ChemInform Abstract: FUNKTIONALISIERTE KETOSAEUREN 1. MITT. AMINOALKYLIERUNGEN MIT GLYOXYLSAEURE

Schreiber, Jean; Wermuth, Camille‐Georges; Meyer, Antoine

doi:10.1002/chin.197320152

Cited by 3 publications

(5 citation statements)

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“…Replacing the methyl group in the 4-position with a hydrogen was always beneficial (compare 10 and 22, 34 and 35, 40 and 41, 42 and 43). Replacement of the 4-methyl group by a phenyl group was detrimental (23). This also seemed to be true when the 4-methyl group was displaced to the 5-position (24) and more generally for 5-substituted analogues (25,26).…”

Section: Resultsmentioning

confidence: 96%

Synthesis and structure-activity relationships of a series of aminopyridazine derivatives of .gamma.-aminobutyric acid acting as selective GABA-A antagonists

Cg¹,

Jj²,

Schlewer³

et al. 1987

J. Med. Chem.

104

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We have recently shown that an arylaminopyridazine derivative of GABA, SR 95103 [2-(3-carboxypropyl)-3-amino-4-methyl-6-phenylpyridazinium chloride], is a selective and competitive GABA-A receptor antagonist. In order to further explore the structural requirements for GABA receptor affinity, we synthesized a series of 38 compounds by attaching various pyridazinic structures to GABA or GABA-like side chains. Most of the compounds displaced [3H]GABA from rat brain membranes. All the active compounds antagonized the GABA-elicited enhancement of [3H]diazepam binding, strongly suggesting that all these compounds are GABA-A receptor antagonists. None of the compounds that displaced [3H]GABA from rat brain membranes interacted with other GABA recognition sites (GABA-B receptor, GABA uptake binding site, glutamate decarboxylase, GABA-transaminase). They did not interact with the Cl- ionophore associated with the GABA-A receptor and did not interact with the benzodiazepine, strychnine, and glutamate binding sites. Thus, these compounds appear to be specific GABA-A receptor antagonists. In terms of structure-activity, it can be concluded that a GABA moiety bearing a positive charge is necessary for optimal GABA-A receptor recognition. Additional binding sites are tolerated only if they are part of a charge-delocalized amidinic or guanidinic system. If this delocalization is achieved by linking a butyric acid moiety to the N(2) nitrogen of a 3-aminopyridazine, GABA-antagonistic character is produced. The highest potency (approximately equal to 250 times bicuculline) was observed when an aromatic pi system, bearing electron-donating substituents, was present on the 6-position of the pyridazine ring.

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Section: Resultsmentioning

confidence: 96%

Synthesis and structure-activity relationships of a series of aminopyridazine derivatives of .gamma.-aminobutyric acid acting as selective GABA-A antagonists

Cg¹,

Jj²,

Schlewer³

et al. 1987

J. Med. Chem.

104

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“…Evidence for the Z configuration about the exocyclic double bond as shown for 10 (eq 4) was obtained when irradiation of the C2 CH3 group during NMR produced a nuclear Overhauser enhancement measured as 49% for the vinylic side-chain proton a to -CO2H. Examination by 7H NMR of crystallization liquors from 10 provided evidence of only a few percent of the E isomer (11), the preponderant material being 10. Isomer 11 was crystallized from mother liquors and characterized.…”

Section: Resultsmentioning

confidence: 86%

“…(E)-6-Fluoro-2-methyl-3-(p-methylthiobenzyl)-l-indenylideneacetic Acid (11). Mother liquors from several isolations of 10 were taken to dryness under vacuum.…”

Section: Direct Colorimetricmentioning

confidence: 99%

“…Each segment was eluted with methanol and checked by TLC. From the combined eluents of segments highly enriched in 16 a yellow solid was obtained, and it was recrystallized from 1:1 methanol-water: 47 mg; mp 178-181 °C; UV max 331 nm (e 15 700), 282 (24 000), and 240 (11 500) in 0.1 N HC1 in CH3OH; NMR (CDC13) 1.8 (s, 3, C2 CH3), 2.8 (s, 3, SCH3), 3.5 (s, 2, CH2), 6.55-7.8 (m, 8, aromatic and vinyl); mass spectrum m/e (rel intensity) 357 (11), 356 (M+, 49), 342 (15), 341 (71), 297 (20), 281 (22), 248 (30), 247 (35), 246 (33), 234 (33), 233 (100), 220 (17).…”

Section: -Fluoro-2-methyl-3-(p-methylthiobenzyl)indene-l-glycolicmentioning

confidence: 99%

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A sterically efficient synthesis of (Z)-5-fluoro-2-methyl-1-(p-methylthiobenzylidene)-3-indenylacetic acid and its S-oxide, sulindac

Shuman¹,

Pines²,

Shearin³

et al. 1977

J. Org. Chem.

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“…Exposure of vinylogous amide 11 to unsaturated keto ester 8 under nitrogen in refluxing pyridine or HOAc led only to hexahydroquinoline 12, which could be easily oxidized to tetrahydro- dation to 13. Vinylogous amide 11 clearly prefers to undergo conjugate addition 1,4 to the ketone under basic, neutral, and even acidic reaction conditions. In contrast, the reaction between enamino ketone 7 and 8 is greatly affected by solvent conditions.…”

mentioning

confidence: 99%

The regioselective behavior of unsaturated keto esters toward vinylogous amides

Bennett¹,

Mason²

1977

J. Org. Chem.

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ChemInform Abstract: FUNKTIONALISIERTE KETOSAEUREN 1. MITT. AMINOALKYLIERUNGEN MIT GLYOXYLSAEURE

Abstract: Die Mannich‐Reaktion des Cyclohexanons (I) mit Glyoxylsäure (II) und 2 Val Morpholin (III) liefert bei Raumtemperatur das Morpholiniumsalz (IV), beim Kochen unter Rückfluß entsteht das Butenolid (V).

Cited by 3 publications

References 0 publications

Synthesis and structure-activity relationships of a series of aminopyridazine derivatives of .gamma.-aminobutyric acid acting as selective GABA-A antagonists

Synthesis and structure-activity relationships of a series of aminopyridazine derivatives of .gamma.-aminobutyric acid acting as selective GABA-A antagonists

A sterically efficient synthesis of (Z)-5-fluoro-2-methyl-1-(p-methylthiobenzylidene)-3-indenylacetic acid and its S-oxide, sulindac

The regioselective behavior of unsaturated keto esters toward vinylogous amides

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