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US 2013/0172351 A1Published application
Dihydropyrazoles
AssigneeMerck Patent GmbH
InventorsHenry Yu, Thomas E. Richardson, Robert James Foglesong, Lizbeth Celeste DeSelm, Andreas Goutopoulos
Life of this patent
Estimating the term…
Abstract
Novel dihydropyrazole derivatives of formula (I) wherein L, R, R3, R4, R5, R6, R7, X1, X2, X3, X4, Y, m and n have the meaning according to the claims, are positive allosteric modulators of the FSH receptor, and can be employed, inter alia, for the treatment of fertility disorders.
Claims14
A compound of formula (I)
- wherein
- R, L denote Ar1 or Het1;
- R1 denotes Hal, A, —(CY2)p—OY, —(CY2)p—NY2, COOY, CONY2, NHCOY, CN, SO2Y, -E-(CY2)p—Ar2, -E-(CY2)p-Het1 or -E-(CY2)p-Het3;
- R2 denotes Hal, A, —(CY2)p—OY, —(CY2)p—NY2, COY, COOY, CONY2, —CONY-Cyc, —O-Cyc, NO2, CN, SY, SOY, SO2Y, SO2NY2, NHSO2Y, alkenyl or -E-(CY2)p—Ar2;
- R3, R4, R5, R6 denote independently from one another H, A or Ar2;
- R7 denotes Y, OY or NY2;
- X1, X2, X3, X4 denote independently from one another O, NY or a single bond, with the proviso that m denotes 0 if X1 and X2 denote a single bond;
- E denotes —C≡C—, SO2, —SO2—NY—, O, NY or a single bond;
- Y denotes H or A;
- A denotes unbranched or branched alkyl having 1-10 C atoms, in which 1-7H atoms can be replaced by Hal;
- Cyc denotes cycloalkyl having 3-7 C atoms, in which 1-4H atoms can be replaced independently from one another by Hal or A;
- Ar1 denotes a saturated, unsaturated or aromatic, mono- or bicyclic carbocycle having 3-10 C atoms, which can be substituted by at least one substituent selected from the group of R1, R2 and —C≡C—C(A)2OH, and/or which can be fused to Cyc, Het1 or Het3;
- Are denotes an aromatic, mono- or bicyclic carbocycle having 6-10 C atoms, which can be substituted by at least one substituent selected from the group of Hal, A and —(CY2)p—OY;
- Het1 denotes an unsaturated or aromatic mono- or bicyclic heterocycle having 3-8 C atoms and 1-4 N, O and/or S atoms, which can be substituted by at least one substituent selected from the group of Hal, A, —(CY2)p—OY, —(CY2)p—NY2, —(CY2)p—Ar2, —CO—Ar2, SO2—Ar2, —(CY2)p-Het2, Het3 and CN;
- Het2 denotes an aromatic monocyclic heterocycle having 5-7 C atoms and 1-3 N atoms,
- which can be substituted by at least one substituent selected from the group of Hal, A and —(CY2)p—OY;
- Het3 denotes a saturated monocyclic heterocycle having 3-7 C atoms and 1-4 N, O and/or S atoms,
- which can be substituted by at least one substituent selected from the group of Hal, A, —(CY2)p—OY, —(CY2)p—NY2, COOY, COY, —CONY2, ═O and CN;
- Hal denotes F, Cl, Br or I;
- and m, n, p denote independently from one another 0, 1, 2, 3 or 4;
- and/or a physiologically acceptable salt thereof.
18 more elements
A method for modulating an FSH receptor comprising the steps of:
- (a) providing (i) a system expressing said FSH receptor and (ii) at least one compound of formula (I)
- wherein
- R, L denote independently from one another Ar1, Het1, A or OY;
- R1 denotes Hal, A, —(CY2)p—OY, —(CY2)p—NY2, COOY, CONY2, NHCOY, CN, SO2Y, -E-(CY2)p—Ar2, -E-(CY2)p-Het1 or -E-(CY2)p-Het3;
- R2 denotes Hal, A, —(CY2)p—OY, —(CY2)p—NY2, COY, COOY, CONY2, —CONY-Cyc, —O-Cyc, NO2, CN, SY, SOY, SO2Y, SO2NY2, NHSO2Y, alkenyl or -E-(CY2)p—Ar2;
- R3, R4, R5, R6 denote independently from one another H, A or Ar2;
- R7 denotes Y, OY or NY2;
- X1, X2, X3, X4 denote independently from one another O, NY or a single bond;
- E denotes —C≡C—, SO2, —SO2—NY—, O, NY or a single bond;
- Y denotes H or A;
- A denotes unbranched or branched alkyl having 1-10 C atoms, in which 1-7H atoms can be replaced by Hal;
- Cyc denotes cycloalkyl having 3-7 C atoms, in which 1-4H atoms can be replaced independently from one another by Hal or A;
- Ar1 denotes a saturated, unsaturated or aromatic, mono- or bicyclic carbocycle having 3-10 C atoms,
- which can be substituted by at least one substituent selected from the group of R1, R2 and —C≡C—C(A)2OH, and/or which can be fused to Cyc, Het1 or Het3;
- Are denotes an aromatic, mono- or bicyclic carbocycle having 6-10 C atoms, which can be substituted by at least one substituent selected from the group of Hal, A and —(CY2)p—OY;
- Het1 denotes an unsaturated or aromatic mono- or bicyclic heterocycle having 3-8 C atoms and 1-4 N, O and/or S atoms,
- which can be substituted by at least one substituent selected from the group of Hal, A, —(CY2)p—OY, —(CY2)p—NY2, —(CY2)p—Ar2, —CO—Ar2, SO2—Ar2, —(CY2)p-Het2, Het3 and CN;
- Het2 denotes an aromatic monocyclic heterocycle having 5-7 C atoms and 1-3 N atoms,
- which can be substituted by at least one substituent selected from the group of Hal, A and —(CY2)p—OY;
- Het3 denotes a saturated monocyclic heterocycle having 3-7 C atoms and 1-4 N, O and/or S atoms,
- which can be substituted by at least one substituent selected from the group of Hal, A, —(CY2)p—OY, —(CY2)p—NY2, COOY, COY, —CONY2, ═O and CN;
- Hal denotes F, Cl, Br or I;
- and
- m, n, p denote independently from one another 0, 1, 2, 3 or 4;
- and/or a physiologically acceptable salt thereof, and
- (b) contacting said system expressing said FSH receptor with said compound of formula (I) under conditions such that said FSH receptor is modulated.
23 more elements
Dependencies are inferred from the claim text.