Joyce A. Reid

A mild and efficient method for the preparation of guanidines

Abstract A mild and efficient method for the preparation of guanidines by reaction of an acylated thiourea with an amine followed by removal of the acyl group(s) from the intermediate acylguanidine is reported.

Synthesis of the hydroxyethylene dipeptide isostere, (2S,4S,5S)-5-amino-6-cyclohexyl-4-hydroxy-2-isopropyl hexanoic acid n-butyl amide☆

Abstract A stereoselective synthesis of the hydroxyethylene dipeptide isostere, (2S,4S,5S)-5-amino-6-cyclohexyl-4-hydroxy-2-isopropyl hexanoic acid n-butyl amide from Boc-L-phenylalanine is described.

Novel methods for syntheses of substituted oxazoles by cyclization of vinyl bromides

Abstract Several methods for converting vinyl bromides and vinyl dibromides to oxazoles are described. Cyclization of vinyl bromide 6 with cesium carbonate in dioxane forms oxazole 7 while 6 is converted to the corresponding bromooxazole 12 by treatment with CuBr 2 /DBU.

Dual metalloprotease inhibitors. IV. Utilization of thiazepines and thiazines as constrained peptidomimetic surrogates in mercaptoacyl dipeptides

Abstract A structure-activity study of the dual acting ACE/NEP inhibitors related to 1a and 1b was undertaken to determine the parameters critical for activity versus ACE and NEP in vitro.

Molecular design and structure-activity relationships leading to the potent, selective, and orally active thrombin active site inhibitor BMS-189664.

A series of structurally novel small molecule inhibitors of human alpha-thrombin was prepared to elucidate their structure-activity relationships (SARs), selectivity and activity in vivo. BMS-189664 (3) is identified as a potent, selective, and orally active reversible inhibitor of human alpha-thrombin which is efficacious in vivo in a mouse lethality model, and at inhibiting both arterial and venous thrombosis in cynomolgus monkey models.

1,4-substituted indoles: a potent and selective class of angiostensin II receptor antagonists

The syntheses and pharmacological activity of a series of 1,4-substituted indoles which function as nonpeptidic antagonists of the angiotensin II (AII) receptor are described. Compounds in this series are orally active and demonstrate long lasting antihypertensive activity.

Thrombin active site inhibitors: chemical synthesis, in vitro and in vivo pharmacological profile of a novel and selective agent BMS-189090 and analogues.

A series of structurally novel small molecule inhibitors of human alpha-thrombin was prepared to elucidate their structure- activity relationships (SAR), selectivity and activity in vivo. BMS-189090 (5) is identified as a potent, selective, and reversible inhibitor of human alpha-thrombin that is efficacious in vivo in a mice lethality model, and in inhibiting both arterial and venous thrombosis in a rat model.

The use of diphenylmethyl as a sulfonamide protecting group

Abstract The use of diphenylmethyl (DPM) as a protecting group for sulfonamides is reported.

Diol sulfonamides: A potent and novel class of inhibitors of human renin

Abstract The syntheses and pharmacological activity of a series of diol sulfonamides which function as inhibitors of human renin are described. The most potent compound in this series, compound 20 (SQ 33,800 ), is a subnanomolar inhibitor of human renin (IC 50 = 0.35 × 10 −9 M).

Thoromboxane A2/endoperoxide receptor antagonists: 1,3-Dioxane and 1,3-dioxolane analogs

Synthesis and in vitro pharmacological profile of several 1,3-dioxane and 1,3-dioxolane analogs are described. Compounds 1c and 1f are the two most potent thromboxane receptor antagonists with Kd values of 8.0± 0.4 nM and 8.2 ±0.4 nM, respectively at the TxA2PGH2 receptor in human platelet membrane.