Compounds, compositions, methods of synthesis, and methods of treatment
Briefly described, embodiments of this disclosure include compounds as described herein, labeled compounds as described herein, pharmaceutical composition including compounds described herein, methods of imaging, method of forming a compound as described herein, and the like. In particular, embodiments of the disclosure include a series of triamino-pyridine derivatives and labeled triamino-pyridine derivatives, methods of synthesizing these compounds, intermediate compounds, methods of treatment using these compounds, methods of imaging, diagnosing, localizing, monitoring, and/or assessing a condition (e.g., corticotropin releasing factor type-1 (CRF1)) and/or related biological events, using triamino-pyridine derivatives, and the like. In addition, the present disclosure includes compositions (e.g., labeled triamino-pyridine derivatives that are ligands for the CRF1 receptor) used in and methods relating to non-invasive imaging (e.g., positron emission tomography (PET) imaging or SPECT imaging).
1. A compound selected from the group consisting of:
and a pharmaceutically acceptable salt of any of the foregoing comprising a label selected from the group consisting of: 2 H, 3 H, 11 C, 13 C, 14 C, 32 Cl, 13 N, 18 F, 75 Br, 76 Br, 123 I, 124 I, 125 I, and 131 I wherein:
R 1 is selected from the group consisting of: —H, alkyl, alkenyl, haloalkyl, haloalkenyl,
R 2 is selected from the group consisting of: —H, alkyl, and haloalkyl;
each R 3 is independently selected from the group consisting of: —H, —X, alkyl, haloalkyl, —OH, —O-alkyl, —O-haloalkyl, —NO 2 , —NH, —NH-alkyl, —N(alkyl) 2 , —N(alkyl) 3 OTf, —N(alkyl) 3 X, —Sn(alkyl) 3 , —SH, —S-alkyl, and —S-haloalkyl, wherein n is 1, 2, or 3 and wherein if n is 2 or 3, each R 3 is chosen independently of any other R 3 ;
each R 4 , R 5 , and R 6 are each independently selected from the group consisting of: —H, —X, alkyl, haloalkyl, —OH, —O-alkyl, —O-haloalkyl, and —Sn(alkyl) 3 , wherein o, p, and q are each independently 1, 2, or 3 and wherein if any of o, p, or q are 2 or 3, each of R 4 , R 5 , and R 6 are chosen independently of each other and any other R 4 , R 5 , and R 6 ;
R 7 is selected from the group consisting of: —H and alkyl;
R 8 is selected from the group consisting of: —H, alkyl, alkenyl, benzyl, haloalkyl, haloalkenyl, and
each R 9 are independently selected from the group consisting of: —H, halogen, alkyl, haloalkyl, and heteroalkyl;
R 10 is selected from the group consisting of: —H, halogen, alkyl, haloalkyl, and heteroalkyl;
R 11 is selected from the group consisting of:
R 12 is selected from the group consisting of: —H, —OH, —O-alkyl, alkyl, X, haloalkyl, and heteroalkyl;
R 14 is selected from the group consisting of: —H, halogen, alkyl, haloalkyl, and heteroalkyl;
R 15 is selected from the group consisting of: —H, halogen, alkyl, haloalkyl, and heteroalkyl;
X is a halogen;
X 2 is selected from the group consisting of: —H, alkyl, —X, and —Sn(alkyl) 3 ;
y is selected from the group consisting of: 1 or 2; and
z is selected from the group consisting of: 1, 2, or 3;
with the proviso that for formula (I), when R 11 is
R 1 is butyl and R 2 is ethyl, R 3 is not: 2-Br-4-i-Pr; 2,4-Cl; 2,4,6-CH 3 ; 2-Cl-4-OCH 3 ; or 2-CH 3 -4-OCH 3 .
2. The compound of formula (1), according to claim 1 , wherein R 9 is H, R 10 is methyl, and R 11 is
and a pharmaceutically acceptable salt of any of the foregoing.
3. The compound of formula (1), according to claim 1 , wherein R 5 and R 9 are H, R 10 is methyl, p is 1, and R 11 is
and a pharmaceutically acceptable salt of any of the foregoing.
4. The compound of formula (1), according to claim 1 , wherein R 4 and R 9 are H, R 10 is methyl, o is 1, and R 11 is
and a pharmaceutically acceptable salt of any of the foregoing.
5. The compound of formula (1), according to claim 1 , wherein R 9 is H, R 10 is methyl, and R 11 is
and a pharmaceutically acceptable salt of any of the foregoing.
6. The compound of formula (2), according to claim 1 , wherein R 9 is H, R 10 is methyl, and R 11 is
and a pharmaceutically acceptable salt of any of the foregoing.
7. The compound of formula (2), according to claim 1 , wherein R 5 and R 9 are H, R 10 is methyl, p is 1, and R 11 is
and a pharmaceutically acceptable salt of any of the foregoing.
8. The compound of formula (2), according to claim 1 , wherein R 4 and R 9 are H, R 10 is methyl, o is 1, and R 11 is
and a pharmaceutically acceptable salt of any of the foregoing.
9. The compound of formula (3), according to claim 1 , wherein R 9 is H and R 10 is methyl, and a pharmaceutically acceptable salt of any of the foregoing.
10. The compound of formula (4), according to claim 1 , wherein R 9 is H and R 10 is methyl, and a pharmaceutically acceptable salt of any of the foregoing.
11. The compound of formula (5), according to claim 1 , wherein R 9 is H and R 10 is methyl, and a stereoisomer thereof, and a pharmaceutically acceptable salt of any of the foregoing.
12. A pharmaceutical composition comprising a compound of any one of claims 1 - 11 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.