	US 7,589,112 B2
	Methylene urea derivatives
Hans-Peter Buchstaller, Weiterstadt (Germany); Matthias Wiesner, Seeheim-Jugenheim (Germany); Oliver Schadt, Rodenbach (Germany); Christiane Amendt, Darmstadt (Germany); Frank Zenke, Darmstadt (Germany); Christian Sirrenberg, Darmstadt (Germany); Matthias Grell, Darmstadt (Germany); and Dirk Finsinger, Darmstadt (Germany)
Assigned to Merck Patent GmbH, Darmstadt (Germany)
Appl. No. 10/532,574 PCT Filed Oct. 08, 2003, PCT No. PCT/EP03/11134 § 371(c)(1), (2), (4) Date Apr. 25, 2005, PCT Pub. No. WO2004/037789, PCT Pub. Date May 06, 2004.
Claims priority of provisional application 60/490285, filed on Jul. 28, 2003.
Claims priority of application No. 02023906 (EP), filed on Oct. 24, 2002.
Prior Publication US 2006/0199844 A1, Sep. 07, 2006
Int. Cl. A61K 31/4412 (2006.01); C07D 213/68 (2006.01)

U.S. Cl. 514—350 [514/345; 546/290; 546/298]

4 Claims

1. A compound of formula II,

wherein

Ar¹is phenyl,

Ar²is pyridinyl,

R⁶, R⁷are independently H or A,

R⁸, R⁹and R¹⁰are independently selected from the group consisting of H, A, cycloalkyl comprising 3 to 7 carbon atoms, Hal, CH₂Hal, CH(Hal)₂, C(Hal)₃, NO₂, (CH₂)_nCN, (CH₂)_nNR¹¹R¹², (CH₂)_nO(CH₂)_kNR¹¹R¹², (CH₂)_nNR¹¹(CH₂)_kNR¹¹R¹², (CH₂)_nO(CH₂)_kOR¹¹, (CH₂)_nNR¹¹(CH₂)_kOR¹², (CH₂)_nCOOR¹³, (CH₂)_nCOR¹³, (CH₂)_nCONR¹¹R¹², (CH₂)_nNR¹¹COR¹³, (CH₂)_nNR¹¹CONR¹¹R¹², (CH₂)_nNR¹¹SO₂A, (CH₂)_nSO₂NR¹¹R¹², (CH₂)_nS(O)_uR¹³, (CH₂)_nOC(O)R¹³, (CH₂)_nCOR¹³, (CH₂)_nSR¹¹, CH═N—OA, CH₂CH═N—OA, (CH₂)_nNHOA, (CH₂)_nCH═N—R¹¹, (CH₂)_nOC(O)NR¹¹R¹², (CH₂)_nNR¹¹COOR¹³, (CH₂)_nN(R¹¹)CH₂CH₂OR¹³, (CH₂)_nN(R¹¹)CH₂CH₂OCF₃, (CH₂)_nN(R¹¹)C(R¹³)HCOOR¹², (CH₂)_nN(R¹¹)C(R¹³)HCOR¹¹, (CH₂)_nN(R¹¹)CH₂CH₂N(R¹²)CH₂COOR¹¹, (CH₂)_nN(R¹¹)CH₂CH₂NR¹¹R¹², CH═CHCOOR¹³, CH═CHCH₂NR¹¹R¹², CH═CHCH₂NR¹¹R¹², CH═CHCH₂OR¹³, (CH₂)_nN(COOR¹³)COOR¹⁴, (CH₂)_nN(CONH₂)COOR¹³, (CH₂)_nN(CONH₂)CONH₂, (CH₂)_nN(CH₂COOR¹³)COOR¹⁴, (CH₂)_nN(CH₂CONH₂)COOR¹³, (CH₂)_nN(CH₂CONH₂)CONH₂, (CH₂)_nCHR¹³COR¹⁴, (CH₂)_nCHR¹³COOR¹⁴, (CH₂)_nCHR¹³CH₂OR¹⁴, (CH₂)_nOCN and (CH₂)_nNCO, wherein

R¹¹R¹²are independently selected from the group consisting of H, A and (CH₂),

R¹³, R¹⁴are independently selected from the group consisting of H, Hal, A and (CH₂)_mAr⁴,

A is selected from the group consisting of alkyl, alkenyl, cycloalkyl, alkylenecycloalkyl, alkoxy and alkoxyalkyl,

Ar³, Ar⁴are independently aromatic hydrocarbon residues comprising 5 to 12 carbon atoms which are optionally substituted by one or more substituents, selected from the group consisting of A, Hal, NO₂, CN, OR¹⁵, NR¹⁵R¹⁶, COOR¹⁵, CONR¹⁵R¹⁶, NR¹⁵COR¹⁶, NR¹⁵CONR¹⁵R¹⁶, NR¹⁶SO₂A, COR¹⁵, SO₂R¹⁵R¹⁶, S(O)_uA and OOCR¹⁵,

R¹⁵, R¹⁶are independently selected from the group consisting of H, A, and (CH₂)_mAr⁶, wherein

Ar⁶is a 5- or 6-membered aromatic hydrocarbon which is optionally substituted by one or more substituents selected from the group consisting of methyl, ethyl, propyl, 2-propyl, tert.-butyl, Hal, CN, OH, NH₂and CF₃,

k, n and m are independently of one another 0, 1, 2, 3, 4, or 5;

X is O,

Y is O or S,

p, r are independently 0, 1, 2, 3, 4 or 5,

q is 0, 1, 2, 3 or 4,

u is 0, 1, 2 or 3,

and

Hal is selected from the group consisting of F, Cl, Br and I;

and a pharmaceutically acceptable salt thereof.