LONG-CHAIN FATTY ACYL ELONGASE INHIBITOR COMPRISING ARYLSULFONYL DERIVATIVE AS ACTIVE INGREDIENT

• US 20110009622A1
• Filed: 04/17/2009
• Published: 01/13/2011
• Est. Priority Date: 04/24/2008
• Status: Active Grant

• Current Assignee: MSD Kabushiki Kaisha (Merck & Co., Inc.)
• Original Assignee: MSD Kabushiki Kaisha (Merck & Co., Inc.)
• Inventors: Nagase, Tsuyoshi, Jitsuoka, Makoto, Tsukahara, Daisuke, Sato, Nagaaki
• Granted Patent: US 8,420,823 B2
• Time in Patent Office: Days
• US Class Current: 540/604
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 1/18 for pancreatic disorders, e.g. pancreatic enzymes
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 15/08 for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 19/06 Antigout agents, e.g. antihyperuricemic or uricosuric agents
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/06 Antihyperlipidemics
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 3/12 for electrolyte homeostasis
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/10 Antimycotics
• CPC Class Codes: A61P 33/00 Antiparasitic agents
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 5/00 : Drugs for disorders of the endocrine system
• CPC Class Codes: A61P 5/50 : for increasing or potentiating the activity of insulin
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/04 : Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
• CPC Class Codes: A61P 9/10 : for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: A61P 9/12 : Antihypertensives
• CPC Class Codes: C07C 2601/02 : with a three-membered ring
• CPC Class Codes: C07C 2601/14 : The ring being saturated
• CPC Class Codes: C07C 311/16 : having the nitrogen atom of at least one of the sulfonamide groups bound to hydrogen atoms or to an acyclic carbon atom
• CPC Class Codes: C07C 311/19 : to an acyclic carbon atom of a hydrocarbon radical substituted by carboxyl groups
• CPC Class Codes: C07C 311/20 : having the nitrogen atom of at least one of the sulfonamide groups bound to a carbon atom of a ring other than a six-membered aromatic ring
• CPC Class Codes: C07C 317/44 : having sulfone or sulfoxide groups and carboxyl groups bound to the same carbon skeleton
• CPC Class Codes: C07D 207/48 : Sulfur atoms
• CPC Class Codes: C07D 211/96 : Sulfur atom
• CPC Class Codes: C07D 213/70 : Sulfur atoms
• CPC Class Codes: C07D 213/75 : Amino or imino radicals, acylated by carboxylic or carbonic acids, or by sulfur or nitrogen analogues thereof, e.g. carbamates
• CPC Class Codes: C07D 231/40 : Acylated on said nitrogen atom
• CPC Class Codes: C07D 231/52 : Oxygen atom in position 3 and nitrogen atom in position 5, or vice versa
• CPC Class Codes: C07D 239/38 : One sulfur atom
• CPC Class Codes: C07D 249/12 : Oxygen or sulfur atoms
• CPC Class Codes: C07D 265/28 : 1,4-Oxazines; Hydrogenated 1,4-oxazines
• CPC Class Codes: C07D 401/04 : directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 401/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 401/14 : containing three or more hetero rings
• CPC Class Codes: C07D 403/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 413/04 : directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 453/06 : containing isoquinuclidine ring systems
• CPC Class Codes: C07D 471/04 : Ortho-condensed systems
• CPC Class Codes: C07D 471/06 : Peri-condensed systems
• CPC Class Codes: C07D 471/08 : Bridged systems
• CPC Class Codes: C07D 487/04 : Ortho-condensed systems
• CPC Class Codes: C07D 487/08 : Bridged systems
• CPC Class Codes: C07D 491/04 : Ortho-condensed systems
• CPC Class Codes: C07D 491/08 : Bridged systems

Abstract

[Problem] To provide compounds useful as preventives or remedies for circular system disorders, nervous system disorders, metabolic disorders, reproduction system disorders, digestive system disorders, neoplasm, infectious diseases, etc., or as herbicides.

[Means for Solution] A long-chain fatty acyl elongase inhibitor comprising, as the active ingredient thereof, a compound or a pharmaceutically-active salt thereof of a formula (I):

[wherein W represents a hydrogen atom, a C_1-6 alkyl, etc.; X represents an aryl, a heteroaryl, etc.; n indicates 0 or 1; Z represents a hydrogen atom, a C_1-6 alkyl, etc.; A₁, A₂, A₃ and A₄ each independently represent CH or N].

Claims

1-11. -11. (canceled)

12. A long-chain fatty acyl elongase (LCE) inhibitor comprising, as the active ingredient thereof, a compound of a formula (I) or a pharmaceutically-acceptable salt thereof:

23. A compound of Formula I-1 or pharmaceutically salt thereof,

24. The long-chain fatty acyl elongase (LCE) inhibitor as claimed in claim 23, wherein W is an aryl or a heteroaryl.

25. The long-chain fatty acyl elongase (LCE) inhibitor as claimed in claim 23, wherein W is —

N(R¹)(R²), and R¹ and R² each are independently a hydrogen atom, a C_1-6 alkyl, a C_3-8 cycloalkyl, an aryl, a heteroaryl, an aralkyl or a heteroaralkyl, or R¹ and R², taken together with the nitrogen atom to which they bond, form a nitrogen-containing hetero ring.

26. The long-chain fatty acyl elongase (LCE) inhibitor as claimed in claim 25, wherein R¹ and R² each are independently a hydrogen atom, a C_1-6 alkyl or a C_3-8 cycloalkyl.

27. The long-chain fatty acyl elongase (LCE) inhibitor as claimed in claim 25, wherein R¹ and R², taken together with the nitrogen atom to which they bond, form a 5- to 7-membered monocyclic nitrogen-containing hetero ring.

28. The long-chain fatty acyl elongase (LCE) inhibitor as claimed in claim 25, wherein R¹ and R², taken together with the nitrogen atom to which they bond, form a 5- to 7-membered bicyclic nitrogen-containing hetero ring.

29. The long-chain fatty acyl elongase (LCE) inhibitor as in claim 23, wherein Z is a hydrogen atom.

30. A compound or pharmaceutically acceptable salt thereof, selected from the group consisting of:

N-(4-methoxyphenyl)-3-(piperidin-1-ylsulfonyl)benzamide;

3-(2-Azabicyclo[2.2.1]hept-2-ylsulfonyl)-N-(3-methoxypyridin-2-yl)benzamide;

3-Isopropoxy-5-{[3-(piperidin-1-ylsulfonyl)benzoyl]amino}-1-1H-pyrazole hydrochloride;

N-(3-ethoxypyridin-2-yl)-3-(pyrrolidin-1-ylsulfonyl)benzamide;

N-(3-isopropoxy-1H-pyrazol-5-yl)-3-(pyridin-2-ylsulfonyl)benzamide;

N-(3-butoxy-1H-pyrazol-5-yl)-3-(pyridin-2-ylsulfonyl)benzamide;

N-(4-isopropylphenyl)-3-(phenylsulfonyl)benzamide;

N-(5-isopropoxypyridin-2-yl)-3-(pyrimidin-2-ylsulfonyl)benzamide; and

[2-{[(4-Isopropoxyphenyl)amino]carbonyl}-4-(piperidin-1-ylsulfonyl)phenoxy]acetic acid.