Bibliographic Details
| Title: |
Thiazolyl-dihydro-indazole |
| Document Number: |
20060100254 |
| Publication Date: |
May 11, 2006 |
| Appl. No: |
11/243796 |
| Application Filed: |
October 05, 2005 |
| Abstract: |
The present invention encompasses compounds of the general formula (1) [chemical expression included] in which R1 to R3 are defined as in Claim 1, which are suitable for treating diseases which are characterized by excessive or anomalous cell proliferation, and their use for producing a pharmaceutical having the abovementioned properties. |
| Inventors: |
Betzemeier, Bodo (Vienna, AT); Brandl, Trixi (Warthausen, DE); Breitfelder, Steffen (Assmannshardt, DE); Brueckner, Ralph (Vienna, AT); Gerstberger, Thomas (Vienna, AT); Gmachl, Michael (Vienna, AT); Grauert, Matthias (Biberach, DE); Hilberg, Frank (Vienna, AT); Hoenke, Christoph (Ingelheim, DE); Hoffmann, Matthias (Mittelbiberach, DE); Impagnatiello, Maria (Vienna, AT); Kessler, Dirk (Vienna, AT); Klein, Christian (Vienna, AT); Krist, Bernd (Vienna, AT); Maier, Udo (Senden, DE); McConnell, Darryl (Vienna, AT); Reither, Charlotte (Vienna, AT); Scheuerer, Stefan (Warthausen, DE); Schoop, Andreas (Vienna, AT); Schweifer, Norbert (Vienna, AT); Simon, Oliver (Vienna, AT); Steegmaier, Martin (Vienna, AT); Steurer, Steffen (Vienna, AT); Waizenegger, Irene (Vienna, AT); Weyer-Czernilofsky, Ulrike (Baden, AT); Zoephel, Andreas (Vienna, AT) |
| Assignees: |
Boehringer Ingelheim International GmbH (Ingelheim, DE) |
| Claim: |
1.) A compound of formula (1), [chemical expression included] in which R1 is selected from the group consisting of —NHRc, —NHC(O)Rc, —NHC(O)ORc, —NHC(O)NRcRc and —NHC(O)SRc; R2 is a radical which is optionally substituted by one or more R4 and which is selected from the group consisting of C1-6alkyl, C3-8cycloalkyl, 3-8-membered heterocycloalkyl, C6-10aryl, C7-16arylalkyl and 5-10-membered heteroaryl; R3 is a radical which is optionally substituted by one or more Re and/or Rf and is selected from the group consisting of C6-10aryl and 5-10-membered heteroaryl; R4 is a radical selected from the group consisting of Ra, Rb and Ra which is substituted by one or more, identical or different, Rc and/or Rb; each Ra is, independently of each other, selected from the group consisting of C1-6alkyl, C3-8cycloalkyl, C4-11cycloalkylalkyl, C6-10aryl, C7-16arylalkyl, 2-6-membered heteroalkyl, 3-8-membered heterocycloalkyl, 4-14-membered heterocycloalkylalkyl, 5-10-membered heteroaryl and 6-16-membered heteroarylalkyl; each Rb is a suitable radical and in each case selected, independently of each other, from the group consisting of ═O, —ORc, C1-3haloalkyloxy, —OCF3, ═S, —SRc, ═NRc, ═NORc, —NRcRc, halogen, —CF3, —CN, —NC, —OCN, —SCN, —NO, —NO2, ═N2, —N3, —S(O)Rc, —S(O)2Rc, —S(O)2ORc, —S(O)NRcRc, —S(O)2NRcRc, —OS(O)Rc, —OS(O)2Rc, —OS(O)2ORc, —OS(O)2NRcRc, —C(O)Rc, —C(O)ORc, —C(O)NRcRc, —C(O)N(Rg)NRcRc, —C(O)N(Rg)ORc, —CN(Rg)NRcRc, —OC(O)Rc, —OC(O)ORc, —OC(O)NR2R2, —OCN(Rg)NRcRc, —N(Rg)C(O)Rc, —N(Rg)C(O)Rc, —N(Rg)C(S)Rc, —N(Rg)S(O)2Rc, —N(Rg)S(O)2NRcRc, —N[S(O)2]2Rc, —N(Rg)C(O)ORc, —N(Rg)C(O)NRcRc, and —N(Rg)CN(Rg)NRcRc; each Rc is, independently of each other, hydrogen or a radical which is optionally substituted by one or more, identical or different, Rd and/or Re and which is selected from the group consisting of C1-6alkyl, C3-8cycloalkyl, C4-11cycloalkylalkyl, C6-10aryl, C7-16arylalkyl, 2-6-membered heteroalkyl, 3-8-membered heterocycloalkyl, 4-14-membered heterocycloalkylalkyl, 5-10-membered heteroaryl and 6-16-membered heteroarylalkyl, each Rd is, independently of each other, hydrogen or a radical which is optionally substituted by one or more, identical or different, Re and/or Rf and which is selected from the group consisting of C1-6alkyl, C3-8cycloalkyl, C4-11cycloalkylalkyl, C6-10aryl, C7-16arylalkyl, 2-6-membered heteroalkyl, 3-8-membered heterocycloalkyl, 4-14-membered heterocycloalkylalkyl, 5-10-membered heteroaryl and 6-16-membered heteroarylalkyl, each Re is a suitable radical and in each case selected, independently of each other, from the group consisting of ═O, —ORf, C1-3haloalkyloxy, —OCF3, ═S, —SRf, ═NRf, ═NORf, —NRfRf, halogen, —CF3, —CN, —NC, —OCN, —SCN, —NO, —NO2, ═N2, —N3, —S(O)Rf, —S(O)2Rf, —S(O)2ORf, —S(O)NRfRf, —S(O)2NRfRf, —OS(O)Rf, —OS(O)2Rf, —OS(O)2ORf, —OS(O)2NRfRf, —C(O)Rf, —C(O)ORf, —C(O)NRfRf, —CN(Rg)NRfRf, —OC(O)Rf, —OC(O)ORf, —OC(O)NRfRf, —OCN(Rg)NRfRf, —N(Rg)C(O)Rf, —N(Rg)C(S)Rf, —N(Rg)S(O)2Rf, —N(Rg)C(O)ORf, —N(Rg)C(O)NRfRf, and —N(Rg)CN(Rg)NRfRf; each Rf is, independently of each other, hydrogen or a radical which is optionally substituted by one or more, identical or different, Rg and is selected from the group consisting of C1-6alkyl, C3-8cycloalkyl, C4-11cycloalkylalkyl, C6-10aryl, C7-16arylalkyl, 2-6-membered heteroalkyl, 3-8-membered heterocycloalkyl, 4-14-membered heterocycloalkylalkyl, 5-10-membered heteroaryl and 6-16-membered heteroarylalkyl, each Rg is, independently of each other, hydrogen, C1-6alkyl, C3-8cycloalkyl, C4-11cycloalkylalkyl, C6-10aryl, C7-16arylalkyl, 2-6-membered heteroalkyl, 3-8-membered heterocycloalkyl, 4-14-membered heterocycloalkylalkyl, 5-10-membered heteroaryl and 6-16-membered heteroarylalkyl, or a pharmaceutically acceptable acid addition salt thereof. |
| Claim: |
2.) The compound according to claim 1, wherein R3 is a radical selected from the group consisting of phenyl, furyl, pyridyl, pyrimidinyl and pyrazinyl, optionally substituted by one or more R4. |
| Claim: |
3.) The compound according to claim 2, wherein R3 is pyridyl. |
| Claim: |
4.) The compound according to claim 1, wherein R1 is —NHC(O)Rc. |
| Claim: |
5.) The compound according to claim 4, wherein R1 is —NHC(O)CH3. |
| Claim: |
6.) A compound of formula (A) [chemical expression included] wherein X is —CH3, —OR4 or —SR4 and Y is phenyl, 5-10-membered heteroaryl or the group —C(O)O, and Ry is hydrogen, —NO2 or C1-6alkyl and R4 is a radical selected from the group consisting of Ra, Rb and Ra which is substituted by one or more, identical or different, Rc and/or Rb; each Ra is, independently of each other, selected from the group consisting of C1-6alkyl, C3-8cycloalkyl, C4-11cycloalkylalkyl, C6-10aryl, C7-16arylalkyl, 2-6-membered heteroalkyl, 3-8-membered heterocycloalkyl, 4-14-membered heterocycloalkylalkyl, 5-10-membered heteroaryl and 6-16-membered heteroarylalkyl; each Rb is a suitable radical and in each case selected, independently of each other, from the group consisting of ═O, —ORc, C1-3haloalkyloxy, —OCF3, ═S, —SRC, ═NRc, ═NORc, —NRcRc, halogen, —CF3, —CN, —NC, —OCN, —SCN, —NO, —NO2, ═N2, —N3, —S(O)Rc, —S(O)2Rc, —S(O)2ORc, —S(O)NRcRc, —S(O)2NRcRc, —OS(O)Rc, —OS(O)2Rc, —OS(O)2ORc, —OS(O)2NRcRc, —C(O)Rc, —C(O)ORc, —C(O)NRcRc, —C(O)N(Rg)NRcRc, —C(O)N(Rg)ORc, —CN(Rg)NRcRc, —OC(O)Rc, —OC(O)ORc, —OC(O)NRcRc, —OCN(Rg)NRcRc, —N(Rg)C(O)Rc, —N(Rg)C(O)Rc, —N(Rg)C(S)Rc, —N(Rg)S(O)2Rc, —N(Rg)S(O)2NRcRc, —N[S(O)2]2Rc, —N(Rg)C(O)ORc, —N(Rg)C(O)NRcRc, and —N(Rg)CN(Rg)NRcRc; each Rc is, independently of each other, hydrogen or a radical which is optionally substituted by one or more, identical or different, Rd and/or Re and which is selected from the group consisting of C1-6alkyl, C3-8cycloalkyl, C4-11cycloalkylalkyl, C6-10aryl, C7-16arylalkyl, 2-6-membered heteroalkyl, 3-8-membered heterocycloalkyl, 4-14-membered heterocycloalkylalkyl, 5-10-membered heteroaryl and 6-16-membered heteroarylalkyl, each Rd is, independently of each other, hydrogen or a radical which is optionally substituted by one or more, identical or different, Re and/or Rf and which is selected from the group consisting of C1-6alkyl, C3-8cycloalkyl, C4-11cycloalkylalkyl, C6-10aryl, C7-16arylalkyl, 2-6-membered heteroalkyl, 3-8-membered heterocycloalkyl, 4-14-membered heterocycloalkylalkyl, 5-10-membered heteroaryl and 6-16-membered heteroarylalkyl, each Re is a suitable radical and in each case selected, independently of each other, from the group consisting of ═O, —ORf, C1-3haloalkyloxy, —OCF3, ═S, —SRf, ═NRf, ═NORf, —NRfRf, halogen, —CF3, —CN, —NC, —OCN, —SCN, —NO, —NO2, ═N2, —N3, —S(O)Rf, —S(O)2Rf, —S(O)2ORf, —S(O)NRfRf, —S(O)2NRfRf, —OS(O)Rf, —OS(O)2Rf, —OS(O)2ORf, —OS(O)2NRfRf, —C(O)Rf, —C(O)ORf, —C(O)NRfRf, —CN(Rg)NRfRf, —OC(O)Rf, —OC(O)ORf, —OC(O)NRfRf, —OCN(Rg)NRfRf, —N(Rg)C(O)Rf, —N(Rg)C(S)Rf, —N(Rg)S(O)2Rf, —N(Rg)C(O)ORf, —N(Rg)C(O)NRfRf, and —N(Rg)CN(Rg)NRfRf; each Rf is, independently of each other, hydrogen or a radical which is optionally substituted by one or more, identical or different, Rg and is selected from the group consisting of C1-6alkyl, C3-8cycloalkyl, C4-11cycloalkylalkyl, C6-10aryl, C7-16arylalkyl, 2-6-membered heteroalkyl, 3-8-membered heterocycloalkyl, 4-14-membered heterocycloalkylalkyl, 5-10-membered heteroaryl and 6-16-membered heteroarylalkyl, each Rg is, independently of each other, hydrogen, C1-6alkyl, C3-8cycloalkyl, C4-11cycloalkylalkyl, C6-10aryl, C7-16arylalkyl, 2-6-membered heteroalkyl, 3-8-membered heterocycloalkyl, 4-14-membered heterocycloalkylalkyl, 5-10-membered heteroaryl and 6-1 6-membered heteroarylalkyl, or a pharmaceutically acceptable acid addition salt thereof. |
| Claim: |
7.) The compound according to claim 6, wherein R4 is —C1-6alkyl. |
| Claim: |
8.) A pharmaceutical preparation which comprises, as active compound, one or more compounds of the formula (1) according to claim 1, in combination with customary auxiliary substances and/or carrier substances. |
| Claim: |
9.) A pharmaceutical preparation which comprises a compound of the formula (1) according to claim 1 and at least one further cytostatic or cytotoxic active substance which differs from such compound according to claim 1. |
| Claim: |
10.) A method for producing an anti-proliferative effect in a warm-blooded animal which may be useful in the treatment of cancer and other disorders of cell growth which comprises administering to the animal a therapeutically effective amount of a compound of formula (1) according to claim 1. |
| Current U.S. Class: |
514366/000 |
| Current International Class: |
61; 07 |
| Accession Number: |
edspap.20060100254 |
| Database: |
USPTO Patent Applications |
