Ho-Jane Shue

Identity of coleonol with forskolin: structure revision of a base-catalysed rearrangement product

Abstract The identity of coleonol and forskolin is shown through structure revision of a rearrangement product isolated earlier from coleonol and is confirmed by direct comparison of authentic coleonol with forskolin 1 ; in addition, coleonol-B should be correctly represented by structure 4 .

Synthesis of a series of sulfinic acid analogs of GABA and evaluation of their GABAB receptor affinities

A series of gamma-aminobutyric acid (GABA) 1 analogs was prepared in which the carboxylic acid group of GABA was replaced with a sulfinic acid group and their affinity for the GABAB receptor investigated.

Substituted morpholine-2S-acetic acid derivatives: Sch 50911 and related compounds as novel GABAB antagonists

Abstract The synthesis and GABA B antagonist activity of a series of substituted morpholine-2-acetic acid derivatives is described. Resolution of the lead compound from the series produces one active and one inactive enantiomer. X-ray analysis of a halogenated derivative ( 25 ) of the active enantiomer Sch 50911 ( 23 ) shows that it possesses the 2 S configuration.

Synthesis and resolution of β-(aminomethyl)-4-chlorobenzeneethanesulfinic acid a potent gabaB receptor ligand

Abstract The synthesis and resolution of β-(Aminomethyl)-4-chlorobenzeneethanesulfinic acid together with the GABAB receptor affinity for the racemate and enantiomers is described. In addition the synthesis and GABAB receptor affinity of the enantiomers of the known GABAB antagonist (Saclofen) is reported for the first time

Synthesis and NK1/NK2 binding activities of a series of diacyl-substituted 2-arylpiperazines

The synthesis and binding affinity for hNK(1) and hNK(2) receptors of a series of diacyl substituted 2-aryl piperazines are described. SAR evaluation led to the racemic derivative 11g as an apparent dual inhibitor. Chiral chromatographic separation of 11g led to the observation that NK(1) activity was shown by one enantiomer (13a) and NK(2) activity was shown by the other enantiomer (13b). X-ray crystallographic analysis of the crystalline di-BOC derivative of the NK(2) active piperazine (15) showed that the 2R configuration was associated with NK(2) activity. Further derivatization indicated that dual NK(1)/NK(2) activity could be built into the 2R series.

A study of 3-amino-N-hydroxypropanesulfonamide derivatives as potential GABAB agonists and their fragmentation to 3-aminopropanesulfinic acid

Abstract A series of 3-amino-N-hydroxypropanesulfonamide analogs was prepared. Several compounds showed potent binding at the GABA B receptor and were active in an in vitro functional assay. The GABA B activity of these compounds appeared to be due to the fragmented product, 3-aminopropanesulfinic acid.

SYNTHESIS AND STRUCTURE–ACTIVITY RELATIONSHIPS IN A NOVEL SERIES OF TOPICALLY ACTIVE CORTICOSTEROIDS

Abstract The influence of 7α-halogeno substitution on topical anti-inflammatory potency was studied in a series of prednisolone derivatives. 7α-Chloro, bromo and iodocorticosteroids were synthesized by hydrogen halide addition to the 6,7-dehydro compounds. 7α-Fluoro substituted steroids were obtained by reaction of the appropriate 7β-hydroxy compounds with N,N-diethyl(2-chloro-1,1,2-trifluoroethyl)amine. Antiinflammatory potencies were obtained using a modification of the croton oil ear test in mice. The greatest effect of a 7α-halogen was observed in the 16α-methylprednisolone series, where both 7α-chloro and 7α-bromo substitution yielded compounds equivalent in potency to betamethasone dipropionate. The enhancing effect of this substitution in other series was variable and less marked.

Recent advances in the structure-activity relationships of substituted corticosteroids

Abstract The influence of the 6-azido-6-ene grouping on corticosteroid activity has been studied. The 6-azido-6-ene-corticosteroids were synthesized by reaction of the methanesulfonate esters of 6β,7β-dihydroxycorti-costeroids with azide ion. These diols were the unexpected products of the reaction between OsO 4 and 6-ene-corticosteroids. Their β-stereochemistry was assigned unambiguously from their n.m.r. spectra and is contrary to that of some published assignments. Anti-inflammatory activity was measured by the suppression of exudate in the rat granuloma pouch assay. Potency of 9α-unsubstituted corticosteroids was found to be increased by 5–8 times on introduction of the 6-azido-6-ene group. Introduction of this modification into 9α-fluorocorticosteroids enhanced potency in the absence of a 1,2-double bond and left the potency substantially unchanged in the presence of a 1,2-double bond.

Anti-allergy agents. 3. Angular tricyclic ether derivatives of the 1,8-naphthyridin-2(1H)-one ring system☆☆☆

Abstract The compounds described are potent, orally active inhibitors of the release of the leukotriene mediators of anaphylaxis in vitro and in vivo . Unlike most “Mediator Release Inhibitors” (MRIs) described in the literature, they do not contain an acidic function. A series of potent, orally-active inhibitors of leukotriene release has been synthesized and tested in vitro and in vivo . The effects of ring size and substituents on anti-allergic activity have been examined.

Forskolin: a convenient degradation to 14,15-dinor-8,13-epoxy-1α,6β,7β,9α-tetrahydroxylabd-12-en-11-one 7-acetate 1,9-carbonate viaβ-elimination of an aldoxime

The title compound (6) was obtained by a an unprecedented β-elimination of the aldoxime (4).