1,2-Amino Alcohols and Their Heterocyclic Derivatives as Chiral Auxiliaries in Asymmetric Synthesis

Isolation and synthesis of biologically active carbazole alkaloids

Recent progress in the synthesis of 1,2,3,4,-tetrahydroquinolines

A nanocrystal capable of light emission includes a nanoparticle having photoluminescence having quantum yields of greater than 30%.

Highly luminescent color-selective nanocrystalline materials

The chemistry of 2-oxazolines (1985–present)

A series of novel 6,7-disubstituted trans-3,4-dihydro-2, 2-dimethyl-4-pyrrolidino-(or piperidino)-2H-1-benzopyran-3-ols was prepared and tested for antihypertensive activity in the conscious spontaneously hypertensive rat (SHR) and compared with certain of their monosubstituted analogues. The potent blood pressure lowering activity of the 6-monosubstituted compounds was enhanced by incorporation of an acetylamino or amino group at C(7) and that of the 7-nitro-substituted compound by incorporation of an amino (but not an acetylamino group) at C(6). The combination of 6-nitro or 6-cyano with 7-(acetylamino) or 7-amino groups and 6-amino with 7-nitro groups in trans-4-pyrrolidino- or -4-piperidino-2,2-dimethyl-2H-1-benzopyranols conferred superior antihypertensive activity to hydralazine and to the calcium antagonist, nifedipine, in SHR. The synthetic route to these compounds involves the conversion of 2H-1-benzopyrans to bromohydrins that were treated with pyrrolidine or piperidine. Preparation of the 6-cyano-7-amino analogue was accomplished when 6-cyano-7-[(trifluoroacetyl)amino]-2,2-dimethylbenzopyran was used as starting material.

Synthesis and antihypertensive activity of substituted trans-4-amino-3,4-dihydro-2,2-dimethyl-2H-1-benzopyran-3-ols.

The synthesis and antihypertensive activity of a series of novel 3-[(substituted-carbonyl)amino]-2H-1-benzopyran-4-ols, administered orally to spontaneously hypertensive rats, are described. Optimum activity in this series was observed for compounds with branched alkyl or branched alkylamino groups flanking the carbonyl or thiocarbonyl group (21, 31-33), which were approximately equipotent to cromakalim. Replacement of the 4-hydroxyl group by hydrogen, methoxy, or amino in this series only led to a slight reduction in potency. These observations are in marked contrast to the structure-activity relationships previously found for the 4-amidobenzopyran-3-ols. The antihypertensive activity of representative compounds 15 and 33 was attempted by preatreatment with glibenclamide, and thus these compounds may belong to the series of drugs which have been classified as potassium channel activators.

Synthesis and antihypertensive activity of 3-[(substituted-carbonyl)amino]-2H-1-benzopyrans.

The action of diethylaminosulphur trifluoride (dast) on trans-4-amido- 3-Chromanols: Preparation of cis-amidoalcohols via oxazolines

The synthesis and antihypertensive activity in the spontaneously hypertensive rat of two new series of analogues related to cromakalim (1) are described. In the first series, where the benzopyran nucleus has been replaced by a pyranopyridine nucleus, the position of the nitrogen atom has been found to be critical for activity, and the most potent compounds are the pyrano[3,2-c]pyridines. In the second series, where the powerful electron-withdrawing cyano group of compound 1 has been replaced by alkyl and phenyl groups, the order of antihypertensive potency is ethyl, isopropyl, tert-butyl greater than propyl, cyclopentyl greater than methyl greater than phenyl.

Variation in the aromatic ring of cromakalim: antihypertensive activity of pyranopyridines and 6-alkyl-2H-1-benzopyrans.

Compounds of the formula (I): ##STR1## and salts and pro-drugs thereof, wherein: R1 is a hydrogen atom or a lower alkyl group; R2 is a hydrogen atom or a lower alkyl group; R3 is a hydrogen atom or a lower alkyl group; R4 is a hydrogen atom or an alkyl group; R5 is a lower alkyl or a substituted alkyl group; or R4 and R5 are joined so that together with the nitrogen atom to which they are attached they form a 5-, 6- or 7-membered ring optionally containing an oxygen or sulphur atom; R6 is an electron donating group; R7 is an electron withdrawing group; and the NR4 R5 and OR3 moieties are trans having antihypertensive activity, pharmaceutical compositions containing them and processes for their preparation.

John M. Evans

Papers

Synthesis and antihypertensive activity of substituted trans-4-amino-3,4-dihydro-2,2-dimethyl-2H-1-benzopyran-3-ols.

Synthesis and antihypertensive activity of 3-[(substituted-carbonyl)amino]-2H-1-benzopyrans.

The action of diethylaminosulphur trifluoride (dast) on trans-4-amido- 3-Chromanols: Preparation of cis-amidoalcohols via oxazolines

Variation in the aromatic ring of cromakalim: antihypertensive activity of pyranopyridines and 6-alkyl-2H-1-benzopyrans.

Anti-hypertensive chromanol derivatives