Benzamides and related inhibitors of factor Xa

1. A compound of the following formula:

A-Q-D-E-G-J-X,

wherein:

A is a member selected from the group consisting of:

Q is a direct link;

D is a member selected from the group consisting of:

E is a member selected from the group consisting of:

—C(═O)—NH— and —NH—C(═O)—;

G is

G is substituted by 0-4 R 1d groups and each R 1d group is independently selected from the group consisting of:

H, —CH 3 , —CF 3 , —Cl, —F, —Br, —NH 2 , —NMe 2 , —OH, —OMe, —NHSO 2 Me, —NO 2 , —CN, —C(═O)—OMe, —CO 2 H, —CONH 2 , —SO 2 NH 2 , —SO 2 CH 3 , —NHC(═O)Me, —C(═O)N(—Me) 2 , —CH 2 NH 2 , —CH 2 N(—Me) 2 , —CH 2 OH, —OCH 2 CO 2 H, —OCH 2 C(═O)—OMe, —OCH 2 C(═O)—NH 2 , —OCH 2 C(═O)N(—Me) 2 ,

J is a member selected from the group consisting of:

—O—, —NH—, —C(═O)—NH— and —NH—C(═O)—;

X is a member selected from the group consisting of:

or a pharmaceutically acceptable isomer, salt, hydrates, solvate or prodrug derivative thereof.

2. A compound of claim 1 having the following structure:

wherein:

R 1e is a member selected from the group consisting of:

H, —F, —Cl, —Br, —OMe, —OH, —Me, —CF 3 and —CH 2 NH 2 ;

A-Q is a member selected from the group consisting of:

D is a member selected from the group consisting of:

or a pharmaceutically acceptable isomer, salt, hydrates, solvate or prodrug derivative thereof.

3. A compound of claim 2 , having the following structure:

wherein:

R 1a is a member selected from the group consisting of:

H, —F, —Cl and —Br;

R 1e is a member selected from the group consisting of:

—F, —Cl, —Br, —OMe, and —Me; and

A-Q is a member selected from the group consisting of:

or a pharmaceutically acceptable isomer, salt, hydrates, solvate or prodrug derivative thereof.

4. A compound of claim 1 having the following structure:

wherein:

R is a member selected from the group consisting of —SO 2 NH 2 , and —SO 2 Me;

R 1a is a member selected from the group consisting of H, —F, —Cl and Br;

R 1e is a member selected from the group consisting of —F, —Cl, —Br, —OMe and —Me;

G is

wherein each G group may be substituted by 0-4 R 1d groups and each such R 1d group is independently selected from the group consisting of:

H, —CH 3 , —CF 3 , —Cl, —F, —Br, —NH 2 , —N(—Me) 2 , —OH, —OMe, —NHSO 2 Me, —NO 2 , —CN, —C(═O)—OMe, —CO 2 H, —C(═O)—NH 2 , —SO 2 NH 2 , —SO 2 CH 3 , —NH—C(═O)—Me, —C(═O)—N(—Me) 2 , —CH 2 NH 2 , —CH 2 —N(—Me) 2 , —CH 2 OH, —OCH 2 CO 2 H, —OCH 2 CO 2 Me, —OCH 2 C(═O)—NH 2 , —OCH 2 C(═O)—N(—Me) 2 ,

or a pharmaceutically acceptable isomer, salt, hydrates, solvate or prodrug derivative thereof.

5. A compound of claim 1 having the following structure:

wherein J-X is collectively a member selected from the group consisting of:

or a pharmaceutically acceptable isomer, salt, hydrates, solvate or prodrug derivative thereof.

6. A compound of claim 1 selected from the group of consisting of:

or a pharmaceutically acceptable isomer, salt, hydrates, solvate or prodrug derivative thereof.

7. A compound of claim 1 selected from the group consisting of:

3-(2-(4-[(2-aminosulfonyl)phenyl]benzoylamino)phenoxy)benzamidine;

3-(4-fluoro-2-(4-[(2-aminosulfonyl)phenyl]phenylcarbonylamino)phenoxy)benzamidine;

3-(4-trifluoromethyl-2-(4-[(2-aminosulfonyl)phenyl]phenylcarbonylamino)phenoxy)benzamidine;

3-(4-methylsulfonyl-2-(4-[(2-aminosulfonyl)phenyl]phenylcarbonylamino)phenoxy)benzamidine;

3-(5hydroxy-2-(4-[(2-aminosulfonyl)phenyl]phenylcarbonylamino)phenoxy)benzamidine;

3-(4-methoxycarbonyl-2-(4-[(2-aminosulfonyl)phenyl]phenylcarbonylamino)phenoxy)benzamidine;

3-(4-hydroxycarbonyl-2-(4-[(2-aminosulfonyl)phenyl]phenylcarbonylamino)phenoxy)benzamidine;

3-(2-(4-[(2-aminosulfonyl)phenyl]phenylcarbonylamino)phenylamino)benzamidine;

7-(2-(4-[(2-aminosulfonyl)phenyl]benzoylamino)phenoxy)-1-aminoisoquinoline;

7-(2-(4-[(2-aminosulfonyl)phenyl]benzoylamino)-4-fluorophenoxy)1-aminoisoquinoline;

7-(2-(4-[(2-aminosulfonyl)phenyl]benzoylamino)-4-trifluoromethylphenoxy)1-aminoisoquinoline;

7-(2-(4-[(2-aminosulfonyl)phenyl]benzoylamino)-4-methylsulfonylphenoxy)1-aminoisoquinoline;

3-(2-(4-[-(2-aminosulfonyl)phenyl]phenylaminocarbonyl-4-nitrophenoxy)benzamidine;

3-(2-(4-[(2-aminosulfonyl)phenyl]phenylaminocarbonyl-4-aminophenoxy)benzamidine;

3-(2-(4-[(2-aminosulfonyl)phenyl]phenylaminocarbonyl-4-chlorophenoxy)benzamidine;

3-(2-(4-[(2-aminosulfonyl)phenyl]phenylaminocarbonyl-4-bromophenoxy)benzamidine;

2-bromo-6-(2-(4-1-[(2-aminosulfonyl)phenyl]phenylcarbonylamino)phenoxy naphthalene;

3-methoxycarbonyl-2-(4-[(2-aminosulfonyl)phenyl]phenylcarbonylamino)phenoxy naphthalene;

3-hydroxycarbonyl-2-(4-[(2-aminosulfonyl)phenyl]phenylcarbonylamino)phenoxy naphthalene;

3-aminocarbonyl-2-(4-[(2-aminosulfonyl)phenyl]phenylcarbonylamino)phenoxy naphthalene;

3-methoxycarbonyl-2-(4-[(2-aminosulfonyl)phenyl]phenylcarbonylamino)phenoxy-6-bromo naphthalene;

3-hydroxycarbonyl-2-(4-[(2-aminosulfonyl)phenyl]phenylcarbonylamino)phenoxy-6-bromo naphthalene;

N-(5-bromo-2-pyridinyl)(2-4-[(2-aminosulfonyl)phenyl]phenylcarbonylamino)phenylcarboxamide;

N-(5-chloro-2-pyridinyl)-(2-4-[(2-aminosulfonyl)phenyl]phenylcarbonylamino)phenylcarboxamide;

N-(5-bromo-2-pyridinyl)-(2-(4-[(2-methylsulfonyl)phenyl]phenylcarbonyl)amino)phenylcarboxamide;

N-(5-chloro-2-pyridinyl)-(2-(4-[(2-methylsulfonyl)phenyl]phenylcarbonyl)amino)phenylcarboxamide;

N-(4-bromo-2-methoxycarbonyphenyl)-(2-(4-[(2-methylsulfonyl)phenyl]phenylcarbonyl)amino)phenylcarboxamide

N-(4-chloro-2-methoxycarbonylphenyl)-(2-(4-[(2-methylsulfonyl)phenyl]phenylcarbonyl)amino)phenylcarboxamide;

N-(4-bromo-2-nitrophenyl)-(2-(4-[(2-methylsulfonyl)phenyl]phenylcarbonyl)amino)phenylcarboxamide;

N-(5-bromo-2-pyridinyl)-(2-(4-[(2-aminosulfonyl)phenyl]phenylcarbonyl)amino)-4-nitrophenylcarboxamide;

N-(5-bromo-2-pyridinyl)-(2(4-[(2-aminosulfonyl)phenyl]phenylcarbonyl)amino)-4-aminophenylcarboxamide;

N-(5-chloro-2-pyridinyl)-(2-(4-[(2-aminosulfonyl)phenyl]phenylcarbonyl)amino)-4-aminophenylcarboxamide;

N-(5-bromo-2-pyridinyl)-(2-(4-[(2-aminosulfonyl)phenyl]phenylcarbonyl)amino)-4-methylsulfonylaminophenylcarboxamide;

N-(5-chloro-2-pyridinyl)-(2-(4-[(2-aminosulfonyl)phenyl]phenylcarbonyl)amino)-4-methylsulfonylaminophenylcarboxamide;

N-(5-bromo-2-pyridinyl)-(2-(4-[(2-aminosulfonyl)phenyl]phenylcarbonyl)amino)-5-aminophenylcarboxamide;

N-(5-chloro-2-pyridinyl)-2-(4-[(2-aminosulfonyl)phenyl]phenylcarbonyl)amino)-5-aminophenylcarboxamide;

N-(5-bromo-2-pyridinyl)-(2-4-[(2-aminosulfonyl)phenyl]phenylcarbonylamino)-4,5-difluorophenylcarboxamide;

3-(2-(4-[(2-aminosulfonyl)phenyl]-2-fluorophenylaminocarbonyl-4-aminophenoxy)benzamidine;

3-(2-(4-[(2-aminosulfonyl)phenyl]-2-fluorophenylaminocarbonyl-4-aminophenoxy)benzamidine;

3-(2-(4-[(2-aminosulfonyl)phenyl]benzoylamino)phenoxy)benzylamine;

2-[4-(N-{2-[N-(5-chloro-2-pyridyl)carbamoyl]phenyl}carbamoyl)phenyl]-benzenecarboxamidine;

(4-{2-[(dimethylamino)iminomethyl]phenyl}phenyl)-N-{2-[N-(5-chloro(2-pyridyl))carbamoyl]phenyl}carboxamide;

N-{2-[N-(5-chloro(2-pyridyl))carbamoyl]phenyl}{4-[2-((hydroxyamino)iminomethyl)-phenyl]phenyl}carboxamide;

2-[4-(N-{2-[N-(5-chloro-2-pyridyl)carbamoyl]phenyl}carbamoyl)phenyl]benzamide;

{4-[2-(aminomethyl)phenyl]phenyl}-N-{2-[N-(5-chloro(2-pyridyl))carbamoyl]-phenyl}carboxamide;

N-(5-bromo-2-pyridinyl)-(2-4-[(2-aminosulfonyl)phenyl]phenylcarbonylamino)-5-fluorophenylcarboxamide;

or a pharmaceutically acceptable isomer, salt, hydrates, solvate or prodrug derivative thereof.

8. A pharmaceutical composition for preventing or treating a condition in a mammal characterized by undesired thrombosis comprising a pharmaceutically acceptable carrier and a pharmaceutically effective amount of a compound of claim 1 .