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zhgyg

铁杆木虫 (正式写手)
7.

[ Last edited by zhgyg on 2008-6-16 at 22:41 ]
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11楼2008-06-16 22:32:23
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fjxin2002

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★ ★ ★ ★ ★
chendiqing(金币+5,VIP+0):呵呵~~~
8.Lanthanide Triflate Catalyzed Biginelli Reaction. One-Pot Synthesis of Dihydropyrimidinones under Solvent-Free Conditions
Ma, Y.; Qian, C.; Wang, L.; Yang, M.
J. Org. Chem.; (Note); 2000; 65(12); 3864-3868.

[ Last edited by fjxin2002 on 2008-6-16 at 22:34 ]
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12楼2008-06-16 22:33:02
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zhgyg

铁杆木虫 (正式写手)
3.Pharmacologic profile of the dihydropyrimidine calcium channel blockers SQ 32,547 and SQ 32,926 [correction of SQ 32,946].Grover GJ, Dzwonczyk S, McMullen DM, Normandin DE, Parham CS, Sleph PG, Moreland S.
Department of Pharmacology, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, NJ 08543, USA.

SQ 32,926 and SQ 32,547, two dihydropyrimidine calcium channel blockers, were characterized as potent inhibitors of depolarization-induced contractions of isolated smooth muscle preparations. In rat aorta, the IC50 values were 5.5 nM for SQ 32,547 and 8.1 nM for SQ 32,926, values which compare favorably with that of 2.9 nM for nifedipine. The dihydropyrimidines were also tested in a model of stable angina: pacing-induced ischemia in dogs. Both SQ 32,547 and SQ 32,926 reduced the ST-segment elevation observed in vehicle-treated animals. No significant changes in hemodynamic status were detected, suggesting that a reduction in cardiac work secondary to afterload reduction was probably not a major contributor to the protective effects. Neither was increased coronary blood flow important for the antiischemic outcome because no significant effects of the dihydropyrimidines were observed on ischemic regional blood flow. SQ 32,547 was also studied in globally ischemic, isolated rat hearts. In this model, SQ 32,547 was protective because it significantly reduced contracture formation and lactate dehydrogenase (LDH) release. Washing out the effect of SQ 32,547 in isolated hearts and smooth muscles was difficult, presumably due to its lipophilicity. In the smooth muscle preparations, the effects of both nifedipine and SQ 32,926 were much more easily washed out. As with other calcium channel blockers, increasing the antiischemic effects of SQ 32,547 was associated with a higher cost in terms of cardiac function. In summary, the two novel dihydropyrimidines, SQ 32,547 and SQ 32,926 showed antiischemic properties in animal models.

PMID: 7475054 [PubMed - indexed for MEDLINE]
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13楼2008-06-16 22:38:08
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fjxin2002

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★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★ ★
chendiqing(金币+15,VIP+0):恩，确实是的~~~~
第七个查到了，比较难找。Design and synthesis of novel α1a adrenoceptor-selective antagonists L structure-activity relationship in dihydropyrimidinones     《Journal of Medicinal Chemistry》  Barrow J C Selnick H C Selnick H C   2000 / 43 / P 2703-2705
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14楼2008-06-16 22:38:11
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zhgyg

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chendiqing(金币+5,VIP+0):呵呵~~~~
4.Dihydropyrimidine calcium channel blockers. 3. 3-Carbamoyl-4-aryl-1, 2, 3, 4-tetrahydro-6-methyl-5

文献全文下载地址：http://pubs.acs.org/cgi-bin/abst ... 8.pdf?sessid=6006l3


比较难下，题目很长，你自己下下了打上把

[ Last edited by zhgyg on 2008-6-16 at 22:49 ]
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15楼2008-06-16 22:47:45
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fjxin2002

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4. Dihydropyrimidine calcium channel blockers:3-carbamoyl-4-aryl-1 2 3 4-tetrahydro-6-methyl-5-pyrimidinecarboxylic acid esters as orally effecitive antihypertensive agent     《Journal of Medicinal Chemistry》  Atwal K S Unger S E Unger S E   1991 / 34 / P 806
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16楼2008-06-16 22:50:17
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zhgyg

铁杆木虫 (正式写手)
详细的4：hydropyrimidine calcium channel blockers. 3. 3-Carbamoyl-4-aryl-1,2,3,4-tetrahydro-6-methyl-5-pyrimidinecarboxylic acid esters as orally effective antihypertensive agents.Atwal KS, Swanson BN, Unger SE, Floyd DM, Moreland S, Hedberg A, O'Reilly BC.
Squibb Institute for Medical Research, Princeton, New Jersey 08543-4000.

In order to explain the potent antihypertensive activity of the modestly active (IC50 = 3.2 microM) dihydropyrimidine calcium channel blocker 5, we carried out drug metabolism studies in the rat and found 5 is metabolized to compounds 6-10. Two of the metabolites, 6 (IC50 = 16 nM) and 7 (IC50 = 12 nM), were found to be responsible for the antihypertensive activity of compound 5. Potential metabolism of 6 into 7 in vivo precluded our interest in pursuing compounds related to 6. Structure-activity studies aimed at identifying additional aryl-substituted analogues of 7 led to 17g,j,p with comparable potential in vivo, though these compounds were less potent than 7 in vitro. To investigate the effects of absolute stereochemistry on potency, we resolved 7 via diastereomeric ureas 19a,b, prepared from 18 by treatment with (R)-alpha-methylbenzylamine. Our results demonstrate that the active R-(-)-enantiomer 20a of 7 is both more potent and longer acting than nifedipine (1) as an antihypertensive agent in the SHR. The in vivo potency and duration of 20a is comparable to the long-acting dihydropyridine amlodipine. The superior oral antihypertensive activity of 20a compared to that of previously described carbamates 2 (R2 = COOEt) could be explained by its improved oral bioavailability, possibly resulting from increased stability of the urea functionality.

PMID: 1995904 [PubMed - indexed for MEDLINE]
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17楼2008-06-16 22:50:18
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zhgyg

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还有金币啊，我还想要
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18楼2008-06-16 22:53:10
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zbcheng163

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8：Lanthanide triflate catalyzed Biginelli reaction. one-pot synthesis of dihydropyrimidinones under
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19楼2008-06-16 23:09:39
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