/pdf/the-lipophilic-bullet-hits-the-targets-medicinal-chemistry-5f1wikoz3q.pdf

The Lipophilic Bullet Hits the Targets: Medicinal Chemistry of Adamantane Derivatives

The present invention relates to 2-adamantylurea derivatives of formula I as selective inhibitors of the enzyme 11-beta-hydroxysteroid dehydrogenase type 1 (11β-HSD1) and the use of such compounds for the treatment and prevention of metabolic syndrome, diabetes, insulin resistance, obesity, lipid disorders, glaucoma, osteoporosis, cognitive disorders, anxiety, depression, immune disorders, hypertension and other diseases and conditions.

2-adamantylurea derivatives as selective 11beta-hsd1 inhibitors

Results on the preparation of N-substituted thioureas by the reaction of organic isothiocyanates with compounds containing an amino-grqup, by the action of alkali-metal thiocyanates on amine hydrochlorides, and by the treatment of primary and secondary amines with thiocarbonyl chloride or carbon disulphide, published in the Soviet and foreign literature including 1972, are systematically discussed. The reactions of hydrogen sulphide with substituted cyanamides and of thiourea with compounds containing various functional groups are also examined. Certain views are presented on the mechanism of the formation of N-substituted thioureas, and the advantages and disadvantages of various methods for their preparation are compared. Practical applications of N-substituted thioureas are considered. A list of 247 references is included.

https://iopscience.iop.org/article/10.1070/RC1973v042n07ABEH002677/pdf

Preparation of N-Substituted Thiourea

Acylimidazolides as Versatile Synthetic Intermediates for the Preparation of Sterically Congested Amides and Ketones: A Practical Synthesis of Proscar®

The chemistry of adamantane and related “cage-like” hydrocarbons has developed rapidly in recent years. These developments, encompassing a broad spectrum of the chemical world, have not been stimulated by any unique properties associated with the cage strutures of these molecules; the chemistry of such systems is typically hydrocarbon in nature. The particular utility of “cage-like” substrates in a variety of chemical investigations arises, for the most part, from their conformational rigidity; variables (e.g. those associated with structure) appropriate to more mobile compounds are often eliminated by the use of “cage-like” systems. The availability, ease of functionalization, and the near ideal structure of adamantane make it extremely useful for this purpose.

Recent developments in the chemistry of adamantane and related polycyclic hydrocarbons

Die Synthese des eine ringgebundene Carbonsaureamidgruppierung enthaltenden 3-[Admantyl-(1)]-3,4-dihydro-4-oxo-benzo[e]-1,2,3-triazins (7) nimmt ihren Ausgang in 2-Nitro-benzoesaure (1), die nach Uberfuhrung in ihr Saurechlorid 2 mit 1-Amino-adamantan (3) zu 2-Nitro-benzoesaure-[adamantyl-(1)]-amid (4) umgesetzt wird. Katalytische Hydrierung von 4 liefert 2-Aminobenzeosaure-[adamantyl-(1)]-amid (5). Uber das korrespondierende Diazoniumsalz 6 erfolgt Cyclisierung zu 7. Die unter der Einwirkung von Hydrazin und Raney-Nickel erfolgende Ringspaltung von 7 wird durch Bildung der Folgeprodukte 8, 10, 13 und 14 nachweisbar.



The Benzo-1,2,3-triazinc Ring System as Basis of Potentially Virustatic Compounds



The synthesis of 3-[1-adamantyl]-3,4-dihydro-4-oxo-benzo-[e]-1,2,3-triazine (7) containing a ring carboxylic acid amide grouping starts with 2-nitrobenzoic acid (1) which, after conversion into its acid chloride 2, is caused to react with 1-aminoadamantane (3) to give 2-nitrobenzoic acid-[1-adamantyl]-amide (4). Catalytic hydrogenation of 4 yields 2-amino-benzoic acid-[1-adamantyl]-amide (5). Cyclization to give 7 takes place via the corresponding diazonium salt 6. The ring cleavage occurring through the action of hydrazine and Raney nickel is substantiated by formation of the derivatives 8, 10, 13, and 14.

Antivirale Wirkstoffe. 5. Mitt. Das Benzo- 1,2,3-triazin-Ringsystem als Basis Potentiell virustatischer Verbindungen

1-Amino-adamantan als nucleophile substitutions-, additions- und ringspaltungskomponente

Aus der Uberfuhrung substituierter aliphatischer Carbonsauren (1a, b, c) in die korrespondierenden Saurechloride(2a, b, c), gefolgt von der Umsetzung mit 1-Amino-adamantan (3), 4-Phenoxyanilin (5a), 4-Amino-antipyrin (5b) oder Ammoniak (5c), gehen die entsprechenden Saureamide (4a, 4b, 4c, 6a, 6b, 6c) hervor. Adamantyl-(1)-acetamid (6c) geht unter der Einwirkung von P2O5 in Adamantyl-(1)-acetonitril (7) uber.



The Aliphatic Acid Amide Grouping as Partial Structure in Virustatics



By conversion of substituted aliphatic carboxylic acids (1a, b, c) into the corresponding carboxylic acid chlorides (2a, b, c) followed by the interaction with 1-aminoadamantane (3), 4-phenoxy-aniline (5a), 4-aminoantipyrine (5b) or ammonia (5c), the particular acid amides (4a, 4b, 4c, 6a, 6b, 6c) are formed. 1-Adamantylacetamide (6c) is converted into 1-adamantylacetonitrile by the action of P2O5.

Die aliphatische Säureamidgruppierung als Partialstruktur in Virustatika 3. Mitt. Antivirale Wirkstoffe

ur synthese und antiviruswirkung von adamantyl-(1)- thioharnstoffen

Die Umsetzung von 1-Amino-adamantan (1) mit Isothiocyanaten (2) resultiert in der Bildung von N-[Adamantyl-(1)]-thioharnstoffen (3). Der chemische Strukturbeweis fur 3 konnte durch Gegensynthese aus Adamantyl-(1)-isothiocyanat (4) und den korrespondierenden Aminen (5) erbracht werden.



Formation and Virus Inhibitory Activity of N-[1-Adamantyl]-thioureas



Interaction of 1-amino-adamantane (1) with isothiocyanates (2) results in the formation of N-[1-adamantyl]-thioureas (3). Chemical structure proof of 3 has been adduced by an independent synthesis involving the reaction of 1-adamantyl-isothiocyanate (4) with the corresponding amines (5).

Hans-Helmut Schröders

Papers

Antivirale Wirkstoffe. 5. Mitt. Das Benzo- 1,2,3-triazin-Ringsystem als Basis Potentiell virustatischer Verbindungen

1-Amino-adamantan als nucleophile substitutions-, additions- und ringspaltungskomponente

Die aliphatische Säureamidgruppierung als Partialstruktur in Virustatika 3. Mitt. Antivirale Wirkstoffe

ur synthese und antiviruswirkung von adamantyl-(1)- thioharnstoffen

Bildung und virushemmende Wirksamkeit von N‐[Adamantyl‐(1)]‐thioharnstoffen