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145733-36-4

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Pyridopyrimidine Angiotensin II Antagonists
A series of pyridopyrimidine angiotensin II (A II) antagonists was synthesized and tested for antagonism of A II. Compounds with a biphenyltetrazole pharmacophore and small alkyl groups at the 2- and 4-positions of the pyridopyrimidine ring were found to be the most potent in an AT1 receptor binding assay and in blocking the A II pressor response in anesthetized, ganglion-blocked A II-infused rats. 5,8-Dihydro-2,4-dimethyl-8--4-yl)methyl>pyridopyrimidin-7(6H)-one (4a) was one of the more potent compounds in the binding assay and was the most efficacious compound in the A II-infused rat model. Further study of 4a in Goldblatt (2K-1C) rats showed the compound to have oral bioavailability and to be an efficacious and potent compound in a high renin form of hypertension.
Ellingboe, John W.,Antane, Madelene,Nguyen, Thomas T.,Collini, Michael D.,Antane, Schuyler,et al.
p. 542 - 550
(2007/10/02)

SUBSTITUTED PYRROLOPYRIMIDINES, AZEPINOPYRIMIDINES AND PYRIDOPYRIMIDINES USEFUL AS ANGIOTENSIN II ANTAGONISTS
This invention relates to pyrrolo-, pyrido-, azepino-, and azocinopyrimidines of the general formula I STR1 wherein R 1, R. sup.2, R 3, and R 4 are independently H, lower alkyl containing 1 to 6 carbon atoms, or perfluoroalkyl containing 1 to 6 carbon atoms; R. sup.5 is H or when n is 1 R 5 taken together with R 3 comprises a double bond; n is 0 to 1; p is 0 to 2; m is 0 to 3; Ar 1 is STR2 wherein W is H, lower alkyl containing 1 to 6 carbon atoms, halogen, hydroxy, or lower alkoxy containing 1 to 6 carbon atoms; Ar 2 is STR3 wherein X is STR4 wherein R. sup.6 is H, tert-butyl, tri-n-butylstannyl, or triphenylmethyl; and the pharmaceutically acceptable salts thereof which by virtue of their ability to antagonize angiotensin II are useful for the treatment of hypertension, congestive heart failure, and restenosis. The compounds are also useful for reducing lipid levels in the blood plasma and are thus useful for treating hyperlipidemia and hypercholesterolemia. Also disclosed are processes for the production of said compounds and pharmaceutical compositions containing said compounds.
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(2008/06/13)

SUBSTITUTED PYRRIDOPYRIMIDINES USEFUL AS ANGIOTENSIN II ANTAGONISTS
This invention relates to pyrrolo-, pyrido-, azepino-, and azocinopyrimidines of the general formula I STR1 useful for treating hypertension and congestive heart failure, to pharmaceutical compositions, and to methods for production thereof.
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(2008/06/13)

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Chemical Properties

Melting Point: 197-199°
Boiling Point: 759.4 °C at 760 mmHg
Flash Point:413.1 °C
Density: 1.328 g/cm³
Solubility:DMSO (Slightly), Methanol (Slightly, Sonicated)
Storage Temp.:2-8°C
Vapor Pressure: 5.87E-23mmHg at 25°C
Refractive Index: 1.665
PKA: 4.16±0.10(Predicted)
PSA: 100.55000
LogP: 3.48490

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