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1246527-18-3

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1246527-18-3 Usage

Check Digit Verification of cas no

The CAS Registry Mumber 1246527-18-3 includes 10 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 7 digits, 1,2,4,6,5,2 and 7 respectively; the second part has 2 digits, 1 and 8 respectively.
Calculate Digit Verification of CAS Registry Number 1246527-18:
(9*1)+(8*2)+(7*4)+(6*6)+(5*5)+(4*2)+(3*7)+(2*1)+(1*8)=153
153 % 10 = 3
So 1246527-18-3 is a valid CAS Registry Number.

1246527-18-3Relevant articles and documents

Pharmacophore-based design of novel oxadiazoles as selective sphingosine-1-phosphate (S1P) receptor agonists with in vivo efficacy

Quattropani, Anna,Sauer, Wolfgang H. B.,Crosignani, Stefano,Dorbais, Jerome,Gerber, Patrick,Gonzalez, Jerome,Marin, Delphine,Muzerelle, Mathilde,Beltran, Fanny,Nichols, Anthony,Georgi, Katrin,Schneider, Manfred,Vitte, Pierre-Alain,Eligert, Valerie,Novo-Perez, Laurence,Hantson, Jennifer,Nock, Sebastien,Carboni, Susanna,De Souza, Adriano Luis Soares,Arrighi, Jean-Fran?ois,Boschert, Ursula,Bombrun, Agnes

, p. 688 - 714 (2015/04/14)

Sphingosine-1-phosphate (S1P) receptor agonists have shown promise as therapeutic agents for multiple sclerosis (MS) due to their regulatory roles within the immune, central nervous system, and cardiovascular system. Here, the design and optimization of novel [1,2,4]oxadiazole derivatives as selective S1P receptor agonists are described. The structure-activity relationship exploration was carried out on the three dominant segments of the series: modification of the polar head group (P), replacement of the oxadiazole linker (L) with different five-membered heterocycles, and the use of diverse 2,2′-disubstituted biphenyl moieties as the hydrophobic tail (H). All three segments have a significant impact on potency, S1P receptor subtype selectivity, physicochemical properties, and in vitro absorption, distribution, metabolism, excretion and toxicity (ADMET) profile of the compounds. From these optimization studies, a selective S1P1 agonist, N-methyl-N-(4-{5-[2-methyl-2′-(trifluoromethyl)biphenyl-4-yl]-1,2,4-oxadiazol-3-yl}benzyl)glycine (45), and a dual S1P1,5 agonist, N-methyl-N-(3-{5-[2′-methyl-2-(trifluoromethyl)biphenyl-4-yl]-1,2,4-oxadiazol-3-yl}benzyl)glycine (49), emerged as frontrunners. These compounds distribute predominantly in lymph nodes and brain over plasma and induce long lasting decreases in lymphocyte count after oral administration. When evaluated head-to-head in an experimental autoimmune encephalomyelitis mouse model, together with the marketed drug fingolimod, a pan-S1P receptor agonist, S1P1,5 agonist 49 demonstrated comparable efficacy while S1P1-selective agonist 45 was less potent. Compound 49 is not a prodrug, and its improved property profile should translate into a safer treatment of relapsing forms of MS.

Compounds and their use as BACE Inhibitors

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Page/Page column 43, (2012/07/13)

The present invention relates to compounds of formula (I) and their pharmaceutical compositions. In addition, the present invention relates to therapeutic methods for the treatment and/or prevention of Aβ-related pathologies such as Down's syndrome, β-amyloid angiopathy such as but not limited to cerebral amyloid angiopathy or hereditary cerebral hemorrhage, disorders associated with cognitive impairment such as but not limited to MCI (“mild cognitive impairment”), Alzheimer's disease, memory loss, attention deficit symptoms associated with Alzheimer's disease, neurodegeneration associated with diseases such as Alzheimer's disease or dementia including dementia of mixed vascular and degenerative origin, pre-senile dementia, senile dementia and dementia associated with Parkinson's disease, progressive supranuclear palsy or cortical basal degeneration.

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