Patent
Heterocyclic spiro-compounds
| العنوان: | Heterocyclic spiro-compounds |
|---|---|
| Patent Number: | 8,324,235 |
| تاريخ النشر: | December 04, 2012 |
| Appl. No: | 12/450521 |
| Application Filed: | March 27, 2008 |
| مستخلص: | The patent application relates to new heterocyclic compounds of the general formula (I), in which R, R1, R2, Q, T, n and p have the definitions elucidated in more detail in the description, to a process for preparing them and to the use of these compounds as medicaments, particularly as aldosterone synthase inhibitors. [chemical expression included] |
| Inventors: | Herold, Peter (Münchenstein, CH); Mah, Robert (Muttenz, CH); Stutz, Stefan (Basel, CH); Tschinke, Vincenzo (Binningen, CH); Stojanovic, Aleksandar (Basel, CH); Jotterand, Nathalie (Basel, CH); Bennacer, Bibia (Altkirch, FR) |
| Assignees: | Novartis AG (Basel, CH) |
| Claim: | 1. A compound of formula (I) [chemical expression included] in which Q is —C(R 3)(R 4)— or a bond; T is —C(R 3)(R 4)—; R is hydrogen or deuterium; R 1 is C 1 -C 8 -alkyl, C 0 -C 8 -alkylcarbonyl, amino, mono- or di-C 1 -C 8 -alkylamino, C 0 -C 8 -alkyl-carbonylamino, C 0 -C 8 -alkylcarbonyl-C 1 -C 8 -alkylamino, carbamoyl, mono- or di-C 1 -C 8 -alkylaminocarbonyl, carboxyl, carboxy-C 1 -C 4 -alkyl, halogen, cyano, methylsulfonyl, nitro, trifluoro-methyl, C 1 -C 8 -alkoxy, C 1 -C 8 -alkoxycarbonyl, heterocyclyl or aryl, which radicals may be unsubstituted or substituted by 1-4 C 1 -C 8 -alkyl, C 0 -C 8 -alkylcarbonyl, halogen, cyano, oxo, trifluoromethyl, trifluoromethoxy, C 0 -C 8 -alkylcarbonylamino, C 0 -C 8 -alkylcarbonyl-C 1 -C 8 -alkylamino, carbamoyl, mono- and di-C 1 -C 8 -alkylaminocarbonyl, carboxy-C 0 -C 4 -alkyl, C 1 -C 8 -alkoxy, C 1 -C 8 -alkoxycarbonyl, aryl or heterocyclyl; R 2 is, if p is not 0, independently of one another, C 1 -C 8 -alkyl, C 0 -C 8 -alkylcarbonyl, amino, mono- and di-C 1 -C 8 -alkylamino, C 0 -C 8 -alkylcarbonylamino, C 0 -C 8 -alkylcarbonyl-C 1 -C 8 -alkyl-amino, carbamoyl, mono- or di-C 1 -C 8 -alkylaminocarbonyl, carboxyl, carboxy-C 1 -C 4 -alkyl, halogen, cyano, methylsulfonyl, nitro, trifluoromethyl, trifluoromethoxy, C 1 -C 8 -alkoxy, C 1 -C 8 -alkoxycarbonyl, heterocyclyl or aryl, which radicals may be unsubstituted or substituted by 1-4 C 1 -C 8 -alkyl, C 0 -C 8 alkylcarbonyl, halogen, cyano, oxo, trifluoromethyl, trifluoromethoxy, C 0 -C 8 -alkylcarbonylamino, C 0 -C 8 -alkylcarbonyl-C 1 -C 8 -alkylamino, carbamoyl, mono- and di-C 1 -C 8 -alkylaminocarbonyl, carboxy-C 0 -C 4 -alkyl, C 1 -C 8 -alkoxy, C 1 -C 8 -alkoxycarbonyl, aryl or hetero-cyclyl; R 3 is, independently of one another: a) hydrogen or C 1 -C 8 -alkyl; or b) together with R 4 oxo; R 4 is, independently of one another: a) hydrogen or C 1 -C 8 -alkyl; or b) together with R 3 oxo; n is a number 0, 1 or 2; p is a number 0, 1 or 2; or its pharmaceutically useful salt. |
| Claim: | 2. The compound according to claim 1 , wherein it conforms to formula (I′) [chemical expression included] wherein the definitions of the substituents R, R 1 , R 2 , Q, T, n and p are as defined according to the compounds of the formula (I) according to claim 1 , having a specific configuration at the asymmetric carbon atom labelled “*”, and which compound shows an aromatase inhibitory activity at least 10 times lower than the compound of the formula (I′) with the opposite configuration around the asymmetric carbon atom labelled “*”. |
| Claim: | 3. The compound according to claim 1 , wherein R 1 is C 1 - C 8 -alkyl, C 0 -C 8 -alkylcarbonyl, halogen, cyano, methylsulfonyl, nitro, trifluoromethyl, trifluoromethoxy, C 0 -C 8 -alkylcarbonylamino, C 0 -C 8 -alkylcarbonyl-C 1 -C 8 -alkylamino, carbamoyl, mono- and di-C 1 -C 8 -alkylaminocarbonyl, carboxy-C 0 -C 4 -alkyl, C 1 -C 8 -alkoxy, C 1 -C 8 -alkoxycarbonyl or heterocyclyl. |
| Claim: | 4. The compound according to claim 1 , wherein R 2 is, if p is not 0, independently of one another, halogen, cyano, methylsulfonyl, nitro, trifluoromethyl, trifluoromethoxy, or C 1 -C 8 -alkyl. |
| Claim: | 5. The compound according to claim 1 , wherein n is a number 0 or 1. |
| Claim: | 6. The compound according to claim 1 , wherein R 1 is acetyl, halogen, cyano, methylsulfonyl or nitro; and R 2 is, if p is not 0, independently of one another, halogen, cyano, methylsulfonyl, nitro or C 1 -C 8 -alkyl. |
| Claim: | 7. The compound according to claim 1 , wherein R 1 is cyano or halogen; R 2 is, if p is not 0, cyano or halogen; n is a number 0 or 1; and p is a number 0 or 1. |
| Claim: | 8. A pharmaceutical composition comprising a compound of the formula (I) or a pharmaceutically useful salt thereof, according to claim 1 , and a conventional excipient. |
| Claim: | 9. A pharmaceutical combination in the form of a product or kit composed of individual components consisting of a) a compound of the formula (I) or a pharmaceutically useful salt thereof, according to claim 1 , and b) at least one pharmaceutical form whose active ingredient has a blood pressure-lowering, an inotropic, an antidiabetic, an obesity reducing or a lipid-lowering effect. |
| Claim: | 10. The compound according to claim 2 , having a specific configuration at the asymmetric carbon atom labelled “*”, which compound shows an aromatase inhibitory activity at least 20 times lower than the compound of the formula (I′) with the opposite configuration around the asymmetric carbon atom labelled “*”. |
| Claim: | 11. The compound according to claim 3 , wherein R 1 is acetyl, halogen, cyano, methylsulfonyl or nitro. |
| Claim: | 12. The compound according to claim 4 , wherein R 2 is, if p is not 0, independently of one another, halogen, cyano, methylsulfonyl, nitro or C 1 -C 8 -alkyl. |
| Claim: | 13. The compound according to claim 7 , wherein R 1 is cyano or fluoro. |
| Current U.S. Class: | 514/278 |
| Patent References Cited: | 2006/128852 December 2006 2006/128853 December 2006 |
| Other References: | Pulmonary fibrosis [online] retrieved on Feb. 11, 2012 from the internet (URL; http://www.mayoclinic.com/health/pulmonary-fibrosis/DS00927). cited by examiner Fibrosis—What is Fibrosis? [online} retrieved from the internet on Feb. 11, 2012 (URL; http://www.news-medical.net/health/Fibrosis-What-is-Fibrosis.aspx. cited by examiner International Search Report issued Aug. 4, 2008 in International (PCT) Application No. PCT/EP2008/053671. cited by other Written Opinion issued Aug. 4, 2008 in International (PCT) Application No. PCT/EP2008/053671. cited by other |
| Primary Examiner: | Young, Shawquia |
| Attorney, Agent or Firm: | Wenderoth, Lind & Ponack, L.L.P. |
| رقم الانضمام: | edspgr.08324235 |
| قاعدة البيانات: | USPTO Patent Grants |
| الوصف غير متاح. |