IP Library › Granted Patent US 8,853,224
Granted Patent B2
US 8,853,224 · App. 12/310,708 · Granted Oct 7, 2014

Acyclic amine inhibitors of nucleoside phosphorylases and hydrolases

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Quick Facts
Patent No.
US 8,853,224
App. No.
12/310,708
Granted
Oct 7, 2014
Kind
B2
Abstract

The invention relates to compounds of the general formula (I) which are inhibitors of purine nucleoside phosphorylases (PNPs) and/or nucleoside hydrolases (NHs). The invention also relates to the use of these compounds in the treatment of diseases and infections including cancer, bacterial infections, protozoal infections, and T-cell mediated disease and to pharmaceutical compositions containing the compounds.

Claims (182)

1. A compound of the formula (I):

where:

R 4 is dihydroxypropyl, dihydroxybutyl, trihydroxybutyl, dihydroxypentyl or trihydroxypentyl;

A is N or CH;

B is OH or alkoxy; and

D is H, OH, NH 2 , or SCH 3 ;

or a tautomer thereof, or a pharmaceutically acceptable salt thereof, or an ester prodrug form thereof.

2. A compound as claimed in claim 1 where A is CH.

3. A compound as claimed in claim 1 where A is N.

4. A compound as claimed in claim 1 where B is OH.

5. A compound as claimed in claim 1 where D is H or NH 2 .

6. A compound as claimed in claim 1 where D is OH or SCH 3 .

7. A compound selected from the group consisting of:

rac-(2R,3S)-3-((4-hydroxy-5H-pyrrolo[3,2-d]pyrimidin-7-yl)methylamino)butane-1,2,4-triol;

7-(((2,4-dihydroxybutyl)(methyl)amino)methyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

(R)3-((4-hydroxy-5H-pyrrolo[3,2-d]pyrimidin-7-yl)methylamino)-propane-1,2-diol hydrochloride;

(2R,3R)-3-((4-hydroxy-5H-pyrrolo[3,2-d]pyrimidin-7-yl)methylamino)butane-1,2,4-triol hydrochloride;

2-amino-7-(2,3-dihydroxy-1-(2-hydroxyethylamino)propyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

7-(2,3-dihydroxy-1-(2-hydroxyethylamino)propyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

2-amino-7-(1-amino-2,3,5-trihydroxypentyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

7-(1-amino-2,3,5-trihydroxypentyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

2-amino-7-(4-amino-2,3,5-trihydroxypentyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

7-(4-amino-2,3,5-trihydroxypentyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

2-amino-7-(1-(1,3-dihydroxypropan-2-ylamino)-2-hydroxyethyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

7-(1-(1,3-dihydroxypropan-2-ylamino)-2-hydroxyethyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

2-amino-7-(((2,4-dihydroxybutyl)(methyl)amino)methyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

2-amino-7-((2,4-dihydroxybutylamino)methyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

7-((2,4-dihydroxybutylamino)methyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

2-amino-7-((3,4-dihydroxy-2-(hydroxymethyl)butylamino)methyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

7-((3,4-dihydroxy-2-(hydroxymethyl)butylamino)methyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

2-amino-7-((3-hydroxy-2-(hydroxymethyl)propylamino)methyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

7-((3-hydroxy-2-(hydroxymethyl)propylamino)methyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

2-amino-7-(((3-hydroxy-2-(hydroxymethyl)propyl)(methyl)amino)methyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

7-(((3-hydroxy-2-(hydroxymethyl)propyl)(methyl)amino)methyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

2-amino-7-(3,4-dihydroxy-5-(methylthiomethyl)pyrrolidin-2-yl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

7-(3,4-dihydroxy-5-(methylthiomethyl)pyrrolidin-2-yl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

2-amino-7-(2,3-dihydroxy-1-(2-(methylthio)ethylamino)propyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

7-(2,3-dihydroxy-1-(2-(methylthio)ethylamino)propyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

2-amino-7-(1-amino-2,3-dihydroxy-5-(methylthio)pentyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

7-(1-amino-2,3-dihydroxy-5-(methylthio)pentyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

2-amino-7-(2-hydroxy-1-(1-hydroxy-3-(methylthio)propan-2-ylamino)ethyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

7-(2-hydroxy-1-(1-hydroxy-3-(methylthio)propan-2-ylamino)ethyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

2-amino-7-((3,4-dihydroxy-1-(methylthio)butan-2-ylamino)methyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

7-((3,4-dihydroxy-1-(methylthio)butan-2-ylamino)methyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

2-amino-7-(((2-hydroxy-4-(methylthio)butyl)(methyl)amino)methyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

7-(((2-hydroxy-4-(methylthio)butyl)(methyl)amino)methyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

2-amino-7-((2-hydroxy-4-(methylthio)butylamino)methyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

7-((2-hydroxy-4-(methylthio)butylamino)methyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

2-amino-7-((3,4-dihydroxy-2-(methylthiomethyl)butylamino)methyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

7-((3,4-dihydroxy-2-(methylthiomethyl)butylamino)methyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

2-amino-7-((3-hydroxy-2-(methylthiomethyl)propylamino)methyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

7-((3-hydroxy-2-(methylthiomethyl)propylamino)methyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

7-(((3-hydroxy-2-(methylthiomethyl)propyl)(methyl)amino)methyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

2-amino-7-(((3-hydroxy-2-(methylthiomethyl)propyl)(methyl)amino)methyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

7-(((2R,3R)-1,3,4-trihydroxybutan-2-ylamino)methyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

7-(((2S,3S)-1,3,4-trihydroxybutan-2-ylamino)methyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

7-(((2R,3S)-1,3,4-trihydroxybutan-2-ylamino)methyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

7-(((2S,3R)-1,3,4-trihydroxybutan-2-ylamino)methyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

2-amino-7-(((2R,3R)-1,3,4-trihydroxybutan-2-ylamino)methyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

2-amino-7-(((2S,3S)-1,3,4-trihydroxybutan-2-ylamino)methyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

2-amino-7-(((2R,3S)-1,3,4-trihydroxybutan-2-ylamino)methyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

2-amino-7-(((2S,3R)-1,3,4-trihydroxybutan-2-ylamino)methyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

5-amino-3-(((2R,3R)-1,3,4-trihydroxybutan-2-ylamino)methyl)-1H-pyrazolo[4,3-d]pyrimidin-7(6H)-one;

5-amino-3-(((2S,3S)-1,3,4-trihydroxybutan-2-ylamino)methyl)-1H-pyrazolo[4,3-d]pyrimidin-7(6H)-one;

5-amino-3-(((2R,3S)-1,3,4-trihydroxybutan-2-ylamino)methyl)-1H-pyrazolo[4,3-d]pyrimidin-7(6H)-one;

5-amino-3-(((2S,3R)-1,3,4-trihydroxybutan-2-ylamino)methyl)-1H-pyrazolo[4,3-d]pyrimidin-7(6H)-one;

7-((1,3-dihydroxy-2-(hydroxymethyl)propan-2-ylamino)methyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

2-amino-7-((1,3-dihydroxy-2-(hydroxymethyl)propan-2-ylamino)methyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

3-((1,3-dihydroxy-2-(hydroxymethyl)propan-2-ylamino)methyl)-1H-pyrazolo[4,3-d]pyrimidin-7(6H)-one;

7-((4-hydroxybutylamino)methyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

2-amino-7-((4-hydroxybutylamino)methyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

3-((4-hydroxybutylamino)methyl)-1H-pyrazolo[4,3-d]pyrimidin-7(6H)-one;

7-((2-hydroxyethylamino)methyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

2-amino-7-((2-hydroxyethylamino)methyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

3-((2-hydroxyethylamino)methyl)-1H-pyrazolo[4,3-d]pyrimidin-7(6H)-one;

7-((3-hydroxy-2-(hydroxymethyl)propylamino)methyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

2-amino-7-((3-hydroxy-2-(hydroxymethyl)propylamino)methyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

3-((3-hydroxy-2-(hydroxymethyl)propylamino)methyl)-1H-pyrazolo[4,3-d]pyrimidin-7(6H)-one;

7-(((3-hydroxy-2-(hydroxymethyl)propyl)(methyl)-amino)methyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

2-amino-7-(((3-hydroxy-2-(hydroxymethyl)propyl)(methyl)-amino)methyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

3-(((1,3-dihydroxypropan-2-yl)(methyl)amino) methyl)-1H-pyrazolo[4,3-d]pyrimidin-7(6H)-one;

7-((3-hydroxy-2-(hydroxymethyl)propylamino)methyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

2-amino-7-((3-hydroxy-2-(hydroxymethyl)propylamino)methyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

3-((1,3-dihydroxypropan-2-ylamino)methyl)-1H-pyrazolo[4,3-d]pyrimidin-7(6H)-one;

7-(((3-hydroxy-2-(hydroxymethyl)propyl)(methyl)-amino)methyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

2-amino-7-(((3-hydroxy-2-(hydroxymethyl)propyl)(methyl)-amino)methyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

3-(((1,3-dihydroxypropan-2-yl)(methyl)amino)methyl)-1H-pyrazolo[4,3-d]pyrimidin-7(6H)-one;

7-(((3-hydroxy-2-(hydroxymethyl)propyl)(hydroxymethyl)amino)methyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

2-amino-7-(((3-hydroxy-2-(hydroxymethyl)propyl)(hydroxymethyl)amino)methyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

5-amino-3-(((3-hydroxy-2-(hydroxymethyl)propyl)(hydroxymethyl)amino)methyl)-1H-pyrazolo[4,3-d]pyrimidin-7(6H)-one;

7-((1,3-dihydroxy-2-(methylthiomethyl)propan-2-ylamino)methyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

2-amino-7-((1,3-dihydroxy-2-(methylthiomethyl)propan-2-ylamino)methyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

5-amino-3-((1,3-dihydroxy-2-(methylthiomethyl)propan-2-ylamino)methyl)-1H-pyrazolo[4,3-d]pyrimidin-7(6H)-one;

7-(((2R,3R)-2,3,4-trihydroxybutylamino)methyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

7-(((2S,3S)-2,3,4-trihydroxybutylamino)methyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

7-(((2R,3S)-2,3,4-trihydroxybutylamino)methyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

7-(((2S,3R)-2,3,4-trihydroxybutylamino)methyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

2-amino-7-(((2R,3R)-2,3,4-trihydroxybutylamino)methyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

2-amino-7-(((2S,3S)-2,3,4-trihydroxybutylamino)methyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

2-amino-7-(((2R,3S)-2,3,4-trihydroxybutylamino)methyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

2-amino-7-(((2S,3R)-2,3,4-trihydroxybutylamino)methyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

5-amino-3-(((2R,3R)-2,3,4-trihydroxybutylamino) methyl)-1H-pyrazolo[4,3-d]pyrimidin-7(6H)-one;

5-amino-3-(((2S,3S)-2,3,4-trihydroxybutylamino)methyl)-1H-pyrazolo[4,3-d]pyrimidin-7(6H)-one;

5-amino-3-(((2R,3S)-2,3,4-trihydroxybutylamino)methyl)-1H-pyrazolo[4,3-d]pyrimidin-7(6H)-one;

5-amino-3-(((2S,3R)-2,3,4-trihydroxybutylamino)methyl)-1H-pyrazolo[4,3-d]pyrimidin-7(6H)-one;

7-((benzyl((2R,3R)-3,4-dihydroxy-2-(methylthiomethyl)butyl)amino)methyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

7-((benzyl((2S,3S)-3,4-dihydroxy-2-(methylthiomethyl)butyl)amino)methyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

7-((benzyl((2R,3S)-3,4-dihydroxy-2-(methylthiomethyl)butyl)amino)methyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

7-((benzyl((2S,3R)-3,4-dihydroxy-2-(methylthiomethyl)butyl)amino)methyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

2-amino-7-((benzyl((2R,3R)-3,4-dihydroxy-2-(methylthiomethyl)butyl)amino)methyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

2-amino-7-((benzyl((2S,3S)-3,4-dihydroxy-2-(methylthiomethyl)butyl)amino)methyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

2-amino-7-((benzyl((2R,3S)-3,4-dihydroxy-2-(methylthiomethyl)butyl)amino)methyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

2-amino-7-((benzyl((2S,3R)-3,4-dihydroxy-2-(methylthiomethyl)butyl)amino)methyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

(S)-7-(1-(1,3-dihydroxypropan-2-ylamino)-2-hydroxyethyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

(R)-7-(1-(1,3-dihydroxypropan-2-ylamino)-2-hydroxyethyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

(S)-2-amino-7-(1-(1,3-dihydroxypropan-2-ylamino)-2-hydroxyethyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

(R)-2-amino-7-(1-(1,3-dihydroxypropan-2-ylamino)-2-hydroxyethyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

(S)-3-(1-(1,3-dihydroxypropan-2-ylamino)-2-hydroxyethyl)-1H-pyrazolo[4,3-d]pyrimidin-7(6H)-one;

(R)-3-(1-(1,3-dihydroxypropan-2-ylamino)-2-hydroxyethyl)-1H-pyrazolo[4,3-d]pyrimidin-7(6H)-one;

7-(((2R,3R)-2,3-dihydroxy-4-(methylthio)butylamino)methyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

7-(((2S,3S)-2,3-dihydroxy-4-(methylthio)butylamino)methyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

7-(((2R,3S)-2,3-dihydroxy-4-(methylthio)butylamino)methyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

7-(((2S,3R)-2,3-dihydroxy-4-(methylthio)butylamino)methyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

2-amino-7-(((2R,3R)-2,3-dihydroxy-4-(methylthio)butylamino)methyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

2-amino-7-(((2S,3S)-2,3-dihydroxy-4-(methylthio)butylamino)methyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

2-amino-7-(((2R,3S)-2,3-dihydroxy-4-(methylthio)butylamino)methyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

2-amino-7-(((2S,3R)-2,3-dihydroxy-4-(methylthio)butylamino)methyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

(R)-7-((benzyl(2,3-dihydroxypropyl)amino)methyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

(S)-7-((benzyl (2,3-dihydroxypropyl)amino)methyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

(R)-2-amino-7-((benzyl (2,3-dihydroxypropyl)amino)methyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

(S)-2-amino-7-((benzyl (2,3-dihydroxypropyl)amino)methyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

(R)-3-((2,3-dihydroxypropylamino)methyl)-1H-pyrazolo[4,3-d]pyrimidin-7(6H)-one;

(S)-3-((2,3-dihydroxypropylamino)methyl)-1H-pyrazolo[4,3-d]pyrimidin-7(6H)-one;

(R)-7-(((2,3-dihydroxypropyl)(2-hydroxyethyl)amino)methyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

(S)-7-(((2,3-dihydroxypropyl)(2-hydroxyethyl)amino)methyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

(R)-2-amino-7-(((2,3-dihydroxypropyl)(2-hydroxyethyl)amino)methyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

(S)-2-amino-7-(((2,3-dihydroxypropyl)(2-hydroxyethyl)amino)methyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

(R)-3-(((2,3-dihydroxypropyl)(2-hydroxyethyl)amino)methyl)-1H-pyrazolo[4,3-d]pyrimidin-7(6H)-one;

(S)-3-(((2,3-dihydroxypropyl)(2-hydroxyethyl)amino)methyl)-1H-pyrazolo[4,3-d]pyrimidin-7(6H)-one;

(2R,3R)-7-((3,4-dihydroxy-2-(hydroxymethyl)butylamino)methyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

(2S,3S)-7-((3,4-dihydroxy-2-(hydroxymethyl)butylamino)methyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one; (2R,3S)-7-((3,4-dihydroxy-2-(hydroxymethyl)butylamino)methyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one; (2S,3R)-7-((3,4-dihydroxy-2-(hydroxymethyl)butylamino)methyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

(2R,3R)-2-amino-7-((3,4-dihydroxy-2-(hydroxymethyl)butylamino)methyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

(2S,3S)-2-amino-7-((3,4-dihydroxy-2-(hydroxymethyl)butylamino)methyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

(2R,3S)-2-amino-7-((3,4-dihydroxy-2-(hydroxymethyl)butylamino)methyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

(2S,3R)-2-amino-7-((3,4-dihydroxy-2-(hydroxymethyl)butylamino) methyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

(2R,3R)-5-amino-3-((3,4-dihydroxy-2-(hydroxymethyl)butylamino)methyl)-1H-pyrazolo[4,3-d]pyrimidin-7(6H)-one;

(2S,3S)-5-amino-3-((3,4-dihydroxy-2-(hydroxymethyl)butylamino)methyl)-1H-pyrazolo[4,3-d]pyrimidin-7(6H)-one;

(2R,3S)-5-amino-3-((3,4-dihydroxy-2-(hydroxymethyl)butylamino)methyl)-1H-pyrazolo[4,3-d]pyrimidin-7(6H)-one;

(2S,3R)-5-amino-3-((3,4-dihydroxy-2-(hydroxymethyl)butylamino)methyl)-1H-pyrazolo[4,3-d]pyrimidin-7(6H)-one;

7-(((2R,3R)-3,4-dihydroxy-1-(methylthio)butan-2-ylamino)methyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

7-(((2S,3S)-3,4-dihydroxy-1-(methylthio)butan-2-ylamino)methyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

7-(((2R,3S)-3,4-dihydroxy-1-(methylthio)butan-2-ylamino)methyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

7-(((2S,3R)-3,4-dihydroxy-1-(methylthio)butan-2-ylamino)methyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

2-amino-7-(((2R,3R)-3,4-dihydroxy-1-(methylthio)butan-2-ylamino)methyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

2-amino-7-(((2S,3S)-3,4-dihydroxy-1-(methylthio)butan-2-ylamino)methyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

2-amino-7-(((2R,3S)-3,4-dihydroxy-1-(methylthio)butan-2-ylamino)methyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

2-amino-7-(((2S,3R)-3,4-dihydroxy-1-(methylthio)butan-2-ylamino)methyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

3-(((2R,3R)-3,4-dihydroxy-1-(methylthio)butan-2-ylamino)methyl)-1H-pyrazolo[4,3-d]pyrimidin-7(6H)-one;

3-(((2S,3S)-3,4-dihydroxy-1-(methylthio)butan-2-ylamino)methyl)-1H-pyrazolo[4,3-d]pyrimidin-7(6H)-one;

3-(((2R,3S)-3,4-dihydroxy-1-(methylthio)butan-2-ylamino)methyl)-1H-pyrazolo[4,3-d]pyrimidin-7(6H)-one;

3-(((2S,3R)-3,4-dihydroxy-1-(methylthio)butan-2-ylamino)methyl)-1H-pyrazolo[4,3-d]pyrimidin-7(6H)-one;

3-(((2R,3R)-3,4-dihydroxy-2-(methylthiomethyl)butylamino)methyl)-1H-pyrazolo[4,3-d]pyrimidin-7(6H)-one;

3-(((2S,3S)-3,4-dihydroxy-2-(methylthiomethyl)butylamino)methyl)-1H-pyrazolo[4,3-d]pyrimidin-7(6H)-one;

3-(((2R,3S)-3,4-dihydroxy-2-(methylthiomethyl)butylamino)methyl)-1H-pyrazolo[4,3-d]pyrimidin-7(6H)-one;

3-(((2S,3R)-3,4-dihydroxy-2-(methylthiomethyl)butylamino)methyl)-1H-pyrazolo[4,3-d]pyrimidin-7(6H)-one;

2-amino-7-(((2R,3R)-3,4-dihydroxy-2-(methylthiomethyl)butylamino)methyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

2-amino-7-(((2S,3S)-3,4-dihydroxy-2-(methylthiomethyl)butylamino)methyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

2-amino-7-(((2R,3S)-3,4-dihydroxy-2-(methylthiomethyl)butylamino)methyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

2-amino-7-(((2S,3R)-3,4-dihydroxy-2-(methylthiomethyl)butylamino)methyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

7-(((2R,3R)-3,4-dihydroxy-2-(methylthiomethyl)butylamino)methyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

7-(((2S,3S)-3,4-dihydroxy-2-(methylthiomethyl)butylamino)methyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

7-(((2R,3S)-3,4-dihydroxy-2-(methylthiomethyl)butylamino)methyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one; and

7-(((2S,3R)-3,4-dihydroxy-2-(methylthiomethyl)butylamino)methyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

7-((1,3-dihydroxypropan-2-ylamino)methyl)-3H-pyrrolo[3,2-d]pyrimidin-4(5H)-one;

or a tautomer thereof, or a pharmaceutically acceptable salt thereof, or an ester prodrug form thereof.

8. A compound of the formula:

where A is N or CH; B is OH or alkoxy; and D is H, OH, NH 2 , or SCH 3 .

9. The compound (2S,3R)-3-((4-hydroxy-5H-pyrrolo[3,2-d]pyrimidin-7-yl)-methylamino)butane-1,2,4-triol having the formula:

10. A pharmaceutical composition comprising a pharmaceutically effective amount of a compound of claim 1 .

11. The compound of claim 1 having the structure

or a tautomer thereof, or a pharmaceutically acceptable salt thereof, or an ester prodrug form thereof.

12. A pharmaceutical composition comprising a pharmaceutically effective amount of a compound of claim 7 .

Assignments (11)
RELEASE OF GRANT OF SECURITY INTEREST IN PATENTS Recorded Apr 18, 2023
From: ATHYRIUM OPPORTUNITIES III CO-INVEST 1 LP
To: BIOCRYST PHARMACEUTICALS, INC.
Reel/Frame 063362/0550 →
RELEASE OF SECURITY INTEREST Recorded Apr 6, 2023
From: MIDCAP FINANCIAL TRUST
To: BIOCRYST PHARMACEUTICALS, INC.; MDCP, LLC
Reel/Frame 063348/0762 →
SECURITY INTEREST Recorded Dec 17, 2020
From: BIOCRYST PHARMACEUTICALS, INC.
To: ATHYRIUM OPPORTUNITIES III CO-INVEST 1 LP
Reel/Frame 054800/0634 →
RELEASE OF SECURITY INTEREST Recorded Dec 16, 2020
From: MIDCAP FINANCIAL TRUST, AS AGENT
To: BIOCRYST PHARMACEUTICALS, INC.; MDCP, LLC
Reel/Frame 054774/0446 →
MERGER AND CHANGE OF NAME Recorded Feb 26, 2019
From: ALBERT EINSTEIN COLLEGE OF MEDICINE, INC.; ALBERT EINSTEIN COLLEGE OF MEDICINE
To: ALBERT EINSTEIN COLLEGE OF MEDICINE
Reel/Frame 048438/0275 →
CHANGE OF NAME Recorded Oct 19, 2015
From: COM AFFILIATION, INC.
To: ALBERT EINSTEIN COLLEGE OF MEDICINE, INC.
Reel/Frame 036888/0817 →
CHANGE OF NAME Recorded Oct 19, 2015
From: COM AFFILIATION, INC.
To: ALBERT EINSTEIN COLLEGE OF MEDICINE, INC.
Reel/Frame 036888/0939 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 16, 2015
From: ALBERT EINSTEIN COLLEGE OF MEDICINE OF YESHIVA UNIVERSITY
To: COM AFFILIATION, INC.
Reel/Frame 036878/0001 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 15, 2015
From: ALBERT EINSTEIN COLLEGE OF MEDICINE OF YESHIVA UNIVERSITY
To: COM AFFILIATION, INC.
Reel/Frame 036875/0147 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 4, 2015
From: CALLAGHAN INNOVATION RESEARCH LIMITED
To: VICTORIA LINK LIMITED
Reel/Frame 035086/0004 →
CHANGE OF NAME Recorded Feb 26, 2015
From: INDUSTRIAL RESEARCH LIMITED
To: CALLAGHAN INNOVATION RESEARCH LIMITED
Reel/Frame 035101/0436 →