1.2.3.4- Tetrahydropyrimidine derivative

Pyrantel pamoate (9.125), a tetrahydropyrimidine derivative, is a broad-spectrum antihelminthic active against pinworm and hookworm. This drug causes release of acetylcholine in the worm, producing stimulation and paralysis, leading to expulsion from the host s intestinal tract. 

Pyrantel pamoate is a tetrahydropyrimidine derivative. It is poorly absorbed from the gastrointestinal tract and active mainly against luminal organisms. Peak plasma levels are reached in 1-3 hours. Over half of the administered dose is recovered unchanged in the feces. 

Pyrimidine thiophosphates (528) are useful insecticides and acaricides (74FRP2197513), whereas the pyrimidine (529) was active against virulent Lewis lung tumour in mice (76JMC524). 2,3,6,7-Tetrahydropyrimidine derivatives (530) can be used in antimicrobial compositions for plants (74FRP2223371) close analogues are claimed to have useful antiinflammatory properties (77GEP2701853). 

Likewise, l-t-butyl-2-carbomethoxyazetidine 310 reacts with p-chlorodiphenylcarbo-diimide in tolnene at 130°C in the presence of bis(benzonitrile)palladium to give the tetrahydropyrimidine derivative 311. ... 

F urther modification of the arecoline structure involved replacement of the ester group of tetrahydropyrimidine derivatives (as in structures 139a-f) with a 1,2,4-oxadiazole ring (structures 168a-h) (199). 

Design and development of selective muscarinic agonists for the treatment of Alzheimer s disease characterization of tetrahydropyrimidine derivatives and development of new approaches for improved affinity and selectivity for Mj receptors... 

Rader et al. (1952) first found active protective fungicides among the tetra-hydropyrimidine derivatives later Nickell et al. (1961) also observed a systemic effect in some of the 2- -alkylmercapto-l,4,5,6-tetrahydropyrimidine derivatives used to combat rust. l- -Dodecyl-2-methyl-l,4,5,6-tetrahydropyrimidine (13) has also been applied in practice. It has proved efficient in orchards when used for the control of the disease caused by Erwinia amylovora which results in shoot withering and crown gall. 

Le Bail JC, Varnat F, Nicolas JC, Habrioux G (1998) Estrogenic and antiproliferative activities on MCF-7 human breast cancer cells by flavonoids. Cancer Lett 130 209 16 Sashidhara KV, Kumar M, Kumar A (2012) A novel route to synthesis of flavones from salicylaldehyde and acetophenone derivatives. Tetrahedron Lett 53 2355 2359 Sarda SR, Jadhav WN, Pawar RP (2009) Ij-AljO a suitable heterogeneous catalyst for the synthesis of flavones under microwave irradiation. Int Chem Tech Res 1 539-543 Kavala V, Lin C, Kuo CW, Fang H, Yao CF (2012) Iodine eatalyzed one-pot synthesis of flavanone and tetrahydropyrimidine derivatives via Mannieh type reaction. Tetrahedron 68 1321-1329... 

Syntheses from [4+2] atom fragments from an aniline and a pyrimidine derivative as sources of the heteroatoms have also been utilized. Heating isatoic anhydride 202 and 2-methylthio-l,4,5,6-tetrahydropyrimidine in DMF yielded 203 (Equation 22) <2000T8735>. 

Complementary triple hydrogen-bond formation involving transition metal complexes has been little studied. Mingos et al. [68] have investigated the cocrystallisation of platinum(II) complexes of the uracil derivative orotic acid (2,6-dioxo-l,2,3,6-tetrahydropyrimidine-4-carboxylic acid), which generally coordinates as the dianion, and 2,6-diaminopyridine (2,6-dap), in which complementary A-D-A---D-A-D triple hydrogen bonds are formed between the orotate... 

Catalytic reduction of cytidine in water over rhodium on alumina yields the tetrahydro derivative [l-(/3-D-ribofuranosyl)-4-aminotetrahydropyrimidin-2(l//)-one] and l-( 3-D-ribofuranosyl)tetrahydropyrimidin-2(l/0-one as the major products [680]. The former hydrolyses readily to give tetrahydrouridine,which is a potent inhibitor of human liver deaminase. The latter compound is also formed by sodium borohydride reduction of 5,6-dihydrouridine. 

It is of interest to note that a simple tetrahydropyrimidine, such as the 2-hydroxy derivative (XCIX), which actually is a cyclic urea, with the two protons probably on the nitrogen atoms, rather than the tautomer shown here. 

Some steps of the sequence proposed, of course, may be others, but key stages including formation of ot,p-unsaturated dicarbonyl derivative 16, cyclization into tetrahydropyrimidine 17, and dehydration are common in the most cases. 

Pyrantel Pyrantel, l,4,5,6-tetrahydro-l-methyl-2-[trans-2-(2-thienyl)vinyl]-pyrimidine (38.1.22), a derivative of tetrahydropyrimidine, is made from 3-(2-thienyl)-acrylonitrile (38.1.19), which is made in a Knoevangel condensation of fnrfnral with cyanoacetic acid. Acidic hydrolysis of this makes 3-2(-thienyl)acrylamide (38.1.20). Reacting this with propansnUone gives an iminoester (38.1.21), which when reacted with A-methyltrimethyl-enediamine gives the desired pyrantel [20-23]. 

There are now a reasonable number of reactions in which derivatives of pyrimidine are converted into pyridines. The tetrahydropyrimidine (792) is converted into a dihydropyridine by heating with silica and alumina (48HCA612). It was assumed that hydrolysis gave a ketoimine (also obtained directly from acetone and ammonia), which recydized. Pyrimidine itself is converted by hot (190 °C) aqueous ammonia or methylamine into 2-methyl-5-ethylpyridine (793) (71RTC1246), while 2-methoxy-5-arylpyrimidines (794) with... 

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