Chapter 39 

 Agents Which Influence Nucleic Acid Metabolism 



R. E. Handschumacher and A. D. Welch 



Department of Pharmacology, School of Medicine, Yale University, 

 New Haven, Connecticut 



I. Introduction 453 



II. Compounds Which Interfere with the Formation of Folic Acid-Derived 

 Coenzymes 456 



1. Aminopterin and Amethopterin 456 



2. Diaminopyrimidines and Diaminodihydrotriazines 469 



III. Compounds Which Interfere with Animation Reactions in Purine and Py- 

 rimidine Synthesis 471 



IV. Structural Analogs of Purines and Their Metabolic Activity 477 



1 . 6-Mercaptopurine 478 



2. Thioguanine ." 484 



3. Azaguanine 487 



4. Diaminopurine 493 



5. Miscellaneous Purines 495 



V. Structural Analogs of Pyrimidines and Their Effects on Nucleic Acid Me- 

 tabolism 498 



1 . 5-Fluoropyrimidines 498 



2. Other Halogenated Pyrimidines 506 



3. 5- Amino-, 5-Mercapto-, and 5-Hydroxypyrimidine Derivatives 511 



4. Azapyrimidines 512 



5. Miscellaneous Pyrimidines 517 



VI. Other Agents Which Influence Nucleic Acid Metabolism 519 



1 . Urethane 519 



2. Miscellaneous 522 



VII. Concluding Remarks 525 



I. Introduction 



The elucidation of the chemical structure of most of the components of 

 both ribonucleic acid (RNA) and deoxyribonucleic acid (DNA) and the 

 pathways of their biosynthesis made possible the design and testing of a 

 variety of compounds which may alter these pathways or modify the com- 

 position of the resultant macromolecules. Appropriate alterations in bio- 

 synthetic pathways have several practical consequences. First, they allow 

 a more detailed study of individual reactions and pathways, as well as in- 

 vestigations of factors which are important in their control. Second, they 



453 



