Delving into the Latest Updates on Daglutril with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

((3S)-3-{1-((2R)-2-Ethoxycarbonyl-4-phenylbutyl)cyclopentanecarboxamido}-2-oxo-2,3,4,5-tetrahydro-1H-1-benzazepin-1-yl)acetic acid

+ [1]

Target

CD10 x ECE

Mechanism

ECE inhibitors(Endothelin-converting enzyme 1 inhibitors), enkephalinase inhibitors(Neprilysin inhibitors)

Therapeutic Areas

Cardiovascular DiseasesEndocrinology and Metabolic DiseaseRespiratory Diseases+ [2]

Active Indication-

Inactive Indication

Diabetes Mellitus, Type 2Heart FailureHypertension+ [2]

Originator Organization

AbbVie, Inc.

Active Organization-

Inactive Organization

Solvay Pharmaceuticals, Inc.

AbbVie, Inc.AbbVie AS

Drug Highest PhasePendingPhase 2

First Approval Date-

Regulation-

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Structure

Molecular FormulaC31H38N2O6

InChIKeyXMQODGUTLZXUGZ-RPBOFIJWSA-N

CAS Registry182821-27-8

AbstractThe penetration of the new psychoactive substances (NPSs) into the market of clandestine drugs is highly dynamic, causing potentially false-negative results using the current analytical instrumentation, particularly in the screening phase. At present, the suggested approach to perform a comprehensive screening requires the use of high-resolution mass spectrometry (MS) with associated high costs of purchase and maintenance and need of skilled and dedicated personnel. Here we describe the development and validation of a simplified approach based on a high-performance liquid chromatography–ion trap MS system with a user-friendly interface dedicated to toxicological analysis. The system, originally intended for a broad toxicological screening, was tuned to identify new synthetic cannabinoids in hair. After a washing step with dichloromethane, hair (about 50 mg) was incubated for 3 h with 1.5 mL ethanol. One milliliter of this solution was then dried, reconstituted with mobile phase and injected. The peak identification was based on the chromatographic retention times and MS2/MS3 data using a database which included up to 158 NPSs. The method was validated according to international guidelines on a selected panel of NPSs, namely methyl 2-[[1-(5-fluoropentyl)indazole-3-carbonyl]amino]-3,3-dimethylbutanoate (5F-ADB), 1-Pentyfluoro-1H-indole-3-carboxylic acid 8-quinolinyl ester (5F-PB 22), N-[(2S)-1-amino-3-methyl-1-oxobutan-2-yl]-1-(5-chloropentyl)indazole-3-carboxamide (5Cl-AB-PINACA), (S)-N-(1-amino-1-oxo-3-phenylpropan-2-yl)-1-(5-fluoropentyl)-1H-indole-3-carboxamide [5F-APP-PICA (PX-1)],: (R)-N-(1-amino-1-oxo-3-phenylpropan-2-yl)-1-(5-fluoropentyl)-1H-indazole-3-carboxamide [5F-APP-PINACA (PX-2)], N-[(2S)-1-Amino-3-methyl-1-oxobutan-2-yl]-1-(cyclohexylmethyl)indazole-3-carboxamide (AB-CHMINACA), N-[(2S)-1-Amino-3-methyl-1-oxobutan-2-yl]-1-[(4-fluorophenyl)methyl] indazole-3-carboxamid (AB-FUBINACA), methyl (2S)-2-[[1-(cyclohexylmethyl)indole-3-carbonyl]amino]-3,3-dimethylbutanoate (MDMB-CHMICA), (S)-Methyl 2-(1-(5-fluoropentyl)-1H-indole-3-carboxamido)-3-methylbutanoate (MMB-2201) and (1-pentylindol-3-yl)-(2,2,3,3-tetramethylcyclopropyl)methanone (UR-144). The tested analytical method showed detection limits between 0.065 and 0.125 ng/mg. The intraday imprecision of the method showed average values within the range of 7.3–20%. The estimation of the trueness (bias) of method showed average values within the range of 1.5–12.3%. The analytical performance was also successfully assessed by four proficiency test samples containing NPS. No synthetic cannabinoids were detected in application to 82 hair samples from forensic cases previously analyzed with liquid chromatography–MS triple quadrupole.

01 Jun 2018·AndrologiaQ4 · MEDICINE

Endopeptidase inhibition attenuates the contraction induced by big endothelin‐1 of isolated human penile erectile tissue

Q4 · MEDICINE

Article

Author: Shahin, P. ; Rahardjo, H. E. ; Kuczyk, M. A. ; Sohn, M. ; Ückert, S. ; Bannowsky, A. ; Tsikas, D.

Peptides, such as C-type natriuretic peptide (CNP), vasoactive intestinal polypeptide (VIP) and endothelin 1 (ET-1), are involved in the control of penile erectile tissue (corpus cavernosum = CC). Inhibiting the degradation of CNP and VIP or conversion of Big ET-1 into ET-1 by endopeptidase enzymes should result in an enhancement of CC smooth muscle relaxation. Using the tissue bath technique, responses of isolated CC, challenged by noradrenaline (NA, 1 μm), to increasing concentrations of the endopeptidase inhibitor KC 12615 (1 nm - 10 μm), CNP and VIP (0.1 nm - 1 μm), were investigated. Effects of CNP, VIP and Big ET-1 (0.1 nm - 100 nm) on the tissue tension were also evaluated following pre-exposure to 10 μm of KC 12615. Big ET-1 induced contraction of the CC amounting to a force generation of 1,200 mg. The contraction was attenuated in the presence of KC 12615 by 35% and 50%, respectively. The tension induced by NA was reversed by VIP and CNP to 38.7% ± 15.8% and 61% ± 13%, respectively, of the initial force. The findings might be of significance with regard to future pharmacological treatment options for male ED, where an endothelial dysfunction exists.

01 Dec 2016·AndrologiaQ4 · MEDICINE

Effects of endopeptidase inhibition on the relaxation response of isolated human penile erectile tissue to vasoactive peptides

Q4 · MEDICINE

Article

Author: Sonnenberg, J. E. ; Reichelt, K. ; Ückert, S. ; Kuczyk, M. A. ; Sohn, M. ; Rahardjo, H. E.

Peptides, such as CNP, CGRP and VIP, are involved in the function of male penile erectile tissue. Tissue levels of said peptides are controlled by the endopeptidase enzymes. Theoretically, the inhibition of the degradation of CNP, CGRP and/or VIP should result in an enhancement in penile smooth muscle relaxation. The effects were investigated of CNP or VIP (0.1 nm-1 μm), without and following pre-exposure of the tissue to a threshold concentration of the endopeptidase inhibitor KC 12615 (10 μm, for 20 min), on the reversion of tension induced by means of electrical field stimulation. Drug effects on the production of cyclic AMP/GMP were also evaluated. Neither KC 12615, CNP and VIP nor the combination of CNP plus KC 12615 or VIP plus KC 12615 increased the response of the tissue to EFS. While no effects were observed of a pre-exposure of the tissue to KC 12615 on the production of cyclic AMP in the presence of VIP, an enhancement was registered in the accumulation of cyclic AMP in the presence of CNP plus KC 12615. Further studies are indicated to investigate whether endopeptidase inhibitors might tend to be more effective in tissues affected by a decreased local production of vasoactive peptides.

100 Deals associated with Daglutril

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External Link

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB05796

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Diabetes Mellitus, Type 2	Phase 2	IT	Solvay Pharmaceuticals, Inc.	01 Jul 2005
Kidney Diseases	Phase 2	IT	Solvay Pharmaceuticals, Inc.	01 Jul 2005
Heart Failure	Phase 2	DE	AbbVie AS	-
Heart Failure	Phase 2	-	AbbVie, Inc.	-
Heart Failure	Phase 2	US	AbbVie AS	-
Hypertension	Phase 2	US	AbbVie AS	-
Hypertension	Phase 2	EU	AbbVie AS	-
Pulmonary Arterial Hypertension	Phase 2	-	AbbVie, Inc.	-