WO2012067965A1 - Nampt and rock inhibitors - Google Patents

Nampt and rock inhibitors Download PDF

Info

Publication number
WO2012067965A1
WO2012067965A1 PCT/US2011/060425 US2011060425W WO2012067965A1 WO 2012067965 A1 WO2012067965 A1 WO 2012067965A1 US 2011060425 W US2011060425 W US 2011060425W WO 2012067965 A1 WO2012067965 A1 WO 2012067965A1
Authority
WO
WIPO (PCT)
Prior art keywords
dihydro
carboxamide
isoindole
phenyl
carbamoyl
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.)
Ceased
Application number
PCT/US2011/060425
Other languages
English (en)
French (fr)
Inventor
Michael L. Curtin
Bryan K. Sorensen
Howard R. Heyman
Richard F. Clark
Kevin R. Woller
Omar J. Shah
Michael Michaelides
Chris Tse
Anil Vasudevan
Helmut Mack
Todd M. Hansen
Ramzi Sweis
Marina A. Pliushchev
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.)
Abbott Laboratories
Original Assignee
Abbott Laboratories
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
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=45034200&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=WO2012067965(A1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Priority to EP11787996.5A priority Critical patent/EP2640698A1/en
Priority to MX2013005454A priority patent/MX2013005454A/es
Priority to AU2011329233A priority patent/AU2011329233A1/en
Priority to BR112013012078A priority patent/BR112013012078A2/pt
Priority to CA2816594A priority patent/CA2816594A1/en
Priority to SG2013037643A priority patent/SG190819A1/en
Priority to RU2013126657/04A priority patent/RU2013126657A/ru
Application filed by Abbott Laboratories filed Critical Abbott Laboratories
Priority to PH1/2013/500975A priority patent/PH12013500975A1/en
Priority to KR1020137015348A priority patent/KR20140009251A/ko
Priority to JP2013538943A priority patent/JP6117104B2/ja
Priority to CN2011800647158A priority patent/CN103313968A/zh
Publication of WO2012067965A1 publication Critical patent/WO2012067965A1/en
Priority to IL225862A priority patent/IL225862A0/en
Anticipated expiration legal-status Critical
Priority to AU2017200079A priority patent/AU2017200079A1/en
Ceased legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/44—Iso-indoles; Hydrogenated iso-indoles
    • 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
    • A61K31/403—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 condensed with carbocyclic rings, e.g. carbazole
    • A61K31/4035—Isoindoles, e.g. phthalimide
    • 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
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/437—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
    • 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
    • A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
    • 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
    • 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
    • A61K31/50—Pyridazines; Hydrogenated pyridazines
    • A61K31/501—Pyridazines; Hydrogenated pyridazines not condensed and containing further heterocyclic 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
    • A61K31/495—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
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic 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
    • A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/5375—1,4-Oxazines, e.g. morpholine
    • A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
    • 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
    • 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
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/06—Antiasthmatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/08—Drugs for disorders of the urinary system of the prostate
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/10—Drugs for disorders of the urinary system of the bladder
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/12—Drugs for disorders of the urinary system of the kidneys
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A61P15/10—Drugs for genital or sexual disorders; Contraceptives for impotence
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/06—Antipsoriatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular 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
    • 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
    • A61P25/04—Centrally acting analgesics, e.g. opioids
    • 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
    • A61P25/08—Antiepileptics; Anticonvulsants
    • 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
    • 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
    • A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
    • 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
    • A61P25/24—Antidepressants
    • 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
    • A61P27/00—Drugs for disorders of the senses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A61P27/06—Antiglaucoma agents or miotics
    • 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]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A61P31/18—Antivirals for RNA viruses for HIV
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/02—Antineoplastic agents specific for leukemia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/04—Antineoplastic agents specific for metastasis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/08—Antiallergic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/12—Antihypertensives
    • 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
    • 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
    • C07D401/14—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 three or more hetero rings
    • 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
    • C07D403/10—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 carbon chain containing aromatic rings
    • 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
    • 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
    • C07D403/14—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 three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic 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
    • C07D405/02—Heterocyclic 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
    • C07D405/12—Heterocyclic 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D407/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00
    • C07D407/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings
    • C07D407/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D407/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00
    • C07D407/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic 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
    • C07D413/12—Heterocyclic 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic 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
    • C07D417/02—Heterocyclic 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
    • C07D417/12—Heterocyclic 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 chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C07D491/04—Ortho-condensed systems
    • C07D491/044—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
    • C07D491/048—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring the oxygen-containing ring being five-membered
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
    • C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D495/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00

Definitions

  • This invention pertains to compounds which inhibit the activity of NAMPT, compositions containing the compounds, and methods of treating diseases during which NAMPT is expressed. This invention also pertains to compounds which inhibit the activity of ROCK, compositions containing the compounds, and methods of treating diseases during which ROCK is expressed.
  • NAD+ (nicotinamide adenine dinucleotide) is a coenzyme that plays a critical role in many physiologically essential processes (Ziegkel, M. Eur. J. Biochem. 267,1550-1564, 2000). NAD is necessary for several signaling pathways including among others poly ADP- ribosylation in DNA repair, mono-ADP-ribosylation in both the immune system and G- protein-coupled signaling, and NAD is also required by sirtuins for their deacetylase activity (Garten, A. et al Trends in Endocrinology and Metabolism, 20, 130-138, 2008).
  • NAMPT also known as pre-B-cell-colony-enhancing factor (PBEF) and visfatin
  • PBEF pre-B-cell-colony-enhancing factor
  • visfatin is an enzyme that catalyzes the phosphoribosylation of nicotinamide and is the rate-limiting enzyme in one of two pathways that salvage NAD.
  • NAMPT inhibitors have potential as anticancer agents. Cancer cells have a higher basal turnover of NAD and also display higher energy requirements compared with normal cells. Additionally, increased NAMPT expression has been reported in colorectal cancer (Van Beijnum, J.R. et al Int. J. Cancer 101, 118-127, 2002) and NAMPT is involved in angiogenesis (Kim, S.R. et al. Biochem. Biophys. Res. Commun. 357, 150-156, 2007). Small-molecule inhibitors of NAMPT have been shown to cause depletion of intracellular NAD+ levels and ultimately induce tumor cell death (Hansen, CM et al. Anticancer Res. 20, 42111-4220, 2000) as well as inhibit tumor growth in xenograft models (Olese, U.H. et al. Mol Cancer Ther. 9, 1609-1617, 2010).
  • NAMPT inhibitors also have potential as therapeutic agents in inflammatory and metabolic disorders (Galli, M. et al Cancer Res. 70, 8-11, 2010).
  • NAMPT is the predominant enzyme in T and B lymphocytes.
  • Selective inhibition of NAMPT leads to NAD+ depletion in lymphocytes blocking the expansion that accompanies autoimmune disease progression whereas cell types expressing the other NAD+ generating pathways might be spared.
  • a small molecule NAMPT inhibitor (FK866) has been shown to selectively block proliferation and induce apoptosis of activated T cells and was efficacious in animal models of arthritis (collagen -induced arthritis) (Busso, N.et al. Plos One 3, e2267, 2008).
  • FK866 ameliorated the manifestations of experimental autoimmune encephalomyelitis (EAE), a model of T-cell mediated autoimmune disorders.
  • EAE experimental autoimmune encephalomyelitis
  • NaMPT activity increases NF-kB transcriptional activity in human vascular endothelial cell, resulting in MMP-2 and MMP-9 activation, suggesting a role for NAMPT inhibitors in the prevention of inflammatory mediated complications of obesity and type 2 diabetes (Adya, R. et. Al. Diabetes Care, 31, 758-760, 2008).
  • Rho kinases the first Rho effectors to be described, are serine/threonine kinases that are important in fundamental processes of cell migration, cell proliferation and cell survival. Abnormal activation of the Rho ROCK pathway has been observed in various disorders. Examples of disease states in which compounds with ROCK inhibition have potentially beneficial therapeutic effects due to their anti vasospasm activity includes cardiovascular diseases such as hypertension, chronic and congestive heart failure, cardiac hypertrophy, restenosis, chronic renal failure, cerebral vasospasm after subarachnoid bleeding, pulmonary hypertension and atherosclerosis. This muscle relaxing property is also beneficial for treating asthma, male erectile dysfunctions, female sexual dysfunction, and over-active bladder syndrome.
  • cardiovascular diseases such as hypertension, chronic and congestive heart failure, cardiac hypertrophy, restenosis, chronic renal failure, cerebral vasospasm after subarachnoid bleeding, pulmonary hypertension and atherosclerosis. This muscle relaxing property is also beneficial for treating asthma, male erectile dysfunctions, female sexual dysfunction, and over
  • Rho ROCK pathway inhibitors therefore have potential for preventing axonal growth, axonal rewiring across lesions within the CNS, accelerated regeneration and enhanced functional recovery after acute neuronal injury in mammals (spinal-cord injury, traumatic brain injury).
  • Rho ROCK pathway inhibitors therefore have potential for preventing axonal growth, axonal rewiring across lesions within the CNS, accelerated regeneration and enhanced functional recovery after acute neuronal injury in mammals (spinal-cord injury, traumatic brain injury).
  • Rho/ROCK pathway inhibitors therefore have potential for preventing axonal growth, axonal rewiring across lesions within the CNS, accelerated regeneration and enhanced functional recovery after acute neuronal injury in mammals (spinal-cord injury, traumatic brain injury).
  • Rho ROCK pathway inhibitors therefore have potential for preventing axonal growth, axonal rewiring across lesions within the CNS, accelerated regeneration and enhanced functional recovery after acute neuronal injury in mammals (spinal-cord injury,
  • compounds of the invention can be used as treatment for neuroinflammatory diseases such as stroke, multiple sclerosis, Alzheimer's disease, Huntington's disease, Parkinson's disease, amyotrophic lateral sclerosis, and inflammatory pain, as well as other diseases such as rheumatoid arthritis, osteoarthritis, asthma, irritable bowel syndrome, Crohn's disease, psoriasis, ulcerative colitis, Lupus, and inflammatory bowel disease.
  • neuroinflammatory diseases such as stroke, multiple sclerosis, Alzheimer's disease, Huntington's disease, Parkinson's disease, amyotrophic lateral sclerosis, and inflammatory pain
  • other diseases such as rheumatoid arthritis, osteoarthritis, asthma, irritable bowel syndrome, Crohn's disease, psoriasis, ulcerative colitis, Lupus, and inflammatory bowel disease.
  • ROCK inhibitors reduce cell proliferation and cell migration, they could be useful in treating cancer and tumor metastasis. Further more, there is evidence suggesting that ROCK inhibitors suppress cytoskeletal rearrangement upon virus invasion, thus they also have potential therapeutic value in anti-viral and anti-bacterial applications. ROCK inhibitors are also useful for the treatment of insulin resistance and diabetes. Further, ROCK inhibitors have been shown to ameliorate progression of cystic fibrosis (Abstract S02.3, 8th World Congress on Inflammation, Copenhagen, Denmark, June 16-20, 2007).
  • Rho-associated coiled-coil forming protein kinases (ROCK)-l and -2, have been shown to enhance myosin light chain (MLC) phosphorylation by inhibiting MLC phosphatase as well as phosphorylating MLC. This results in the regulation of actin-myosin contraction.
  • ROCK myosin light chain
  • Rho ROCK pathway may be useful for the treatment of asthma.
  • One embodiment of this invention pertains to compounds and pharmaceutically acceptable salts thereof, which are useful as inhibitors of NAMPT or ROCK, the compounds having Formula (Ic)
  • X 1 , X 2 , and X 3 are CH; or
  • X 1 and X 3 are CH; and X 2 is N; or X 1 and X 3 are CH; and X 2 is CR 1 ; or
  • X 2 and X 3 are CH; and X 1 is CR 1 ; or
  • X 1 is CH; and X 2 and X 3 are CR 1 ; or
  • X 2 is CH; and X 1 and X 3 are N; or
  • X 2 and X 3 are CH; and X 1 is N; or
  • X 1 is CH; X 2 is N; and X 3 is CR 1 ; or
  • X 1 is N;
  • X 2 is CR 1 ; and
  • X 3 is N;
  • R 1 is R 3 , OR 3 , SR 3 , S(0)R 3 , S0 2 R 3 , C(0)R 3 , C(0)OR 3 , OC(0)R 3 , NHR 3 , N(R 3 ) 2 ,
  • R 2 is alkyl, alkenyl, alkynyl, phenyl, heterocyclyl, cycloalkyl, or cycloalkenyl;
  • each R 2 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R 4 , OR 4 , SR 4 , S(0)R 4 , S0 2 R 4 , C(0)R 4 , CO(0)R 4 , OC(0)R 4 , OC(0)OR 4 , NHC(0)R 4 , NR 4 C(0)R 4 , NHS(0) 2 R 4 , NR 4 S(0) 2 R 4 , NHC(0)OR 4 , NR 4 C(0)OR 4 , NHC(0)NH 2 , NHC(0)NHR 4 , NHC(0)N(R 4 ) 2 , NR 4 C(0)NHR 4 , NR 4 C(0)N(R 4 ) 2 , C(0)NH 2 , C(0)NHR 4 , C(0)N(R 4 ) 2 , C(0)NHOH, C(0)NHOR 4 , C(0)NHS0 2 R 4 , C(0)NR 4 S0 2 R 4 , C(0)NHOH, C(0)NHOR 4 ,
  • each R 2 phenyl is optionally substituted at the para position with one independently selected R 5 , OR 5 , SR 5 , S(0)R 5 , S0 2 R 5 , C(0)R 5 , CO(0)R 5 , OC(0)R 5 , OC(0)OR 5 , NH 2 , NHR 5 , N(R 5 ) 2 , NHC(0)R 5 , NR 5 C(0)R 5 , NHS(0) 2 R 5 , NR 5 S(0) 2 R 5 , NHC(0)OR 5 , NR 5 C(0)OR 5 , NHC(0)NH 2 , NHC(0)NHR 5 , NHC(0)N(R 5 ) 2 , NR 5 C
  • C(0)NHOR 6 C(0)NHS0 2 R 6 , C(0)NR 6 S0 2 R 6 , S0 2 NH 2 , S0 2 NHR 6 , S0 2 N(R 6 ) 2 , C(0)H, C(0)OH, OH, (O), CN, N 3 , N0 2 , CF 3 , CF 2 CF 3 , OCF 3 , OCF 2 CF 3 , F, CI, Br or I;
  • R 4 at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, cycloalkyl, or heterocyclyl; wherein each R 4 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R 7 , OR 7 , SR 7 , S(0)R 7 , S0 2 R 7 , C(0)R 7 , OC(0)R 7 , OC(0)OR 7 , NH 2 , NHR 7 , NHC(0)R 7 , NR 7 C(0)R 7 , NHS(0) 2 R 7 ,
  • R 5 is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R 5 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R 9 , OR 9 , SR 9 , S(0)R 9 , S0 2 R 9 , C(0)R 9 , CO(0)R 9 , OC(0)R 9 , OC(0)OR 9 , NH 2 , NHR 9 , N(R 9 ) 2 , NHC(0)R 9 , NR 9 C(0)R 9 , NHS(0) 2 R 9 , NR 9 S(0) 2 R 9 , NHC(0)OR 9 , NR 9 C(0)OR 9 , NHC(0)NH 2 ,
  • R 6 is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R 6 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R 10 , OR 10 , SR 10 , S(0)R 10 , S0 2 R 10 , NHR 10 , N(R 10 ) 2 , C(0)R 10 , C(0)NH 2 , C(0)NHR 10 , C(O)N(R 10 ) 2 , NHC(0)R , NR 1U C(0)R , NHS0 2 R , NHC(0)OR , S0 2 NH 2 , S0 2 NHR 1U , S0 2 N(R 1U ) 2 , NHC(0)NH 2 , NHC(0)NHR 10 , OH, (O), C(0)OH, N 3 , CN, NH 2 , CF
  • R 7 is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R 7 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R 11 , OR 11 , SR. 11 , S(0)R n , S0 2 R n , NHR 11 , N(R n ) 2 , C(0)R n , C(0)NH 2 , C(0)NHR n , C(0)N(R n ) 2 ,
  • NHC(0)R n NR n C(0)R n , NHS0 2 R n , NHC(0)OR n , S0 2 NH 2 , S0 2 NHR n , S0 2 N(R n ) 2 , NHC(0)NH 2 , NHC(0)NHR n , OH, (O), C(0)OH, N 3 , CN, NH 2 , CF 3 , CF 2 CF 3 , F, CI, Br or I;
  • R 8 at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R 8 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R 12 , OR 12 , SR 12 , S(0)R 12 , S0 2 R 12 , NHR 12 , N(R 12 ) 2 , C(0)R 12 , C(0)NH 2 , C(0)NHR 12 , C(0)N(R 12 ) 2 ,
  • R 9 is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R 9 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected alkoxy, OH, cycloalkyl, aryl, or heterocyclyl;
  • R 10 is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl;
  • R 11 at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl;
  • R 12 at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R 12 alkyl, alkenyl, and alkynyl is optionally substituted with one or more alkoxy;
  • R 3 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , and R 12 are optionally substituted with one, two, three, four, five, or six independently selected R 13 , OR 13 , SR 13 , S(0)R 13 , S0 2 R 13 , C(0)R 13 , CO(0)R 13 , OC(0)R 13 , OC(0)OR 13 , NH 2 , NHR 13 , N(R 13 ) 2 , NHC(0)R 13 , NR 13 C(0)R 13 , NHS(0) 2 R 13 , NR 13 S(0) 2 R 13 , NHC(0)OR 13 , NR 13 C(0)OR 13 , NHC(0)NH 2 , NHC(0)NHR 13 , NHC(0)N(R 13 ) 2 , NR 13 C(0)NHR 13 , NR 13 C(0)N(R 13 ) 2 , C(0)NH 2 , C(0)NHR 13 , C(0)N(R 13 ) 2 , C(0)NH 2
  • R 13 is independently selected alkyl, alkenyl, alkynyl, aryl, tetrahydrofuranyl, pyridazinyl, pyrazinyl, pyrimidinyl, pyridinyl, thieno[3,2-c]pyridinyl, furo[3,2-c]pyridinyl, pyrrolidin-2-onyl, l,l-dioxidotetrahydrothien-3-yl, 1,1- dioxidotetrahydro-2/f-thiopyran-3-yl, dioxanyl, tetrahydropyranyl, piperidinyl, pyrimidinyl, oxazolyl, pyrazolyl, thiazolyl, pyrrolidinyl, pyrrolyl, thienyl, furanyl, morpholinyl, isooxazolyl, cycloalkyl, or cycloalkeny
  • R 14 is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R 14 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected heterocyclyl, alkoxy, NH 2 , S0 2 NH 2 , C(0)H, C(0)OH, OH, (O), CN, N 3 , N0 2 , CF 3 , CF 2 CF 3 , OCF 3 , OCF 2 CF 3 , F, CI, Br or I; wherein each R 14 aryl, heterocyclyl, cycloalkyl, and cycloalkenyl is optionally substituted with one, two, three or four independently selected R 16 , OR 16 , OH, F, CI, Br, or I; wherein the R 16 alkyl is optionally substituted with one, two, three or four independently selected R 16
  • R 15 at each occurrence, is independently selected alkyl; wherein the R 15 alkyl is optionally substituted with one, two, three or four alkoxy;
  • R 16 at each occurrence, is independently selected alkyl, wherein the R 16 alkyl is optionally substituted with one, two, three or four alkoxy;
  • R 2 is unsubstituted alkyl or optionally substituted alkyl;
  • R 2 is C 4 -C 6 -alkyl;
  • X 1 , X 2 , and X 3 are CH; or
  • X 1 and X 3 are CH; and X 2 is N; or
  • X 1 and X 3 are CH; and X 2 is CR 1 ; or
  • X 2 and X 3 are CH; and X 1 is CR 1 ; or
  • X 1 is CH; and X 2 and X 3 are CR 1 ; or
  • X 2 is CH; and X 1 and X 3 are N; or
  • X 2 and X 3 are CH; and X 1 is N; or
  • X 1 is CH; X 2 is N; and X 3 is CR 1 ; or
  • X 1 is N;
  • X 2 is CR 1 ; and
  • X 3 is N;
  • R 1 is R 3 , OR 3 , SR 3 , S(0)R 3 , S0 2 R 3 , C(0)R 3 , C(0)OR 3 , OC(0)R 3 , NHR 3 , N(R 3 ) 2 , C(0)NH 2 , C(0)NHR 3 , C(0)N(R 3 ) 2 , NHC(0)R 3 , NR 3 C(0)R 3 , NHC(0)OR 3 , NR 3 C(0)OR 3 , S0 2 NH 2 , S0 2 NHR 3 , S0 2 N(R 3 ) 2 , NHS0 2 R 3 , NR 3 S0 2 R 3 , NHS0 2 NHR 3 , NHS0 2 N(R 3 ) 2 , NR 3 S0 2 NHR 3 , NR 3 S0 2 N(R 3 ) 2 , C(0)NHS0 2 R 3 , NHS0 2 NHR 3 , F, CI, Br, I, CN, NH 2 , N0 2 , N 3 ,
  • R 3 is independently selected alkyl, alkenyl, alkynyl, aryl, or heterocyclyl; wherein each R 3 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R 6 , OR 6 , SR 6 , S(0)R 6 , S0 2 R 6 , C(0)R 6 , CO(0)R 6 , OC(0)R 6 , OC(0)OR 6 , NH 2 , NHR 6 , N(R 6 ) 2 , NHC(0)R 6 , NR 6 C(0)R 6 , NHS(0) 2 R 6 , NR 6 S(0) 2 R 6 , NHC(0)OR 6 , NR 6 C(0)OR 6 , NHC(0)NH 2 , NHC(0)NHR 6 , NHC(0)N(R 6 ) 2 , NR 6 C(0)N(R 6 ) 2 , NR 6 C(0)N(R 6 ) 2 , C(0)NH 2 , C(0)NHR 6 , C
  • R 5 is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R 9 , OR 9 , SR 9 , S(0)R 9 , S0 2 R 9 , C(0)R 9 , CO(0)R 9 , OC(0)R 9 , OC(0)OR 9 , NH 2 , NHR 9 , N(R 9 ) 2 , NHC(0)R 9 , NR 9 C(0)R 9 , NHS(0) 2 R 9 , NR 9 S(0) 2 R 9 , NHC(0)OR 9 , NR 9 C(0)OR 9 , NHC(0)NH 2 , NHC(0)NHR 9 , NHC(0)N(R 9 ) 2 , NR 9 C(0)NHR 9 , NR 9 C(0)N(R 9 ) 2
  • R 6 at each occurrence, is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R 6 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected R 10 , OR 10 , SR 10 , S(0)R 10 , S0 2 R 10 , NHR 10 , N(R 10 ) 2 , C(0)R 10 , C(0)NH 2 , C(0)NHR 10 , C(O)N(R 10 ) 2 ,
  • NHC(0)R 10 NR 10 C(O)R 10 , NHS0 2 R 10 , NHC(0)OR 10 , S0 2 NH 2 , S0 2 NHR 10 , SO 2 N(R 10 ) 2 , NHC(0)NH 2 , NHC(0)NHR 10 , OH, (O), C(0)OH, N 3 , CN, NH 2 , CF 3 , CF 2 CF 3 , F, CI, Br or I;
  • R 9 is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R 9 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected alkoxy, OH, cycloalkyl, aryl, or heterocyclyl;
  • R 10 is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl;
  • R 3 , R 5 , R 6 , R 9 , and R 10 are optionally substituted with one, two, three, four, five, or six independently selected R 13 , OR 13 , SR 13 , S(0)R 13 , S0 2 R 13 , C(0)R 13 , CO(0)R 13 , OC(0)R 13 , OC(0)OR 13 , NH 2 , NHR 13 , N(R 13 ) 2 , NHC(0)R 13 , NR 13 C(0)R 13 , NHS(0) 2 R 13 , NR 13 S(0) 2 R 13 , NHC(0)OR 13 , NR 13 C(0)OR 13 , NHC(0)NH 2 , NHC(0)NHR 13 , NHC(0)N(R 13 ) 2 , NR 13 C(0)NHR 13 , NR 13 C(0)N(R 13 ) 2 , C(0)NH 2 , C(0)NHR 13 , C(0)N(R 13 ) 2 , C(0)NHOH, C(0)NHOR 13
  • R 13 is independently selected alkyl, alkenyl, alkynyl, aryl, tetrahydrofuranyl, pyridazinyl, pyrazinyl, pyrimidinyl, pyridinyl, thieno[3,2-c]pyridinyl, furo[3,2-c]pyridinyl, pyrrolidin-2-onyl, l,l-dioxidotetrahydrothien-3-yl, 1,1- dioxidotetrahydro-2/f-thiopyran-3-yl, dioxanyl, tetrahydropyranyl, piperidinyl, pyrimidinyl, oxazolyl, pyrazolyl, thiazolyl, pyrrolidinyl, pyrrolyl, thienyl, furanyl, morpholinyl, isooxazolyl, cycloalkyl, or cycloalkeny
  • R 14 is independently selected alkyl, alkenyl, alkynyl, aryl, heterocyclyl, cycloalkyl, or cycloalkenyl; wherein each R 14 alkyl, alkenyl, and alkynyl is optionally substituted with one, two, three or four independently selected heterocyclyl, alkoxy, NH 2 , S0 2 NH 2 , C(0)H, C(0)OH, OH, (O), CN, N 3 , N0 2 , CF 3 , CF 2 CF 3 , OCF 3 , OCF 2 CF 3 , F, CI, Br or I; wherein each R 14 aryl, heterocyclyl, cycloalkyl, and cycloalkenyl is optionally substituted with one, two, three or four independently selected R 16 , OR 16 , OH, F, CI, Br, or I;
  • R 15 at each occurrence, is independently selected alkyl, wherein the R 15 alkyl is optionally substituted with one, two, three or four alkoxy;
  • R 16 at each occurrence, is independently selected alkyl, wherein the R 16 alkyl is optionally substituted with one, two, three or four alkoxy;
  • Another embodiment pertains to compounds having Formula (Ic) or Formula (Vc), and pharmaceutically acceptable salts thereof; wherein X 1 , X 2 , and X 3 are CH, or X 1 and X 3 are CH; and X 2 is CR 1 ; or X 2 and X 3 are CH; and X 1 is CR 1 ; or X 1 is CH; and X 2 and X 3 are CR 1 .
  • Another embodiment pertains to compounds having Formula (Ic) or Formula (Vc), and pharmaceutically acceptable salts thereof; wherein X 1 and X 3 are CH; and X 2 is N; or X 2 is CH; and X 1 and X 3 are N; X 2 and X 3 are CH; and X 1 is N; or X 1 is CH; X 2 is N; and X 3 is CR 1 ; or X 1 is CR 1 ; X 2 is N; and X 3 is CH; or X 1 is N; X 2 is CR 1 ; and X 3 is CH; or X 1 is N; X 2 is CR 1 ; and X 3 is CH; or X 1 is N; X 2 is CR 1 ; and X 3 is N.
  • Another embodiment pertains to compounds having Formula (Ic), and
  • R 2 is phenyl which is substituted at the para position with R 5 ; and R 5 is phthalazin-l(2H)-onyl, isoquinolinyl, isoquinolin-l(2H)-onyl, 5,6,7, 8-tetrahydrophthalazin- 1 (2H)-onyl, 5-fluorophthalazin- 1 (2H)-onyl, (Z)-3H- benzo[d][l,2]diazepin-4(5H)-onyl, 5-(trifluoromethyl)phthalazin-l(2H)-onyl, pyrrolo[l,2- d][l,2,4]triazin-l(2H)-one, or isoindolin-l-onyl.
  • Still another embodiment pertains to compounds of Formula (Ic), which are

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Epidemiology (AREA)
  • Neurology (AREA)
  • Biomedical Technology (AREA)
  • Neurosurgery (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Immunology (AREA)
  • Diabetes (AREA)
  • Oncology (AREA)
  • Cardiology (AREA)
  • Rheumatology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Pulmonology (AREA)
  • Endocrinology (AREA)
  • Urology & Nephrology (AREA)
  • Pain & Pain Management (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Hematology (AREA)
  • Virology (AREA)
  • Psychiatry (AREA)
  • Communicable Diseases (AREA)
  • Ophthalmology & Optometry (AREA)
  • Obesity (AREA)
  • Dermatology (AREA)
  • Reproductive Health (AREA)
  • Hospice & Palliative Care (AREA)
PCT/US2011/060425 2010-11-15 2011-11-11 Nampt and rock inhibitors Ceased WO2012067965A1 (en)

Priority Applications (13)

Application Number Priority Date Filing Date Title
CN2011800647158A CN103313968A (zh) 2010-11-15 2011-11-11 Nampt和rock抑制剂
PH1/2013/500975A PH12013500975A1 (en) 2010-11-15 2011-11-11 Nampt and rock inhibitors
AU2011329233A AU2011329233A1 (en) 2010-11-15 2011-11-11 NAMPT and ROCK inhibitors
BR112013012078A BR112013012078A2 (pt) 2010-11-15 2011-11-11 inibidores de nampt e rock
CA2816594A CA2816594A1 (en) 2010-11-15 2011-11-11 Nampt and rock inhibitors
SG2013037643A SG190819A1 (en) 2010-11-15 2011-11-11 Nampt and rock inhibitors
RU2013126657/04A RU2013126657A (ru) 2010-11-15 2011-11-11 Ингибиторы nampt и rock
EP11787996.5A EP2640698A1 (en) 2010-11-15 2011-11-11 Nampt and rock inhibitors
JP2013538943A JP6117104B2 (ja) 2010-11-15 2011-11-11 Ｎａｍｐｔおよびｒｏｃｋ阻害薬
MX2013005454A MX2013005454A (es) 2010-11-15 2011-11-11 Inhibidores de nampt y rock.
KR1020137015348A KR20140009251A (ko) 2010-11-15 2011-11-11 Ｎａｍｐｔ 및 ｒｏｃｋ 억제제
IL225862A IL225862A0 (en) 2010-11-15 2013-04-21 Inhibitors for Nampt and Rock
AU2017200079A AU2017200079A1 (en) 2010-11-15 2017-01-06 NAMPT and ROCK Inhibitors

Applications Claiming Priority (6)

Application Number Priority Date Filing Date Title
US41372210P 2010-11-15 2010-11-15
US61/413,722 2010-11-15
US201161474015P 2011-04-11 2011-04-11
US61/474,015 2011-04-11
US201161525405P 2011-08-19 2011-08-19
US61/525,405 2011-08-19

Publications (1)

Publication Number Publication Date
WO2012067965A1 true WO2012067965A1 (en) 2012-05-24

Family

ID=45034200

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2011/060425 Ceased WO2012067965A1 (en) 2010-11-15 2011-11-11 Nampt and rock inhibitors

Country Status (24)

Country Link
US (2) US9302989B2 (enExample)
EP (1) EP2640698A1 (enExample)
JP (2) JP6117104B2 (enExample)
KR (1) KR20140009251A (enExample)
CN (1) CN103313968A (enExample)
AR (1) AR083855A1 (enExample)
AU (2) AU2011329233A1 (enExample)
BR (1) BR112013012078A2 (enExample)
CA (1) CA2816594A1 (enExample)
CL (1) CL2013001340A1 (enExample)
CO (1) CO6761389A2 (enExample)
CR (1) CR20130267A (enExample)
DO (1) DOP2013000106A (enExample)
EC (1) ECSP13012993A (enExample)
GT (1) GT201300124A (enExample)
IL (1) IL225862A0 (enExample)
MX (1) MX2013005454A (enExample)
PE (1) PE20140913A1 (enExample)
PH (1) PH12013500975A1 (enExample)
RU (1) RU2013126657A (enExample)
SG (3) SG10202010119TA (enExample)
TW (1) TW201238950A (enExample)
UY (1) UY33726A (enExample)
WO (1) WO2012067965A1 (enExample)

Cited By (48)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2013067710A1 (en) 2011-11-11 2013-05-16 Abbott Laboratories Nampt inhibitors
JP2013234180A (ja) * 2012-04-13 2013-11-21 Mitsubishi Tanabe Pharma Corp アミド誘導体の医薬用途
JP2013544872A (ja) * 2010-12-13 2013-12-19 カソリック ユニヴェルシテイト ルーヴェン，ケー．ユー． ルーヴェン アール アンド ディー 神経変性疾患の治療のための新規化合物
JP2015503594A (ja) * 2012-01-09 2015-02-02 エックス−アールエックス，インコーポレーテッド キナーゼ阻害活性を有するトリプトリン誘導体及びその使用
WO2014141035A3 (en) * 2013-03-11 2015-04-09 Aurigene Discovery Technologies Limited Fused heterocyclyl derivatives as nampt inhibitors
US9132129B2 (en) 2010-11-15 2015-09-15 Katholieke Universiteit Leuven Antiviral compounds
JP2015528435A (ja) * 2012-08-10 2015-09-28 エフ．ホフマン−ラ ロシュ アーゲーＦ． Ｈｏｆｆｍａｎｎ−Ｌａ Ｒｏｃｈｅ Ａｋｔｉｅｎｇｅｓｅｌｌｓｃｈａｆｔ ピラゾールカルボキサミド化合物、組成物及び使用方法
US9499563B2 (en) 2009-05-15 2016-11-22 Katholieke Universiteit Leuven Thieno [2, 3-B] pyridine derivatives as viral replication inhibitors
US9555039B2 (en) 2011-05-09 2017-01-31 Forma Tm, Llc. Piperidine derivatives and compositions for the inhibition of nicotinamide phosphoribosyltransferase (NAMPT)
US9673344B2 (en) * 2014-08-07 2017-06-06 Lumeta, Llc Apparatus and method for photovoltaic module with tapered edge seal
WO2018086703A1 (en) 2016-11-11 2018-05-17 Bayer Pharma Aktiengesellschaft Dihydropyridazinones substituted with phenylureas
JP2019073521A (ja) * 2013-01-18 2019-05-16 ブリストル−マイヤーズ スクイブ カンパニーＢｒｉｓｔｏｌ−Ｍｙｅｒｓ Ｓｑｕｉｂｂ Ｃｏｍｐａｎｙ Ｒｏｃｋ阻害剤としてのフタラジノンおよびイソキノリノン
WO2019149637A1 (en) 2018-01-31 2019-08-08 Bayer Aktiengesellschaft Antibody drug conjugates (adcs) with nampt inhibitors
RU2732297C2 (ru) * 2018-11-14 2020-09-15 Общество с ограниченной ответственностью "Гурус БиоФарм" Производные нестероидных противовоспалительных средств
WO2021013693A1 (en) 2019-07-23 2021-01-28 Bayer Pharma Aktiengesellschaft Antibody drug conjugates (adcs) with nampt inhibitors
US20210171513A1 (en) * 2016-03-17 2021-06-10 Checkmate Therapeutics Inc. Novel compound for inhibiting nicotinamide phosphoribosyltransferase and composition containing same
WO2022053651A2 (en) 2020-09-10 2022-03-17 Precirix N.V. Antibody fragment against fap
EP2903618B1 (en) 2012-10-05 2022-06-01 Kadmon Corporation, LLC Rho kinase inhibitors
US20230050653A1 (en) * 2019-11-15 2023-02-16 Wuhan Ll Science And Technology Development Co., Ltd. Rock inhibitor and preparation method therefor and use thereof
US11638762B2 (en) 2016-10-18 2023-05-02 Seagen Inc. Targeted delivery of nicotinamide adenine dinucleotide salvage pathway inhibitors
WO2023203135A1 (en) 2022-04-22 2023-10-26 Precirix N.V. Improved radiolabelled antibody
WO2023213801A1 (en) 2022-05-02 2023-11-09 Precirix N.V. Pre-targeting
US11905284B2 (en) 2016-07-01 2024-02-20 Pfizer Inc. 5,7-dihydro-pyrrolo-pyridine derivatives
US11931414B2 (en) 2017-04-27 2024-03-19 Seagen Inc. Quaternized nicotinamide adenine dinucleotide salvage pathway inhibitor conjugates
WO2024229406A1 (en) 2023-05-04 2024-11-07 Revolution Medicines, Inc. Combination therapy for a ras related disease or disorder
WO2025034702A1 (en) 2023-08-07 2025-02-13 Revolution Medicines, Inc. Rmc-6291 for use in the treatment of ras protein-related disease or disorder
WO2025072437A1 (en) * 2023-09-26 2025-04-03 Alphina Therapeutics, Inc. Heteroaryl compounds and their use in treating medical conditions
WO2025080946A2 (en) 2023-10-12 2025-04-17 Revolution Medicines, Inc. Ras inhibitors
WO2025171296A1 (en) 2024-02-09 2025-08-14 Revolution Medicines, Inc. Ras inhibitors
WO2025240847A1 (en) 2024-05-17 2025-11-20 Revolution Medicines, Inc. Ras inhibitors
WO2025255438A1 (en) 2024-06-07 2025-12-11 Revolution Medicines, Inc. Methods of treating a ras protein-related disease or disorder
WO2025265060A1 (en) 2024-06-21 2025-12-26 Revolution Medicines, Inc. Therapeutic compositions and methods for managing treatment-related effects
WO2026006747A1 (en) 2024-06-28 2026-01-02 Revolution Medicines, Inc. Ras inhibitors
WO2026015790A1 (en) 2024-07-12 2026-01-15 Revolution Medicines, Inc. Methods of treating a ras related disease or disorder
WO2026015801A1 (en) 2024-07-12 2026-01-15 Revolution Medicines, Inc. Methods of treating a ras related disease or disorder
WO2026015796A1 (en) 2024-07-12 2026-01-15 Revolution Medicines, Inc. Methods of treating a ras related disease or disorder
WO2026015825A1 (en) 2024-07-12 2026-01-15 Revolution Medicines, Inc. Use of ras inhibitor for treating pancreatic cancer
WO2026050446A1 (en) 2024-08-29 2026-03-05 Revolution Medicines, Inc. Ras inhibitors
WO2026072904A2 (en) 2024-09-26 2026-04-02 Revolution Medicines, Inc. Compositions and methods for treating lung cancer
WO2026090116A2 (en) 2024-10-21 2026-04-30 Revolution Medicines, Inc. Ras inhibitors
WO2026090127A1 (en) 2024-10-22 2026-04-30 Revolution Medicines, Inc. Methods of treating a ras protein-related disease or disorder
WO2026090245A1 (en) 2024-10-22 2026-04-30 Revolution Medicines, Inc. Use of ras inhibitors for treating cancer
WO2026106912A1 (en) 2024-11-12 2026-05-21 Revolution Medicines, Inc. Ras inhibitors
WO2026112260A1 (en) 2024-11-21 2026-05-28 Revolution Medicines, Inc. Ras inhibitors
US12649729B2 (en) 2020-12-21 2026-06-09 Cytokinetics, Inc. Pyrazole derivatives useful as NAMPT modulators
WO2026122764A2 (en) 2024-12-06 2026-06-11 Revolution Medicines, Inc. Ras inhibitors
WO2026128688A2 (en) 2024-12-13 2026-06-18 Revolution Medicines, Inc. Ras inhibitors
WO2026161839A1 (en) 2025-01-27 2026-07-30 Revolution Medicines, Inc. Ras inhibitors

Families Citing this family (33)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
SG10202010119TA (en) * 2010-11-15 2020-11-27 Abbvie Inc NAMPT And Rock Inhibitors
US8569283B2 (en) * 2011-09-01 2013-10-29 Valentina Molteni Compounds and compositions as c-Kit kinase inhibitors
US9199981B2 (en) * 2011-09-01 2015-12-01 Novartis Ag Compounds and compositions as C-kit kinase inhibitors
WO2014074715A1 (en) * 2012-11-07 2014-05-15 Genentech, Inc. Cyclopropyl amide derivatives
MX364895B (es) 2013-03-13 2019-05-10 Forma Therapeutics Inc Nuevos compuestos y composiciones para la inhibicion de fasn.
WO2015142001A2 (ko) * 2014-03-21 2015-09-24 충남대학교산학협력단 강심 활성을 갖는 화합물 및 이를 함유하는 심부전 예방 또는 치료용 약학적 조성물
US9902702B2 (en) 2014-07-15 2018-02-27 Bristol-Myers Squibb Company Spirocycloheptanes as inhibitors of rock
EP3172205A1 (en) 2014-07-23 2017-05-31 Aurigene Discovery Technologies Limited 4,5-dihydroisoxazole derivatives as nampt inhibitors
CN107108581B (zh) 2014-08-21 2020-06-23 百时美施贵宝公司 作为强效rock抑制剂的回接苯甲酰胺衍生物
EP3185860A4 (en) 2014-08-29 2018-08-29 The Board of Regents of the University of Texas System Novel capsazepine analogs for the treatment of cancer and other proliferative diseases
US20160108406A1 (en) * 2014-10-08 2016-04-21 University Of Iowa Research Foundation Method of regulating cftr expression and processing
CN106928252B (zh) * 2015-12-31 2019-09-27 成都先导药物开发股份有限公司 一种抑制rock的化合物及其制备方法与应用
TWI730032B (zh) 2016-01-13 2021-06-11 美商必治妥美雅史谷比公司 作為ｒｏｃｋ抑制劑之螺庚烷水楊酸醯胺及相關化合物
WO2017170830A1 (ja) * 2016-03-31 2017-10-05 武田薬品工業株式会社 複素環化合物
JP7155102B2 (ja) 2016-07-07 2022-10-18 ブリストル－マイヤーズ スクイブ カンパニー Ｒｏｃｋ阻害剤としてのスピロ縮合環尿素
WO2018094362A1 (en) * 2016-11-21 2018-05-24 Translational Drug Development, Llc Heterocyclic compounds as kinase inhibitors
EP3610018B1 (en) 2017-04-14 2023-06-07 Arizona Board of Regents on Behalf of the University of Arizona Compositions and methods for treating pulmonary fibrosis
US10975167B2 (en) 2017-04-14 2021-04-13 Arizona Board Of Regents On Behalf Of The University Of Arizona Method to reduce pulmonary arterial hypertension by administering inhibitors of nicotinamide phosphoribotransferase
FI3642202T3 (fi) 2017-06-22 2023-03-01 Dihydro-pyrrolo-pyridiinijohdannaisia
CN107118157A (zh) * 2017-06-23 2017-09-01 南京大学 一类含吡唑骨架的二苯基脲类衍生物抗肿瘤化合物的设计与合成
WO2019014300A1 (en) 2017-07-12 2019-01-17 Bristol-Myers Squibb Company PHENYLACETAMIDES AS ROCK INHIBITORS
JP7234201B2 (ja) 2017-07-12 2023-03-07 ブリストル－マイヤーズ スクイブ カンパニー 心不全の治療のためのｒｏｃｋの５員アミノヘテロ環および５，６－または６，６員二環式アミノヘテロ環の阻害剤
CN110914257B (zh) 2017-07-12 2023-05-26 百时美施贵宝公司 作为rock抑制剂的螺庚基乙内酰脲
TW201908293A (zh) 2017-07-12 2019-03-01 美商必治妥美雅史谷比公司 作為rock抑制劑之5員及雙環雜環醯胺
US11319295B2 (en) * 2017-10-09 2022-05-03 Merck Sharp & Dohme Corp. Substituted phenyloxetane and phenyltetrahydrofuran compounds as indoleamine 2,3-dioxygenase (IDO) inhibitors
HU231223B1 (hu) * 2018-09-28 2022-01-28 Richter Gedeon Nyrt. GABAA A5 receptor modulátor hatású biciklusos vegyületek
CN113382633A (zh) 2018-10-29 2021-09-10 福马治疗股份有限公司 (4-(2-氟-4-(1-甲基-1H-苯并[d]咪唑-5-基)苯甲酰基)哌嗪-1-基)(1-羟基环丙基)甲酮的固体形式
KR20230038697A (ko) * 2020-07-14 2023-03-21 우한 엘엘 사이언스 앤드 테크놀로지 디벨롭먼트 컴퍼니, 리미티드 Rock 억제제 및 이의 제조 방법과 용도
WO2023245470A1 (zh) * 2022-06-22 2023-12-28 南方医科大学珠江医院 Mdp类似物在制备用于治疗炎症性肠病的药物中的用途
IL319081A (en) * 2022-09-23 2025-04-01 Sironax Ltd NAMPT modulators, their preparations and uses
WO2025168575A1 (en) 2024-02-05 2025-08-14 Institut National de la Santé et de la Recherche Médicale Inhibitors of nad biosynthesis for the treatment of dengue virus infections
US20260183268A1 (en) * 2024-12-27 2026-07-02 Alphina Therapeutics, Inc. Heteroaryl Compounds and Their Use in Treating Medical Conditions
WO2026165047A1 (en) * 2025-01-29 2026-08-06 Rapport Therapeutics, Inc. Nicotinic acetylcholine receptor modulators and uses therein

Citations (28)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3535323A (en) * 1964-03-18 1970-10-20 Dresden Arzneimittel Amides of isoindoline-2-carboxylic acid
WO1995007271A1 (en) 1993-09-09 1995-03-16 The Upjohn Company Substituted oxazine and thiazine oxazolidinone antimicrobials
WO1997010223A1 (en) 1995-09-15 1997-03-20 Pharmacia & Upjohn Company Aminoaryl oxazolidinone n-oxides
US20050084506A1 (en) * 2003-08-06 2005-04-21 Catherine Tachdjian Novel flavors, flavor modifiers, tastants, taste enhancers, umami or sweet tastants, and/or enhancers and use thereof
WO2005099353A2 (en) 2004-04-19 2005-10-27 Symed Labs Limited A novel process for the preparation of linezolid and related compounds
WO2006008754A1 (en) 2004-07-20 2006-01-26 Symed Labs Limited Novel intermediates for linezolid and related compounds
WO2007026920A2 (en) * 2005-09-02 2007-03-08 Astellas Pharma Inc. Amide derivatives as rock inhibitors
WO2007121124A2 (en) * 2006-04-11 2007-10-25 Novartis Ag Hcv inhibitors comprising beta amino acids and their uses
WO2007137955A1 (en) * 2006-05-30 2007-12-06 F. Hoffmann-La Roche Ag Piperidinyl pyrimidine derivatives
WO2008086047A1 (en) * 2007-01-03 2008-07-17 Boehringer Ingelheim International Gmbh Rho kinase inhibitors
US20090082471A1 (en) 2007-09-26 2009-03-26 Protia, Llc Deuterium-enriched fingolimod
US7511013B2 (en) 2004-09-29 2009-03-31 Amr Technology, Inc. Cyclosporin analogues and their pharmaceutical uses
US20090088416A1 (en) 2007-09-26 2009-04-02 Protia, Llc Deuterium-enriched lapaquistat
US7514068B2 (en) 2005-09-14 2009-04-07 Concert Pharmaceuticals Inc. Biphenyl-pyrazolecarboxamide compounds
US20090093422A1 (en) 2006-10-23 2009-04-09 Roger Tung Oxazolidinone derivatives and methods of use
US7521421B2 (en) 1997-10-08 2009-04-21 Isotechnika Inc. Deuterated cyclosporine analogs and methods of making the same
US20090105147A1 (en) 2007-10-18 2009-04-23 Concert Pharmaceuticals Inc. Deuterated etravirine
US20090105307A1 (en) 2007-02-15 2009-04-23 Guido Galley 2-aminooxazolines as taar1 ligands
US20090105338A1 (en) 2007-10-18 2009-04-23 Protia, Llc Deuterium-enriched gabexate mesylate
US20090111840A1 (en) 2005-05-31 2009-04-30 Peter Herold Heterocyclic spiro-compounds as aldosterone synthase inhibitors
US7528131B2 (en) 2007-04-19 2009-05-05 Concert Pharmaceuticals Inc. Substituted morpholinyl compounds
US20090118238A1 (en) 2007-09-17 2009-05-07 Protia, Llc Deuterium-enriched alendronate
US7531685B2 (en) 2007-06-01 2009-05-12 Protia, Llc Deuterium-enriched oxybutynin
US7534814B2 (en) 1999-07-30 2009-05-19 Nabriva Therapeutics Ag Mutilin derivatives and their use as antibacterials
US20090131485A1 (en) 2007-09-10 2009-05-21 Concert Pharmaceuticals, Inc. Deuterated pirfenidone
US20090131363A1 (en) 2007-10-26 2009-05-21 Harbeson Scott L Deuterated darunavir
US20090137457A1 (en) 2007-10-02 2009-05-28 Concert Pharmaceuticals, Inc. Pyrimidinedione derivatives
WO2010066709A1 (en) * 2008-12-09 2010-06-17 Topotarget A/S Novel pyridinyl acrylamide derivatives

Family Cites Families (66)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CH433312A (de) * 1963-10-18 1967-04-15 Dresden Arzneimittel Verfahren zur Herstellung therapeutisch wertvoller Amide der Isoindolin-2-carbonsäure
CH443312A (fr) * 1963-10-29 1967-09-15 Ajinomoto Kk Procédé de préparation du 1-N-oxyde d'hypoxanthine et du 1-N-oxyde d'inosine substituée ou non, et utilisation des produits obtenus par ce procédé poutilisation des produits obtenus par ce procédé pour la préparation de la 2,6-dichloro-purine et 9-B-D-ribofuranosyl purine substitua ée ou non
BE648616A (fr) 1964-05-29 1964-09-16 Dresden Arzneimittel Amides d'acides isoindolin-2-carboxyliques et leur procédé de préparation.
US4419360A (en) 1979-10-31 1983-12-06 Rohm And Haas Company Arthropod repellants
SI9011830B (sl) 1990-09-27 1999-12-31 Univerza V Ljubljani, Fakulteta Za Farmacijo Novi N-acildipeptidi, postopki za njihovo pripravo in farmacevtski pripravki, ki jih vsebujejo
US5726197A (en) * 1992-11-02 1998-03-10 Syntex (U.S.A.) Inc. Isoindolinyl derivatives
AU4534696A (en) 1995-02-09 1996-08-27 Novo Nordisk A/S Compounds with growth hormone releasing properties
FR2733750B1 (fr) 1995-05-03 1997-06-13 Synthelabo Derives de l'acide gamma-oxo-alpha-(phenylmethyl)-5,6- dihydro-4h-thieno(3,4-c)pyrrole-5-butanoique, leur preparation et leur application en therapeutique
DE19624659A1 (de) 1996-06-20 1998-01-08 Klinge Co Chem Pharm Fab Neue Pyridylalken- und Pyridylalkinsäureamide
DE19624668A1 (de) 1996-06-20 1998-02-19 Klinge Co Chem Pharm Fab Verwendung von Pyridylalkan-, Pyridylalken- bzw. Pyridylalkinsäureamiden
KR20010101675A (ko) 1999-01-26 2001-11-14 우에노 도시오 2ｈ-프탈라진-1-온 유도체 및 그 유도체를 유효 성분으로하는 약제
AU2002235277A1 (en) * 2000-10-23 2002-05-06 Smith Kline Beecham Corporation Compounds and methods
WO2002081443A1 (en) 2001-04-09 2002-10-17 Chiron Corporation Novel guanidino compounds
US6649606B1 (en) 2001-11-09 2003-11-18 Bristol-Myers Squibb Co. Tetrahydroisoquinoline analogs as modulators of chemokine receptor activity
JP2003277340A (ja) 2002-03-22 2003-10-02 Toray Ind Inc 接着分子阻害剤及び新規アミノ酸誘導体
EP1348434A1 (en) 2002-03-27 2003-10-01 Fujisawa Deutschland GmbH Use of pyridyl amides as inhibitors of angiogenesis
AR042064A1 (es) 2002-11-19 2005-06-08 Takeda Pharmaceutical Compuestos de amina con actividad inhibidora de la union al receptor de somastotina
AU2004207731B2 (en) 2003-01-31 2009-08-13 Sanwa Kagaku Kenkyusho Co., Ltd. Compound inhibiting dipeptidyl peptidase iv
GB0310865D0 (en) 2003-05-12 2003-06-18 Black James Foundation Gastrin and cholecystokinin receptor ligands
WO2004101533A1 (en) 2003-05-12 2004-11-25 Janssen Pharmaceutica, N.V. 1, 3, 4-benzotriazepin-2-one salts and their use as cck receptor ligands
EP1660454A1 (en) 2003-07-07 2006-05-31 Vernalis (R&D) Limited Azacyclic compounds as inhibitors of sensory neurone specific channels
CA2534428A1 (en) 2003-08-13 2005-03-03 Paul A. Tempest Melanin concentrating hormone receptor antagonists
WO2005037214A2 (en) * 2003-10-14 2005-04-28 Intermune, Inc. Macrocyclic carboxylic acids and acylsulfonamides as inhibitors of hcv replication
WO2005051945A1 (en) 2003-11-20 2005-06-09 Eli Lilly And Company Heterocyclic compounds as modulators of peroxisome proliferator activated receptors, useful for the treatment and/or prevention of disorders modulated by a ppar
GB0329214D0 (en) * 2003-12-17 2004-01-21 Glaxo Group Ltd Novel compounds
EP1749007A2 (en) 2004-03-30 2007-02-07 Intermune, Inc. Macrocyclic compounds as inhibitors of viral replication
US20060045953A1 (en) 2004-08-06 2006-03-02 Catherine Tachdjian Aromatic amides and ureas and their uses as sweet and/or umami flavor modifiers, tastants and taste enhancers
ATE412636T1 (de) 2004-12-16 2008-11-15 Hoffmann La Roche Piperazinylpyridinderivate als mittel gegen adipositas
MX2007008008A (es) * 2004-12-30 2007-11-12 Astex Therapeutics Ltd Compuestos de pirazol que modulan la actividad de las cinasas cdk, gsk y aurora.
MX2007013049A (es) * 2005-04-19 2008-01-11 Bayer Pharmaceuticals Corp Preparacion y uso de derivados de aril alquil acido para el tratamiento de la obesidad.
WO2007011290A1 (en) 2005-07-18 2007-01-25 Respiratorius Ab Bronchorelaxing agents based on indol- and isoquinoline derivatives
BRPI0618523A2 (pt) 2005-11-11 2011-09-06 Hoffmann La Roche compostos de aminas cìclicas fundidas carbocìclicas, composições farmacêuticas e usos dos mesmos
WO2007076055A2 (en) 2005-12-22 2007-07-05 Entremed, Inc. Compositions and methods comprising proteinase activated receptor antagonists
JP4047365B2 (ja) * 2006-01-11 2008-02-13 生化学工業株式会社 シクロアルカンカルボキサミド誘導体及びその製造方法
JP4012239B2 (ja) * 2006-01-11 2007-11-21 生化学工業株式会社 オキサゾロン誘導体
BRPI0707916A2 (pt) * 2006-01-13 2011-05-17 Hoffmann La Roche compostos, processo para a sua manufatura, composições farmacêuticas que os compreendem e uso destes compostos
KR101062513B1 (ko) * 2006-02-17 2011-09-06 에프. 호프만-라 로슈 아게 5ｈｔ2/ｄ3 조절제로서의 벤조일-피페리딘 유도체
US8148417B2 (en) 2006-05-18 2012-04-03 Arena Pharmaceuticals, Inc. Primary amines and derivatives thereof as modulators of the 5-HT2A serotonin receptor useful for the treatment of disorders related thereto
KR101077295B1 (ko) 2006-05-18 2011-10-26 에프. 호프만-라 로슈 아게 아데노신 ａ2ｂ 수용체 길항물질로서의 티아졸로-피라미딘/피리딘 우레아 유도체
CN101547890A (zh) 2006-08-29 2009-09-30 知识产权和技术办公室 通过用螺硼酸酯进行硼烷还原肟醚而催化不对称合成伯胺
WO2008026018A1 (en) 2006-09-01 2008-03-06 Topotarget Switzerland Sa New method for the treatment of inflammatory diseases
US8338437B2 (en) 2007-02-28 2012-12-25 Methylgene Inc. Amines as small molecule inhibitors
GB0705882D0 (en) 2007-03-27 2007-05-02 Glaxo Group Ltd Novel compounds
WO2008130319A2 (en) 2007-04-23 2008-10-30 Astrazeneca Ab Novel n-tetrahydronaphtalene or n-chromane carboxamide derivatives for the treatment of pain
WO2009017838A2 (en) * 2007-08-01 2009-02-05 Exelixis, Inc. Combinations of jak-2 inhibitors and other agents
KR20100082349A (ko) * 2007-10-17 2010-07-16 사노피-아벤티스 치환된 ｎ－페닐-비피롤리딘 우레아 및 이의 치료적 용도
GB0721332D0 (en) * 2007-10-31 2007-12-12 Motac Neuroscience Ltd Medicaments
EP2067771A1 (en) 2007-12-03 2009-06-10 EPFL Ecole Polytechnique Fédérale de Lausanne Derivatives of Dihydroxypyrrolidine as Anti-Cancer Compounds
KR20100097725A (ko) 2007-12-05 2010-09-03 아스트라제네카 아베 신규 화합물 ⅲ
WO2009086835A1 (en) 2008-01-11 2009-07-16 Topotarget A/S Novel cyanoguanidines
JP2011088826A (ja) * 2008-01-31 2011-05-06 Astellas Pharma Inc 芳香族カルボン酸化合物
EP2098231A1 (en) 2008-03-05 2009-09-09 Topotarget Switzerland SA Use of NAD formation inhibitors for the treatment of ischemia-reperfusion injury
WO2009118712A2 (en) 2008-03-27 2009-10-01 Ecole Polytechnique Federale De Lausanne (Epfl) Novel dihydroxypyrrolidine derivatives as anti-cancer agents
MX2010014310A (es) 2008-06-24 2011-02-15 Topotarget As Derivados de acido escuarico como inhibidores de la nicotinamida.
CN102186822A (zh) 2008-08-29 2011-09-14 顶标公司 新脲和硫脲衍生物
US20110318266A1 (en) 2008-09-16 2011-12-29 Mccauley John A Phthalimide derivative metabotropic glutamate r4 ligands
CA2739491A1 (en) 2008-10-16 2010-04-22 Schering Corporation Azine derivatives and methods of use thereof
WO2010057101A2 (en) * 2008-11-17 2010-05-20 Schering Corporation Compounds useful as hiv blockers
TW201030007A (en) 2009-02-06 2010-08-16 Gruenenthal Gmbh Substituted spiro-amides as b1r modulators
CA2759264A1 (en) 2009-04-21 2010-10-28 Astellas Pharma Inc. Diacylethylenediamine compound
WO2011006803A1 (en) 2009-07-14 2011-01-20 Nerviano Medical Sciences S.R.L. 3-0x0-2, 3, -dihydro-lh-isoindole-4-carboxamides with selective parp-1 inhibition
BR112012021806A2 (pt) 2010-03-01 2015-09-08 Myrexis Inc compostos e seus usos terapêusticos.
AR082886A1 (es) 2010-09-03 2013-01-16 Forma Therapeutics Inc Compuestos y composiciones farmaceuticas que los contienen
CN106986856A (zh) 2010-09-03 2017-07-28 福马Tm有限责任公司 作为用于治疗疾病诸如癌症的nampt抑制剂的4‑{[(吡啶‑3‑基‑甲基)氨基羰基]氨基}苯‑砜衍生物
AR082885A1 (es) 2010-09-03 2013-01-16 Genentech Inc Compuestos y composiciones para la inhibicion de nampt
SG10202010119TA (en) * 2010-11-15 2020-11-27 Abbvie Inc NAMPT And Rock Inhibitors

Patent Citations (29)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3535323A (en) * 1964-03-18 1970-10-20 Dresden Arzneimittel Amides of isoindoline-2-carboxylic acid
WO1995007271A1 (en) 1993-09-09 1995-03-16 The Upjohn Company Substituted oxazine and thiazine oxazolidinone antimicrobials
WO1997010223A1 (en) 1995-09-15 1997-03-20 Pharmacia & Upjohn Company Aminoaryl oxazolidinone n-oxides
US7538189B2 (en) 1997-10-08 2009-05-26 Isotechnika Inc. Methods of making deuterated cyclosporin analogs
US7521421B2 (en) 1997-10-08 2009-04-21 Isotechnika Inc. Deuterated cyclosporine analogs and methods of making the same
US7534814B2 (en) 1999-07-30 2009-05-19 Nabriva Therapeutics Ag Mutilin derivatives and their use as antibacterials
US20050084506A1 (en) * 2003-08-06 2005-04-21 Catherine Tachdjian Novel flavors, flavor modifiers, tastants, taste enhancers, umami or sweet tastants, and/or enhancers and use thereof
WO2005099353A2 (en) 2004-04-19 2005-10-27 Symed Labs Limited A novel process for the preparation of linezolid and related compounds
WO2006008754A1 (en) 2004-07-20 2006-01-26 Symed Labs Limited Novel intermediates for linezolid and related compounds
US7511013B2 (en) 2004-09-29 2009-03-31 Amr Technology, Inc. Cyclosporin analogues and their pharmaceutical uses
US20090111840A1 (en) 2005-05-31 2009-04-30 Peter Herold Heterocyclic spiro-compounds as aldosterone synthase inhibitors
WO2007026920A2 (en) * 2005-09-02 2007-03-08 Astellas Pharma Inc. Amide derivatives as rock inhibitors
US7514068B2 (en) 2005-09-14 2009-04-07 Concert Pharmaceuticals Inc. Biphenyl-pyrazolecarboxamide compounds
WO2007121124A2 (en) * 2006-04-11 2007-10-25 Novartis Ag Hcv inhibitors comprising beta amino acids and their uses
WO2007137955A1 (en) * 2006-05-30 2007-12-06 F. Hoffmann-La Roche Ag Piperidinyl pyrimidine derivatives
US20090093422A1 (en) 2006-10-23 2009-04-09 Roger Tung Oxazolidinone derivatives and methods of use
WO2008086047A1 (en) * 2007-01-03 2008-07-17 Boehringer Ingelheim International Gmbh Rho kinase inhibitors
US20090105307A1 (en) 2007-02-15 2009-04-23 Guido Galley 2-aminooxazolines as taar1 ligands
US7528131B2 (en) 2007-04-19 2009-05-05 Concert Pharmaceuticals Inc. Substituted morpholinyl compounds
US7531685B2 (en) 2007-06-01 2009-05-12 Protia, Llc Deuterium-enriched oxybutynin
US20090131485A1 (en) 2007-09-10 2009-05-21 Concert Pharmaceuticals, Inc. Deuterated pirfenidone
US20090118238A1 (en) 2007-09-17 2009-05-07 Protia, Llc Deuterium-enriched alendronate
US20090088416A1 (en) 2007-09-26 2009-04-02 Protia, Llc Deuterium-enriched lapaquistat
US20090082471A1 (en) 2007-09-26 2009-03-26 Protia, Llc Deuterium-enriched fingolimod
US20090137457A1 (en) 2007-10-02 2009-05-28 Concert Pharmaceuticals, Inc. Pyrimidinedione derivatives
US20090105147A1 (en) 2007-10-18 2009-04-23 Concert Pharmaceuticals Inc. Deuterated etravirine
US20090105338A1 (en) 2007-10-18 2009-04-23 Protia, Llc Deuterium-enriched gabexate mesylate
US20090131363A1 (en) 2007-10-26 2009-05-21 Harbeson Scott L Deuterated darunavir
WO2010066709A1 (en) * 2008-12-09 2010-06-17 Topotarget A/S Novel pyridinyl acrylamide derivatives

Non-Patent Citations (23)

* Cited by examiner, † Cited by third party
Title
ADYA, R., DIABETES CARE, vol. 31, 2008, pages 758 - 760
BLAGOJEVIC N ET AL.: "Dosimetry & Treatment Planning for Neutron Capture Therapy", 1994, ADVANCED MEDICAL PUBLISHING, pages: 125 - 134
BLAKE ET AL., J. PHARM. SCI., vol. 64, no. 3, 1975, pages 367 - 391
BRICKNER, S J ET AL., J MED CHEM, vol. 39, no. 3, 1996, pages 673
BUSSO, N. ET AL., PLOS ONE, vol. 3, 2008, pages E2267
CZAJKA D M; FINKEL A J, ANN. N.Y. ACAD. SCI., vol. 84, 1960, pages 770
CZAKJA D M ET AL., AM. J. PHYSIOL., vol. 201, 1961, pages 357
DIABETES METAB., vol. 23, 1997, pages 251
FOSTER ET AL.: "Advances in Drug Research", vol. 14, 1985, ACADEMIC PRESS, pages: 2 - 36
GALLI, M. ET AL., CANCER RES., vol. 70, 2010, pages 8 - 11
GARTEN, A. ET AL., TRENDS IN ENDOCRINOLOGY AND METABOLISM, vol. 20, 2008, pages 130 - 138
HANSEN, CM ET AL., ANTICANCER RES., vol. 20, 2000, pages 42111 - 4220
KATO ET AL., J. LABELLED COMP. RADIOPHARMACEUT., vol. 36, no. 10, 1995, pages 927 - 932
KIM, S.R. ET AL., BIOCHEM. BIOPHYS. RES. COMMUN., vol. 357, 2007, pages 150 - 156
KUSHNER ET AL., CAN. J. PHYSIOL. PHARMACOL., vol. 77, 1999, pages 79 - 88
LIZONDO, J ET AL., DRUGS FUT, vol. 21, no. 11, 1996, pages 1116
MALLESHAM, B ET AL., ORG LETT, vol. 5, no. 7, 2003, pages 963
OLESE, U.H. ET AL., MOL CANCER THER., vol. 9, 2010, pages 1609 - 1617
See also references of EP2640698A1
SHOEB A ET AL: "STUDIES IN POSSIBLE ORAL HYPOGLYCAEMIC AGENTS: PART V-SYNTHESIS OF CARBAMOYLINDOLES, CARBAMOYLISOINDOLINES, 3-INDOLYLETHYL UREA (OR THIOUREA) & 2-ISOINDOLINYLPROPYL UREA (OR THIOUREA) DERIVATIVES & THEIR BIOLOGICAL ACTIVITY", INDIAN JOURNAL OF CHEMISTRY : IJC, COUNCIL OF SCIENTIFIC AND INDUSTRIAL RESEARCH, IN, vol. 5, 1 April 1967 (1967-04-01), pages 142 - 144, XP009010912, ISSN: 0019-5103 *
THOMSON J F, ANN. NEW YORK ACAD. SCI, vol. 84, 1960, pages 736
VAN BEIJNUM, J.R. ET AL., INT. J. CANCER, vol. 101, 2002, pages 118 - 127
ZIEGKEL, M., EUR. J. BIOCHEM., vol. 267, 2000, pages 1550 - 1564

Cited By (56)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9499563B2 (en) 2009-05-15 2016-11-22 Katholieke Universiteit Leuven Thieno [2, 3-B] pyridine derivatives as viral replication inhibitors
US9132129B2 (en) 2010-11-15 2015-09-15 Katholieke Universiteit Leuven Antiviral compounds
JP2013544872A (ja) * 2010-12-13 2013-12-19 カソリック ユニヴェルシテイト ルーヴェン，ケー．ユー． ルーヴェン アール アンド ディー 神経変性疾患の治療のための新規化合物
US9266832B2 (en) 2010-12-13 2016-02-23 Katholieke Universiteit Levun Compounds for the treatment of neurodegenerative diseases
US11479564B2 (en) 2011-05-09 2022-10-25 Valo Health, Inc. Piperidine derivatives and compositions for the inhibition of nicotinamide phosphoribosyltransferase (NAMPT)
US9555039B2 (en) 2011-05-09 2017-01-31 Forma Tm, Llc. Piperidine derivatives and compositions for the inhibition of nicotinamide phosphoribosyltransferase (NAMPT)
WO2013067710A1 (en) 2011-11-11 2013-05-16 Abbott Laboratories Nampt inhibitors
EP2776393A4 (en) * 2011-11-11 2015-05-27 Abbvie Inc NAMPT INHIBITORS
US20160031813A1 (en) * 2011-11-11 2016-02-04 Michael L. Curtin Nampt Inhibitors
JP2018058863A (ja) * 2012-01-09 2018-04-12 エックス−アールエックス，インコーポレーテッド キナーゼ阻害活性を有するトリプトリン誘導体及びその使用
JP2015503594A (ja) * 2012-01-09 2015-02-02 エックス−アールエックス，インコーポレーテッド キナーゼ阻害活性を有するトリプトリン誘導体及びその使用
AU2013208087B2 (en) * 2012-01-09 2017-11-23 X-Chem, Inc. Tryptoline derivatives having kinase inhibitory activity and uses thereof
JP2013234180A (ja) * 2012-04-13 2013-11-21 Mitsubishi Tanabe Pharma Corp アミド誘導体の医薬用途
JP2015528435A (ja) * 2012-08-10 2015-09-28 エフ．ホフマン−ラ ロシュ アーゲーＦ． Ｈｏｆｆｍａｎｎ−Ｌａ Ｒｏｃｈｅ Ａｋｔｉｅｎｇｅｓｅｌｌｓｃｈａｆｔ ピラゾールカルボキサミド化合物、組成物及び使用方法
EP2903618B1 (en) 2012-10-05 2022-06-01 Kadmon Corporation, LLC Rho kinase inhibitors
JP2019073521A (ja) * 2013-01-18 2019-05-16 ブリストル−マイヤーズ スクイブ カンパニーＢｒｉｓｔｏｌ−Ｍｙｅｒｓ Ｓｑｕｉｂｂ Ｃｏｍｐａｎｙ Ｒｏｃｋ阻害剤としてのフタラジノンおよびイソキノリノン
JP2019077689A (ja) * 2013-01-18 2019-05-23 ブリストル−マイヤーズ スクイブ カンパニーＢｒｉｓｔｏｌ−Ｍｙｅｒｓ Ｓｑｕｉｂｂ Ｃｏｍｐａｎｙ Ｒｏｃｋ阻害剤としてのフタラジノンおよびイソキノリノン
WO2014141035A3 (en) * 2013-03-11 2015-04-09 Aurigene Discovery Technologies Limited Fused heterocyclyl derivatives as nampt inhibitors
US9673344B2 (en) * 2014-08-07 2017-06-06 Lumeta, Llc Apparatus and method for photovoltaic module with tapered edge seal
US11795163B2 (en) * 2016-03-17 2023-10-24 Checkmate Therapeutics Inc. Compound for inhibiting nicotinamide phosphoribosyltransferase and composition containing same
US20210171513A1 (en) * 2016-03-17 2021-06-10 Checkmate Therapeutics Inc. Novel compound for inhibiting nicotinamide phosphoribosyltransferase and composition containing same
US11905284B2 (en) 2016-07-01 2024-02-20 Pfizer Inc. 5,7-dihydro-pyrrolo-pyridine derivatives
US11638762B2 (en) 2016-10-18 2023-05-02 Seagen Inc. Targeted delivery of nicotinamide adenine dinucleotide salvage pathway inhibitors
WO2018086703A1 (en) 2016-11-11 2018-05-17 Bayer Pharma Aktiengesellschaft Dihydropyridazinones substituted with phenylureas
US11931414B2 (en) 2017-04-27 2024-03-19 Seagen Inc. Quaternized nicotinamide adenine dinucleotide salvage pathway inhibitor conjugates
WO2019149637A1 (en) 2018-01-31 2019-08-08 Bayer Aktiengesellschaft Antibody drug conjugates (adcs) with nampt inhibitors
RU2732297C2 (ru) * 2018-11-14 2020-09-15 Общество с ограниченной ответственностью "Гурус БиоФарм" Производные нестероидных противовоспалительных средств
WO2021013693A1 (en) 2019-07-23 2021-01-28 Bayer Pharma Aktiengesellschaft Antibody drug conjugates (adcs) with nampt inhibitors
US20230050653A1 (en) * 2019-11-15 2023-02-16 Wuhan Ll Science And Technology Development Co., Ltd. Rock inhibitor and preparation method therefor and use thereof
WO2022053651A2 (en) 2020-09-10 2022-03-17 Precirix N.V. Antibody fragment against fap
US12649729B2 (en) 2020-12-21 2026-06-09 Cytokinetics, Inc. Pyrazole derivatives useful as NAMPT modulators
WO2023203135A1 (en) 2022-04-22 2023-10-26 Precirix N.V. Improved radiolabelled antibody
WO2023213801A1 (en) 2022-05-02 2023-11-09 Precirix N.V. Pre-targeting
WO2024229406A1 (en) 2023-05-04 2024-11-07 Revolution Medicines, Inc. Combination therapy for a ras related disease or disorder
WO2025034702A1 (en) 2023-08-07 2025-02-13 Revolution Medicines, Inc. Rmc-6291 for use in the treatment of ras protein-related disease or disorder
WO2025072437A1 (en) * 2023-09-26 2025-04-03 Alphina Therapeutics, Inc. Heteroaryl compounds and their use in treating medical conditions
WO2025080946A2 (en) 2023-10-12 2025-04-17 Revolution Medicines, Inc. Ras inhibitors
WO2025171296A1 (en) 2024-02-09 2025-08-14 Revolution Medicines, Inc. Ras inhibitors
WO2025240847A1 (en) 2024-05-17 2025-11-20 Revolution Medicines, Inc. Ras inhibitors
WO2025255438A1 (en) 2024-06-07 2025-12-11 Revolution Medicines, Inc. Methods of treating a ras protein-related disease or disorder
WO2025265060A1 (en) 2024-06-21 2025-12-26 Revolution Medicines, Inc. Therapeutic compositions and methods for managing treatment-related effects
WO2026006747A1 (en) 2024-06-28 2026-01-02 Revolution Medicines, Inc. Ras inhibitors
WO2026015825A1 (en) 2024-07-12 2026-01-15 Revolution Medicines, Inc. Use of ras inhibitor for treating pancreatic cancer
WO2026015790A1 (en) 2024-07-12 2026-01-15 Revolution Medicines, Inc. Methods of treating a ras related disease or disorder
WO2026015801A1 (en) 2024-07-12 2026-01-15 Revolution Medicines, Inc. Methods of treating a ras related disease or disorder
WO2026015796A1 (en) 2024-07-12 2026-01-15 Revolution Medicines, Inc. Methods of treating a ras related disease or disorder
WO2026050446A1 (en) 2024-08-29 2026-03-05 Revolution Medicines, Inc. Ras inhibitors
WO2026072904A2 (en) 2024-09-26 2026-04-02 Revolution Medicines, Inc. Compositions and methods for treating lung cancer
WO2026090116A2 (en) 2024-10-21 2026-04-30 Revolution Medicines, Inc. Ras inhibitors
WO2026090127A1 (en) 2024-10-22 2026-04-30 Revolution Medicines, Inc. Methods of treating a ras protein-related disease or disorder
WO2026090245A1 (en) 2024-10-22 2026-04-30 Revolution Medicines, Inc. Use of ras inhibitors for treating cancer
WO2026106912A1 (en) 2024-11-12 2026-05-21 Revolution Medicines, Inc. Ras inhibitors
WO2026112260A1 (en) 2024-11-21 2026-05-28 Revolution Medicines, Inc. Ras inhibitors
WO2026122764A2 (en) 2024-12-06 2026-06-11 Revolution Medicines, Inc. Ras inhibitors
WO2026128688A2 (en) 2024-12-13 2026-06-18 Revolution Medicines, Inc. Ras inhibitors
WO2026161839A1 (en) 2025-01-27 2026-07-30 Revolution Medicines, Inc. Ras inhibitors

Also Published As

Publication number Publication date
SG10202010119TA (en) 2020-11-27
BR112013012078A2 (pt) 2019-09-24
CA2816594A1 (en) 2012-05-24
GT201300124A (es) 2014-12-12
PH12013500975A1 (en) 2013-07-08
UY33726A (es) 2012-06-29
DOP2013000106A (es) 2013-10-15
EP2640698A1 (en) 2013-09-25
CL2013001340A1 (es) 2013-09-06
SG10201602857UA (en) 2016-05-30
MX2013005454A (es) 2013-06-24
AR083855A1 (es) 2013-03-27
ECSP13012993A (es) 2014-01-31
AU2011329233A1 (en) 2013-05-23
RU2013126657A (ru) 2014-12-27
US20160031880A1 (en) 2016-02-04
TW201238950A (en) 2012-10-01
PE20140913A1 (es) 2014-08-22
US9302989B2 (en) 2016-04-05
JP2013542265A (ja) 2013-11-21
AU2017200079A1 (en) 2017-02-02
US20120122842A1 (en) 2012-05-17
CO6761389A2 (es) 2013-09-30
IL225862A0 (en) 2013-06-27
US10093624B2 (en) 2018-10-09
SG190819A1 (en) 2013-07-31
CR20130267A (es) 2013-10-04
JP2017132792A (ja) 2017-08-03
KR20140009251A (ko) 2014-01-22
CN103313968A (zh) 2013-09-18
JP6117104B2 (ja) 2017-04-19

Similar Documents

Publication Publication Date Title
US10093624B2 (en) NAMPT and ROCK inhibitors
US8975398B2 (en) NAMPT inhibitors
US9193723B2 (en) NAMPT inhibitors
WO2013170113A1 (en) Nampt inhibitors
CN107849012B (zh) 一类激酶抑制剂
JP2015516437A (ja) Ｎａｍｐｔ阻害薬として使用されるチアゾールカルボキサミド誘導体
US9758511B2 (en) NAMPT inhibitors
HK1189589A (en) Nampt and rock inhibitors

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 11787996

Country of ref document: EP

Kind code of ref document: A1

WWE Wipo information: entry into national phase

Ref document number: 225862

Country of ref document: IL

ENP Entry into the national phase

Ref document number: 2816594

Country of ref document: CA

ENP Entry into the national phase

Ref document number: 2013538943

Country of ref document: JP

Kind code of ref document: A

WWE Wipo information: entry into national phase

Ref document number: 2013001340

Country of ref document: CL

NENP Non-entry into the national phase

Ref country code: DE

WWE Wipo information: entry into national phase

Ref document number: 001089-2013

Country of ref document: PE

Ref document number: 12013500975

Country of ref document: PH

Ref document number: MX/A/2013/005454

Country of ref document: MX

ENP Entry into the national phase

Ref document number: 2011329233

Country of ref document: AU

Date of ref document: 20111111

Kind code of ref document: A

WWE Wipo information: entry into national phase

Ref document number: 2011787996

Country of ref document: EP

WWE Wipo information: entry into national phase

Ref document number: CR2013-000267

Country of ref document: CR

ENP Entry into the national phase

Ref document number: 20137015348

Country of ref document: KR

Kind code of ref document: A

WWE Wipo information: entry into national phase

Ref document number: A201307593

Country of ref document: UA

Ref document number: 14216228

Country of ref document: CO

Ref document number: 13143136

Country of ref document: CO

ENP Entry into the national phase

Ref document number: 2013126657

Country of ref document: RU

Kind code of ref document: A

WWP Wipo information: published in national office

Ref document number: CR2013-000267

Country of ref document: CR

REG Reference to national code

Ref country code: BR

Ref legal event code: B01A

Ref document number: 112013012078

Country of ref document: BR

ENP Entry into the national phase

Ref document number: 112013012078

Country of ref document: BR

Kind code of ref document: A2

Effective date: 20130515