Monatsh Chem 139, 1409–1415 (2008) DOI 10.1007/s00706-008-0937-x Printed in The Netherlands Synthesis, and analgesic and antiparkinsonian activities of thiopyrimidine, pyrane, pyrazoline, and thiazolopyrimidine derivatives from 2-chloro-6-ethoxy-4-acetylpyridine Abd El-Galil E. Amr 1 , Soher S. Maigali 2 , Mohamed M. Abdulla 3 1 National Research Center, Applied Organic Chemistry Department, Dokki, Cairo, Egypt 2 National Research Center, Organometallic and Organometalloid Chemistry Department, Dokki, Cairo, Egypt 3 Research Units, Hi-Care Pharmaceutical Co., Cairo, Egypt Received 13 March 2008; Accepted 17 March 2008; Published online 2 June 2008 # Springer-Verlag 2008 Abstract A series of substituted pyridine derivatives were prepared from 2-chloro-6-ethoxy-4-acetylpyri- dine, which was prepared from the corresponding citrazinic acid as starting material. Reaction of ace- tylpyridine with thiophene-2-carboxaldehyde afforded the 2-chloro-6-ethoxy-4--(2-thienyl)acryloylpyridine, which was reacted with malononitrile in refluxing ethanol in the presence of piperidine as a catalyst to afford the cyanoaminopyrane derivative. Acryloylpyr- idine was treated with urea or guanidine hydrochlo- ride in refluxing ethanolic potassium hydroxide to give the corresponding pyrimidinone and aminopyrimidine derivatives. The latter was condensed with hydrazine hydrate or phenyl hydrazine to give pyrazoline and N-phenylpyrazoline derivatives. Finally, cycloaddition reaction of acryloylpyridine with thiourea yielded thioxopyrimidine, which was treated with 2-bromo- propionic acid, 3-bromopropionic acid, or bromo- acetic acid to yield methylthiazolo-, thiazino-, and thiazolopyrimidine derivatives. The arylmethylene derivative was prepared by reacting thiazolopyrimi- dine with benzaldehyde or by reacting thioxopyrimi- dine with benzaldehyde and bromoacetic acid in one step. The pharmacological screening showed that many of these compounds have good analgesic and antiparkinsonian activities comparable to Valdecoxib + and Benzatropine + as reference drugs. Keywords Citrazinic acid; 2-Chloro-6-ethoxy-4-acetylpyri- dine; Thiazolopyrimidine; Analgesic; Antiparkinsonian. Introduction In previous work we have reported that certain substituted pyridines and their chiral macrocyclic derivatives have antimicrobial [1–5], anticancer [6, 7], analgesic, and anticonvulsant [8, 9] activities. In addition, the biological and antiandrogenic activities of many heterocyclic compounds have been reviewed [10, 11]. On the other hand, thioxopyrimidine and thiazolopyrimidine derivatives have promising bio- logical activities, e.g., anticancer properties [12–16] and androgenic anabolic activities [17]. Recently, some new thienopyrimidinone derivatives have been synthesized and tested for their analgesic, anticonvul- sant, antiparkinsonian [18, 19], and antiinflammatory [20–23] activity. In view of these observations and in continuation of our previous work in heterocyclic chemistry, we synthesized some new thiopyrimidine, pyrane, pyrazoline, and thiazolopyrimidine deriva- tives using citrazinic acid as starting material and tested their analgesic and antiparkinsonian activities. Correspondence: Abd El-Galil E. Amr, National Research Center, Applied Organic Chemistry Department, Dokki, Cairo, Egypt. E-mail: aamr1963@yahoo.com