as important in modulating the tonic pulsatile gonadotropin-releasing hormone (GnRH) release. We therefore decided to explore NK3R antagonists as therapeutics for sex-hormone disorders that can potentially benefit from lowering GnRH pulsatility with consequent diminished levels of plasma luteinizing hormone (LH) and correspondingly attenuated levels of circulating androgens and estrogens. The discovery and lead optimization of a novel N-acyl-triazolopiperazine NK3R antagonist chemotype achieved through bioisosteric lead change from the high-throughput screening (HTS) hit is described. A concomitant improvement in the antagonist bioactivity and ligand lipophilic efficiency (LLE) parameter were the principal guidelines in the lead optimization efforts. Examples of advanced lead analogues to demonstrate the amenability of this chemotype to achieving a suitable pharmacokinetic (PK) profile are provided as well as pharmacokinetic-pharmacodynamic (PKPD) correlations to analyze the trends observed for LH inhibition in castrated rats and monkeys that served as preliminary in vivo efficacy models. (Chemical Presented).

5,6,7,8-TETRAHYDRO[1,2,4]TRIAZOLO[4,3-a]PYRAZINE DERIVATIVES AS P2X7 MODULATORS

The present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof wherein A is hydrogen, C1-4alkyl, C3-6cycloalkyl, C1-3alkoxy, C1-3alkoxy C1-4alkyl, C1-2fluoroalkyl, halogen, NR6 R7, optionally substituted heteroaryl (Het), or optionally substituted phenyl, and R1, R2, R3, R4, R5, R6 and R7 are as defined in the description. The compounds or salts are thought to modulate P2X7 receptor function and to be capable of antagonizing the effects of ATP at the P2X7 receptor. The invention also provides the use of the compound or salt in the treatment or prophylaxis of, for example, inflammatory pain, neuropathic pain, visceral pain, rheumatoid arthritis, osteoarthritis or neurodegenerative disorders.