EP4392413A1 - Treatment for neuroinflammatory disorders - Google Patents

Treatment for neuroinflammatory disorders

Info

Publication number
EP4392413A1
EP4392413A1 EP22860750.3A EP22860750A EP4392413A1 EP 4392413 A1 EP4392413 A1 EP 4392413A1 EP 22860750 A EP22860750 A EP 22860750A EP 4392413 A1 EP4392413 A1 EP 4392413A1
Authority
EP
European Patent Office
Prior art keywords
compound
formula
indacen
carbamoyl
hexahydro
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
EP22860750.3A
Other languages
German (de)
English (en)
French (fr)
Inventor
Sameer Agarwal
Deven V. PARMAR
Mukul Jain
Rajiv Sharma
Binu PHILIP
Harilal PATEL
Abhijit Chatterjee
Kasinath VISWANATHAN
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Zydus Lifesciences Ltd
Original Assignee
Zydus Lifesciences Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Zydus Lifesciences Ltd filed Critical Zydus Lifesciences Ltd
Publication of EP4392413A1 publication Critical patent/EP4392413A1/en
Pending legal-status Critical Current

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/18—Sulfonamides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
    • A61K31/341—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide not condensed with another ring, e.g. ranitidine, furosemide, bufetolol, muscarine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/38—Heterocyclic compounds having sulfur as a ring hetero atom
    • A61K31/381—Heterocyclic compounds having sulfur as a ring hetero atom having five-membered rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic 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
    • A61K31/4164—1,3-Diazoles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic 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
    • A61K31/425—Thiazoles
    • A61K31/426—1,3-Thiazoles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/4985—Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A61P25/16—Anti-Parkinson drugs
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • 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
    • C07D207/08—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 hydrocarbon radicals, substituted by hetero atoms, attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
    • C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
    • C07D233/64—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
    • C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
    • C07D277/08—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
    • C07D277/12—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member 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
    • C07D277/16—Sulfur atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
    • C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D307/56—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three 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
    • C07D307/64—Sulfur atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
    • C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
    • C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
    • C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom 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
    • C07D333/30—Hetero atoms other than halogen
    • C07D333/34—Sulfur atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic 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
    • C07D487/04—Ortho-condensed systems

Definitions

  • NLRP3 pyrin domain-containing 3
  • IL-1 ⁇ mucosal interleukin-1 ⁇
  • NLRP3 pyrin domain-containing 3
  • IL mucosal interleukin-1 ⁇
  • IL-1 ⁇ mucosal interleukin-1 ⁇
  • NLRP3 is a cytosolic pattern recognition receptor (PRR) that senses exogenous and endogenous danger signals.
  • PRR cytosolic pattern recognition receptor
  • the NLRP3 protein is made up of three domains: a leucine-rich repeat domain (LRR), a NOD containing a caspase activation and recruitment domain (CARD) (NACHT), and a pyrin domain (PYD).
  • LRR leucine-rich repeat domain
  • CARD caspase activation and recruitment domain
  • PYD pyrin domain
  • carbocycle is intended to include, wherever applicable, the groups representing cycloalkyl, phenyl and other saturated, partially saturated or aromatic residues;
  • cycloalkyl and cycloalkenyl refers to optionally substituted, saturated and unsaturated mono-cyclic, bicyclic or tricyclic carbon groups.
  • the cycloalkyl or cycloalkenyl group may have a specified number of carbon atoms, for example, C 3 -C 6 cycloalkyl or cycloalkenyl includes within its scope a carbocyclic group having 3, 4, 5 or 6 carbon atoms.
  • heteroaryl groups include; pyrrolyl, isoxazolyl, isothiazolyl, pyrazolyl, pyridyl, oxazolyl, oxadiazolyl, thiadiazolyl, thiazolyl, imidazolyl, triazolyl, tetrazolyl, furyl, triazinyl, thienyl, pyrimidyl, benzisoxazolyl, benzoxazolyl, benzthiazolyl, benzothiadiazolyl, dihydrobenzofuranyl, indolinyl, pyridazinyl, indazolyl, isoindolyl, dihydrobenzothienyl, indolinyl, pyridazinyl, indazolyl, isoindolyl, dihydrobenzothienyl, indolizinyl, cinnolinyl, phthalazinyl, quinazolin
  • Rilonacept Canakinumab, and Anakinra
  • immune-suppressants e.g., Methotrexate, Mercaptopurine, Cyclophosphamide
  • metabolic disorders drugs e.g., glucocorticoids, non-steroidal anti-inflammatory drugs, Gasdermin D inhibitors (e.g., Necrosulfonamide); Cox-2 specific inhibitors, TNF- ⁇ binding proteins (e.g.,Infliximab, Etanercept), Interferon-13, Interferon, Interleukin-2, antihistamines, beta-agonist, BTK inhibitors, anticolinergics, anti- cancer agents; anti-viral drugs, for example: Remdesivir, Lopinavir/Ritonavir, Favipiravir, Molnupiravir,Tamiflu; anti-malarial agents, for example: Choloroquinone, Hydroxyl Chloroquinone; or their suitable pharmaceutically acceptable salts.
  • TNF- ⁇ binding proteins
  • the compounds and compositions of the present invention are also intended for use with general care provided patients with Arenaviridae viral infections, including parenteral fluids (including dextrose saline and Ringer's lactate) and nutrition, antibiotic (including Metronidazole and Cephalosporin antibiotics, such as Ceftriaxone and Cefuroxime) and/or antifungal prophylaxis, fever and pain medication, antiemetic (such as Metoclopramide) and/or antidiarrheal agents, vitamin and mineral supplements (including Vitamin C or/and K and zinc sulfate), anti- inflammatory agents (such as Ibuprofen), pain medications, and medications for other common diseases in the patient population, such anti-malarial agents (including Artemether and Artesunate-lumefantrine combination therapy), typhoid (including quinolone antibiotics, such as Ciprofloxacin, macrolide antibiotics, such as Azithromycin, cephalosporin antibiotics, such as Cef
  • compound of formula (I) or its pharmaceutically acceptable salts is provided in the form of pharmaceutical composition.
  • present invention provides a pharmaceutical composition comprising compound of formula (I) or its pharmaceutically acceptable salts for treatment of neuroinflammatory disorders or neurodegenerative disorder diseases such as Traumatic brain injury (TBI), Amyotrophic lateral sclerosis (ALS), Alzheimer disease (AD), Parkinson’s disease (PD), Multiple sclerosis (MS), Huntington disease and other related forms of disorders preferably Parkinson’s disease (PD) wherein compound of formula (I) is Formula (I)
  • the present invention provides pharmaceutical composition comprising compound of formula (I) and suitable pharmaceutically acceptable excipients for the treatment of neuroinflammatory disorders or neurodegenerative disorder diseases such as Traumatic brain injury (TBI), Amyotrophic lateral sclerosis (ALS), Alzheimer disease (AD), Parkinson’s disease (PD), Multiple sclerosis (MS), Huntington disease and other related forms of disorders preferably Parkinson’s disease (PD).
  • the pharmaceutically acceptable excipients may be selected at least one from diluents, carriers, binders, disintegrating agents, lubricating agents, surface active agents and the like.
  • the present invention provides a pharmaceutical composition comprising compound of formula (I) or its pharmaceutically acceptable salts wherein effective amount of compound of formula (I) or its pharmaceutically acceptable salt may be selected from 1 mg to 500 mg; preferably 1 mg to 250 mg and more preferably 1 mg to 150 mg for the treatment of neuroinflammatory disorders or neurodegenerative disorder diseases.
  • the present invention provides pharmaceutical composition comprising compound of formula (I) or its pharmaceutically acceptable salts may be administered by oral, topical, parenteral, intravenous or intramuscular route of administration.
  • the pharmaceutical composition may be administered by oral route of administration.
  • a process for the preparation of a stable pharmaceutical composition of compounds of formula (1) or its pharmaceutically acceptable salts may be made by dry mixing, wet granulation or dry granulation methods by techniques known to persons skilled in the art.
  • the drug is mixed with one or more pharmaceutical excipients and granulated with suitable binding solution as described earlier, to form wet granules, the wet granules are dried and optionally sieved.
  • the dried granules are mixed with one or more suitable excipients from those described elsewhere and then compressed into tablets or filled into capsules.
  • the drug In dry mixing process, the drug is mixed with all the pharmaceutical excipients required. The blend is mixed with one or more suitable excipients from those described elsewhere and then final blend is either compressed into tablets or filled in capsules.
  • dry granulation process the drug is mixed with one or more pharmaceutical excipients and compressed into slugs and these slugs are passed through required sieve. The sieved granules are mixed with one or more suitable excipients from those described elsewhere and then compressed into tablets or filled into capsules.
  • One or more solvents or vehicle used in the formulation are selected from water, acetone, chloroform, dichloromethane, ethyl alcohol, ethyl acetate, methyl alcohol, isopropyl alcohol and combinations thereof and other such materials known to those of ordinary skill in the art.
  • the present invention further discloses use of said compound of formula (I) or their suitable pharmaceutical compositions for the treatment of neuroinflammatory or neurodegenerative disorder diseases such as Traumatic brain injury (TBI), Amyotrophic lateral sclerosis (ALS), Alzheimer disease (AD), Parkinson’s disease (PD), Multiple sclerosis (MS), Huntington disease and other related forms of disorders preferably Parkinson’s disease (PD).
  • the present invention provides use of the compound of formula (11) or their suitable pharmaceutical compositions for the treatment of neuroinflammatory disorders or neurodegenerative disorder diseases such as Traumatic brain injury (TBI), Amyotrophic lateral sclerosis (ALS), Alzheimer disease (AD), Parkinson’s disease (PD), Multiple sclerosis (MS), Huntington disease and other related forms of disorders preferably Parkinson’s disease (PD).
  • the present invention provides effective amount of compound of formula (11) or its pharmaceutically acceptable salt may be selected from 1 mg to 500 mg; preferably 1 mg to 250 mg and more preferably 1 mg to 150 mg for the treatment of neuroinflammatory disorders or neurodegenerative disorder diseases.
  • the compound is administered orally in an amount to provide compound of formula (11) or a pharmaceutically acceptable salt thereof in the range of about 50 mg to about 75 mg on each day the compound is administered to the subject. In certain embodiments, the compound is administered orally in an amount to provide compound of formula (11) or a pharmaceutically acceptable salt thereof in the range of about 75 mg to about 100 mg on each day the compound is administered to the subject. In certain embodiments, the compound is administered orally in an amount to provide compound of formula (11) or a pharmaceutically acceptable salt thereof in the range of about 100 mg to about 125 mg on each day the compound is administered to the subject.
  • the compound is administered orally in an amount to provide compound of formula (11) or a pharmaceutically acceptable salt thereof in the range of about 1 mg to about 50 mg on each day the compound is administered to the subject. In certain embodiments, the compound is administered orally in an amount to provide compound of formula (11) or a pharmaceutically acceptable salt thereof in the range of about 1 mg to about 75 mg on each day the compound is administered to the subject. In certain embodiments, the compound is administered orally in an amount to provide compound of formula (11) or a pharmaceutically acceptable salt thereof in the range of about 1 mg to about 100 mg on each day the compound is administered to the subject.
  • the compound is administered orally in an amount to provide compound of formula (11) or a pharmaceutically acceptable salt thereof in the range of about 1 mg to about 125 mg on each day the compound is administered to the subject. In certain embodiments, the compound is administered orally in an amount to provide compound of formula (11) or a pharmaceutically acceptable salt thereof in the range of about 1 mg to about 150 mg on each day the compound is administered to the subject. In certain embodiments, the compound is administered orally in an amount to provide compound of formula (11) or a pharmaceutically acceptable salt thereof in the range of about 1 mg to about 175 mg on each day the compound is administered to the subject.
  • the compound is administered orally in an amount to provide compound of formula (11) or a pharmaceutically acceptable salt thereof in the range of about 1 mg to about 200 mg on each day the compound is administered to the subject. In certain embodiments, the compound is administered orally in an amount to provide compound of formula (11) or a pharmaceutically acceptable salt thereof in the range of about 1 mg to about 225 mg on each day the compound is administered to the subject. In certain embodiments, the compound is administered orally in an amount to provide compound of formula (11) or a pharmaceutically acceptable salt thereof in the range of about 1 mg to about 250 mg on each day the compound is administered to the subject.
  • Rilonacept Canakinumab, and Anakinra
  • immune-suppressants e.g., Methotrexate, Mercaptopurine, Cyclophosphamide
  • metabolic disorders drugs e.g., glucocorticoids, non-steroidal anti-inflammatory drugs, Gasdermin D inhibitors (e.g., Necrosulfonamide); Cox-2 specific inhibitors, TNF- ⁇ binding proteins (e.g.,Infliximab, Etanercept), Interferon-13, Interferon, Interleukin-2, antihistamines, beta-agonist, BTK inhibitors, anticolinergics, anti-cancer agents; anti-viral drugs, for example: Remdesivir, Lopinavir/Ritonavir, Favipiravir, Molnupiravir, Tamiflu; anti-malarial agents, for example: Choloroquinone, Hydroxyl Chloroquinone; or their suitable pharmaceutically acceptable salts.
  • Non- Alcoholic Steato- Hepatitis and fibrosis drugs
  • anticancer antibiotics, for example Azithromycin
  • Drugs originally developed for SARS (ACE2 protein decoy) Intravenous vitamin C; inhibitors of mitogen-activated protein kinase signaling (ex: BAY 43-9006); Syk inhibitors; mTOR inhibitors; antibodies (Rituxan); and BCR/ABL antagonist may also be used in combination with compound of formula (11) for treatment of neuroinflammatory disorders or neurodegenerative disorder diseases.
  • the compound of formula (11) of the present invention or its pharmaceutically acceptable salts may be used further in combination with one or more suitable pharmaceutically active agents selected from following therapeutic agents in any combinations.
  • MAO B inhibitors selegiline (Zelapar), rasagiline (Azilect) and safinamide (Xadago); Catechol O-methyltransferase (COMT) inhibitors, Entacapone (Comtan) and opicapone (Ongentys); benztropine (Cogentin), trihexyphenidyl, Amantadine; cholinesterase inhibitors, donepezil (Aricept), galantamine (Razadyne) and rivastigmine (Exelon), Memantine (Namenda), aducanumab (Aduhelm); Riluzole (Rilutek), Edaravone (Radicava); ocrelizumab (Ocrevus), prednisone and methylprednisolone; te
  • the compounds of formula (11) and its compositions of the present invention are also intended for use with general care provided patients with Arenaviridae viral infections, including parenteral fluids (including dextrose saline and Ringer's lactate) and nutrition, antibiotic (including Metronidazole and Cephalosporin antibiotics, such as Ceftriaxone and Cefuroxime) and/or antifungal prophylaxis, fever and pain medication, antiemetic (such as Metoclopramide) and/or antidiarrheal agents, vitamin and mineral supplements (including Vitamin C or/and K and zinc sulfate), anti-inflammatory agents (such as Ibuprofen), pain medications, and medications for other common diseases in the patient population, such anti-malarial agents (including Artemether and Artesunate-lumefantrine combination therapy), typhoid (including quinolone antibiotics, such as Ciprofloxacin, macrolide antibiotics, such as Azithromycin, cephalosporin antibiotics,
  • present invention provides a pharmaceutical composition comprising compound of formula (11) or its pharmaceutically acceptable salts for treatment of neuroinflammatory disorders or neurodegenerative disorder diseases.
  • These severe and persistent illnesses include Traumatic brain injury (TBI), Amyotrophic lateral sclerosis (ALS), Alzheimer disease (AD), Parkinson’s disease (PD), Multiple sclerosis (MS), Huntington disease and other related forms of disorders.
  • neuroinflammatory disorders or neurodegenerative disorder diseases is Parkinson’s disease.
  • the present invention provides pharmaceutical composition comprising compound of formula (11) and suitable pharmaceutically acceptable excipients for the treatment of neuroinflammatory disorders or neurodegenerative disorder diseases.
  • the pharmaceutically acceptable excipients may be selected at least one from diluents, carriers, binders, disintegrating agents, lubricating agents, surface active agents and the like.
  • the present invention further discloses use of said compound of formula (11) or their suitable pharmaceutical compositions for the treatment of neuroinflammatory disorders or neurodegenerative disorder diseases such as Traumatic brain injury (TBI), Amyotrophic lateral sclerosis (ALS), Alzheimer disease (AD), Parkinson’s disease (PD), Multiple sclerosis (MS), Huntington disease and other related forms of disorders preferably Parkinson’s disease.
  • the present invention provides a method of treating neuroinflammatory disorders or neurodegenerative disorder diseases using pharmaceutical composition of compound of formula (11) or its pharmaceutically acceptable salts.
  • a method of treating neuroinflammatory disorders or neurodegenerative disorder diseases using compound of formula (11) or its pharmaceutical composition provides a process for the preparation of a stable pharmaceutical composition of compounds of formula (11).
  • the stable pharmaceutical composition may be made by dry mixing, wet granulation or dry granulation methods by techniques known to persons skilled in the art.
  • wet granulation process the drug is mixed with one or more pharmaceutical excipients and granulated with suitable binding solution as described earlier, to form wet granules, the wet granules are dried and optionally sieved.
  • the dried granules are mixed with one or more suitable excipients from those described elsewhere and then compressed into tablets or filled into capsules.
  • the drug In dry mixing process, the drug is mixed with all the pharmaceutical excipients required. The blend is mixed with one or more suitable excipients from those described elsewhere and then final blend is either compressed into tablets or filled in capsules.
  • dry granulation process the drug is mixed with one or more pharmaceutical excipients and compressed into slugs and these slugs are passed through required sieve. The sieved granules are mixed with one or more suitable excipients from those described elsewhere and then compressed into tablets or filled into capsules.
  • One or more solvents or vehicle used in the formulation are selected from water, acetone, chloroform, dichloromethane, ethyl alcohol, ethyl acetate, methyl alcohol, isopropyl alcohol and combinations thereof and other such materials known to those of ordinary skill in the art.
  • the pharmaceutically acceptable excipients described in the present invention are selected at least one from diluents, carriers, binders, disintegrating agents, lubricating agents, surface active agents and the like.
  • Diluents include, but are not limited to lactose monohydrate, polymethacrylates selected from Eudragit, potassium chloride, sulfobutylether b-cyclodextrin, sodium chloride and spray dried lactose, combinations thereof and other such materials known to those of ordinary skill in the art.
  • Carriers include, but are not limited to lactose, white sugar, sodium chloride, glucose, urea, starch, calcium carbonate and kaolin, crystalline cellulose and silicic acid, combinations thereof and other such materials known to those of ordinary skill in the art.
  • Nonionic surfactant selected from alkyl polyglucosides, cocamide DEA, cocamide MBA, cocamide TEA, decyl maltoside and octyl glucoside
  • anionic surfactant selected from arachnidan acid and arachidonic acid
  • cationic surfactant selected from cetyl trimethylammonium bromide and cetylpyridinium chloride, combinations thereof and other such materials known to those of ordinary skill in the art.
  • General Process for Preparation The novel compounds of the present invention can be prepared using the reactions and techniques described below, together with conventional techniques known to those skilled in the art of organic synthesis, or variations thereon as appreciated by those skilled in the art.

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  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Neurosurgery (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Neurology (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Psychology (AREA)
  • Hospice & Palliative Care (AREA)
  • Psychiatry (AREA)
  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
EP22860750.3A 2021-08-25 2022-08-25 Treatment for neuroinflammatory disorders Pending EP4392413A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IN202121038491 2021-08-25
PCT/IB2022/057951 WO2023026222A1 (en) 2021-08-25 2022-08-25 Treatment for neuroinflammatory disorders

Publications (1)

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EP4392413A1 true EP4392413A1 (en) 2024-07-03

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EP (1) EP4392413A1 (ko)
KR (1) KR20240052009A (ko)
CN (1) CN117858871A (ko)
CA (1) CA3226855A1 (ko)
WO (1) WO2023026222A1 (ko)

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
PL3661925T3 (pl) * 2017-07-07 2022-02-28 Inflazome Limited Nowe związki sulfonamidowo karboksyamidowe
SG11202107680PA (en) * 2019-01-14 2021-08-30 Cadila Healthcare Ltd Novel substituted sulfonylurea derivatives

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KR20240052009A (ko) 2024-04-22
CN117858871A (zh) 2024-04-09
CA3226855A1 (en) 2023-03-02

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