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NZ745187B2 - 3-(carboxyethyl)-8-amino-2-oxo-1,3-diaza-spiro-[4.5]-decane derivatives - Google Patents
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NZ745187B2 - 3-(carboxyethyl)-8-amino-2-oxo-1,3-diaza-spiro-[4.5]-decane derivatives - Google Patents

3-(carboxyethyl)-8-amino-2-oxo-1,3-diaza-spiro-[4.5]-decane derivatives Download PDF

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NZ745187B2
NZ745187B2 NZ745187A NZ74518717A NZ745187B2 NZ 745187 B2 NZ745187 B2 NZ 745187B2 NZ 745187 A NZ745187 A NZ 745187A NZ 74518717 A NZ74518717 A NZ 74518717A NZ 745187 B2 NZ745187 B2 NZ 745187B2
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unsubstituted
diazaspiro
methyl
cis
propionamide
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NZ745187A
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NZ745187A (en
Inventor
Florian Jakob
Ruth Jostock
Achim Kless
Thomas Koch
Rene Michael Koenigs
Sven Kuhnert
Klaus Linz
Paul Ratcliffe
Wolfgang Schroder
Anita Wegert
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Grünenthal GmbH
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Priority claimed from PCT/EP2017/025004 external-priority patent/WO2017121646A1/en
Publication of NZ745187A publication Critical patent/NZ745187A/en
Publication of NZ745187B2 publication Critical patent/NZ745187B2/en

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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/41641,3-Diazoles
    • A61K31/41661,3-Diazoles having oxo groups directly attached to the heterocyclic ring, e.g. phenytoin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/04Centrally acting analgesics, e.g. opioids
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/18Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/28Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/30Drugs for disorders of the nervous system for treating abuse or dependence
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/30Drugs for disorders of the nervous system for treating abuse or dependence
    • A61P25/36Opioid-abuse
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D235/00Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
    • C07D235/02Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D401/00Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/06Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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    • C07DHETEROCYCLIC COMPOUNDS
    • C07D401/00Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D403/00Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/06Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D403/00Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/12Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D405/00Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/12Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D413/00Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/12Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
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    • C07DHETEROCYCLIC COMPOUNDS
    • C07D417/00Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/06Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D487/00Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/04Ortho-condensed systems

Abstract

The invention relates to 3-(carboxyethyl)-8-amino-2-oxo-1,3-diaza-spiro-[4.5]-decane derivatives, their preparation and their use in medicine, particularly in the treatment of pain.

Claims (10)

1.Patent claims : 1. A compound according to general formula (I) 13 16 R 14 R wherein R and R independently of one another mean -C -C -alkyl, linear or branched, saturated or unsaturated, unsubstituted or substituted with one, two, three or four substituents independently of one another selected from the group consisting of -F, -Cl, -Br, -I, - OH, -OCH , -CN and -CO CH ; 3 2 3 a 3membered cycloalkyl moiety, saturated or unsaturated, unsubstituted or substituted with one, two, three or four substituents independently of one another selected from the group consisting of -F, -Cl, -Br, - I, -OH, -OCH , -CN and -CO CH ; wherein said 3membered cycloalkyl moiety is optionally connected 3 2 3 through -C -C -alkylene-, linear or branched, saturated or unsaturated, unsubstituted; or a 3membered heterocycloalkyl moiety, saturated or unsaturated, unsubstituted or substituted with one, two, three or four substituents independently of one another selected from the group consisting of -F, -Cl, -Br, -I, -OH, -OCH , -CN and -CO CH ; wherein said 3membered heterocycloalkyl moiety is 3 2 3 optionally connected through -C -C -alkylene-, linear or branched, saturated or unsaturated, unsubstituted; R and R together with the nitrogen atom to which they are attached form a ring and mean -(CH ) -; - 2 3-6 (CH ) -O-(CH ) -; or -(CH ) -NR -(CH ) -, wherein R means -H or -C -C -alkyl, linear or branched, 2 2 2 2 2 2 2 2 1 6 saturated or unsaturated, unsubstituted or substituted with one, two, three or four substituents independently of one another selected from the group consisting of -F, -Cl, -Br and -I; R means -C -C -alkyl, linear or branched, saturated or unsaturated, unsubstituted, mono- or polysubstituted; a 3membered cycloalkyl moiety, saturated or unsaturated, unsubstituted, mono- or polysubstituted; wherein said 3membered cycloalkyl moiety is optionally connected through -C -C -alkylene-, linear or branched, saturated or unsaturated, unsubstituted, mono- or polysubstituted; a 3membered heterocycloalkyl moiety, saturated or unsaturated, unsubstituted, mono- or polysubsti- tuted; wherein said 3membered heterocycloalkyl moiety is optionally connected through -C -C - alkylene-, linear or branched, saturated or unsaturated, unsubstituted, mono- or polysubstituted; a 6membered aryl moiety, unsubstituted, mono- or polysubstituted; wherein said 6membered aryl moiety is optionally connected through -C -C -alkylene-, linear or branched, saturated or unsaturated, unsubstituted, mono- or polysubstituted; or a 5membered heteroaryl moiety, unsubstituted, mono- or polysubstituted; wherein said 5membered heteroaryl moiety is optionally connected through -C -C -alkylene-, linear or branched, saturated or unsaturated, unsubstituted, mono- or polysubstituted; R means -C -C -alkyl, linear or branched, saturated or unsaturated, unsubstituted, mono- or polysubstituted; wherein said -C -C -alkyl is optionally connected through -C(=O)-, -C(=O)O-, or -S(=O) -; 1 6 2 a 3membered cycloalkyl moiety, saturated or unsaturated, unsubstituted, mono- or polysubstituted; wherein said 3membered cycloalkyl moiety is optionally connected through -C1-C6-alkylene-, linear or branched, saturated or unsaturated, unsubstituted, mono- or polysubstituted; or wherein said 3 membered cycloalkyl moiety is optionally connected through -C(=O)-, -C(=O)O-, -C(=O)O-CH -, or - S(=O) -; a 3membered heterocycloalkyl moiety, saturated or unsaturated, unsubstituted, mono- or polysubsti- tuted; wherein said 3membered heterocycloalkyl moiety is optionally connected through -C -C - alkylene-, linear or branched, saturated or unsaturated, unsubstituted, mono- or polysubstituted; or wherein said 3membered heterocycloalkyl moiety is optionally connected through -C(=O)-, -C(=O)O-, - C(=O)O-CH2-, or -S(=O)2-; a 6membered aryl moiety, unsubstituted, mono- or polysubstituted; wherein said 6membered aryl moiety is optionally connected through -C -C -alkylene-, linear or branched, saturated or unsaturated, unsubstituted, mono- or polysubstituted; or wherein said 6membered aryl moiety is optionally connected through -C(=O)-, -C(=O)O-, -C(=O)O-CH -, or -S(=O) -; or a 5membered heteroaryl moiety, unsubstituted, mono- or polysubstituted; wherein said 5membered heteroaryl moiety is optionally connected through -C -C -alkylene-, linear or branched, saturated or unsaturated, unsubstituted, mono- or polysubstituted; or wherein said 5membered heteroaryl moiety is optionally connected through -C(=O)-, -C(=O)O-, -C(=O)O-CH -, or -S(=O) -; X means -O-, -S- or -NR -; R means -C -C -alkyl, linear or branched, saturated or unsaturated, unsubstituted, mono- or polysubstituted; a 3membered cycloalkyl moiety, saturated or unsaturated, unsubstituted, mono- or polysubstituted; wherein said 3membered cycloalkyl moiety is optionally connected through -C -C -alkylene-, linear or branched, saturated or unsaturated, unsubstituted, mono- or polysubstituted; a 3membered heterocycloalkyl moiety, saturated or unsaturated, unsubstituted, mono- or polysubsti- tuted; wherein said 3membered heterocycloalkyl moiety is optionally connected through -C -C - alkylene-, linear or branched, saturated or unsaturated, unsubstituted, mono- or polysubstituted; a 6membered aryl moiety, unsubstituted, mono- or polysubstituted; wherein said 6membered aryl moiety is optionally connected through -C -C -alkylene-, linear or branched, saturated or unsaturated, unsubstituted, mono- or polysubstituted; or a 5membered heteroaryl moiety, unsubstituted, mono- or polysubstituted; wherein said 5membered heteroaryl moiety is optionally connected through -C -C -alkylene-, linear or branched, saturated or unsaturated, unsubstituted, mono- or polysubstituted; in case X means NR , R means -C1-C6-alkyl, linear or branched, saturated or unsaturated, unsubstituted, mono- or polysubstituted; a 3membered cycloalkyl moiety, saturated or unsaturated, unsubstituted, mono- or polysubstituted; wherein said 3membered cycloalkyl moiety is optionally connected through -C -C -alkylene-, linear or branched, saturated or unsaturated, unsubstituted, mono- or polysubstituted; a 3membered heterocycloalkyl moiety, saturated or unsaturated, unsubstituted, mono- or polysubsti- tuted; wherein said 3membered heterocycloalkyl moiety is optionally connected through -C -C - alkylene-, linear or branched, saturated or unsaturated, unsubstituted, mono- or polysubstituted; a 6membered aryl moiety, unsubstituted, mono- or polysubstituted; wherein said 6membered aryl moiety is optionally connected through -C1-C6-alkylene-, linear or branched, saturated or unsaturated, unsubstituted, mono- or polysubstituted; or a 5membered heteroaryl moiety, unsubstituted, mono- or polysubstituted; wherein said 5membered heteroaryl moiety is optionally connected through -C -C -alkylene-, linear or branched, saturated or unsaturated, unsubstituted, mono- or polysubstituted; 6 5 6 or in case X means NR , R and R together with the nitrogen atom to which they are attached form a 3- 12-membered heterocycloalkyl moiety, saturated or unsaturated, unsubstituted, mono- or polysubstituted; 7 8 9 10 11 12 13 14 15 16 17 18 19 20 R , R , R , R , R , R , R , R , R , R , R , R , R , and R independently of one another mean -H, -F, -Cl, -Br, -I, -OH, or -C -C -alkyl, linear or branched, saturated or unsaturated, unsubstituted, mono- or polysubstituted; or R and R together with the carbon atom to which they are attached form a 3membered cycloalkyl moiety, saturated or unsaturated, unsubstituted, mono- or polysubstituted; or a 3membered heterocycloalkyl moiety, saturated or unsaturated, unsubstituted, mono- or polysubstituted; wherein "mono- or polysubstituted" means that one or more hydrogen atoms are replaced by a substituent 21 21 independently of one another selected from the group consisting of -F, -Cl, -Br, -I, -CN, -R , -C(=O)R , 21 21 22 21 21 -C(=O)OR , -C(=O)NR R , -O-(CH CH -O) -H, -O-(CH CH -O) -CH , =O, -OR , -OC(=O)R , - 2 2 1-30 2 2 1-30 3 21 21 22 21 22 21 22 21 22 OC(=O)OR , -OC(=O)NR R , -NO , -NR R , -NR -(CH ) -C(=O)R , -NR -(CH ) -C(=O)OR , 2 2 1-6 2 1-6 23 21 22 21 22 21 22 23 21 22 -NR -(CH ) -C(=O)NR R , -NR C(=O)R , -NR C(=O)-OR , -NR C(=O)NR R , - 2 1-6 21 22 21 21 21 21 21 22 NR S(=O) R , -SR , -S(=O)R , -S(=O) R , -S(=O) OR , and -S(=O) NR R ; 2 2 2 2 wherein 21 22 23 R , R and R independently of one another mean -C -C -alkyl, linear or branched, saturated or unsaturated, unsubstituted or substituted with one, two, three or four substituents independently of one another selected from the group consisting of -F, -Cl, -Br, -I, - CN, -OH, -NH , and -O-C -C -alkyl; 2 1 6 a 3membered cycloalkyl moiety, saturated or unsaturated, unsubstituted; wherein said 3membered cycloalkyl moiety is optionally connected through -C -C -alkylene-, linear or branched, saturated or unsaturated, unsubstituted or substituted with one, two, three or four substituents independently of one another selected from the group consisting of -F, -Cl, -Br, -I, -CN, -OH, -NH , -C -C -alkyl and -O-C -C - 2 1 6 1 6 alkyl; a 3membered heterocycloalkyl moiety, saturated or unsaturated, unsubstituted; wherein said 3 membered heterocycloalkyl moiety is optionally connected through -C1-C6-alkylene-, linear or branched, saturated or unsaturated, unsubstituted or substituted with one, two, three or four substituents independently of one another selected from the group consisting of -F, -Cl, -Br, -I, -CN, -OH, -NH , -C -C -alkyl and -O- 2 1 6 C -C -alkyl; a 6membered aryl moiety, unsubstituted, mono- or polysubstituted; wherein said 6membered aryl moiety is optionally connected through -C -C -alkylene-, linear or branched, saturated or unsaturated, unsubstituted or substituted with one, two, three or four substituents independently of one another selected from the group consisting of -F, -Cl, -Br, -I, -CN, -OH, -NH , -C -C -alkyl and -O-C -C -alkyl; 2 1 6 1 6 a 5membered heteroaryl moiety, unsubstituted, mono- or polysubstituted; wherein said 5membered heteroaryl moiety is optionally connected through -C -C -alkylene-, linear or branched, saturated or unsaturated, unsubstituted or substituted with one, two, three or four substituents independently of one another selected from the group consisting of -F, -Cl, -Br, -I, -CN, -OH, -NH , -C -C -alkyl and -O-C -C - 2 1 6 1 6 alkyl; 21 22 21 22 21 22 21 22 23 21 22 or R and R within -C(=O)NR R , -OC(=O)NR R , -NR R , -NR -(CH ) -C(=O)NR R , - 2 1-6 23 21 22 21 22 NR C(=O)NR R , or -S(=O) NR R together with the nitrogen atom to which they are attached form a ring and mean -(CH ) -; -(CH ) -O-(CH ) -; or -(CH ) -NR -(CH ) -, wherein R means -H or -C -C - 2 3-6 2 2 2 2 2 2 2 2 1 6 alkyl, linear or branched, saturated or unsaturated, unsubstituted or substituted with one, two, three or four substituents independently of one another selected from the group consisting of -F, -Cl, -Br and -I; or a physiologically acceptable salt thereof.
2. The compound according to claim 1, wherein (i) R and R independently of one another mean -H or -C - C -alkyl; or (ii) R and R together with the carbon atom to which they are attached form a ring selected from the group consisting of cyclopropyl, cyclobutyl or cyclopentyl, oxetanly, tetrahydrofuranyl or tetrahydropyranyl, in each case unsubstituted. 9 10 11 12 13 14 15 16
3. The compound according to any one of the preceding claims, wherein R , R , R , R , R , R , R , R , 17 18 19 20 R , R , R , and R independently of one another mean -H, -F, -OH, or -C -C -alkyl.
4. The compound according to any one of the preceding claims, wherein (i) R means -H; and R means -C - C6-alkyl, linear or branched, saturated or unsaturated, unsubstituted, mono- or polysubstituted; or (ii) R means -CH ; and R means -C -C -alkyl, linear or branched, saturated or unsaturated, unsubstituted, mono- 3 1 6 or polysubstituted; or (iii) R means -H or -CH ; and wherein R means -CH -cycloalkyl, -CH -cyclobutyl, 3 2 2 -CH -cyclopentyl, -CH -oxetanyl or -CH -tetrahydrofuranyl; or (iv) R and R together with the nitrogen 2 2 2 atom to which they are attached form a ring and mean -(CH2)3.
5. The compound according to any one of the preceding claims, wherein (i) R means -C -C -alkyl, linear or branched, saturated or unsaturated, unsubstituted, mono- or polysubstituted; or (ii) R means a 6 membered aryl moiety, unsubstituted, mono- or polysubstituted; or (iii) R means a 5membered heteroaryl moiety, unsubstituted, mono- or polysubstituted.
6. The compound according to any one of the preceding claims, wherein (i) R means -H; or (ii) R means - C -C -alkyl, linear or branched, saturated or unsaturated, unsubstituted, mono- or polysubstituted; or (iii) R means a 3membered cycloalkyl moiety, saturated or unsaturated, unsubstituted, mono- or polysubstituted; wherein the 3membered cycloalkyl moiety is connected through -C -C -alkylene-, linear or branched, saturated or unsaturated, unsubstituted, mono- or polysubstituted; or (iv) R means a 3- 12-membered heterocycloalkyl moiety, saturated or unsaturated, unsubstituted, mono- or polysubstituted; wherein said 3membered heterocycloalkyl moiety is connected through -C -C -alkylene-, linear or branched, saturated or unsaturated, unsubstituted, mono- or polysubstituted; or (v) R means a 6 membered aryl moiety, unsubstituted, mono- or polysubstituted; wherein said 6membered aryl moiety is connected through -C -C -alkylene-, linear or branched, saturated or unsaturated, unsubstituted, mono- or polysubstituted; or (vi) R means a 5membered heteroaryl moiety, unsubstituted, mono- or polysubstituted; wherein said 5membered heteroaryl moiety is connected through -C -C -alkylene-, linear or branched, saturated or unsaturated, unsubstituted, mono- or polysubstituted.
7. The compound according to any one of the preceding claims, wherein (i) R means -H; or (ii) R means - C -C -alkyl, linear or branched, saturated or unsaturated, unsubstituted, mono- or polysubstituted; or (iii) R means a 3membered cycloalkyl moiety, saturated or unsaturated, unsubstituted, mono- or polysubstituted, wherein said 3membered cycloalkyl moiety is optionally connected through -C -C - alkylene-, linear or branched, saturated or unsaturated, unsubstituted, mono- or polysubstituted; or (iv) R means a 3membered heterocycloalkyl moiety, saturated or unsaturated, unsubstituted, mono- or polysubstituted; wherein said 3membered heterocycloalkyl moiety is optionally connected through - C -C -alkylene-, linear or branched, saturated or unsaturated, unsubstituted, mono- or polysubstituted; or (v) R means a 5membered heteroaryl moiety, unsubstituted, mono- or polysubstituted; wherein said 5membered heteroaryl moiety is optionally connected through -C -C -alkylene-, linear or branched, saturated or unsaturated, unsubstituted, mono- or polysubstituted. 6 5 6
8. The compound according to any one of the preceding claims, wherein (i) X means NR and R and R together with the nitrogen atom to which they are attached form a 3membered heterocycloalkyl moiety, saturated or unsaturated, unsubstituted, mono- or polysubstituted; or (ii) X means NR and R means -H or -C -C -alkyl, linear or branched, saturated or unsaturated, unsubstituted, mono- or polysubstituted.
9. The compound according to any one of the preceding claims, which has a structure according to any of general formulas (II-A) to (VIII-C): X N R (II-B) (II-A) X N R (II-C) R (III-A) X N X N 8 7 8 7 R R R R (III-C) (III-B) X N R R 8 7 (CH ) 2 2-3 (CH ) 2 2-3 (IV-A) (IV-B) X N R X N 8 7 (CH ) D 2 2-3 (IV-C) (V-A) X N X N R R R R (V-B) (V-C) X N R R R 8 (CH ) 2 2-3 (CH ) 2 2-3 H CO R 3 H CO (VI-A) (VI-B) X N R (CH ) 2 2-3 (VII-A) (VI-C) X N X N 8 7 8 7 R R R (VII-C) (VII-B) X N R (VIII-A) (VIII-B) (VIII-C) wherein in each case 1 2 3 4 5 6 7 8 R , R , R , R , R , R , R , R , and X are defined as in any one of the preceding claims, R means -H, -OH, -F, -CN or -C -C -alkyl; R means -H or -F; or a physiologically acceptable salt thereof.
10. The compound according to any one of the preceding claims, wherein the substructure has a meaning selected from the group consisting of: HO H N N H N H N H N N N N N N O N O N O N N N N N N NC N O N N CH CH , -CH F, -CHF , -CF , -OCF3, -OH, -OCH , -C(=O)NH , C(=O)NHCH , -C(=O)N(CH ) , -NH , - 2 3 2 2 3 3 2 3 3 2 2 NHCH , -N(CH ) , -NHC(=O)CH , -CH OH, -SOCH and -SO CH ; 3 3 2 3 2 3 2 3 R means -C -C -alkyl, linear or branched, saturated, unsubstituted or substituted with one, two, three or four substituents independently of one another selected from the group consisting of -F, -Cl, -Br, -I, -CN, -OH, and -O-C -C -alkyl; 3membered cycloalkyl, unsubstituted or substituted with one, two, three or four substituents independently of one another selected from the group consisting of -F, -Cl, -Br, -I, -CN, -OH, and -O-C - C -alkyl, wherein said 3membered cycloalkyl is connected through -C -C -alkylene; or 4 1 6 3membered heterocycloalkyl, unsubstituted or substituted with one, two, three or four substituents independently of one another selected from the group consisting of -F, -Cl, -Br, -I, -CN, -OH, and -O-C - C -alkyl, wherein said 3membered heterocycloalkyl is connected through -C -C -alkylene; 4 1 6 X means -O- or -NR -; R means -C -C -alkyl, linear or branched, saturated or unsaturated, unsubstituted or substituted with one, two, three or four substituents independently of one another selected from the group consisting of -F, -Cl, -Br, -I, - CN, -O-C -C -alkyl, -C(=O)OH, -C(=O)OC -C -alkyl, -C(=O)NH , -C(=O)NHC -C -alkyl, -C(=O)N(C - 1 4 1 4 2 1 4 1 C -alkyl) , -OH, -S(=O)C -C -alkyl and -S(=O) C -C -alkyl; 4 2 1 4 2 1 4 -cyclobutyl, unsubstituted or monosubstituted with -OH; wherein said -cyclobutyl is connected through - CH -; -heterocyclobutyl, unsubstituted; or -oxazolyl, -pyridinyl, -pyridazinyl or -pyrimidinyl, in each case unsubstituted or substituted with one, two, three or four substituents independently of one another selected from the group consisting of -F, -Cl, Br, - I, -OH, -O-C -C -alkyl, -CN, and -S(=O) C -C -alkyl; wherein said -oxazolyl, -pyridinyl, -pyridazinyl or - 1 4 2 1 4 pyrimidinyl is optionally connected through -CH -; in case X means NR , R means -H or -CH ; 6 5 6 or in case X means NR , R and R together with the nitrogen atom to which they are attached form a piperidine moiety, a pyrrolidine moiety, a morpholine moiety, a thiomorpholine moiety, a thiomorpholine dioxide moiety, or a piperazine moiety, in each case unsubstituted or substituted with one, two, three or four substituents independently of one another selected from the group consisting of =O, -OH, and - C(=O)NH ; wherein said piperidine moiety, pyrrolidine moiety, morpholine moiety, thiomorpholine moiety, thiomorpholine dioxide moiety, or piperazine moiety is optionally condensed with an imidazole moiety, unsubstituted; R and R independently of one another mean -H or -CH ; or R and R together with the carbon atom to which they are attached form a ring selected from the group consisting of cyclopropyl, cyclobutyl, heterocyclobutyl and heterocyclohexyl, in each case unsubstituted; 9 10 11 12 13 14 15 16 17 18 19 20 R , R , R , R , R , R , R , R , R , R , R , and R mean -H. 12. The compound according to any one of the preceding claims, which has (i) a structure according to general formula (I') 13 16 14 15 X N R 17 20 1 5 7 20 wherein R to R , R to R , and X are defined as in any one of the preceding claims, or a physiologically acceptable salt thereof; or which has (ii) a structure according to general formula (IX) (CH ) 2 1-2 wherein R means -H or -OH; R means -H or -F; R means -H, -CH , or -CH CH -OH; 3 2 2 R means -H or -CH ; and 7 8 7 8 R means -CH and R means -CH ; or R and R together with the carbon atom to which they are attached form a cyclopropyl ring; or a physiologically acceptable salt thereof. 13. The compound according to any one of the preceding claims, which is selected from the group consisting cis[8-Dimethylamino[(1-hydroxy-cyclobutyl)-methyl]oxophenyl-1,3-diazaspiro[4.5]decan yl]-N-pyridazinyl-propionamide; cis[8-Dimethylamino[(1-hydroxy-cyclobutyl)-methyl]oxophenyl-1,3-diazaspiro[4.5]decan yl]-propionamide; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-(2- methoxy-pyridinyl)-propionamide; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-(6- methoxy-pyridinyl)-propionamide; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-(3- methoxy-pyridinyl)-propionamide; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-(6- methoxy-pyridazinyl)-propionamide; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-(5- methylsulfonyl-pyridinyl)-propionamide; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-(5- methoxy-pyridinyl)-propionamide; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-(6- methylsulfonyl-pyridinyl)-propionamide; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-(6- methoxy-pyrazinyl)-propionamide; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-(4- methoxy-pyridinyl)-propionamide; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N- (oxazolyl-methyl)-propionamide; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N- (oxazolyl-methyl)-propionamide; cis(Cyclobutyl-methyl)[3-[3,4-dihydroxy-piperidinyl]oxo-propyl]dimethylaminophenyl- 1,3-diazaspiro[4.5]decanone; cis(Cyclobutyl-methyl)[3-[3,4-dihydroxy-pyrrolidinyl]oxo-propyl]dimethylamino phenyl-1,3-diazaspiro[4.5]decanone; cis(Cyclobutyl-methyl)[3-[(3S,4R)-3,4-dihydroxy-pyrrolidinyl]oxo-propyl]dimethylamino- 8-phenyl-1,3-diazaspiro[4.5]decanone; cis(Cyclobutyl-methyl)dimethylamino[3-(3-hydroxy-piperidinyl)oxo-propyl]phenyl-1,3- diazaspiro[4.5]decanone; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-[(1- hydroxy-cyclobutyl)-methyl]-propionamide; cis(Cyclobutyl-methyl)dimethylamino[3-oxo(5,6,7,8-tetrahydro-[1,2,4]triazolo[1,5-a]pyrazin- 7-yl)-propyl]phenyl-1,3-diazaspiro[4.5]decanone; cis[3-[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]- propanoylamino]-N,N-dimethyl-propionamide; cis-N-(2-Cyano-pyrimidinyl)[8-dimethylamino[(1-hydroxy-cyclobutyl)-methyl]oxophenyl- 1,3-diazaspiro[4.5]decanyl]-propionamide; cis[8-Dimethylamino[(1-hydroxy-cyclobutyl)-methyl]oxophenyl-1,3-diazaspiro[4.5]decan yl]-N-pyrimidinyl-propionamide; cis[8-Dimethylamino[(1-hydroxy-cyclobutyl)-methyl]oxophenyl-1,3-diazaspiro[4.5]decan yl]-N-(4-hydroxy-pyrimidinyl)-propionamide; cis[8-Dimethylamino[(1-hydroxy-cyclobutyl)-methyl]oxophenyl-1,3-diazaspiro[4.5]decan yl]-N-(4-methoxy-pyrimidinyl)-propionamide; cis[1-(Cyclobutyl-methyl)methylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-2,2- dimethyl-propionamide; cis[1-[(1-Hydroxy-cyclobutyl)-methyl]methylaminooxophenyl-1,3-diazaspiro[4.5]decan yl]-N-(2-hydroxy-ethyl)-propionamide; cis[1-[(1-Hydroxy-cyclobutyl)-methyl]methylaminooxophenyl-1,3-diazaspiro[4.5]decan yl]-propionamide; cis[1-[(1-Hydroxy-cyclobutyl)-methyl]methylaminooxophenyl-1,3-diazaspiro[4.5]decan yl]-N-methyl-propionamide; cis[1-[(1-Hydroxy-cyclobutyl)-methyl]methylaminooxophenyl-1,3-diazaspiro[4.5]decan yl]-N-pyridazinyl-propionamide; cis[8-Dimethylamino(2-methoxy-ethyl)oxophenyl-1,3-diazaspiro[4.5]decanyl]-N-(2- hydroxy-ethyl)-propionamide; cis[8-Dimethylamino(2-methoxy-ethyl)oxophenyl-1,3-diazaspiro[4.5]decanyl]-N-methyl- propionamide; cis[8-Dimethylamino(2-methoxy-ethyl)oxophenyl-1,3-diazaspiro[4.5]decanyl]-N- pyrimidinyl-propionamide; cis[8-Dimethylamino(3-methoxy-propyl)oxophenyl-1,3-diazaspiro[4.5]decanyl]-2,2- dimethyl-propionamide; cis[8-Dimethylamino(2-methoxy-ethyl)oxophenyl-1,3-diazaspiro[4.5]decanyl]-2,2- dimethyl-propionamide; cis[8-Dimethylamino[(1-hydroxy-cyclobutyl)-methyl]oxophenyl-1,3-diazaspiro[4.5]decan yl]-N-pyridinyl-propionamide; cis[8-Dimethylamino[(1-hydroxy-cyclobutyl)-methyl]oxophenyl-1,3-diazaspiro[4.5]decan yl]-N-pyridinyl-propionamide; cis[3-[8-Dimethylamino(3-methoxy-propyl)oxophenyl-1,3-diazaspiro[4.5]decanyl]- propanoylamino]methyl-propionamide; cis[8-Dimethylamino(3-methoxy-propyl)oxophenyl-1,3-diazaspiro[4.5]decanyl]-N-(2- methylsulfonyl-ethyl)-propionamide; cis[8-Dimethylamino(3-methoxy-propyl)oxophenyl-1,3-diazaspiro[4.5]decanyl]-N-(2- hydroxy-ethyl)-propionamide; cisDimethylamino(3-methoxy-propyl)[3-oxo(3-oxo-piperazinyl)-propyl]phenyl-1,3- diazaspiro[4.5]decanone; cis-(2R)[3-[8-Dimethylamino(3-methoxy-propyl)oxophenyl-1,3-diazaspiro[4.5]decanyl]- propanoyl]-pyrrolidinecarboxylic acid amide; cis-N-(Carbamoyl-methyl)[8-dimethylamino(3-methoxy-propyl)oxophenyl-1,3- diazaspiro[4.5]decanyl]-propionamide; cis[8-Dimethylamino[(1-hydroxy-cyclobutyl)-methyl]oxophenyl-1,3-diazaspiro[4.5]decan yl]-N-pyridinyl-propionamide; cis[1-(Cyclobutyl-methyl)(ethyl-methyl-amino)oxophenyl-1,3-diazaspiro[4.5]decanyl]-2,2- dimethyl-propionamide; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-2,2- dimethyl-propionamide; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]- propionamide; cis[1-(Cyclobutyl-methyl)[methyl-(2-methyl-propyl)-amino]oxophenyl-1,3- diazaspiro[4.5]decanyl]-N-methyl-propionamide; cis[1-(Cyclobutyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-N-methyl- propionamide; cis[8-Dimethylamino[(1-hydroxy-cyclobutyl)-methyl]oxophenyl-1,3-diazaspiro[4.5]decan yl]-N-pyrimidinyl-propionamide; cis[8-Dimethylamino[(1-hydroxy-cyclobutyl)-methyl]oxophenyl-1,3-diazaspiro[4.5]decan yl]-N-methyl-propionamide; cis[8-Dimethylamino[(1-hydroxy-cyclobutyl)-methyl]oxophenyl-1,3-diazaspiro[4.5]decan yl]-N-(2-methoxy-ethyl)-propionamide; cis[8-Dimethylamino[(1-hydroxy-cyclobutyl)-methyl]oxophenyl-1,3-diazaspiro[4.5]decan yl]-N-(2-hydroxy-ethyl)-propionamide; cis[8-Dimethylamino[(1-hydroxy-cyclobutyl)-methyl]oxophenyl-1,3-diazaspiro[4.5]decan yl]-N-(oxetanyl)-propionamide; cis-N-(Carbamoyl-methyl)[1-(cyclobutyl-methyl)dimethyl-aminooxophenyl-1,3- diazaspiro[4.5]decanyl]-2,2-dimethyl-propionamide; cis-N-(Carbamoyl-methyl)[1-(cyclobutyl-methyl)methylaminooxophenyl-1,3- diazaspiro[4.5]decanyl]-2,2-dimethyl-propionamide; cis[8-Dimethylamino[(1-hydroxy-cyclobutyl)-methyl]oxophenyl-1,3-diazaspiro[4.5]decan yl]-2,2-dimethyl-propionamide; cis[1-[(1-Hydroxy-cyclobutyl)-methyl]methylaminooxophenyl-1,3-diazaspiro[4.5]decan yl]-N-(oxetanyl)-propionamide; cis[1-[(1-Hydroxy-cyclobutyl)-methyl]methylaminooxophenyl-1,3-diazaspiro[4.5]decan yl]-2,2-dimethyl-propionamide; cis[8-(Ethyl-methyl-amino)oxophenyl-1,3-diazaspiro[4.5]decanyl]-2,2-dimethyl- propionamide; cis[8-(Ethyl-methyl-amino)methyloxophenyl-1,3-diazaspiro[4.5]decanyl]-2,2-dimethyl- propionamide; cis-2,2-Dimethyl(8-methylaminooxophenyl-1,3-diazaspiro[4.5]decanyl)-propionamide; cis(8-Ethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl)-2,2-dimethyl-propionamide; cis(8-Dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl)-2,2-dimethyl-propionamide; cis[1-(Cyclobutyl-methyl)ethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-2,2-dimethyl- propionamide; cis[8-Dimethylamino(oxetanyl-methyl)oxophenyl-1,3-diazaspiro[4.5]decanyl]-2,2- dimethyl-propionamide; cis[1-(Cyclopropyl-methyl)dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl]-2,2- dimethyl-propionamide; cis[8-(Ethyl-methyl-amino)[(1-hydroxy-cyclobutyl)-methyl]oxophenyl-1,3- diazaspiro[4.5]decanyl]-2,2-dimethyl-propionamide; cisDimethylamino(2,2-dimethylmorpholinyloxo-propyl)[(1-hydroxy-cyclobutyl)- methyl]phenyl-1,3-diazaspiro[4.5]decanone; cis[8-Dimethylamino[(1-hydroxy-cyclobutyl)-methyl]oxophenyl-1,3-diazaspiro[4.5]decan yl]-N-(2-hydroxy-ethyl)-2,2-dimethyl-propionamide; cis[1-[(1-Cyano-cyclobutyl)-methyl]dimethylaminooxophenyl-1,3-diazaspiro[4.5]decan yl]-2,2-dimethyl-propionamide; cisDimethylamino[3-(1,1-dioxo-[1,4]thiazinanyl)-2,2-dimethyloxo-propyl][(1-hydroxy- cyclobutyl)-methyl]phenyl-1,3-diazaspiro[4.5]decanone; TRANS[8-Dimethylamino[(1-hydroxy-cyclobutyl)-methyl]oxophenyl-1,3- diazaspiro[4.5]decanyl]-2,2-dimethyl-propionamide TRANS(8-Dimethylaminooxophenyl-1,3-diazaspiro[4.5]decanyl)-2,2-dimethyl- propionamide; cis[1-(Cyclopropyl-methyl)dimethylamino(3-fluorophenyl)oxo-1,3-diazaspiro[4.5]decan yl]-N,N-dimethyl-propionamide; cis[1-(Cyclopropyl-methyl)dimethylamino(3-fluorophenyl)oxo-1,3-diazaspiro[4.5]decan yl]-2,2-dimethyl-propionamide; cis((1-(cyclopropylmethyl)(dimethylamino)oxophenyl-1,3-diazaspiro[4.5]decan yl)methyl)cyclopropanecarboxamide; cis((1-(cyclopropylmethyl)(dimethylamino)oxophenyl-1,3-diazaspiro[4.5]decan yl)methyl)oxetanecarboxamide; cis(1-(cyclopropylmethyl)(methylamino)oxophenyl-1,3-diazaspiro[4.5]decanyl)-2,2- dimethylpropanamide; cis(1-(cyclopropylmethyl)(dimethylamino)oxophenyl-1,3-diazaspiro[4.5]decan yl)propanamide; cis(8-(dimethylamino)((1-fluorocyclopropyl)methyl)oxophenyl-1,3-diazaspiro[4.5]decan yl)-2,2-dimethylpropanamide and the physiologically acceptable salts thereof. 14. Use of the compound according to any one of the preceding claims for the manufacture of a medicament for treating pain. 15. A medicament comprising a compound according to any one of claims 1 to 13.
NZ745187A 2017-01-13 3-(carboxyethyl)-8-amino-2-oxo-1,3-diaza-spiro-[4.5]-decane derivatives NZ745187B2 (en)

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EP16151011 2016-01-13
PCT/EP2017/025004 WO2017121646A1 (en) 2016-01-13 2017-01-13 3-(carboxyethyl)-8-amino-2-oxo-1,3-diaza-spiro-[4.5]-decane derivatives

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NZ745187B2 true NZ745187B2 (en) 2024-06-25

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