Anthranilic acid amides and the use thereof as medicaments

• US 7,122,547 B1
• Filed: 11/09/1999
• Issued: 10/17/2006
• Est. Priority Date: 11/10/1998
• Status: Expired due to Fees

• Current Assignee: Novartis Ag
• Original Assignee: Schering Ag (Merck & Co., Inc.), Novartis Ag
• Inventors: Mestan, Jürgen, Brüggen, Jose, Furet, Pascal, Thierauch, Karl-Heinz, Huth, Andreas, Seidelmann, Dieter, Schirner, Michael, Bold, Guido, Wood, Jeanette Marjorie, Manley, Paul William, Ferrari, Stefano, Ottow, Eckhard, Menrad, Andreas, Krüger, Martin
• Primary Examiner(s): Wilson, James O.
• Assistant Examiner(s): Ward, Paul V.
• Application Number:
  US09/831,506
• Time in Patent Office: 2,534 Days
• Field of Search: 546/337, 546/280.4, 546/277.4, 546/171, 546/265, 546/143, 546/268.7, 546/275.4, 546/282.4, 546/275.7, 546/270.1, 546/140, 514/357, 514/336, 514/339, 514/314, 514/332, 514/310, 514/272, 514/342, 514/341, 514/338, 514/308, 514/256, 514/307, 514/311, 514/351, 514/365, 514/374, 514/400, 514/406, 514/438, 514/469, 514/620, 544/331, 548/345.1, 548/238.1, 548/236, 548/205, 549/493, 549/462, 549/77, 564/168
• US Class Current: 514/241
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 27/06 Antiglaucoma agents or miotics
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• 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 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 9/14 Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
• CPC Class Codes: C07C 237/32 having the nitrogen atom of the carboxamide group bound to an acyclic carbon atom of a hydrocarbon radical substituted by oxygen atoms

Abstract

The invention relates to anthranilic acid amides and the use thereof as medicaments for the treatment of diseases that are triggered by persistent angiogenesis, in addition to intermediate products in the production of anthranilic acid amides.

Claims

1. A compound of formula I

2. A compound of I according to claim 1 in which

A stands for the group =NR²,

W stands for oxygen, sulfur, two hydrogen atoms or the group =NR⁸,

Z stands for the group =NR¹⁰, =N—

or —

N(R¹⁰)—

(CH₂)_q—

, branched or unbranced C_1-6 alkyl or the group

3. A compound of formula I according to claim 1, in which

A stands for the group =NR²,

W stands for oxygen, sulfur or two hydrogen atoms,

Z stands for the group =NR¹⁰, =N, —

N(R¹⁰)—

(CH₂)_q—

or the group

4. A compound of formula I according to claim 1, in which

A stands for the group =NR²,

W stands for oxygen,

Z stands for the group =NR¹⁰, =N—

, —

N(R¹⁰)—

(CH₂)_q—

or the group

5. A compound of formula I according to claim 1, in which

A stands for the group =NR²,

W stands for sulfur,

Z stands for the group =NR¹⁰, =N—

, —

N(R¹⁰)—

(CH₂)_q—

or the group

6. A compound of formula I according to claim 1, in which

A stands for the group =NR²,

W stands for two hydrogen atoms,

Z stands for the group =NR¹⁰, =N—

, —

N(R¹⁰)—

(CH₂)_q—

or the group

7. A compound of claim 1, wherein

R³ stands for pyridyl, or 1,2,3,4-tetrahydronaphthyl that is substituted by hydroxy, halogen, methyl or methoxy, or for the group

9. A composition according to claim 1, wherein R³ is pyridyl or substituted pyridyl.

10. A composition according to claim 1, wherein R³ is a heteroaryl.

11. A pharmaceutical composition comprising a therapeutical effective amount of at least one compound according to claim 1 and a pharmaceutical acceptable carrier.

12. A method of producing a pharmaceutical preparation for enteral, parenteral and oral administration comprising mixing a compound of claim 1 with a suitable pharmaceutical carrier.

13. A method of inhibiting the tyrosine kinase KDR and/or FLT, comprising administering to a patient in need thereof a therapeutically effective amount of a compound according to claim 1.

14. A method of claim 13 wherein said patient is suffering from a disease or condition mediated by VEGF which is a tumor, psoriasis, arthritis, hemangioma, angiofibroma, an eye disease, neovascular glaucoma, a renal disease, a fibrotic disease, a mesangial-cell-proliferative disease, arteriosclerosis, an injury to the nerve tissue, and for inhibiting the reocclusion of a vessel after balloon catheter treatment, a vascular prosthetic or a mechanical device is used to keep a vessel open.

8. A compound of formula I