Antiulceratives

Anti tussive Antitussives Antiulcer therapy Antivert Antiviral agents... 

Thermodynamic properties such as heats of reaction and heats of formation can be computed mote rehably by ab initio theory than by semiempirical MO methods (55). However, the Hterature of the method appropriate to the study should be carefully checked before a technique is selected. Finally, the role of computer graphics in evaluating quantum mechanical properties should not be overlooked. As seen in Figures 2—6, significant information can be conveyed with stick models or various surfaces with charge properties mapped onto them. Additionally, information about orbitals, such as the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO), which ate important sites of reactivity in electrophilic and nucleophilic reactions, can be plotted readily. Figure 7 shows representations of the HOMO and LUMO, respectively, for the antiulcer dmg Zantac. 

The market for antiulcer agents (Fig. 1) is large and is comprised of both prescription and over the counter (OTC) products. The estimated prescription market is over 3 biUion aimuaHy in the United States, whereas the more difficult to estimate OTC market is in the range of 500 million aimuaHy. Several pharmaceutical companies are attempting to obtain approval for OTC use of prescription-only agents, and patent protection for several of the histamine antagonists mns out in the mid-1990s. 

CH2=CHCH(NH2)CH2CH2C00H (18), obtained through condensation of diethyl malonate with l,4-dichloro-2-butene [764-41-0] (43), or the antiulcer Rebamipide [90098-04-7] (19), whose synthesis involves the use of 2-(acetylamino)malonate (44), are examples of new pharmaceuticals recently launched. 

Nitromethane also is used in the synthesis of the antiulcer dmg, ranitidine [66357-35-5]. A two-step process utilizing nitromethane, carbon disulfide, potassium hydroxide, and dimethyl sulfate yields l,l-bis(methylthio)-2-nitroethene [13623-94 ] which reacts further to produce ranitidine. 

The therapeutic iadication (TI) is antiulcer, unless otherwise noted. 

Pyridine A Oxides. Analgesic and antiinflammatory dmgs niflumic acid [4394-00-7] (68) and pranoprofen [52549-17-4] (69) are manufactured from nicotinic acid N-oxide [2398-81 -4]. The antiulcer dmg omeprazole (66) is produced from 2,3,5-trimethylpyridine N-oxide [74409-42-0]. Zinc pyrithione, the zinc salt of pyrithione (45), is a fungicide derived from 2-chloropyridine N-oxide (45). 

Sucralfate [54182-58-0] an aluminum salt of sucrose octasulfate, is used as an antacid and antiulcer medication (59). Bis- and tris-platinum complexes of sucrose show promise as antitumor agents (60). Sucrose monoesters are used in some pharmaceutical preparations (21). A sucrose polyester is under evaluation as a contrast agent for magnetic resonance imaging (mri) (61). Oral adrninistration of this substance opacifies the gastrointestinal tract and eliminates the need for purging prior to mri. 

Another antiulcer histamine Hj receptor antagonist containing a thiazole moiety is zalb-dine (131) Its synthesis can be accomplished readily by brominating 4 acetyl 2 methylimidazole (129) to give haloketone 130 Displacement with amidinothiourea completes the synthesis of zaltidme (131) via a displacement cyclodehydration sequence [45]... 

The discovery of the antiulcer activity of H2 antihistamine antagonists has revolutionized the treatment of that disease. A benzimidazole. Omeprazole (55), inhibits gastric secretion and subsequent ulcer formation by a quite different mechanism. Studies at the molecular level suggest that this compound inhibits K /H dependent ATPase and consequently shuts down the proton pumping action of this enzyme system. 

A partially reduced quinoline derivative with antiulcerative and antisecretory activities is isotiquimide (14). It may be synthesized by metallating (with n-BuLi) 4-methyl-5,6,7,8-tetrahy-droquinoline and condensing this with dimethylmethoxysilylisothiocyanate to produce the desired thioamide isotiquimide (14) [4],... 

Therapeutic Function Antiulcer (free base as psychostimulant)... 

Therapeutic Function Anticholinergic, antiulcer Chemical Name Benzilic acid, 2i3iperidinoethyl ester ethobromide Common Name Piperilate ethyl bromide Structural Formula /= ... 

Yanagisawa, T., Wakabayashi, S., Tomiyama, T., Yasunami, M., and Takase, K. (1998). Synthesis and antiulcer activities of sodium alkylazulene sulfonates. Chem. Pharm. Bull. 36 641. 

---