KR890701587A - Imidazo (1,2-a) for treating diseases related to bone loss - Google Patents

Abstract

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Description

Imidazo (1,2-a) (pyridazine or pyrazine) for the treatment of diseases related to bone loss

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Claims (15)

A therapeutically effective amount of a compound of formula I below is administered to a patient in need thereof for treatment with a pharmaceutically acceptable salt thereof, in particular acid addition salts (e.g. hydrochloride and hydrobromide) and optionally How to treat notarization. Where G is (From here, The carbon atom of is linked to the 2-position of the imidazo moiety to form an imidazole (1,2-a) pyrazine nucleus, and A is a non-aromatic containing 0 or 1 hetero atom selected from nitrogen, sulfur and oxygen atoms 5- or 6-membered ring), R ² is H, lower alkyl, CF ₃ , B-CF ₃ , B-Ar, B-halogen, BOR ⁸ , B-SOm-lower alkyl, BOC (= 0) R ¹ , B-NR ⁴ R ⁵ , COOR ⁶ , C (═O) —NR ⁴ R ⁵ , B-CN or NR ⁴ R ⁵ , wherein R ³ is H lower alkyl, lower alkenyl, lower alkynyl, Lower alkadienyl, lower alkenyloxy (lower) alkyl, lower alkynyloxy (lower) alkyl, carboxy (lower) alkynyloxy (lower) alkyl, protective carboxy (lower) alkoxy (lower) alkyl, BCN, BOR ⁸ , BOC (= 0) -R ¹ , B-NR ⁴ R ⁵ BC (= S) -NR ⁴ R ⁵ , BC (= O) NR ⁴ R ^{5 </ SP, B-NO} ₂ B-halogen, B -NC, NO represents NR ⁴ R ⁵ , R ^x , R ^y , R ^z and R ^u are H, R ⁹ or R ¹⁰ , R ⁹ is H, lower alkyl, halogen, OH, CF ₃ or lower Alkoxy and R ¹⁰ is -ZT- Ar (where Z represents -O-, -NH-, -SOm- or a single bond, T represents a straight or branched chain lower alkylene group, and when Z is a single bond, T is also an unsaturated carbon And when Z is -O-, T also represents an allene group in which saturated carbon is in oxygen), and Ar represents phenyl, pyridyl, thienyl, furanyl, amidazolyl or Each X ', Y' and Z 'is independently hydrogen, halogen, lower alkyl, lower alkoxy, CN, CF ₃ , OH, NO ₂ , -NR ⁴ R ⁵ , -COOR ⁶ , -C (= 0) NR ⁴ R ⁵ , —NR ⁷ C (═O) R ¹ , —NR ⁷ SO _m R ¹ or —SO _m R ¹ represents X′-, Y′- and Z′-substituted phenyl, B is straight or branched A chain lower alkylene group, n is 0,1 or 2, m is 0.1 or 2 and R ⁴ and R ₅ are each independently H, lower alkyl, lower alkoxy lower alkyl, trifluoromethyl lower alkyl, Ar-lower Alkyl, Ar, or the nitrogen atom to which they are attached When taken together, it represents a 4-, 5- or 6-membered cycloamino group, R 'represents Ar, lower alkyl, NR ⁴ R ⁵ , B-NR ⁴ R ⁵ or Ar-lower alkyl, R ⁶ is H, C ₁ -To C ₁₂ -alkyl, Ar or Ar-lower alkyl, R ⁷ represents H or lower alkyl and R ⁴ is H, lower alkyl, lower alkoxy lower alkyl, trifluorotomethyl lower alkyl, Ar- lower alkyl or Wherein acid addition salts such as hydrochloride and hydrobromide salts represent (a) one and only one of the groups R ^x , R ^y , R ^z and R ^u are R ¹⁰ and (b) the groups R ^x , R ^y , R ^z And at least one of R ^u is R ⁹ and (c) G is a group Where R ^x is R ⁹ and R ^y is H. A method of treating Paget's disease in bone by administering to a patient in need thereof a therapeutically effective amount of a compound of Formula I as defined in claim 1 and optionally a pharmaceutically acceptable carrier. Primary and secondary hyperthyroidism by administering a therapeutically effective amount of a compound of Formula I as defined in claim 1 and optionally a pharmaceutically acceptable carrier to a patient in need of treatment for primary and secondary How to treat it. A method of treating said disease by administering to a patient in need thereof a therapeutically effective amount of a compound of Formula I as defined in claim 1 and optionally a pharmaceutically acceptable tumor cell producing an osteoclast activator. A method of treating said disease by administering a therapeutically optionally pharmaceutically acceptable carrier as defined in claim 1 to a patient in need of treatment for a disease around the teeth. A method of treating said disease by administering a therapeutically effective amount of a Formula I compound as defined in claim 1 and optionally a pharmaceutically acceptable or carrier to a patient in need of treatment for prosthetic and graft fracture loss. A method of treating said disease by administering a therapeutically effective amount of a compound of Formula I as defined in claim 1 and optionally a pharmaceutically acceptable carrier to a patient in need of treatment for increased absorption of bone. A compound of formula I as defined in claim 1 for use in the manufacture of a medicament for the treatment of osteoporosis. A compound of formula I as defined in claim 1 for use in the manufacture of a medicament for the treatment of Paget's disease in bone. A compound of formula I as defined in claim 1 for use in the manufacture of a medicament for the treatment of primary and secondary hyperthyroidism. A compound of formula I as defined in claim 1 for use in the manufacture of a medicament for the treatment of a weak neoplasm in which the tumor cell produces an osteoclast activator. A compound of formula I as defined in claim 1 for use in the manufacture of a medicament for the treatment of diseases around the teeth. A compound of formula I as defined in claim 1 for use in the manufacture of a medicament for the treatment of prosthetic and graft bone loss. A compound of formula I as defined in claim 1 for use in the manufacture of a medicament for the treatment of diseases associated with increased bone absorption. As an active ingredient, a compound of Formula I as defined in claim 1, wherein increased bone resorption, osteoporosis, Paget's disease of bone, primary and secondary epithelial hyperplasia, tumor cells produce osteoclast activator A drug for use in the treatment of said weak neoplasm, said periodontal disease associated with bone loss or a disease associated with prosthetic and transplant related bone loss. ※ Note: The disclosure is based on the initial application.