61085-38-9Relevant academic research and scientific papers
1,3,8-TRIAZASPIRO COMPOUNDS AND THEIR USE AS MEDICAMENTS FOR THE TREATMENT OF REPERFUSION INJURY
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Page/Page column 23, (2020/02/16)
The present invention relates to a 1,3,8-triazaspiro compound of Formula (I), wherein A is -CH2, -SO2 -, -NH-CO-, -NH-CS- or -CO-; the dashed line represents a single or double bond; R1 is a substituent selected from (C1-C3) alkyl, phenyl, thienyl and cyclohexyl, said substituent being optionally substituted by halogen or (C1 -C3) alkyl; and R2 is a substituent selected from H, (C1-C3) alkyl, (C1-C3) alkoxy, -CF3 and halogen; and wherein, when the dashed line is a double bond, A is -CH2 - and R1 is phenyl, or a pharmaceutically acceptable salt thereof for use in the treatment of reperfusion injury diseases. The 1,3,8-triazaspiro compound of the invention is a selective inhibitor of the C subunit of the F1/Fo-ATP synthase complex and a modulator of the mitochondrial permeability transition pore activity in mammalian cells and tissues, in the treatment of reperfusion injury diseases.
Discovery of Novel 1,3,8-Triazaspiro[4.5]decane Derivatives That Target the c Subunit of F1/FO-Adenosine Triphosphate (ATP) Synthase for the Treatment of Reperfusion Damage in Myocardial Infarction
Morciano, Giampaolo,Preti, Delia,Pedriali, Gaia,Aquila, Giorgio,Missiroli, Sonia,Fantinati, Anna,Caroccia, Natascia,Pacifico, Salvatore,Bonora, Massimo,Talarico, Anna,Morganti, Claudia,Rizzo, Paola,Ferrari, Roberto,Wieckowski, Mariusz R.,Campo, Gianluca,Giorgi, Carlotta,Trapella, Claudio,Pinton, Paolo
supporting information, p. 7131 - 7143 (2018/08/17)
Recent cardiology research studies have reported the role, function, and structure of the mitochondrial permeability transition pore (mPTP) and have shown that its opening plays a key role in the progression of myocardial cell death secondary to reperfusion. In this manuscript, we validated a new pharmacological approach as an adjunct to reperfusion in myocardial infarction (MI) treatment and describe the discovery, optimization, and structure-activity relationship (SAR) studies of the first small-molecule mPTP opening inhibitors based on a 1,3,8-triazaspiro[4.5]decane scaffold that targets the c subunit of the F1/FO-ATP synthase complex. We identified three potential compounds with good mPTP inhibitory activity and beneficial effects in a model of MI, including a decreased apoptotic rate in the whole heart and overall improvement of cardiac function upon administration during reperfusion. The selected compounds did not show off-target effects at the cellular and mitochondrial levels. Moreover, the compounds preserved the mitochondrial ATP content despite interacting with the ATP synthase complex.
TRIAZA-SPIRODECANONES AS DDR1 INHIBITORS
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Page/Page column 128; 176, (2017/01/26)
The present invention relates to compounds of formula (I) or pharmaceutically acceptable salts thereof, wherein L and R1 to R5 are as described herein, as well as processes for their manufacture, pharmaceutical compositions comprising them, and their use as medicaments.
N-(4-piperidinyl)-N-phenylamides
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, (2008/06/13)
Novel N-(4-piperidinyl)-N-phenylamides and -carbamates having very potent analgesic activity, methods of preparing same and useful intermediates therefor.
N-(4-piperidinyl)-N-phenylamides and -carbamates
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, (2008/06/13)
Novel N-(4-piperidinyl)-N-phenylamides and -carbamates having very potent analgesic activity, methods of preparing same and useful intermediates therefor.
