George deStevens

Investigations in heterocycles. VIII. Quinazolines and pyrimidines

Abstract Various cycloalkenopyrimidines and quinazolines have been prepared from β-amino esters, β-keto esters and β-cyanoamines. Each of these intermediates has led to parent heterocyclic compounds which were easily correlated by alkylation reactions. The effect of hydrazine hydrate on 6,7-dihydro-2-methylthio-5 H -cyclopentapyrimidine-4-one ( XIII ) and on 5,6,7,8-tetrahydro-2-methylthio-4-quinazolinone has led to an unusual rearrangement. The nature of the rearranged product has been established by chemical and physical means, and a mechanism has been postulated to account for this transformation.

Stereochemical and polar effects in bromination of androstan-3-one mannich bases

Mannich-Basen von 5α-Androstan-3-one wurden unter thermodynamisch und kinetisch kontrollierten Bedingungen bromiert. Die Konformation der unter diesen Bedingungen erhaltenen Produkte wurde stark durch die sterischen und polaren Eigenschaften des Substituenten in 2-Stellung beeinflusst.

The chemistry of some new analgetics

In the period between January 1964 and June 1965, I was most fortunate in having been engaged in a collaborative effort with a number of highly capable people in bringing forth an edited work entitled Analgetics1. This work had as its goal to bring together between two covers the pertinent knowledge on the chemistry, pharmacology and clinical aspects of analgetics up to early 1965. Therefore, it is the purpose of these introductory comments to consider that the information on analgetics accrued up to 1965 to be essentially documented in the monograph just mentioned. En so doing our discourse will concern itself principally with the new body of knowledge which has become evident within the past three years; however, it is obvious that the knowledge of the past must form a necessary backdrop for the enfolding events of the present and future. To this end some basic concepts and definitions are in order. All animal species are capable of experiencing pain although the degree to which individuals react to this phenomenon is relative. This then refers to what is generally known as the pain threshold. It is that minimum level at which an animal, man or otherwise, responds to a painful stimulus. Obviously, the psychic influence to such a reaction is most important. Whether or not a lower animal realizes the full significance of exogenous induced pain and is able to associate this with environmental factors and at the same time relate this stimulus with pain resulting from a pathological disorder is a philosophical point. However, man does know the difference and is able to relate and distinguish them both to their immediate effect on his well-being and also as in the case of pathological pain, to his ultimate demise. Thus, the psychological effect on man experiencing pain is conditioned by the intrinsic nature of this stimulus. No doubt the impact of the stimulus on his mental and physical well-being is not without profound effects. These fine distinctions cannot be made, as far as we know, by the lower animals. It is for this reason that the laboratory study of pain and the alleviation of pain by means of drugs in experimental animals has proceeded so slowly. In fact, all we can note with animals is a response to an outside stimulus which we define as a reaction to pain. From these experiments we then seek to obtain an analgetic agent which is defined as a drug which depresses pain without loss of consciousness. Dr. Winter (the preceding lecture) has already referred to the various laboratory methods employed for detecting analgetic compounds in animals but none of these can truly be considered adequate. It is probably for this reason that the literature abounds with references to new analgetics. In a recent