Non-imidazole aryl alkylamines compounds as histamine h3 receptor antagonists, preparation and therapeutic uses

A compound structurally represented by Formula I

• 468
• or pharmaceutically acceptable salts thereof wherein:
• X is O, NR7 or S;
• R1 is hydrogen,
• C1-C8 alkyl optionally substituted with 1 to 4 halogens,
• (CHR5)n—C3-C7 cycloalkyl,
• (CHR5)n aryl,
• (CHR5)n heteroaryl, or
• (CHR5)n—O(CHR5)n-aryl;
• R2 is independently R1, or
• COR1, or cyclized with the attached nitrogen atom at the R1 position to form a 4, 5, or 6 member carbon ring, wherein one of said carbons is optionally replaced by one of O, S, NR1 or CO, or wherein the ring formed by R1 and R2 is optionally substituted one to two times with C1-C4 alkyl;
• R3 is independently C3-C7 cycloalkylene, or C1-C4 alkylene optionally substituted;
• R4 is hydrogen,
• halogen,
• C1-C4 alkyl,
• (CHR5)n—C3-C7 cycloalkyl,
• (CHR5)n aryl,
• (CHR5)n heteroaryl,
• (CHR5)n—O(CHR5)r-aryl or
• CO or
• cyclized with R5 to from a cyclopropyl ring;
• R5 is hydrogen, or
• C1-C4 alkyl;
• R6 is hydrogen,
• halo or
• cyclized with the attached carbon atom at the R5 position to form a 5 to 6 member carbon ring,
• cyclized with the attached carbon atom at the R7 position to form a 5 to 6 member heterocyclic ring or
• R7 is hydrogen,
• C1-C8 alkyl optionally substituted with 1 to 4 halogens,
• (CHR5)n—C3-C7 cycloalkyl,
• (CHR5)n aryl,
• (CHR5)n heteroaryl,
• (CHR5)—O(CHR5)n-aryl,
• SO2R1 or
• Cyclized with attached carbon on R8 to from a 5, 6, or 7 membered carbon ring optionally substituted with R9, CF3, or CN, optionally one of the said carbons is replaced by N, NR1, CO;
• R8 is hydrogen,
• a bond,
• C1-C8 alkyl
• —SO2 R9,
• —CO2 R10,
• —CO R9,
• —CONH R10;
• R9 is hydrogen,
• halogen,
• C1-C8 alkyl optionally substituted with 1 to 4 halogens,
• C3-C7 cycloalkyl,
• aryl,
• CH2 aryl,
• heteroaryl,
• heterocycle,
• —O(CHR5)n-aryl,
• —COR1,
• —CONR1 R2,
• —SO2R1,
• —OR1,
• —N(R1)2,
• NR1R2,
• —CH2NR1, R2,
• —CONR1R2
• —NHSO2R1,
• —NO2,
• —CO2R1,
• —SO2N(R1)2,
• —S(O)nR1,
• —OCF3,
• —CH2SR5,
• R10 is hydrogen,
• halogen,
• C1-C8 alkyl optionally substituted with 1 to 4 halogens,
• C3-C7 cycloalkyl,
• aryl,
• CH2 aryl,
• heteroaryl,
• heterocycle,
• —COR1,
• —CONR1R2,
• —SO2R1,
• —N(R1)2,
• —NR1R2,
• —CH2NR1, R2,
• —CONR1R2
• —CO2R1,
• —SO2N(R1)2,
• —S(O)nR1,
• —CH2SR5,
• and n is 0-4.