The synthesis and biological activity of a series of 2,4-diaminopyrido[2,3-d]pyrimidine based antifolates as antineoplastic and antiarthritic agents.
A new series of 2,4-diaminopyrido[2,3-d]pyrimidine based antifolates 1-3 were synthesized through an efficient conversion of 2-pivaloyl-4-oxo-6-ethynylpyrido[2,3-d]pyrimidine 5 to the corresponding 4-amino analog 7 via the activated 1,2,4-triazole intermediate 6. Compound 7 was used as the key intermediate for the preparation of the final products. The detailed biological evaluation of these compounds both as antineoplastic and antiarthritic agents will be discussed.
Gossett
L S
LS
Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, IN 46285, USA.
Habeck
L L
LL
Shackelford
K A
KA
Mendelsohn
L G
LG
Gates
S B
SB
Worzalla
J F
JF
Self
T D
TD
Theobald
K S
KS
Andis
S L
SL
Schultz
R M
RM
Shih
C
C
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D001169:Arthritis, Experimental / Q000188:drug therapy*; D004353:Drug Evaluation, Preclinical; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D005493:Folic Acid Antagonists / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D005971:Glutamates / Q000737:chemistry / Q000494:pharmacology; D006147:Guanine / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D019877:Hydroxymethyl and Formyl Transferases / Q000037:antagonists & inhibitors; D007938:Leukemia / Q000188:drug therapy; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy; D051379:Mice; D000068437:Pemetrexed; D010453:Peptide Synthases / Q000378:metabolism; D051026:Phosphoribosylglycinamide Formyltransferase; D011743:Pyrimidines / Q000737:chemistry; D051381:Rats; D013329:Structure-Activity Relationship; D013763:Tetrahydrofolates / Q000737:chemistry / Q000494:pharmacology; D013940:Thymidylate Synthase / Q000037:antagonists & inhibitors