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Ng HP May K Bauman JG Ghannam A Islam I Liang M Horuk R Hesselgesser J Snider RM Perez HD Morrissey MM 《Journal of medicinal chemistry》1999,42(22):4680-4694
Ligands for the CCR1 receptor (MIP-1alpha and RANTES) have been implicated in a number of chronic inflammatory diseases, most notably multiple sclerosis and rheumatoid arthritis. Because these ligands share a common receptor, CCR1, we sought to discover antagonists for this receptor as an approach to treating these disorders. A novel series of 4-hydroxypiperidines has been discovered by high throughput screening (HTS) which potently inhibits the binding of MIP-1alpha and RANTES to the recombinant human CCR1 chemokine receptor. The structure-activity relationships of various segments of this template are described as the initial HTS lead 1 was optimized synthetically to the highly potent receptor antagonist 6s. This compound has been shown to have at least 200-fold selectivity for inhibition of CCR1 over other human 7-TM receptors, including other chemokine receptors. In addition, data obtained from in vitro functional assays demonstrate the functional antagonism of compound 6s and structurally related analogues against the CCR1 receptor in a concentration dependent manner. The discovery and optimization of potent and selective CCR1 receptor antagonists represented by compound 6s potentially represent a novel approach to the treatment of chronic inflammatory diseases. 相似文献
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Yusuf HK Quazi S Kahn MR Mohiduzzaman M Nahar B Rahman MM Islam MN Khan MA Shahidullah M Hoque T Baquer M Pandav CS 《Indian journal of pediatrics》1996,63(1):105-110
An extensive iodine deficiency disorders survery was conducted in Bangladesh in 1993 to assess the latest iodine nutriture
status of the country. The clinical variables of the survey were goitre and cretinism, and the biochemical variable was urinary
iodine. The “EPI-30 cluster” sampling methodology was followed for selecting the survey sites. In each survey site, the study
population consisted of boys and girls, aged 5–11 years, and men and women, aged 15–44 years, in about equal populations.
the total number of survey sites was 78 and the total number of respondents was 30 072. The total number of urine samples
was 4512 (15% sub-sample). The current total goitre rate (grade 1+grade 2) in Bangladesh is 47.1% (hilly, 44.4%; flood-prone,
50.7%; and plains, 45.6%). The prevalence of cretinism in the country is 0.5% (hilly, 0.8%; flood-prone, 0.5%; and plains,
0.3%). Nearly 69% of Bangladeshi population have biochemical iodine deficiency (urinary iodine excretion [UIE]<10 mg/dl) (hilly,
84.4; flood-prone, 67.1%; and plains 60.4%). Women and children are more affected than men, in terms of both goitre prevalence
and UIE. The widespread severe iodine deficiency in all ecological zones indicates that the country as a whole is an iodine-deficient
region. Important recommendations of global interest are made from the experience of the survey.
An erratum to this article is available at . 相似文献
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