Alkylamine derivative

A method of activating CaSR, comprising:

• administering a compound of Formula)(I0) or a pharmaceutically acceptable salt thereof:
• wherein R1 and R2, each independently, represent a hydrogen atom, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl or substituted or unsubstituted C2-6 alkynyl, or R1 and R2 may integrally form a substituted or unsubstituted 5- or 6-membered hetero ring which may further include a heteroatom(s);
• R3 represents a hydrogen atom, halogeno or substituted or unsubstituted C1-6 alkyl;
• R4 and R5, each independently, represent a hydrogen atom, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl or halogeno;
• X represents NH;
• Y represents C═O, SO, SO2, C═S or C═NRd, where Rd represents a hydrogen atom or C1-6 alkyl, and Rd and R6 may integrally form a substituted or unsubstituted 5- or 6-membered hetero ring;
• R6 represents a hydrogen atom, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl or hydroxy;
• G0 represents unsubstituted or substituted aryl with one or more R70 or unsubstituted or substituted heteroaryl with one or more R70, where the R70-substituted aryl or the R70-substituted heteroaryl may further be substituted, where aryl in G° is phenyl or naphthyl, and heteroaryl in G0 is one of pyridyl, pyridazinyl, pyrazinyl, pyrimidinyl, thiazolyl, isothiazolyl, oxazolyl, isooxazolyl, oxadiazolyl, pyrazolyl, imidazolyl, furyl, thiophenyl and pyrrolyl;
• R70 represents substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, halogeno, hydroxy, substituted or unsubstituted C1-6 alkoxy, nitro, amino, mono-C1-6 alkylamino, di-C1-6 alkylamino, sulfo, carboxyl, phosphono, C1-3 alkylcarbonylamino or mono-C1-6 alkylphosphono, where they may be different when more than one R70 exist;
• Q represents a hydrogen atom, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, carboxyl, CONReRf, CONHNHRg, CORh, substituted or unsubstituted aryl or substituted or unsubstituted heteroaryl;
• Re and Rf, each independently, represent a hydrogen atom, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C1-6 alkylsulfonyl, substituted or unsubstituted arylsulfonyl, substituted or unsubstituted C3-8 cycloalkyl, hydroxy or C1-6 alkoxy, or alternatively, Re and Rf may integrally form a substituted or unsubstituted 5- or 6-membered hetero ring which may further have a heteroatom(s);
• Rg represents substituted or unsubstituted C1-6 alkylcarbonyl, substituted or unsubstituted benzoyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
• and
• Rh represents substituted or unsubstituted C1-6 alkoxy, substituted or unsubstituted mercapto, or the following group:
• where Z represents a bivalent group of substituted or unsubstituted C1-6 hydrocarbon;
• E1 represents substituted or unsubstituted C1-6 acyloxy, substituted or unsubstituted C1-6 alkoxycarbonyloxy, substituted or unsubstituted amino, carboxyl, substituted or unsubstituted C1-6 alkoxycarbonyl, halogeno, aryl, heteroaryl, substituted or unsubstituted C1-6 alkoxy or substituted or unsubstituted carbamoyl;
• E2 represents a hydrogen atom or C1-6 alkyl;
• and Z and E1 may integrally form a ring.

A method of treating a disease that is ameliorated through CaSR activation, comprising:

• administering a compound of Formula (I0) or a pharmaceutically acceptable salt thereof:
• wherein R1 and R2, each independently, represent a hydrogen atom, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl or substituted or unsubstituted C2-6 alkynyl, or R1 and R2 may integrally form a substituted or unsubstituted 5- or 6-membered hetero ring which may further include a heteroatom(s);
• R3 represents a hydrogen atom, halogeno or substituted or unsubstituted C1-6 alkyl;
• R4 and R5, each independently, represent a hydrogen atom, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl or halogeno;
• X represents NH;
• Y represents C═O, SO, SO2, C═S or C═NRd, where Rd represents a hydrogen atom or C1-6 alkyl, and Rd and R6 may integrally form a substituted or unsubstituted 5- or 6-membered hetero ring;
• R6 represents a hydrogen atom, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl or hydroxy;
• G0 represents unsubstituted or substituted aryl with one or more R70 or unsubstituted or substituted heteroaryl with one or more R70, where the R70-substituted aryl or the R70-substituted heteroaryl may further be substituted, where aryl in G0 is phenyl or naphthyl, and heteroaryl in G0 is one of pyridyl, pyridazinyl, pyrazinyl, pyrimidinyl, thiazolyl, isothiazolyl, oxazolyl, isooxazolyl, oxadiazolyl, pyrazolyl, imidazolyl, furyl, thiophenyl and pyrrolyl;
• R70 represents substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, halogeno, hydroxy, substituted or unsubstituted C1-6 alkoxy, nitro, amino, mono-C1-6 alkylamino, di-C1-6 alkylamino, sulfo, carboxyl, phosphono, C1-3 alkylcarbonylamino or mono-C1-6 alkylphosphono, where they may be different when more than one R70 exist;
• Q represents a hydrogen atom, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, carboxyl, CONReRf, CONHNHRg, CORh, substituted or unsubstituted aryl or substituted or unsubstituted heteroaryl;
• Re and Rf, each independently, represent a hydrogen atom, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C1-6 alkylsulfonyl, substituted or unsubstituted arylsulfonyl, substituted or unsubstituted C3-8 cycloalkyl, hydroxy or C1-6 alkoxy, or alternatively, Re and Rf may integrally form a substituted or unsubstituted 5- or 6-membered hetero ring which may further have a heteroatom(s);
• Rg represents substituted or unsubstituted C1-6 alkylcarbonyl, substituted or unsubstituted benzoyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
• and
• Rh represents substituted or unsubstituted C1-6 alkoxy, substituted or unsubstituted mercapto, or the following group:
• where Z represents a bivalent group of substituted or unsubstituted C1-6 hydrocarbon;
• E1 represents substituted or unsubstituted C1-6 acyloxy, substituted or unsubstituted C1-6 alkoxycarbonyloxy, substituted or unsubstituted amino, carboxyl, substituted or unsubstituted C1-6 alkoxycarbonyl, halogeno, aryl, heteroaryl, substituted or unsubstituted C1-6 alkoxy or substituted or unsubstituted carbamoyl;
• E2 represents a hydrogen atom or C1-6 alkyl;
• and Z and E1 may integrally form a ring.

A method of activating CaSR, comprising:

• administering a composition including a compound of Formula (I0) or an edible salt thereof:
• wherein the composition is a seasoning or a kokumi-imparting agent;
• R1 and R2, each independently, represent a hydrogen atom, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl or substituted or unsubstituted C2-6 alkynyl, or R1 and R2 may integrally form a substituted or unsubstituted 5- or 6-membered hetero ring which may further include a heteroatom(s);
• R3 represents a hydrogen atom, halogeno or substituted or unsubstituted C1-6 alkyl;
• R4 and R5, each independently, represent a hydrogen atom, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl or halogeno;
• X represents NH;
• Y represents C═O, SO, SO2, C═S or C═NRd, where Rd represents a hydrogen atom or C1-6 alkyl, and Rd and R6 may integrally form a substituted or unsubstituted 5- or 6-membered hetero ring;
• R6 represents a hydrogen atom, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl or hydroxy;
• G0 represents unsubstituted or substituted aryl with one or more R70 or unsubstituted or substituted heteroaryl with one or more R70, where the R70-substituted aryl or the R70-substituted heteroaryl may further be substituted, where aryl in G0 is phenyl or naphthyl, and heteroaryl in G0 is one of pyridyl, pyridazinyl, pyrazinyl, pyrimidinyl, thiazolyl, isothiazolyl, oxazolyl, isooxazolyl, oxadiazolyl, pyrazolyl, imidazolyl, furyl, thiophenyl and pyrrolyl;
• R70 represents substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, halogeno, hydroxy, substituted or unsubstituted C1-6 alkoxy, nitro, amino, mono-C1-6 alkylamino, alkylamino, sulfo, carboxyl, phosphono, C1-3 alkylcarbonylamino or mono-C1-6 alkylphosphono, where they may be different when more than one R70 exist;
• Q represents a hydrogen atom, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, carboxyl, CONReRf, CONHNHRg, CORh, substituted or unsubstituted aryl or substituted or unsubstituted heteroaryl;
• Re and Rf, each independently, represent a hydrogen atom, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C1-6 alkylsulfonyl, substituted or unsubstituted arylsulfonyl, substituted or unsubstituted C3-8 cycloalkyl, hydroxy or C1-6 alkoxy, or alternatively, Re and Rf may integrally form a substituted or unsubstituted 5- or 6-membered hetero ring which may further have a heteroatom(s);
• Rg represents substituted or unsubstituted C1-6 alkylcarbonyl, substituted or unsubstituted benzoyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
• and
• Rh represents substituted or unsubstituted C1-6 alkoxy, substituted or unsubstituted mercapto, or the following group:
• where Z represents a bivalent group of substituted or unsubstituted C1-6 hydrocarbon;
• E1 represents substituted or unsubstituted C1-6 acyloxy, substituted or unsubstituted C1-6 alkoxycarbonyloxy, substituted or unsubstituted amino, carboxyl, substituted or unsubstituted C1-6 alkoxycarbonyl, halogeno, aryl, heteroaryl, substituted or unsubstituted C1-6 alkoxy or substituted or unsubstituted carbamoyl;
• E2 represents a hydrogen atom or C1-6 alkyl;
• and Z and E1 may integrally form a ring.