Potential antitumor agents. 27. Quantitative structure--antileukemic (L1210) activity relationships for the omega-[4-(9-acridinylamino)phenyl]alkanoic acids. 1978

W A Denny, and B F Cain

Simple carboxylic acid derivatives of 9-anilinoacridine (e.g., 1,R=-COOH) provide high experimental antileukemic (L1210) activity. The homologous 1'-(CH2)nCOOH congeners also prove active, and there is a parabolic interrelationship between maximum increase in life span in L1210 tests and Rm values used as a measure of agent lipophilic--hydrophilic balance. The corresponding carboxamides [1'-(CH2)nCONH2] provide a similar parabolic relationship, which has an optimum Rm value displaced from that of the acids. Earlier examined 1'-NHSO2(CH2)nCH3 variants, the 3-NHCOCH3 congeners of these, and the carboxamide [1'-(CH2)nCONH2] and sulfonamide [1'-(CH2)nSO2NH2] homologues can be treated as one group and a correlation equation derived that is identical with that for the carboxamide variants alone. The optimum Rm value for this group is displaced from that of the acids by the equivalent of 1.8 log P units on the octanol--water scale. In this drug series a carboxylic acid residue acts as an acceptable hydrophilic unit, providing a log P contribution intermediate between that of the un-ionized acid and the totally ionized carboxylate anion. Quantitative effects of acridine ring substituents on L1210 activity differ in analogues containing either carboxylic acid or alkanesulfonanilde side chains, supporting the view that different site-binding orientations may be involved with these two drug classes.

UI MeSH Term Description Entries
D007939 Leukemia L1210 An experimental LYMPHOCYTIC LEUKEMIA of mice. Leukemia L 1210,L 1210, Leukemia,L1210, Leukemia
D008809 Mice, Inbred C3H An inbred strain of mouse that is used as a general purpose strain in a wide variety of RESEARCH areas including CANCER; INFECTIOUS DISEASES; sensorineural, and cardiovascular biology research. Mice, C3H,Mouse, C3H,Mouse, Inbred C3H,C3H Mice,C3H Mice, Inbred,C3H Mouse,C3H Mouse, Inbred,Inbred C3H Mice,Inbred C3H Mouse
D008811 Mice, Inbred DBA An inbred strain of mouse. Specific substrains are used in a variety of areas of BIOMEDICAL RESEARCH such as DBA/1J, which is used as a model for RHEUMATOID ARTHRITIS. Mice, DBA,Mouse, DBA,Mouse, Inbred DBA,DBA Mice,DBA Mice, Inbred,DBA Mouse,DBA Mouse, Inbred,Inbred DBA Mice,Inbred DBA Mouse
D008954 Models, Biological Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment. Biological Model,Biological Models,Model, Biological,Models, Biologic,Biologic Model,Biologic Models,Model, Biologic
D000166 Acridines Compounds that include the structure of acridine. Acridine
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000970 Antineoplastic Agents Substances that inhibit or prevent the proliferation of NEOPLASMS. Anticancer Agent,Antineoplastic,Antineoplastic Agent,Antineoplastic Drug,Antitumor Agent,Antitumor Drug,Cancer Chemotherapy Agent,Cancer Chemotherapy Drug,Anticancer Agents,Antineoplastic Drugs,Antineoplastics,Antitumor Agents,Antitumor Drugs,Cancer Chemotherapy Agents,Cancer Chemotherapy Drugs,Chemotherapeutic Anticancer Agents,Chemotherapeutic Anticancer Drug,Agent, Anticancer,Agent, Antineoplastic,Agent, Antitumor,Agent, Cancer Chemotherapy,Agents, Anticancer,Agents, Antineoplastic,Agents, Antitumor,Agents, Cancer Chemotherapy,Agents, Chemotherapeutic Anticancer,Chemotherapy Agent, Cancer,Chemotherapy Agents, Cancer,Chemotherapy Drug, Cancer,Chemotherapy Drugs, Cancer,Drug, Antineoplastic,Drug, Antitumor,Drug, Cancer Chemotherapy,Drug, Chemotherapeutic Anticancer,Drugs, Antineoplastic,Drugs, Antitumor,Drugs, Cancer Chemotherapy
D012995 Solubility The ability of a substance to be dissolved, i.e. to form a solution with another substance. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed) Solubilities
D013329 Structure-Activity Relationship The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus

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