The discovery of a series of new non-indole 5HT1D agonists

Lommen, Guy Van; Bruyn, Marcel De; Schroven, Marc; Verschueren, Wim; Janssens, W. J.; Verrelst, Jan; Leysen, Josée E.

doi:10.1016/0960-894x(95)00473-7

Cited by 24 publications

(4 citation statements)

References 13 publications

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“…In 1995, the Janssen laboratories described the synthesis and a SAR study of a series of 5HT 1D receptor agonists 249 . Among these compounds, a molecule with a 1,3‐diazepine moiety (compound 55 , Figure 29) demonstrated potent activity on 5HT 1D (pIC 50 = 6.8) and even better activity on 5HT 1A (pIC 50 = 8.7).…”

Section: Activity On G Protein‐coupled Receptors (Gpcrs)mentioning

confidence: 99%

1,3‐Diazepine: A privileged scaffold in medicinal chemistry

Malki

Martinez

Masurier

2021

Medicinal Research Reviews

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Privileged structures have been widely used as effective templates for drug discovery. While benzo‐1,4‐diazepine constitutes the first historical example of such a structure, the 1,3 analogue is just as rich in terms of applications in medicinal chemistry. The 1,3‐diazepine moiety is present in numerous biological active compounds including natural products, and is used to design compounds displaying a large range of biological activities. It is present in the clinically used anticancer compound pentostatin, in several recent FDA approved β‐lactamase inhibitors (e.g., avibactam) and also in coformycin, a natural product known as a ring‐expanded purine analogue displaying antiviral and anticancer activities. Several other 1,3‐diazepine containing compounds have entered into clinical trials. This heterocyclic structure has been and is still widely used in medicinal chemistry to design enzyme inhibitors, GPCR ligands, and so forth. This review endeavours to highlight the main use of the 1,3‐diazepine scaffold and its derivatives, and their applications in medicinal chemistry, drug design, and therapy. We will focus more particularly on the development of enzyme inhibitors incorporating this scaffold, with a strong emphasis on the molecular interactions involved in the inhibition mechanism.

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Section: Activity On G Protein‐coupled Receptors (Gpcrs)mentioning

confidence: 99%

1,3‐Diazepine: A privileged scaffold in medicinal chemistry

Malki

Martinez

Masurier

2021

Medicinal Research Reviews

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“…The 13 C NMR spectra were recorded on a solid-state high-resolution Bruker Avance-300 spectrometer operating at 75.47 MHz. The 15 N and 35 Cl NMR spectra were recorded on a Bruker Avance-500 spectrometer operating at 50.67 MHz for 15 N and 49.00 MHz for 35 Cl.…”

Section: Nmr and Ir Measurementsmentioning

confidence: 99%

“…In all cases a classical 4 mm probehead allowing spinning rates up to 10 kHz was used. 13 C and 15 N NMR chemical shifts are given relative to tetramethylsilane and neat nitromethane, respectively (precision 0.5 ppm). The spectra were recorded by use of cross-polarization (CP) from protons (contact time 2 ms) and magic angle spinning (MAS).…”

Section: Nmr and Ir Measurementsmentioning

confidence: 99%

Crystal structure, quantum mechanical investigation, IR and NMR spectroscopy of two new organic salts: (C8H12NO)·[NO3] (I) and (C8H14N4)·[ClO4]2 (II)

Bayar

Khedhiri

Soudani

et al. 2018

Journal of Molecular Structure

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Two new organic-inorganic hybrid materials, 4-methoxybenzylammonium nitrate, (C 8 H 12 NO)$[NO 3 ] (I), and 2-(1-piperazinyl)pyrimidinium bis(perchlorate), (C 8 H 14 N 4)$[ClO 4 ] 2 (II), have been synthesized by an acid/base reaction at room temperature, their structures were determined by single crystal X-ray diffraction. Compound (I) crystallizes in the orthorhombic system and Pnma space group with a ¼ 15.7908 (7), b ¼ 6.8032 (3), c ¼ 8.7091 (4) Å, V ¼ 935.60 (7) Å 3 with Z ¼ 4. Full-matrix least-squares refinement converged at R ¼ 0.038 and wR(F 2) ¼ 0.115. Compound (II) belongs to the monoclinic system, space group P2 1 /c with the following parameters: a ¼ 10.798(2), b ¼ 7.330(1), c ¼ 21.186(2) Å, b ¼ 120.641 (4) , V ¼ 1442.7 (3) Å 3 and Z ¼ 4. The structure was refined to R ¼ 0.044, wR(F 2) ¼ 0.132. In the structures of (I) and (II), the anionic and cationic entities are interconnected by hydrogen bonding contacts forming three-dimensional networks. Intermolecular interactions were investigated by Hirshfeld surfaces and the contacts of the four different chloride atoms in (II) were compared. The Molecular Electrostatic Potential (MEP) maps and the HOMO and LUMO energy gaps of both compounds were computed. The vibrational absorption bands were identified by infrared spectroscopy. These compounds were also investigated by solid-state 13 C, 35 Cl and 15 N NMR spectroscopy. DFT calculations allowed the attribution of the IR and NMR bands.

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“…Alniditan, a 5-HT 1B/D receptor agonist with no significant binding at the 5-HT 1F receptor, was developed for use in the treatment of acute migraine attacks (1). Alniditan is the first nonindole, nonergolide benzopyran derivative within the group of 5-HT 1B/D receptor agonists (2). It has a similarly high affinity for 5-HT 1B and 5-HT 1D serotonin receptors in radioligand binding studies (3) but differs from other sumatriptan successors in that it has very little affinity for 5-HT 1F receptors (4).…”

Section: Introductionmentioning

confidence: 99%

Treatment of Migraine Attacks with Intranasal Alniditan: An Open Study

Hc¹,

Louis²,

Schellens³

et al. 2001

Cephalalgia

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In this open phase-II clinical tolerability trial 17 neurologists enrolled a total of 112 patients and instructed them to administer a maximum of two doses of intranasal alniditan, a 5-HT1B/D receptor agonist, for the treatment of three consecutive migraine attacks of moderate to severe intensity. A second dose of the trial medication was allowed within 1-24 h after the first administration. At 1 h after intranasal administration, 70/103 (68%) patients had responded to treatment (reduction from severe or moderate headache before treatment to mild or no headache) after their first migraine attack, 65/94 (69%) after their second and 52/75 (71%) after their third. In 187/270 (69%) of all attacks, patients were considered responders at 1 h. The median time to onset of effect was 30 min. The migraine headache recurred in 44% (attack 1), 55% (attack 2) and 44% (attack 3) after 4-5 h. Sixty-eight per cent of the patients reported nasal irritation, 19% taste disturbance and 44% throat irritation. Alniditan 2 mg, administered via the intranasal route, was effective in relieving migraine headaches in over two-thirds of the patients at 1 h.

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The discovery of a series of new non-indole 5HT1D agonists

Cited by 24 publications

References 13 publications

1,3‐Diazepine: A privileged scaffold in medicinal chemistry

1,3‐Diazepine: A privileged scaffold in medicinal chemistry

Crystal structure, quantum mechanical investigation, IR and NMR spectroscopy of two new organic salts: (C8H12NO)·[NO3] (I) and (C8H14N4)·[ClO4]2 (II)

Treatment of Migraine Attacks with Intranasal Alniditan: An Open Study

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