Pyrimidine compounds as serotonin receptor modulators

• US 7,598,255 B2
• Filed: 07/27/2006
• Issued: 10/06/2009
• Est. Priority Date: 08/04/2005
• Status: Active Grant

• Current Assignee: Janssen Pharmaceutica NV (Johnson & Johnson)
• Original Assignee: Janssen Pharmaceutica NV (Johnson & Johnson)
• Inventors: Dvorak, Curt A.
• Primary Examiner(s): Berch; Mark L
• Assistant Examiner(s): Jaisle; Cecilia M
• Application Number:
  US11/460,294
• Publication Number:
  US 20070032481A1
• Time in Patent Office: 1,167 Days
• Field of Search: 514/215, 514/228.2, 514/228.5, 514/234.2, 514/234.5, 514/252.17, 514/252.16, 514/264.1, 514/266.1, 514/265.1, 540/578, 544/57, 544/61, 544/62, 544/69, 544/115, 544/116, 544/117, 544/229, 544/249, 544/250, 544/253, 544/279, 544/280, 544/333, 544/334, 544/335
• US Class Current: 514/264.1
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/343 condensed with a carbocyclic ring, e.g. coumaran, bufuralol, befunolol, clobenfurol, amiodarone
• CPC Class Codes: A61K 31/404 Indoles, e.g. pindolol
• CPC Class Codes: A61K 31/437 the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
• CPC Class Codes: A61K 31/445 Non condensed piperidines, e.g. piperocaine
• CPC Class Codes: A61K 31/55 having seven-membered rings, e.g. azelastine, pentylenetetrazole
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 13/02 of urine or of the urinary tract, e.g. urine acidifiers
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/22 Anxiolytics
• CPC Class Codes: A61P 25/24 Antidepressants
• CPC Class Codes: A61P 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: C07D 239/26 with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
• CPC Class Codes: C07D 239/74 with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, attached to ring carbon atoms of the hetero ring
• CPC Class Codes: C07D 471/04 Ortho-condensed systems
• CPC Class Codes: C07D 487/04 Ortho-condensed systems

Abstract

Certain pyrimidine-containing compounds are serotonin receptor modulators useful in the treatment of serotonin-mediated diseases.

Claims

1. A compound that is 4-(4-fluoro-phenyl)-2-isopropyl-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidine or a pharmaceutically acceptable salt thereof.

2. A compound of claim 1 isotopically-labelled to be detectable by PET or SPECT.

3. The compound of claim 1 wherein said pharmaceutically acceptable salt is selected from the group consisting of hydrobromide, hydrochloride, sulfate, bisulfate, nitrate, acetate, oxalate, valerate, oleate, palmitate, stearate, laurate, borate, benzoate, lactate, phosphate, tosylate, citrate, maleate, fumarate, succinate, tartrate, naphthylate, mesylate, glucoheptonate, lactiobionate, and laurylsulfonate.

4. The compound of claim 3 wherein said pharmaceutically acceptable salt is hydrochloride.

8. The compound of claim 3 wherein said pharmaceutically acceptable salt is citrate.

5. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound that is 4-(4-fluoro-phenyl)-2-isopropyl-5,6,7,8-tetrahydro-pyrido [4,3-d]pyrimidine or a pharmaceutically acceptable salt thereof.

6. The composition of claim 5 wherein said pharmaceutically acceptable salt is selected from the group consisting of hydrobromide, hydrochloride, sulfate, bisulfate, nitrate, acetate, oxalate, valerate, oleate, palmitate, stearate, laurate, borate, benzoate, lactate, phosphate, tosylate, citrate, maleate, fumarate, succinate, tartrate, naphthylate, mesylate, glucoheptonate, lactiobionate, and laurylsulfonate.

7. The composition of claim 6 wherein said pharmaceutically acceptable salt is hydrochloride.

9. The composition of claim 6 wherein said pharmaceutically acceptable salt is citrate.

10. A compound which is a citric acid salt of 4-(4-fluoro-phenyl)-2-isopropyl-5,6,7,8-tetrahydro-pyrido [4,3-d]pyrimidine.

11. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound that is a citric acid salt of 4-(4-fluoro-phenyl)-2-isopropyl-5,6,7,8-tetrahydro-pyrido [4,3-d]pyrimidine.