IP Library › Granted Patent US 9,844,553

Granted Patent B2

US 9,844,553 · App. 15/139,361 · Granted Dec 19, 2017

Pyrazolopyridyl compounds as aldosterone synthase inhibitors

Inventors: D. Jonathan Bennett (Doylestown, PA); Jaiqiang Cai (Glasgow, GB); Emma Carswell (Great Shelford, GB); Andrew Cooke (Doylestown, PA); Scott B. Hoyt (Hoboken, NJ); Clare London (Chatham, NJ); John MacLean (Brookline, MA); Min K. Park (Whippany, NJ); Paul Ratcliffe (Strathaven, GB); Yusheng Xiong (Plainsboro, NJ); Swapan Kumar Samanta (Nandi Layout, IN); Bheemashankar A. Kulkarni (Rajajinagar, IN)

Assignee: Merck Sharp & Dohme Corp.

A61K31/519 A61K31/437 A61K31/444 C07D471/04 C07D487/04

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Quick Facts

Patent No.: US 9,844,553
App. No.: 15/139,361
Granted: Dec 19, 2017
Kind: B2

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Abstract

This invention relates to pyrazolopyridyl compounds of the structural formula: or their pharmaceutically acceptable salts, wherein the variable are defined herein. The inventive compounds selectively inhibit aldosterone synthase. This invention also provides for pharmaceutical compositions comprising the compounds of Formula I or their salts as well as potentially to methods for the treatment, amelioration or prevention of conditions that could be treated by inhibiting aldosterone synthase.

Claims (86)

1. A compound of the structural formula

or a pharmaceutically acceptable salt thereof

wherein:

Ring A is attached to Ring B via positions D and E and is:

D is C;

E is N;

R 1 is H or alkyl;

R 2 is halogen; —CN; —OR 7 ; —N(R 10 )C(O)R 7 ; —NR 11 R 12 ; —C(O)R 7 ; —C(O)N(R 11 )(R 12 ); —C(O)OR 7 ; —SO 2 N(R 10 )—R 7 ; —N(R 10 )SO 2 —R 7 ; —S(O) m —R 7 ; alkyl optionally substituted one or more times by halogen, —OR 7 , NR 8 R 9 , —CN, —N(R 10 )C(O)R 7 , —C(O)N(R 8 )(R 9 ), —C(O)OR 7 , —SO 2 N(R 10 )—R 7 , —N(R 10 )SO 2 —R 7 or —S(O) m —R 7 ; cycloalkyl optionally substituted one or more times by halogen, alkyl, haloalkyl, —OR 7 , —NR 8 R 9 , —CN, —N(R 10 )C(O)R 7 , —C(O)N(R 8 )(R 9 ), —C(O)OR 7 , —SO 2 N(R 10 )—R 7 , —N(R 10 )SO 2 —R 7 or —S(O) m —R 7 ; heterocycloalkyl optionally substituted one or more times by halogen, alkyl, haloalkyl, —OR 7 , —CN, —NR 8 R 9 —N(R 10 )C(O)R 7 , —C(O)N(R 8 )(R 9 ), —C(O)OR 7 , —SO 2 N(R 10 )—R 7 , —N(R 10 )SO 2 —R 7 or —S(O) m —R 7 ; aryl optionally substituted one or more times by halogen, alkyl, haloalkyl, cycloalkyl, —OR 7 , —CN, —NR 8 R 9 —N(R 10 )C(O)R 7 , —C(O)N(R 8 )(R 9 ), —C(O)OR 7 , —SO 2 N(R 10 )—R 7 , —N(R 10 )SO 2 —R 7 or —S(O) m —R 7 ; or heteroaryl optionally substituted one or more times by halogen, alkyl, haloalkyl, cycloalkyl, —OR 7 , —CN, —NR 8 R 9 , —N(R 10 )C(O)R 7 , —C(O)N(R 8 )(R 9 ), —C(O)OR 7 , —SO 2 N(R 10 )—R 7 , —N(R 10 )SO 2 —R 7 or —S(O) m —R 7 ;

R 3 is H; halogen; —CN; alkyl optionally substituted one or more times by halogen or cycloalkyl optionally substituted once or twice by alkyl or halogen; cycloalkyl optionally substituted once or twice by alkyl or halogen; or —C(O)OR 7 ;

R 4 is H; halogen; —CN; —OR 7 ; —NR 8 R 9 ; —N(R 10 )C(O)R 7 ; —C(O)N(R 8 )(R 9 ); —C(O)R 7 ; —C(O)OR 7 ; —SO 2 N(R 10 )—R 7 ; —N(R 10 )S(O) 2 —R 7 ; —S(O) n —R 7 ; alkyl optionally substituted one or more times by halogen, —OR 7 , —NR 8 R 9 , —CN, —N(R 11 )C(O)R 7 , —C(O)N(R 8 )(R 9 ), —C(O)OR 7 , —SO 2 N(R 10 )—R 7 , —N(R 10 )S(O) 2 —R 7 , or —S(O) n —R 7 ; cycloalkyl optionally substituted one or more times by halogen, alkyl, haloalkyl, —OR 7 , —NR 8 R 9 , —CN, —N(R 10 )C(O)R 7 , —C(O)N(R 8 )(R 9 ), —C(O)OR 8 , —SO 2 N(R 10 )—R 7 , —N(R 10 )SO 2 —R 7 , or —S(O) m —R 7 ; aryl optionally substituted one or more times by halogen, alkyl, haloalkyl, cycloalkyl, —OR 7 , —CN, —NR 8 R 9 , —N(R 10 )C(O)(R 7 ), —C(O)N(R 8 )(R 9 ), —C(O)OR 7 —SO 2 N(R 10 )—R 7 , —N(R 10 )SO 2 —R 7 , or —S(O) m —R 7 ; heterocycloalkyl optionally substituted one or more times by halogen, alkyl, haloalkyl, cycloalkyl, —OR 7 , —CN, —NR 8 R 9 , —N(R 10 )C(O)R 7 , —C(O)N(R 8 )(R 9 ), —C(O)OR 7 —SO 2 N(R 10 )—R 7 , —N(R 10 )SO 2 —R 7 or —S(O) m —R 7 ; or heteroaryl optionally substituted one or more times by halogen, alkyl, haloalkyl, cycloalkyl, —OR 7 , —CN, —NR 8 R 9 , —N(R 10 )C(O)R 7 , —C(O)N(R 8 )(R 9 ), —C(O)OR 7 , —SO 2 N(R 10 )—R 7 , —N(R 10 )SO 2 —R 7 or —S(O) m —R 7 ;

R 5 is H; halogen; —CN; —OR 7 ; —NR 8 R 9 ; —N(R 10 )C(O)R 7 ; —C(O)N(R 8 )(R 9 ); —C(O)R 7 ; —C(O)OR 7 ; —SO 2 N(R 10 )—R 7 ; —N(R 10 )S(O) 2 —R 7 ; —S(O) n —R 7 ; alkyl optionally substituted one or more times by halogen, —OR 7 , —NR 8 R 9 , —CN, —N(R 11 )C(O)R 7 , —C(O)N(R 8 )(R 9 ), —C(O)OR 7 , —SO 2 N(R 10 )—R 7 , —N(R 10 )S(O) 2 —R 7 , or —S(O) n —R 7 ; cycloalkyl optionally substituted one or more times by halogen, alkyl, haloalkyl, —OR 7 , —NR 8 R 9 , —CN, —N(R 10 )C(O)R 7 , —C(O)N(R 8 )(R 9 ), —C(O)OR 7 , —SO 2 N(R 10 )—R 7 , —N(R 10 )SO 2 —R 7 or —S(O) m —R 7 ; aryl optionally substituted one or more times by halogen, alkyl, haloalkyl, cycloalkyl, —OR 7 , —CN, —NR 8 R 9 —N(R 10 )C(O)(R 7 ), —C(O)N(R 8 )(R 9 ), —C(O)OR 7 , —SO 2 N(R 10 )—R 7 , —N(R 10 )SO 2 —R 7 or —S(O) m —R 7 ; heterocycloalkyl optionally substituted one or more times by halogen, alkyl, haloalkyl, cycloalkyl, —OR 7 , —CN, —NR 8 R 9 —N(R 10 )C(O)R 7 , —C(O)N(R 8 )(R 9 ), —C(O)OR 7 , —SO 2 N(R 10 )—R 7 , —N(R 10 )SO 2 —R 7 or —S(O) m —R 7 ; or heteroaryl optionally substituted one or more times by halogen, alkyl, haloalkyl, cycloalkyl, —OR 7 , —CN, —NR 8 R 9 , —N(R 10 )C(O)R 7 , —C(O)N(R 8 )(R 9 ), —C(O)OR 7 , —SO 2 N(R 10 )—R 7 , —N(R 10 )SO 2 —R 7 or —S(O) m —R 7 ;

or R 4 and R 5 are joined together to form a 5-7 membered carbocyclic or heterocyclic ring that is fused to the pyridyl ring to which R 4 and R 5 are attached, wherein the ring formed by R 4 and R 5 is optionally substituted by 1 to 3 R 6 ;

R 6 is independently H; halogen; —CN; —OR 7 ; —NR 8 R 9 ; —N(R 10 )C(O)R 7 ; —C(O)N(R 7 )(R 8 ); —C(O)N(R 8 )(R 9 ); —C(O)OR 7 ; —SO 2 N(R 10 )—R 7 ; —N(R 10 )SO 2 —R 7 ; —S(O) m —R 7 ; alkyl optionally substituted one or more times by halogen, —OR 7 , —NR 8 R 9 , —CN, —N(R 10 )C(O)R 7 , —C(O)N(R 8 )(R 9 ), —C(O)OR 7 , —SO 2 N(R 10 )—R 7 , —N(R 10 )SO 2 —R 7 or —S(O) m —R 7 ; cycloalkyl optionally substituted one or more times by halogen, alkyl, haloalkyl, —OR 7 , —NR 8 R 9 , —CN, —N(R 10 )C(O)R 7 , —C(O)N(R 8 )(R 9 ), —C(O)OR 7 —SO 2 N(R 10 )—R 7 , —N(R 10 )SO 2 —R 7 or —S(O) m —R 7 ; aryl optionally substituted one or more times by halogen, alkyl, haloalkyl, cycloalkyl, —OR 7 , —CN, —NR 8 R 9 —N(R 10 )C(O)(R 7 ), —C(O)N(R 7 )(R 8 ), —C(O)OR 7 , —SO 2 N(R 10 )—R 7 , —N(R 10 )SO 2 —R 7 or —S(O) m —R 7 ; heterocycloalkyl optionally substituted one or more times by halogen, alkyl, haloalkyl, —OR 7 , —CN, —NR 8 R 9 —N(R 10 )C(O)R 7 , —C(O)N(R 8 )(R 9 ), —C(O)OR 7 , —SO 2 N(R 10 )—R 7 , —N(R 10 )SO 2 —R 7 or —S(O) m —R 7 ; or heteroaryl optionally substituted one or more times by halogen, alkyl, haloalkyl, cycloalkyl, —OR 7 , —CN, —NR 8 R 9 , —N(R 10 )C(O)R 7 , —C(O)N(R 8 )(R 9 ), —C(O)OR 7 , —SO 2 N(R 10 )—R 7 , —N(R 10 )SO 2 —R 7 or —S(O) m —R 7 ;

R 7 is independently H; alkyl optionally substituted one or more times by halogen, —OR 10 , —NR 8 R 9 , —CN, —N(R 10 )C(O)R 10 , —C(O)N(R 8 )(R 9 ), —C(O)OR 10 or —S(O) m —R 10 ; cycloalkyl optionally substituted one or more times by halogen, alkyl, haloalkyl, —OR 10 , —NR 8 R 9 , —CN, —N(R 10 )C(O)R 10 , —C(O)N(R 8 )(R 9 ), —C(O)OR 10 or —S(O) m —R 10 ; aryl optionally substituted one or more times by halogen, alkyl, haloalkyl, cycloalkyl, —OH, —OR 10 , —NR 8 R 9 , —CN, —N(R 10 )C(O)R 10 , —C(O)N(R 8 )(R 9 ), —C(O)OR 10 or —S(O) m —R 10 ; or heteroaryl optionally substituted one or more times by halogen, alkyl, haloalkyl, cycloalkyl, —OR 10 , —NR 8 R 9 , —CN, —N(R 9 )C(O)R 1 , —C(O)N(R 8 )(R 9 ), —C(O)OR 10 or —S(O) m —R 10 ;

R 8 is independently H or alkyl;

R 9 is independently H or alkyl;

or R 8 and R 9 are joined together with the nitrogen to which they are attached form a saturated 5- to 7-membered heterocyclic ring;

R 10 is independently H or alkyl;

R 11 is independently H; alkyl optionally substituted one or more times by halogen, —OR 7 , —NR 8 R 9 , —CN, —N(R 10 )C(O)R 7 , —C(O)N(R 8 )(R 9 ), —C(O)OR 7 or —S(O) m —R 7 ; cycloalkyl optionally substituted one or more times by halogen, alkyl, haloalkyl, —OR 7 , —NR 8 R 9 , —CN, —N(R 10 )C(O)R 7 , —C(O)N(R 8 )(R 9 ), —C(O)OR 10 or —S(O) m —R 10 ; aryl optionally substituted one or more times by halogen, alkyl, haloalkyl, cycloalkyl, —OR 7 , —CN, —NR 8 R 9 —N(R 10 )C(O)(R 7 ), —C(O)N(R 7 )(R 8 ), —C(O)OR 7 or —S(O) m —R 7 ; heterocycloalkyl optionally substituted one or more times by halogen, alkyl, haloalkyl, —OR 7 , —CN, —NR 8 R 9 —N(R 10 )C(O)R 7 , —C(O)N(R 8 )(R 9 ), —C(O)OR 7 or —S(O) m —R 7 ; or heteroaryl optionally substituted one or more times by halogen, alkyl, haloalkyl, cycloalkyl, —OR 7 , —CN, —NR 8 R 9 , —N(R 10 )C(O)R 7 , —C(O)N(R 8 )(R 9 ), —C(O)OR 7 or —S(O) m —R 7 ;

R 12 is independently H; alkyl optionally substituted one or more times by halogen, —OR 7 , —NR 8 R 9 , —CN, —N(R 10 )C(O)R 7 , —C(O)N(R 8 )(R 9 ), —C(O)OR 7 or —S(O) m —R 7 ; cycloalkyl optionally substituted one or more times by halogen, alkyl, haloalkyl, —OR 7 , —NR 8 R 9 , —CN, —N(R 10 )C(O)R 7 , —C(O)N(R 8 )(R 9 ), —C(O)OR 10 or —S(O) m —R 1 ; aryl optionally substituted one or more times by halogen, alkyl, haloalkyl, cycloalkyl, —OR 7 , —CN, —NR 8 R 9 —N(R 10 )C(O)(R 7 ), —C(O)N(R 7 )(R 8 ), —C(O)OR 7 or —S(O) m —R 7 ; heterocycloalkyl optionally substituted one or more times by halogen, alkyl, haloalkyl, —OR 7 , —CN, —NR 8 R 9 —N(R 10 )C(O)R 7 , —C(O)N(R 8 )(R 9 ), —C(O)OR 7 or —S(O) m —R 7 ; or heteroaryl optionally substituted one or more times by halogen, alkyl, haloalkyl, cycloalkyl, —OR 7 , —CN, —NR 8 R 9 , —N(R 10 )C(O)R 7 , —C(O)N(R 8 )(R 9 ), —C(O)OR 7 or —S(O) m —R 7 ;

a is 0, 1, 2, 3 or 4;

n is 1 or 2; and

m is 0, 1 or 2.

2. A compound as defined in claim 1 or a pharmaceutically acceptable salt thereof wherein:

R 1 is H or alkyl;

R 2 is halogen; —CN; —OR 7 ; —N(R 10 )C(O)R 7 ; —NR 11 R 12 ; —C(O)R 7 ; —C(O)N(R 11 )(R 12 ); —C(O)OR 7 ; —SO 2 N(R 10 )—R 7 ; —N(R 10 )SO 2 —R 7 ; —S(O) m —R 7 ; alkyl optionally substituted one or more times by halogen, —OR 7 , NR 8 R 9 , —CN, —N(R 10 )C(O)R 7 , —C(O)N(R 8 )(R 9 ), —C(O)OR 7 , —SO 2 N(R 10 )—R 7 , —N(R 10 )SO 2 —R 7 or —S(O) m —R 7 ; cycloalkyl optionally substituted one or more times by halogen, alkyl, haloalkyl, —OR 7 , —NR 8 R 9 , —CN, —N(R 10 )C(O)R 7 , —C(O)N(R 8 )(R 9 ), —C(O)OR 7 , —SO 2 N(R 10 )—R 7 , —N(R 10 )SO 2 —R 7 or —S(O) m —R 7 ; heterocycloalkyl optionally substituted one or more times by halogen, alkyl, haloalkyl, —OR 7 , —CN, —NR 8 R 9 —N(R 10 )C(O)R 7 , —C(O)N(R 8 )(R 9 ), —C(O)OR 7 , —SO 2 N(R 10 )—R 7 , —N(R 10 )SO 2 —R or —S(O) m —R 7 ; aryl optionally substituted one or more times by halogen, alkyl, haloalkyl, cycloalkyl, —OR 7 , —CN, —NR 8 R 9 —N(R 10 )C(O)R 7 , —C(O)N(R 8 )(R 9 ), —C(O)OR 7 , —SO 2 N(R 10 )—R 7 , —N(R 10 )SO 2 —R 7 or —S(O) m —R 7 ; or heteroaryl optionally substituted one or more times by halogen, alkyl, haloalkyl, cycloalkyl, —OR 7 , —CN, —NR 8 R 9 , —N(R 10 )C(O)R 7 , —C(O)N(R 8 )(R 9 ), —C(O)OR 7 , —SO 2 N(R 10 )—R 7 , —N(R 10 )SO 2 —R 7 or —S(O) m —R 7 ;

R 4 is H; halogen; —CN; —OR 7 ; —NR 8 R 9 ; —N(R 10 )C(O)R 7 ; —C(O)R 7 ; —C(O)N(R 8 )(R 9 ); —C(O)OR 7 ; —SO 2 N(R 10 )—R 7 ; —N(R 10 )S(O) 2 —R 7 ; —S(O) n —R 7 ; alkyl optionally substituted one or more times by halogen, —OR 7 , —NR 8 R 9 , —CN, —SO 2 N(R 10 )—R 7 , —N(R 10 )C(O)R 7 , —C(O)N(R 8 )(R 9 ), —C(O)OR 7 , —N(R 10 )S(O) 2 —R 7 or —S(O) n R 7 ; cycloalkyl optionally substituted one or more times by halogen, alkyl, haloalkyl, —OR 7 , —NR 8 R 9 , —CN, —N(R 10 )C(O)R 7 , —C(O)N(R 8 )(R 9 ), —C(O)OR 7 , —SO 2 N(R 10 )—R 7 , —N(R 10 )SO 2 —R 7 or —S(O) m —R 7 ; aryl optionally substituted one or more times by halogen, alkyl, haloalkyl, cycloalkyl, —OR 7 , —CN, —NR 8 R 9 —N(R 10 )C(O)R 7 , —C(O)N(R 8 )(R 9 ), —C(O)OR 7 , —SO 2 N(R 10 )—R 7 , —N(R 10 )SO 2 —R 7 or —S(O) m —R 7 ; heterocycloalkyl optionally substituted one or more times by halogen, alkyl, haloalkyl, —OR 7 , —CN, —NR 8 R 9 —N(R 10 )C(O)R 7 , —C(O)N(R 8 )(R 9 ), —C(O)OR 7 , —SO 2 N(R 10 )—R 7 , —N(R 10 )SO 2 —R 7 or —S(O) m —R 7 ; or heteroaryl optionally substituted one or more times by halogen, alkyl, haloalkyl, cycloalkyl, —OR 7 , —CN, —NR 8 R 9 , —N(R 10 )C(O)R 7 , —C(O)N(R 8 )(R 9 ), —C(O)OR 7 , —SO 2 N(R 10 )—R 7 , —N(R 10 )SO 2 —R 7 or —S(O) m —R 7 ;

R 5 is H; halogen; —CN; —OR 7 ; —NR 8 R 9 ; —N(R 10 )C(O)R 7 ; C(O)R 7 ; —C(O)N(R 8 )(R 9 ); —C(O)OR 7 ; —SO 2 N(R 10 )—R 7 ; —N(R 10 )S(O) 2 —R 7 ; —S(O) n —R 7 ; alkyl optionally substituted one or more times by halogen, —OR 7 , —NR 8 R 9 , —CN, —SO 2 N(R 10 )—R 7 , —N(R 10 )C(O)R 7 , —C(O)N(R 8 )(R 9 ), —C(O)OR 7 , —N(R 10 )S(O) 2 —R 7 , or —S(O) n —R 7 ; cycloalkyl optionally substituted one or more times by halogen, alkyl, haloalkyl, —OR 7 , —NR 8 R 9 , —CN, —N(R 10 )C(O)R 7 , —C(O)N(R 8 )(R 9 ), —C(O)OR 7 , —SO 2 N(R 10 )—R 7 , —N(R 10 )SO 2 —R 7 or —S(O) m —R 7 ; aryl optionally substituted one or more times by halogen, alkyl, haloalkyl, cycloalkyl, —OR 7 , —CN, —NR 8 R 9 , —N(R 10 )C(O)(R 7 ), —C(O)N(R 8 )(R 9 ), —C(O)OR 7 , —SO 2 N(R 10 )—R 7 , —N(R 10 )SO 2 —R 7 or —S(O) m —R 7 ; heterocycloalkyl optionally substituted one or more times by halogen, alkyl, haloalkyl, cycloalkyl, —OR 7 , —CN, —NR 8 R 9 , —N(R 10 )C(O)R 7 , —C(O)N(R 8 )(R 9 ), —C(O)OR 7 , —SO 2 N(R 10 )—R 7 , —N(R 10 )SO 2 —R 7 or —S(O) m —R 7 ; or heteroaryl optionally substituted one or more times by halogen, alkyl, haloalkyl, cycloalkyl, —OR 7 , —CN, —NR 8 R 9 , —N(R 10 )C(O)R 7 , —C(O)N(R 8 )(R 9 ), —C(O)OR 7 , —SO 2 N(R 10 )—R 7 , —N(R 10 )SO 2 —R 7 or —S(O) m —R 7 ;

R 6 is independently H; halogen; —CN; —OR 7 ; —NR 8 R 9 ; —N(R 10 )C(O)R 7 ; —C(O)N(R 7 )(R 8 ); —C(O)N(R 8 )(R 9 ); —C(O)OR 7 ; —SO 2 N(R 10 )—R 7 ; —N(R 10 )SO 2 —R 7 ; —S(O) m —R 7 ; alkyl optionally substituted one or more times by halogen, —OR 7 , —NR 8 R 9 , —CN, —N(R 10 )C(O)R 7 , —C(O)N(R 8 )(R 9 ), —C(O)OR 7 , —SO 2 N(R 10 )—R 7 , —N(R 10 )SO 2 —R 7 or —S(O) m —R 7 ; cycloalkyl optionally substituted one or more times by halogen, alkyl, haloalkyl, —OR 7 , —NR 8 R 9 , —CN, —N(R 10 )C(O)R 7 , —C(O)N(R 8 )(R 9 ), —C(O)OR 7 , —SO 2 N(R 10 )—R 7 , —N(R 10 )SO 2 —R 7 or —S(O) m —R 7 ; aryl optionally substituted one or more times by halogen, alkyl, haloalkyl, cycloalkyl, —OR 7 , —CN, —NR 8 R 9 —N(R 10 )C(O)(R 7 ), —C(O)N(R 7 )(R 8 ), —C(O)OR 7 , —SO 2 N(R 10 )—R 7 , —N(R 10 )SO 2 —R 7 or —S(O) m —R 7 ; heterocycloalkyl optionally substituted one or more times by halogen, alkyl, haloalkyl, —OR 7 , —CN, —NR 8 R 9 —N(R 10 )C(O)R 7 , —C(O)N(R 8 )(R 9 ), —C(O)OR 7 , —SO 2 N(R 10 )—R 7 , —N(R 10 )SO 2 —R 7 or —S(O) m —R 7 ; or heteroaryl optionally substituted one or more times by halogen, alkyl, haloalkyl, cycloalkyl, —OR 7 , —CN, —NR 8 R 9 , —N(R 10 )C(O)R 7 , —C(O)N(R 8 )(R 9 ), —C(O)OR 7 , —SO 2 N(R 10 )—R 7 , —N(R 10 )SO 2 —R 7 or —S(O) m —R 7 ;

R 8 is independently H or alkyl;

R 9 is independently H or alkyl;

or R 8 and R 9 are joined together with the nitrogen to which they are attached form a saturated 5- to 7-membered heterocyclic ring;

R 10 is independently H or alkyl;

a is 0, 1, 2, 3 or 4;

n is 1 or 2; and

m is 0, 1 or 2.

3. The compound as defined in claim 1 or a pharmaceutically acceptable salt thereof, which has the structural formula

wherein:

R 1 is independently H or alkyl;

R 2 is independently halogen, —CN, alkyl, haloalkyl, cycloalkyl, OR 7 ;

R 3 is H, halogen, —CN, alkyl, cycloalkyl or phenyl optionally substituted by halogen, alkyl or haloalkyl;

R 4 is H, cycloalkyl or alkyl;

R 5 is:

i.) H, halogen, —CN, alkyl, cycloalkyl, —OR 7 , haloalkyl or phenyl optionally substituted by halogen or haloalkyl; or

ii.) a group of the formula:

where:

R a is H, OH, or —C 1 -C 3 -alkyl optionally substituted with 1 to 3 -F;

R b is H, —OH, or —C 1 -C 3 -alkyl optionally substituted with 1 to 3 -F;

R c is —C 1 -C 3 -alkyl optionally substituted with 1 to 3 -F; —OC 1 -C 3 -alkyl; —N(H)S(O) 2 —C 1 -C 3 -alkyl; optionally substituted with 1 to 3 -F; or —N(H)C(O)C 1 -C 3 -alkyl, optionally substituted with 1 to 3 -F.;

R 7 is H, alkyl, haloalkyl, cycloalkyl, or phenyl optionally substituted by halogen; and

a is 0, 1 or 2.

4. The compound as defined in claim 1 or a pharmaceutically acceptable salt thereof, which has the structural formula

wherein:

R 1 is H or alkyl;

R 2 is independently halogen, —CN, alkyl, haloalkyl, cycloalkyl, OR 7 or phenyl optionally substituted by halogen;

R 3 is H, halogen, —CN, alkyl, cycloalkyl optionally substituted once or twice by halogen, alkyl or haloalkyl;

R 7 is H, alkyl, haloalkyl, cycloalkyl, or phenyl optionally substituted by halogen;

R 10 is alkyl or H;

a is 0, 1 or 2; and

b is 0, 1 or 2.

5. The compound as defined in claim 1 which is:

3-methyl-2-(5-methylpyridin-3-yl)-6,7-dihydropyrazolo [1,5-a]pyrimidin-5(4H)-one;

3,4-dimethyl-2-(5-methylpyridin-3-yl)-6,7-dihydropyrazolo [1,5-a]pyrimidin-5(4H)-one;

3-ethyl-4-methyl-2-(5-methylpyridin-3-yl)-6,7-dihydropyrazolo [1,5-a]pyrimidin-5(4H)-one;

3-cyclopropyl-2-(5-methylpyridin-3-yl)-6,7-dihydropyrazolo[1,5-a]pyrimidin-5(4H)-one;

2-(5-fluoropyridin-3-yl)-3,4-dimethyl-6,7-dihydropyrazolo [1,5-a]pyrimidin-5(4H)-one;

3-ethyl-2-(5-fluoropyridin-3-yl)-6,7-dihydropyrazolo [1,5-a]pyrimidin-5(4H)-one;

2-(5-fluoropyridin-3-yl)-3-methyl-6,7-dihydropyrazolo [1,5-a]pyrimidin-5(4H)-one;

3-cyclopropyl-2-(5-fluoropyridin-3-yl)-6,7-dihydropyrazolo [1,5-a]pyrimidin-5(4H)-one;

3ethyl-2-(5-methylpyridin-3-yl)-6,7-dihydropyrazolo [1,5-a]pyrimidin-5(4H)-one;

3-cyclopropyl-2-(4-methylpyridin-3-yl)-6,7-dihydropyrazolo[1,5-a]pyrimidin-5(4H)-one;

3ethyl-2-(4-methylpyridin-3-yl)-6,7-dihydropyrazolo [1,5-a]pyrimidin-5(4H)-one;

3-ethyl-2-(5fluoropyridin-3-yl)-4-methyl-6,7-dihydropyrazolo[1,5-a]pyrimidin-5(4H)-one;

3-ethyl-4-methyl-2-(4methylpyridin-3-yl)-6,7-dihydropyrazolo[1,5-a]pyrimidin-5(4H)-one;

3-cyclopropyl-4-methyl-2-(5-methylpyridin-3-yl)-6,7-dihydropyrazolo[1,5-a]pyrimidin-5(4H)-one;

4-methyl-5-oxo-2-(pyridin-3yl)-4,5,6,7-tetrahydropyrazolo [1,5-a]pyrimidine-3-carbonitrile;

2-(5-methylpyridin-3-yl)-5-oxo-4,5,6,7-tetrahydropyrazolo [1,5-a]pyrimidine-3-carbonitrile; and

2-(5-cloropyridin-3-yl)-5-oxo-4,5,6,7-tetrahydropyrazolo [1,5-a]pyrimidine-3-carbonitrile;

or a pharmaceutically acceptable salt thereof.

6. A pharmaceutical composition comprising at least one compound of Formula I as defined in claim 1 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.

7. A pharmaceutical composition comprising of at least one compound Formula I as defined in claim 1 or a pharmaceutically acceptable salt thereof, a therapeutically effective amount of at least one additional therapeutic agent and a pharmaceutically acceptable carrier.

Assignments (1)

MERGER Recorded Aug 8, 2022

From: MERCK SHARP & DOHME CORP.

To: MERCK SHARP & DOHME LLC

Reel/Frame 061102/0145 →

Continuity (3)

Continuation 14346518

Provisional Application 61537928 · Sep 22, 2011

Related Publication 20170020879A1 · Jan 26, 2017