Pyrimidines pharmaceuticals

Many patents have been issued on the use of pyrogaUol derivatives as pharmaceuticals. PyrogaUol has been used extemaUy in the form of an ointment or a solution in the treatment of skin diseases, eg, psoriasis, ringworm, and lupus erythematosus. GaUamine triethiodide (16) is an important muscle relaxant in surgery it also is used in convulsive-shock therapy. Trimethoprim (2,4-diamino-5-(3,4,5-trimethoxybenzyl)pyrimidine) is an antimicrobial and is a component of Bactrin and Septra. Trimetazidine (l(2,3,4-trimethoxybenzyl)piperazine (Vastarel, Yosimilon) is used as a coronary vasodilator. l,2,3,4-Tetrahydro-6-methoxy-l-(3,4,5-trimethoxyphenyl)-9JT-pyrido[3,4- ]indole hydrochloride is useful as a tranquilizer (52) (see Hypnotics, sedatives, ANTICONVULSANTS, AND ANXIOLYTICS). Substituted indanones made from pyrogaUol trimethyl ether depress the central nervous system (CNS) (53). Tyrosine-and glycine(2,3,4-trihydroxybenzyl)hydrazides are characterized by antidepressant and anti-Parkinson activity (54). 

Cyclopent-2-en-l-one, 2-hydroxy-3-methyl-synthesis, 3, 693 Cyclopentenone, 4-methoxy-formation, 1, 423 Cyclopenthiazide as diuretic, 1, 174 Cyclopent[2,3-d]isoxazol-4-one structure, 6, 975 Cyclophane conformation, 2, 115 photoelectron spectroscopy, 2, 140 [2,2]Cyclophane conformation, 2, 115 Cyclophanes nomenclature, 1, 27 Cyclophosphamide as pharmaceutical, 1, 157 reviews, 1, 496 Cyclopiloselloidin synthesis, 3, 743 Cyclopolymerization heterocycle-forming, 1, 292-293 6H-Cyclopropa[5a,6a]pyrazolo[l,5-a]pyrimidine pyrazoles from, 5, 285 Cydopropabenzopyran synthesis, 3, 700 Cyclopropachromenes synthesis, 3, 671 Cyclopropa[c]dnnolines synthesis, 7, 597 Cyclopropanation by carbenes... 

Pyrimidine, 2-phenyl-1,4,5,6-tetrahydro-synthesis, 3, 115 Pyrimidine, 2-phenylthio-synthesis, 3, 136 Pyrimidine, polychloro-as pharmaceuticals, 1, 157 Pyrimidine, polyfluoroalkyl-synthesis, 3, 77 Pyrimidine, 5-(2-pyrrolyl)-synthesis, 4, 228 Pyrimidine, styryl-oxidation, 3, 76 polymers, 1, 289 synthesis, 3, 76... 

The initial pyrido[2,3-d]pyrimidines were first reported as Src inhibitors by Parke-Davis, now Pfizer, and the first disclosures of Abl activity were done in collaboration with academic researchers. Although the recent studies with these analogs were reported by academic groups, it has been stated that Sloan-Kettering is working with a pharmaceutical company to develop a compoimd from this class [92]. 

In addition to theophylline, purine or pyrimidine derivatives of pharmaceutical interest which have been analyzed include ftorafur, a fluorouracii derivative (429), arabinosides of adenine and hypoxanthine (408), ace-phylline (430), and allopurinol and oxipurinol (431). 

Other examples of pyrimidine-based pharmaceuticals include busipirone 1130, used to treat anxiety disorders, piribedil 1131 used for Parkinson s disease, epirizole 1132, a nonsteroidal antinflammatory (NSAID), pyrimethamine 1133, an antimalarial, minoxidil 1134, which is used for treating alopecia (male baldness), primidone 1135, which is used as an antiepileptic agent, and pyrantel pamoate 1136, which is used as an antiparasitic. 

The pyrazolo[3,4- pyrimidines 425 and 426 are claimed to be useful as pharmaceuticals for treatment of hyperuricemia and prevention of gout. 

Several pyrimidine aminoketones 108 (Scheme 32) have been prepared for potential use as intermediates in the synthesis of pharmaceutically interesting pyrimido-l,4-diazepines (86S886 87AP704). 

Ring transformations are common in pharmaceuticals. The API lorazepam containing a seven-membered non-aromatic ring can lose a molecule of water and rearrange with the driving force being formation of a six-membered aromatic pyrimidine ring (Fig. 115) (165). 

Of course, not all methods of cocrystal production require the use of auxiliary solvents. Thermal microscopy was used to determine if a particular carboxylic acid could cocrystallize with 2-[4-(4-chloro-2-fluorophe-noxy)phenyl]pyrimidine-4-carboxamide, with positive interactions being detected as crystalline material being produced at the binary interface [35]. Once identified, authentic cocrystal systems were prepared on a larger scale using solution-phase methods. In a similar study, hot-state microscopy was used to screen the possible interactions of nicotinamide with seven compounds of pharmaceutical interest that contained carboxylic acid groups [36]. A screening method for cocrystal formation based on differential scanning calorimetry has also been described, and used to demonstrate cocrystal formation in 16 out of 20 tested binary systems [37],... 

Tsuchiya, T., Kurita, J. and Takayama, K. (1980) Studies on diazepines. XIII. Photochemical behaviour of pyrazine, pyrimidine, and pyridazine N-imides. Chemical el Pharmaceutical Bulletin, 28 (9), 2676-2681. 

As pointed out, 5-FU derivatives are prodrugs and generally have to be converted into free 5-FU after administration for pharmaceutical activity. Therefore, 1 JV-carbamoyl and 1 V-carbonyl substituted 5-FUs have been synthesized. Scheme 3 shows the structure of 5-FU derivatives. The chemical shifts of C6—H of pyrimidine ring of 5-FU derivatives clearly differ from 5-FU. The solvolysis rates of lV-substituted 5-FUs, MAFU, VBFU, 1 -V-stearoyl-5-FU (STFU) and 1 -N-benzoyl-5-FU (BzFU) were estimated in DMSO-d6/CD3OD (2/1, v/v) at 60 °C by 1H NMR spectroscopy. From a typical time-course of an NMR spectrum of MAFU the first-order plots are obtained (Fig. 1). The observed... 

In many cases, the literature since CHEC-I of those systems in class (i) has been extensive, mainly because most are related to the purine nucleus by the inclusion of a further heteroatom for example azapurine derivatives which have shown pharmaceutical or physiological action. The methods of synthesis, except in a few cases, have not changed since the publication of CHEC-I and thus more emphasis has been placed on the physical properties, reactivity, and reactivity of substituents of compounds within these systems. In contrast, in most cases very little literature is available for systems of class (ii) and synthesis has assumed paramount importance. Only two reviews since the early 1980s are applicable to this chapter the conversion of [l,2,5]oxadiazolo[3,4- f]pyrimidines (9) to pteridines <82MI 713-01) and the chemistry and physical properties of 1,2,3-triazolo[4,5-djpyrimidines (7) <86AHC(39)l 17>. The incidence of publications relating to the use of Structures (1)-(50) in such applications as pharmaceuticals, agrochemicals, and even explosives has increased since the publication of CHEC-I and these are discussed in Section 7.13.10. 

New 3/ -acylamino-nortropanes (19) with a variety of A—CO (aroyl, pyrimidine-carboxylic, etc.) and R (benzyl, heteroarylmethyl, etc.) groups have been synthesized as potential pharmaceutical agents.23... 

As a class, the compounds derived from purine and pyrimidine bases are of considerable biochemical interest, particularly if they are the constituents of the nucleic adds. With their many hydrogen-bonding donor and acceptor functions, these molecules can interact specifically with the enzymes involved in the metabolism of the nucleic acids and with regulatory proteins. Purines, pyrimidines, and their derivatives have been used most successfully in the investigations of biological processes and have found application in pharmacology [520, 521]. The same is true for the barbiturates, where the main emphasis is in pharmaceutical industry. 

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