SUBSTITUTED CHROMAN COMPOUNDS AS CALCIUM SENSING RECEPTOR MODULATORS

摘要

The present invention provides calcium sensing receptor modulators (CaSR). In particular, the compounds described herein are useful for treating, managing, and/or lessening the severity of diseases, disorders, syndromes and/or conditions associated with the modulation of calcium sensing receptors (CaSR). The invention also provides herein the pharmaceutical compositions thereof, and methods for treating, managing, and/or lessening the severity of diseases, disorders, syndromes and/or conditions associated with the modulation of CaSR. The invention also relates to process for the preparation of the compounds of the invention.;

主权项

1. A compound of Formula (I):wherein,
Ra is selected from hydrogen, halogen, substituted or unsubstituted alkyl, cyano, substituted or unsubstituted cycloalkyl and substituted or unsubstituted haloalkyl; Rb, which may be same or different at each occurrence, is independently selected from hydrogen, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl and substituted or unsubstituted haloalkyl; R, which may be same or different at each occurrence, is independently selected from halogen, hydroxy, substituted or unsubstituted alkyl, substituted or unsubstituted haloalkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cycloalkyl, OR6, nitro, cyano, —C(O)OR6, —(CH2)r—C(O)OR6, —O—C(O)OR6, —O(CH2)r—C(O)OR6, —NR7R8, —(CH2)rNR7R8—, —C(O)R9, —C(O)NR7R8, —(CH2)rC(O)NR7R8, —NR7C(O)R9, —S(O)0-2R6, —S(O)2NR7R8, and —NR7S(O)2R9; X is selected from a bond, —(CRcRd)r—, —O—, —NR7—, —NR7(CRcRd)r—, —O(CRcRd)r—, —C(O)NR7—, —C(O)NR7(CRcRd)r—, —(CRcRd)rNR7(CRcRd)r—, —(CRcRd)rcycloalkylene-, cycloalkylene, -cycloalkylene(CRcRd)r— and —O-cycloalkylene where cycloalkylene may be substituted or unsubstituted; Rc and Rd, which may be same or different at each occurrence, are independently selected from hydrogen, halogen, hydroxy, cyano, nitro, substituted or unsubstituted alkyl, substituted or unsubstituted haloalkyl and substituted or unsubstituted cycloalkyl; or Rc and Rd, together with the carbon atom to which they are attached, may form a substituted or unsubstituted 3 to 7 membered saturated carbocyclic ring; Z is —OR6 or —NR10R11; R1, which may be same or different at each occurrence, is independently selected from halogen, nitro, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted haloalkyl, substituted or unsubstituted cycloalkyl, —OR6, —C(O)R9, —NR7R8, —(CH2)rNR7R8—, —(CH2)r—C(O)OR6, —O—C(O)OR6, —O(CH2)r—C(O)OR6, —C(O)NR7R8, —(CH2)r—C(O)NR7R8, —NR7C(O)R9, —S(O)0-2R7, —S(O)2NR7R8 and —NR7S(O)2R9; R2 is selected from substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl and substituted or unsubstituted heterocyclyl; R3 and R4 may be same or different and are independently selected from hydrogen, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted haloalkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkoxy, substituted or unsubstituted haloalkoxy and substituted or unsubstituted cycloalkyl; R5 is substituted or unsubstituted alkyl; R6, which may be same or different at each occurrence, is independently selected from hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted haloalkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, and substituted or unsubstituted aryl; R7 and R8, which may be same or different at each occurrence, are independently selected from hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkylalkyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heteroarylalkyl, substituted or unsubstituted heterocyclyl, and substituted or unsubstituted heterocyclylalkyl; or R7 and R8, together with the nitrogen atom to which they are attached, may form a substituted or unsubstituted, saturated or unsaturated 3 to 12 membered cyclic ring, wherein the unsaturated cyclic ring may have one or two double bonds; at each occurrence, R9 is substituted or unsubstituted alkyl or substituted or unsubstituted aryl; R10 and R11 may be same or different and are independently selected from hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, —(CRcRd)r—C(O)OR6, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkylalkyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heteroarylalkyl, substituted or unsubstituted heterocyclyl, and substituted or unsubstituted heterocyclylalkyl; or R10 and R11, together with the nitrogen atom to which they are attached, may form a substituted or unsubstituted, saturated or unsaturated 3 to 12 membered cyclic ring, wherein the unsaturated cyclic ring may have one or two double bonds;‘n’ is an integer ranging from 1 to 3, both inclusive;‘m’ is an integer ranging from 0 to 3, both inclusive;‘p’ is an integer ranging from 0 to 4, both inclusive;‘q’ is an integer ranging from 0 to 3, both inclusive; and‘r’ is an integer ranging from 1 to 3, both inclusive;or its pharmaceutically acceptable salt thereof.