Abstract

One of the approaches to the treatment of psoriasis is via the antiproliferative and prodifferentiative activities of Vitamin D analogs or metabolites. The usefulness of this approach has been partially validated by the recent introduction by Bristol-Myers Squibb of calcipotriene, an effective topical treatment for psoriasis. Penederm Incorporated has recently acquired proprietary rights to 26,26,26,27,27,27-Hexafluoro-1-a,25-dihydroxy Vitamin D3 which is being developed by Sumitomo Pharmaceutical Company, Ltd. as a systemic medication for osteoporosis and has potential for use as a psoriasis treatment. Due to the high potency of the compound, safety evaluation and formulation development require the use of high specific activity radiolabeled material which is not commercially available. Because of metabolic considerations, it is desirable to label the compound in a position other than the alkyl side chain. The labeling scheme, developed by Dr. H. Paaren, utilizes a 9,11 unsaturated C D ring fragment for the tritiation step followed by coupling of an A ring precursor and deprotection to yield the desired product. The proposed scheme provides a facile means for the preparation of a non-labile, high specific activity tritium labeled Vitamin D3 analog for use in safety studies and formulation development. User Details: Experiment Details: State: Fo ster City, CA HPLC Funding Source: Industry NMR Charge: $4115.99 3.5 days Program Income: $3594.90 1 compound

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR001237-16
Application #
6119718
Study Section
Project Start
1998-08-01
Project End
2000-07-31
Budget Start
1997-10-01
Budget End
1998-09-30
Support Year
16
Fiscal Year
1998
Total Cost
Indirect Cost

  Institution

Name
Lawrence Berkeley National Laboratory
Department
Type
DUNS #
078576738
City
Berkeley
State
CA
Country
United States
Zip Code
94720

  Publications

Singh, Navneet; Moody, Alan R; Zhang, Bowen et al. (2017) Age-Specific Sex Differences in Magnetic Resonance Imaging-Depicted Carotid Intraplaque Hemorrhage. Stroke 48:2129-2135
Paul-Pletzer, Kalanethee; Yamamoto, Takeshi; Ikemoto, Noriaki et al. (2005) Probing a putative dantrolene-binding site on the cardiac ryanodine receptor. Biochem J 387:905-9
Wang, Huimin; Shimizu, Eiji; Tang, Ya-Ping et al. (2003) Inducible protein knockout reveals temporal requirement of CaMKII reactivation for memory consolidation in the brain. Proc Natl Acad Sci U S A 100:4287-92
Paul-Pletzer, Kalanethee; Yamamoto, Takeshi; Bhat, Manjunatha B et al. (2002) Identification of a dantrolene-binding sequence on the skeletal muscle ryanodine receptor. J Biol Chem 277:34918-23
Westler, William M; Frey, Perry A; Lin, Jing et al. (2002) Evidence for a strong hydrogen bond in the catalytic dyad of transition-state analogue inhibitor complexes of chymotrypsin from proton-triton NMR isotope shifts. J Am Chem Soc 124:4196-7
Tomizawa, M; Wen, Z; Chin, H L et al. (2001) Photoaffinity labeling of insect nicotinic acetylcholine receptors with a novel [(3)H]azidoneonicotinoid. J Neurochem 78:1359-66
Than, C; Morimoto, H; Williams, P G et al. (2001) Preparation, NMR characterization, and labeling reactions of tritiated triacetoxy sodium borohydride. J Org Chem 66:3602-5
Saljoughian, M; Williams, P G (2000) Recent developments in tritium incorporation for radiotracer studies. Curr Pharm Des 6:1029-56
Cianci, C; Yu, K L; Dischino, D D et al. (1999) pH-dependent changes in photoaffinity labeling patterns of the H1 influenza virus hemagglutinin by using an inhibitor of viral fusion. J Virol 73:1785-94
Palnitkar, S S; Bin, B; Jimenez, L S et al. (1999) [3H]Azidodantrolene: synthesis and use in identification of a putative skeletal muscle dantrolene binding site in sarcoplasmic reticulum. J Med Chem 42:1872-80

Showing the most recent 10 out of 28 publications