AR116905A1 - PYRROLIDINE-2-CARBOXYL ACID DERIVATIVES TO TREAT PAIN AND PAIN-RELATED CONDITIONS - Google Patents
PYRROLIDINE-2-CARBOXYL ACID DERIVATIVES TO TREAT PAIN AND PAIN-RELATED CONDITIONSInfo
- Publication number
- AR116905A1 AR116905A1 ARP190103622A ARP190103622A AR116905A1 AR 116905 A1 AR116905 A1 AR 116905A1 AR P190103622 A ARP190103622 A AR P190103622A AR P190103622 A ARP190103622 A AR P190103622A AR 116905 A1 AR116905 A1 AR 116905A1
- Authority
- AR
- Argentina
- Prior art keywords
- radical
- unbranched
- branched
- hydrogen atom
- independently
- Prior art date
Links
- 239000002253 acid Substances 0.000 title 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 abstract 12
- TUJKJAMUKRIRHC-UHFFFAOYSA-N hydroxyl Chemical compound [OH] TUJKJAMUKRIRHC-UHFFFAOYSA-N 0.000 abstract 5
- 150000001875 compounds Chemical class 0.000 abstract 4
- 102000038650 voltage-gated calcium channel activity Human genes 0.000 abstract 3
- 108091023044 voltage-gated calcium channel activity Proteins 0.000 abstract 3
- 125000005843 halogen group Chemical group 0.000 abstract 2
- 125000005842 heteroatom Chemical group 0.000 abstract 2
- 229910052760 oxygen Inorganic materials 0.000 abstract 2
- 229910052717 sulfur Inorganic materials 0.000 abstract 2
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 abstract 1
- 229910052799 carbon Inorganic materials 0.000 abstract 1
- 239000003814 drug Substances 0.000 abstract 1
- 230000009977 dual effect Effects 0.000 abstract 1
- 239000000203 mixture Substances 0.000 abstract 1
- 229910052757 nitrogen Inorganic materials 0.000 abstract 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 abstract 1
- 230000000144 pharmacologic effect Effects 0.000 abstract 1
- 239000000651 prodrug Substances 0.000 abstract 1
- 229940002612 prodrug Drugs 0.000 abstract 1
- 150000003839 salts Chemical class 0.000 abstract 1
- 239000012453 solvate Substances 0.000 abstract 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic 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
- C07D401/02—Heterocyclic 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
- C07D401/12—Heterocyclic 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D207/16—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic 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
- C07D403/04—Heterocyclic 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 directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic 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
- C07D403/12—Heterocyclic 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
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
La presente se refiere a compuestos que muestran actividad farmacológica dual respecto a la subunidad a2d de canales de calcio dependientes de voltaje (VGCC), especialmente la subunidad a2d-1 de canales de calcio dependientes de voltaje, y el receptor de opioides m (MOR o mu-opioide). La presente también se refiere al proceso para la preparación de dichos compuestos, así como también a las composiciones que los comprenden y su uso como medicamentos. Reivindicación 1: Un compuesto de fórmula general (1), donde: W¹ es -O-, -NRᵃ o -CH₂-; Rᵃ es un átomo de hidrógeno o un radical alquilo C₁₋₆ ramificado o no ramificado; n y m son independientemente el uno del otro 0 ó 1; R¹, R² y R⁴ son independientemente el uno del otro un átomo de hidrógeno; un radical alquilo C₁₋₆ ramificado o no ramificado; un átomo de halógeno; un radical C(O)H; un radical alcoxi C₁₋₆ ramificado o no ramificado; un radical -NRᵇRᶜ; un radical -CN; un radical hidroxilo; o un radical haloalquilo C₁₋₆; Rᵇ y Rᶜ son independientemente el uno del otro un átomo de hidrógeno o un radical alquilo C₁₋₆ ramificado o no ramificado; R³ se selecciona entre: los compuestos de fórmula (2) y (3); W² es -C(O)-, -CH₂- o un enlace; A es C o N; la línea discontinua representa un doble enlace opcional; R³ᵃ y R³ᵇ son independientemente el uno del otro un átomo de hidrógeno o un radical alquilo C₁₋₆ ramificado o no ramificado; o R³ᵃ y R³ᵇ junto con el nitrógeno puente forman un radical heterocicloalquilo de 4, 5 ó 6 miembros que contiene opcionalmente un heteroátomo adicional seleccionado entre N, O y S sustituido opcionalmente con un radical alquilo C₁₋₆ ramificado o no ramificado o un radical alcoxi C₁₋₆ ramificado o no ramificado; R³ᶜ es un átomo de hidrógeno; un átomo de halógeno; un radical hidroxilo; un radical alquilo C₁₋₆ ramificado o no ramificado; un radical alcoxi C₁₋₆ ramificado o no ramificado; un radical -CN; un radical haloalquilo C₁₋₆; o un radical -NR³ᶜR³ᵈ; R³ᵈ y R³ᵉ son independientemente el uno del otro un átomo de hidrógeno o un radical alquilo C₁₋₆ ramificado o no ramificado; R⁵ es un átomo de hidrógeno o un radical -C(O)R⁵ᵃ; R⁵ᵃ es un átomo de hidrógeno; un radical alquilo C₁₋₆ ramificado o no ramificado; un radical alcoxi C₁₋₆ ramificado o no ramificado; un radical -(CH₂)ʳ-NR⁵ᵇR⁵ᶜ; un radical -OCH(CH₃)OC(O)CH(CH₃)₂; o un radical -NR⁵ᵍ-(CH₂)ₛ-CH(R⁵ᶠ)-NR⁵ᵉR⁵ᵈ; r es 1, 2, 3, 4, 5 ó 6; s es 1, 2, 3, 4, 5 ó 6; R⁵ᵇ, R⁵ᶜ, R⁵ᵈ, R⁵ᵉ, R⁵ᵍ son independientemente unos de otros un átomo de hidrógeno; o un radical alquilo C₁₋₆ ramificado o no ramificado; R⁵ᶠ es un átomo de hidrógeno o un radical -COR⁵ʰ; R⁵ʰ es un radical hidroxilo o un radical alquilo C₁₋₆ ramificado o no ramificado; R⁶ es un radical -C(O)R⁶ᵃ; un anillo heteroarilo de 5 ó 6 miembros sustituido opcionalmente que contiene al menos un heteroátomo seleccionado entre N, O y S; R⁶ᵃ es un radical hidroxilo, un radical alcoxi C₁₋₆ ramificado o no ramificado; un radical -(CH₂)ₜ-NR⁶ᵇR⁶ᶜ; un radical -OCH(CH₃)OC(O)CH(CH₃)₂; o un radical -NR⁶ᵍ-(CH₂)ᵛCH(R⁶ᶠ)-NR⁶ᵉR⁶ᵈ; t es 1, 2, 3, 4, 5 ó 6; v es 1, 2, 3, 4, 5 ó 6; R⁶ᵇ, R⁶ᶜ, R⁶ᵈ, R⁶ᵉ, R⁶ᵍ son independientemente unos de otros un átomo de hidrógeno; o un radical alquilo C₁₋₆ ramificado o no ramificado; R⁶ᶠ es un átomo de hidrógeno o un radical -COR⁶ʰ; R⁶ʰ es un radical hidroxilo o un radical alquilo C₁₋₆ ramificado o no ramificado; o una sal, isómero, profármaco o solvato farmacéuticamente aceptable de estos.This refers to compounds that show dual pharmacological activity with respect to the a2d voltage-gated calcium channel (VGCC) subunit, especially the a2d-1 voltage-gated calcium channel subunit, and the m-opioid receptor (MOR or mu-opioid). The present also refers to the process for the preparation of said compounds, as well as to the compositions comprising them and their use as medicaments. Claim 1: A compound of general formula (1), where: W¹ is -O-, -NRᵃ or -CH₂-; Rᵃ is a hydrogen atom or a branched or unbranched C₁₋₆ alkyl radical; n and m are independently of each other 0 or 1; R¹, R² and R⁴ are independently of each other a hydrogen atom; a branched or unbranched C₁₋₆ alkyl radical; a halogen atom; a C (O) H radical; a branched or unbranched C₁₋₆ alkoxy radical; a radical -NRᵇRᶜ; a -CN radical; a hydroxyl radical; or a C₁₋₆ haloalkyl radical; Rᵇ and Rᶜ are independently of each other a hydrogen atom or a branched or unbranched C₁₋₆ alkyl radical; R³ is selected from: the compounds of formula (2) and (3); W² is -C (O) -, -CH₂- or a bond; A is C or N; the dashed line represents an optional double bond; R³ᵃ and R³ᵇ are independently of each other a hydrogen atom or a branched or unbranched C₁₋₆ alkyl radical; or R³ᵃ and R³ᵇ together with the bridging nitrogen form a 4-, 5- or 6-membered heterocycloalkyl radical optionally containing an additional heteroatom selected from N, O and S optionally substituted with a branched or unbranched C₁₋₆ alkyl radical or an alkoxy radical C₁₋₆ branched or unbranched; R³ᶜ is a hydrogen atom; a halogen atom; a hydroxyl radical; a branched or unbranched C₁₋₆ alkyl radical; a branched or unbranched C₁₋₆ alkoxy radical; a -CN radical; a C₁₋₆ haloalkyl radical; or a radical -NR³ᶜR³ᵈ; R³ᵈ and R³ᵉ are independently of each other a hydrogen atom or a branched or unbranched C₁₋₆ alkyl radical; R⁵ is a hydrogen atom or a radical -C (O) R⁵ᵃ; R⁵ᵃ is a hydrogen atom; a branched or unbranched C₁₋₆ alkyl radical; a branched or unbranched C₁₋₆ alkoxy radical; a radical - (CH₂) ʳ-NR⁵ᵇR⁵ᶜ; a radical -OCH (CH₃) OC (O) CH (CH₃) ₂; or a radical -NR⁵ᵍ- (CH₂) ₛ-CH (R⁵ᶠ) -NR⁵ᵉR⁵ᵈ; r is 1, 2, 3, 4, 5, or 6; s is 1, 2, 3, 4, 5, or 6; R⁵ᵇ, R⁵ᶜ, R⁵ᵈ, R⁵ᵉ, R⁵ᵍ are independently of one another a hydrogen atom; or a branched or unbranched C₁₋₆ alkyl radical; R⁵ᶠ is a hydrogen atom or a radical -COR⁵ʰ; R⁵ʰ is a hydroxyl radical or a branched or unbranched C₁₋₆ alkyl radical; R⁶ is a radical -C (O) R⁶ᵃ; an optionally substituted 5- or 6-membered heteroaryl ring containing at least one heteroatom selected from N, O, and S; R⁶ᵃ is a hydroxyl radical, a branched or unbranched C₁₋₆ alkoxy radical; a radical - (CH₂) ₜ-NR⁶ᵇR⁶ᶜ; a radical -OCH (CH₃) OC (O) CH (CH₃) ₂; or a radical -NR⁶ᵍ- (CH₂) ᵛCH (R⁶ᶠ) -NR⁶ᵉR⁶ᵈ; t is 1, 2, 3, 4, 5, or 6; v is 1, 2, 3, 4, 5, or 6; R⁶ᵇ, R⁶ᶜ, R⁶ᵈ, R⁶ᵉ, R⁶ᵍ are independently of one another a hydrogen atom; or a branched or unbranched C₁₋₆ alkyl radical; R⁶ᶠ is a hydrogen atom or a radical -COR⁶ʰ; R⁶ʰ is a hydroxyl radical or a branched or unbranched C₁₋₆ alkyl radical; or a pharmaceutically acceptable salt, isomer, prodrug, or solvate thereof.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP18382915 | 2018-12-12 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AR116905A1 true AR116905A1 (en) | 2021-06-23 |
Family
ID=64746482
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ARP190103622A AR116905A1 (en) | 2018-12-12 | 2019-12-11 | PYRROLIDINE-2-CARBOXYL ACID DERIVATIVES TO TREAT PAIN AND PAIN-RELATED CONDITIONS |
Country Status (3)
| Country | Link |
|---|---|
| AR (1) | AR116905A1 (en) |
| TW (1) | TW202026281A (en) |
| WO (1) | WO2020120539A1 (en) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AR112463A1 (en) * | 2017-07-27 | 2019-10-30 | Esteve Pharmaceuticals Sa | PROPANAMINE DERIVATIVES TO TREAT PAIN AND PAIN RELATED STATES |
| CN115190815B (en) | 2019-12-26 | 2024-06-18 | 吉尔伽美什制药公司 | Arylcyclohexylamine derivatives and their use in the treatment of psychotic disorders |
| WO2021168082A1 (en) | 2020-02-18 | 2021-08-26 | Gilgamesh Pharmaceuticals, Inc. | Specific tryptamines for use in the treatment of mood disorders |
| US12129234B1 (en) | 2023-08-03 | 2024-10-29 | Gilgamesh Pharmaceuticals, Inc. | Crystalline salts of N-ethyl-(5-fluoro-1H-indol-3-yl)-N-methylethan-1-amine |
| US12157722B1 (en) | 2023-08-03 | 2024-12-03 | Gilgamesh Pharmaceuticals, Inc. | Crystalline hydrochloride salts of N-ethyl-2-(5-fluoro-1H-indol-3-yl)-N-methylethan-1-amine |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB0225379D0 (en) * | 2002-10-31 | 2002-12-11 | Pfizer Ltd | Therapeutic proline derivatives |
| DE10252666A1 (en) * | 2002-11-11 | 2004-08-05 | Grünenthal GmbH | N-piperidyl-cyclohexane derivatives |
| WO2004043900A2 (en) * | 2002-11-12 | 2004-05-27 | Grünenthal GmbH | 4-alkyl/4-alkenyl/4-alkynyl methyl/-1-arylcyclohexylamine derivatives |
-
2019
- 2019-12-03 TW TW108144189A patent/TW202026281A/en unknown
- 2019-12-11 AR ARP190103622A patent/AR116905A1/en unknown
- 2019-12-11 WO PCT/EP2019/084577 patent/WO2020120539A1/en not_active Ceased
Also Published As
| Publication number | Publication date |
|---|---|
| TW202026281A (en) | 2020-07-16 |
| WO2020120539A1 (en) | 2020-06-18 |
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| FB | Suspension of granting procedure |