3β-Chloro-5α-cholestan-6-one

The asymmetric unit of the title compound, C27H45ClO, consists of two crystallographically independent mol­ecules. In both mol­ecules, the three cyclo­hexane rings in the steroid fused-ring systems adopt chair conformations, while the cyclo­pentane ring adopts a half-chair conformation in one mol­ecule and an envelope conformation in the other. In the crystal, the mol­ecules are linked into a two-dimensional network by weak C—H⋯O hydrogen bonds. The crystal studied is a nonmerohedral twin with a refined ratio of twin components of 0.264 (3):0.736 (3)

Theobald Palm and His Remarkable Observation: How the Sunshine Vitamin Came to Be Recognized

The seminal discovery that sunlight was important in the prevention of nutritional rickets was made in 1890 by Theobald A. Palm, a medical missionary who contrasted the prevalence of rickets in northern European urban areas with similar areas in Japan and other tropical countries. He surmised that exposure to sunlight prevented rickets. Over the next 40 years his observation led to an understanding of ultraviolet irradiation and its role in vitamin D synthesis. This opened a new era of appreciation for the curative powers of the sun and “the sunshine vitamin”. While Palm’s observations were in some ways obscure, they had a potent effect on the development of photobiology

Structure‐Activity Relationship of Hetarylpropylguanidines Aiming at the Development of Selective Histamine Receptor Ligands †

New classes of alkylated hetarylpropylguanidines with different functionality and variation in spacer length were synthesized to determine their behavior at the four histamine receptor (H1R, H2R, H3R, H4R) subtypes. Alkylated guanidines with different terminal functional groups and varied basicity, like amine, guanidine and urea were developed, based on the lead structure SK&F 91486 (2). Furthermore, heteroatomic exchange at the guanidine structure of 2 led to simple analogues of the lead compound. Radioassays at all histamine receptor subtypes were accomplished, as well as organ bath studies at the guinea pig (gp) ileum (gpH(1)R) and right atrium (gpH(2)R). Ligands with terminal functionalization led to, partially, highly affine and potent structures (two digit nanomolar), which showed up a bad selectivity profile within the histamine receptor family. While the benzoylurea derivative 144 demonstrated a preference towards the human (h) H3R, S-methylisothiourea analogue 143 obtained high affinity at the hH(4)R (pK(i)=8.14) with moderate selectivity. The molecular basis of the latter finding was supported by computational studies