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US 2020/0399298 A1Published application
Prodrugs of prostate specific membrane antigen (psma) inhibitor
AssigneesThe Johns Hopkins University, Institute of Organic Chemistry and Biochemistry of the AS CR, V.V.I.
InventorsBARBARA SLUSHER, RANA RAIS, MARCELA KRECMEROVA, TOMAS TICHY, PAVEL MAJER, ANDREJ JANCARIK
Life of this patent
Estimating the term…
Abstract
Methods and compounds are disclosed for treating a disease or condition by inhibiting PSMA (Prostate Specific Membrane Antigen) using prodrugs of 2-PMPA
Claims20
-40. (canceled)
A composition comprising a dose of a compound of formula (I) or formula (II) dissolved in an aqueous solution, wherein the aqueous solution comprises a pharmaceutically acceptable carrier and a physiologically compatible buffer, and wherein the compound of formula (I) or formula (II) are:
- wherein:
- (a) each R1 is H;
- each R2 is selected from the group consisting of H, alkyl, Ar, —(CR5R6)n—Ar, —(CR5R6)n—O—C(═O)—R7, —(CR5R6)n—C(═O)—O—R7, —(CR5R6)n—O—C(═O)—O—R7, —(CR5R6)n—O—R7, —(CR5R6)n—O—[(CR5R6)n—O]m—R7, —(CR5R6)n—Ar—O—C(═O)—R7, —Ar—C(═O)—O—(CR5R6)n—R7, —(CR5R6)n—NR8R9, and —(CR5R6)n—C(═O)—NR8R9;
- each R3 is selected from the group consisting of H, alkyl, Ar, —(CR5R6)n—Ar, —(CR5R6)n—O—C(═O)—R7, —(CR5R6)n—C(═O)—O—R7, —(CR5R6)n—O—C(═O)—O—R7, —(CR5R6)n—O—R7, —(CR5R6)n—O—[(CR5R6)n—O]m—R7, —(CR5R6)n—Ar—O—C(═O)—R7, —Ar—C(═O)—O—(CR5R6)n—R7, —(CR5R6)n—NR8R9, and —(CR5R6)n—C(═O)—NR8R9;
- and
- each R4 is selected from the group consisting of —(CR5R6)n—O—C(═O)—R7, —(CR5R6)n—C(═O)—O—R7, —(CR5R6)n—O—C(═O)—O—R7, —(CR5R6)n—O—R7, —(CR5R6)n—O—[(CR5R6)n—O]m—R7, —(CR5R6)n—Ar—O—C(═O)—R7, —Ar—C(═O)—O—(CR5R6)n—R7, —(CR5R6)n—NR8R9, and —(CR5R6)n—C(═O)—NR8R9;
- (b) each R1 is alkyl;
- each R2 is selected from the group consisting of H, alkyl, Ar, —(CR5R6)n—Ar, —(CR5R6)n—O—C(═O)—R7, —(CR5R6)n—C(═O)—O—R7, —(CR5R6)n—O—C(═O)—O—R7, —(CR5R6)n—O—R7, —(CR5R6)n—O—[(CR5R6)n—O]m—R7, —(CR5R6)n—Ar—O—C(═O)—R7, —Ar—C(═O)—O—(CR5R6)n—R7, —(CR5R6)n—NR8R9, and —(CR5R6)n—C(═O)—NR8R9;
- each R3 is selected from the group consisting of H, alkyl, Ar, —(CR5R6)n—Ar, —(CR5R6)n—O—C(═O)—R7, —(CR5R6)n—C(═O)—O—R7, —(CR5R6)n—O—C(═O)—O—R7, —(CR5R6)n—O—R7, —(CR5R6)n—O—[(CR5R6)n—O]m—R7, —(CR5R6)n—Ar—O—C(═O)—R7, —Ar—C(═O)—O—(CR5R6)n—R7, —(CR5R6)n—NR8R9, and —(CR5R6)n—C(═O)—NR8R9;
- and
- each R4 is selected from the group consisting of Ar, —(CR5R6)n—O—C(═O)—R7, —(CR5R6)n—C(═O)—O—R7, —(CR5R6)n—O—C(═O)—O—R7, —(CR5R6)n—O—R7, —(CR5R6)n—O—[(CR5R6)n—O—]m—R7, —(CR5R6)n—Ar—O—C(═O)—R7, —Ar—C(═O)—O—(CR5R6)n—R7, —(CR5R6)n—NR8R9, and —(CR5R6)n—C(═O)—NR8R9;
- (c) each R1 is —(CR5R6)n—Ar;
- each R2 is selected from the group consisting of H, alkyl, Ar, —(CR5R6)n—Ar, —(CR5R6)n—O—C(═O)—R7, —(CR5R6)n—C(═O)—O—R7, —(CR5R6)n—O—C(═O)—O—R7, —(CR5R6)n—O—R7, —(CR5R6)n—O—[(CR5R6)n—O]m—R7, —(CR5R6)n—Ar—O—C(═O)—R7, —Ar—C(═O)—O—(CR5R6)n—R7, —(CR5R6)n—NR8R9, and —(CR5R6)n—C(═O)—NR8R9;
- each R3 is selected from the group consisting of H, alkyl, Ar, —(CR5R6)n—Ar, —(CR5R6)n—O—C(═O)—R7, —(CR5R6)n—C(═O)—O—R7, —(CR5R6)n—O—C(═O)—O—R7, —(CR5R6)n—O—R7, —(CR5R6)n—O—[(CR5R6)n—O]m—R7, —(CR5R6)n—Ar—O—C(═O)—R7, —Ar—C(═O)—O—(CR5R6)n—R7, —(CR5R6)n—NR8R9, and —(CR5R6)n—C(═O)—NR8R9;
- and
- each R4 is selected from the group consisting of Ar, —(CR5R6)n—O—C(═O)—R7, —(CR5R6)n—C(═O)—O—R7, —(CR5R6)n—O—C(═O)—O—R7, —(CR5R6)n—O—R7, —(CR5R6)n—O—[(CR5R6)n—O]m—R7, —(CR5R6)n—Ar—O—C(═O)—R7, —Ar—C(═O)—O—(CR5R6)n—R7, —(CR5R6)n—NR8R9, and —(CR5R6)n—C(═O)—NR8R9;
- or
- (d) each R1 is selected from Ar, —(CR5R6)n—O—C(═O)—R7, —(CR5R6)n—C(═O)—O—R7, —(CR5R6)n—O—C(═O)—O—R7, —(CR5R6)n—O—R7, —(CR5R6)n—O—[(CR5R6)n—O]m—R7, —(CR5R6)n—Ar—O—C(═O)—R7, —Ar—C(═O)—O—(CR5R6)n—R7, —(CR5R6)n—NR8R9, and —(CR5R6)n—C(═O)—NR8R9;
- each R2 is selected from the group consisting of H, alkyl, Ar, —(CR5R6)n—Ar, —(CR5R6)n—O—C(═O)—R7, —(CR5R6)n—C(═O)—O—R7, —(CR5R6)n—O—C(═O)—O—R7, —(CR5R6)n—O—R7, —(CR5R6)n—O—[(CR5R6)n—O]m—R7, —(CR5R6)n—Ar—O—C(═O)—R7, —Ar—C(═O)—O—(CR5R6)n—R7, —(CR5R6)n—NR8R9, and —(CR5R6)n—C(═O)—NR8R9;
- each R3 is selected from the group consisting of H, alkyl, Ar, —(CR5R6)n—Ar, —(CR5R6)n—O—C(═O)—R7, —(CR5R6)n—C(═O)—O—R7, —(CR5R6)n—O—C(═O)—O—R7, —(CR5R6)n—O—R7, —(CR5R6)n—O—[(CR5R6)n—O]m—R7, —(CR5R6)n—Ar—O—C(═O)—R7, —Ar—C(═O)—O—(CR5R6)n—R7, —(CR5R6)n—NR8R9, and —(CR5R6)n—C(═O)—NR8R9;
- and
- each R4 is selected from the group consisting of H, alkyl, Ar, —(CR5R6)n—Ar, —(CR5R6)n—O—C(═O)—R7, —(CR5R6)n—C(═O)—O—R7, —(CR5R6)n—O—C(═O)—O—R7, —(CR5R6)n—O—R7, —(CR5R6)n—O—[(CR5R6)n—O]m—R7, —(CR5R6)n—Ar—O—C(═O)—R7, —Ar—C(═O)—O—(CR5R6)n—R7, —(CR5R6)n—NR8R9, and —(CR5R6)n—C(═O)—NR8R9;
- wherein:
- each n is an integer from 1 to 20;
- each m is an integer from 1 to 20;
- each R5 and R6 is independently selected from the group consisting of H, alkyl, and alkylaryl;
- each R7 is independently straight chain or branched alkyl;
- each Ar is aryl, substituted aryl, heteroaryl or substituted heteroaryl;
- each R5 and R9 are independently H or alkyl;
- and
- each R3′ and R4′ are independently H or alkyl;
- or
- pharmaceutically acceptable salts thereof
30 more elements
Dependencies are inferred from the claim text.