P a-methylene

Ap4A, diadenosine tetraphosphate BBG, Brilliant blue green BzATP, 2 - 3 -0-(4-benzoyl-benzoyl)-ATP cAMP, cyclic AMP CCPA, chlorocyclopentyl adenosine CPA, cyclopentyl adenosine CTP, cytosine triphosphate DPCPX, 8-cyclopentyl-1,3-dipnopylxanthine IP3, inosine triphosphate lpsl, diinosine penta phosphate a,p-meATP, a,p-methylene ATP p.y-meATP, p.y-meihylene ATP 2-MeSADP, 2-methylthio ADP 2-MeSAMP, 2-methylthio AMP 2-MeSATP, 2-methylthio ATP NECA, 5 -W-ethylcarboxamido adenosine PPADS, pyridoxal-phosphate-6-azophenyl-2, 4 -disulfonic acid PLC, phospholipase C RB2, reactive blue 2 TNP-ATP, 2, 3 -0-(2,4,6-trinitrophenyl) ATP. 

AOPCP, a, P-methylene-adenosine diphosphate APnA, diadenosine polyphosphate (n=3-6) ARL 67156,6-N,N-diethyl-D- 3,y-dibromomethylene ATP CMTA, 2-(3-cyano-4-isobutoxyphenyl)-4-methyl-5-thiazolecarboxylic acid EHNA, erythro-9-(2-hydroxy-3-nonyl)adenine NBTI, nitrobenzylthioinosine. 

Although a very reliable radioligand binding assay with use The search for P2X receptor of a stable ATP analog (e.g. a, p-methylene ATP) and subtype selective ligands... 

At low cure times, doublet peaks at 50.7 and 50.2 ppm were detected along with the peak at 37 ppm, and these peaks disappeared at longer cure times. The intensities of these two peaks were comparable for every detected pair. In the previous studies, the peaks at 50.7, 50.2, and 37 ppm were assigned to a quaternary carbon of Ale polysulfide, a methine carbon of Ale polysulfide, and a P methylene carbon of Ale polysulfide, respectively. 

Methylene-y-butyrolaciones. Alkylation of p-methylene-y-butyrolactone itself is impracticable, but substituted p-methylene-y-butyrolactones can be prepared by deprotonation and alkylation of 1 to afford 2, which cyclizes to a p-methylene-y-butyrolactone (3) on treatment with 40% aqueous HF in acetonitrile (9, 238-239). 

P2X, receptors show an order of potency for the natural ligands ATP > ADP and the unnatural ligands a.P-methylene-ATP and ATP-y-S are useful investigational agonists, but desensitization is very evident. These receptors are found in a number of smooth muscle preparations including arterioles, vas deferens and the urinary bladder, where they cause depolarization and contraction. They are found only in neonate brains. The form of the receptor here seems to be a homopolymer formed of identical units. At these sites, the ejps (excitatory junction potentials) seen on sympathetic nerve stimulation are caused in response to ATP action at P2X purinoceptors when it is liberated - as a cotransmilter - from sympathetic varicosities. 

P2X2 receptors are similar to P2X, receptors but a.P-methylene-ATP is not active and desensitization is not evident. These receptors were found originally in the adrenal medulla, and have now been demonstrated in a number of neuronal sites including sensory neurons and a number of areas in the central nervous system. 

P2Xs receptors have been cloned from rat. Here a,P-methylene-ATP is not active and desensitization is not evident. 

Rat vagus nerve, a, 3-methylene ATP as agonist [54], Guinea-pig aorta, 2-methylthio ATP as agonist [55]. Rat vas deferens [54]. iApparent pKg, derived fi-om a double-reciprocal regression. PPADS interacted with two affinity states of the P2X"Puri" PfO for [ H]a,p -methylene ATP. 

Figure 3. Effect of PPADS on the mechanical response of the rabbit isolated vas deferens to exogenous a,P-methylene ATP (a,P-mATP).

Two concentration response curves were constructed non-cumulatively on each preparation, the first in the absence ( ) and the second in the presence of PPADS ( 1 pM, 3 pM, and 10 pM). In order to prevent desensitization, very high concentrations of a,P methylene ATP were avoided in the first concentration-response curve. 

Figure 4. Schild plots for the antagonism by PPADS in the carbachol-contracted guinea-pig taenia coli using a, P-methylene ATP (a,P-mATP) and 2-methylthio ATP (2-MeSATP) as agonists. Lines, which connect the mean log (DR - 1) values at the respective PPADS concentration, are drawn to highlight the biphasic nature of the Schild plots. The slopes of the overall regression lines (not shown) were 1.46 for a,p-mATP and 0.58 for 2-MeSATP. These values were significantly different from unity.

Bovey et al.(3) also observed both H-links and Y branches in an NMR study of a normal alkane irradiated in vacuum in the molten state. The long chain Y branch was easy to recognize in the present study because of the presence of a methine resonance at 38.19 ppm, an a methylene resonance at 34.55 ppm and a P methylene resonance at 27.30 ppm. These assignments are in excellent agreement with those of Bovey et al. (3) and correspond closely to the methine and a, p methylene resonances observed for an ethylene-l-octene copolymer as shown below ... 

Various triphosphate analogues have been reported. Eckstein s group has prepared the 1,3-dithiotriphosphate of AZT, the first example of this modification, and also the 1,1-dithioderivative of TTP.226 xhc same workers have also made the 2 epimers of 1,2-dithio-GDP, and converted them to the four diastereomers of l,2-dithio-GTP.227 jhe a,p-methylene, fluoromethylene and difluoromethylene analogues of dATP and TTP have been synthesized,22S as has the p.y-difluoromethylene analogue of AZT triphosphate, the phosphonate proving to be some 30 times less inhibitory towards HIV reverse transcriptase than the triphosphate.229... 

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