Classifications

• • 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
• • A—HUMAN NECESSITIES
  • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
  • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
  • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
  • A01N43/90—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having two or more relevant hetero rings, condensed among themselves or with a common carbocyclic ring system
• • 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
  • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
• • 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
  • A61P3/04—Anorexiants; Antiobesity agents
• • 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
  • A61P3/06—Antihyperlipidemics
• • 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
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P35/00—Antineoplastic agents
• • 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
• • 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

Definitions

• Compounds provided by this invention are also useful for the study of ACC enzymes in biological and pathological phenomena; the study of intracellular signal transduction pathways occurring in lipogenic tissues; and the comparative evaluation of new ACC inhibitors or other regulators of fatty acid levels in vitro or in vivo.
• DETAILED DESCRIPTION OF CERTAIN EMBODIMENTS
• such compounds include those of formula I:
• R 1 and R 2 may optionally be taken together to form an optionally substituted 3-8 membered
• each instance of R 7 is independently selected from -R 6 , -OR, -SR, -N(R) 2 , - N(R)C(0)R, -C(0)N(R) 2 , -N(R)C(0)N(R) 2 , -N(R)C(0)OR, -OC(0)N(R) 2 , -N(R)S0 2 R, - S0 2 N(R) 2 , -C(0)R, -C(0)OR, -OC(0)R, -S(0)R, and -S(0) 2 R;
• Y is selected from -0-, -S-, or -N(R)-;
• Hy is an optionally substituted 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, Hy is an optionally substituted 5 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, Hy is an optionally substituted 5 membered monocyclic heteroaryl ring having 2 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, Hy is an optionally substituted 5 membered monocyclic heteroaryl ring having 2 nitrogen atoms. In some embodiments, Hy is optionally substituted pyrazolyl. In some embodiments, Hy is pyrazolyl. In some embodiments, Hy is pyrazolyl.
• R 3 (R 5 ) m taken together, is:
• R 3 (R 5 ) m taken together, is:
• R 4 is hydrogen.
• R 4 is an optionally substituted ring selected from a 3-10 membered saturated or partially unsaturated monocyclic carbocyclic ring; phenyl; a 6-10 membered bicyclic saturated, partially unsaturated, or aryl ring; a 3-8 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; a 6-10 membered saturated or partially unsaturated bicyclic heterocyclic ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur; and a 7-10 membered bicyclic heteroaryl ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur; wherein R 4 substituted with n instances of -R 8 .
• At least one instance of R is oxo, -R 6 , -OR, -SR, -N(R) 2 , -N(R)C(0)R, -C(0)N(R) 2 , -N(R)C(0)N(R) 2 , -N(R)C(0)OR, -OC(0)N(R) 2 , -N(R)S0 2 R, -S0 2 N(R) 2 , -C(0)R, -C(0)OR, -OC(0)R, -S(0)R, or -S(0) 2 R.
• At least two instances of R 5 together with the atom(s) to which they are attached, form an optionally substituted 3-10 membered saturated, partially unsaturated or aromatic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur.
• At least one instance of R is oxo. In some embodiments, at least one instance of R 5 is -R 6 . In some embodiments, at least one instance of R 5 is optionally substituted Ci -6 aliphatic. In some embodiments, each instance of R 5 is oxo, -R 6 ,
• one R 5 is oxo and another R 5 is R 6 .
• R 7 is -OR.
• R 7 is -OR, wherein R in this instance is an optionally substituted group selected from Ci -6 aliphatic, 3-8 membered saturated or partially unsaturated monocyclic carbocyclic ring, or a 3-8 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur.
• the resent invention provides a compound of formula III:
• the present invention provides a compound of formula Ill-a or Ill-b:
• step S-4 comprises deprotection of the amine of a compound of formula G-4, thereby forming a compound of formula G-5.
• the PG is acetyl.
• deprotection is achieved through use of hydrazine.
• water is added to the reaction mixture.
• ethanol is added to the reaction mixture.
• interconversions may require one or more of the aforementioned techniques, and certain methods for synthesizing compounds of the invention are described below in the Exemplification.
• CP-640186 also stimulated FA oxidation in C2C12 cells and in rat muscle slices and increased CPT-I activity in Hep-G2 cells.
• CP-640186 acutely reduced malonyl-CoA concentration in both lipogenic and oxidative tissues in both the fed and fasted state, reduced liver and adipose tissue FA synthesis, and increased whole body FA oxidation.
• the metabolic disorder, disease or condition is non-alcoholic fatty liver disease or hepatic insulin resistance.
• Collectotrichum graminicola, Diplodia maydis, Fusarium moniliforme, Fusarium virguliforme, Phytophthora capsici, Rhizoctonia solani, and Septoria at a concentration of 1 ⁇ / ⁇ . or less.
• a compound of the present invention inhibits at least two of Botrtyis cinerea, Collectotrichum graminicola, Diplodia maydis, Fusarium moniliforme, Fusarium virguliforme, Phytophthora capsici, Rhizoctonia solani, and Septoria at a concentration of 2 ⁇ / ⁇ . or less.
• a provided compound or composition, according to the method of the present invention may be administered using any amount and any route of administration effective for treating or lessening the severity of a viral infection (Munger et al. Nat. Biotechnol. (2008) 26, 1179-1186).
• the viral infection is Hepatitis C.
• a provided compound or composition, according to the method of the present invention may be administered using any amount and any route of administration effective for treating or lessening the severity of a neurological disease
• tissues containing cancerous cells whose proliferation is inhibited by the a provided compound or composition thereof described herein and against which the methods described herein are useful include but are not limited to breast, prostate, brain, blood, bone marrow, liver, pancreas, skin, kidney, colon, ovary, lung, testicle, penis, thyroid, parathyroid, pituitary, thymus, retina, uvea, conjunctiva, spleen, head, neck, trachea, gall bladder, rectum, salivary gland, adrenal gland, throat, esophagus, lymph nodes, sweat glands, sebaceous glands, muscle, heart, and stomach.
• the diseases which can be treated by a provided compound or composition thereof are neurological disorders.
• the neurological disorder is Alzheimer's Disease, Parkinson's Disease, epilepsy, ischemia, Age Associated Memory Impairment, Mild Cognitive Impairment, Friedreich's Ataxia, GLUT 1 -deficient epilepsy, Leprechaunism, Rabson-Mendenhall Syndrome, Coronary Arterial Bypass Graft dementia, anaesthesia-induced memory loss, amyotrophic lateral sclerosis, glioma, or Huntington's Disease.
• the disease which can be treated by a provided compound or composition thereof is an infectious disease.
• the infectious disease is a viral infection.
• the viral infection is cytomegalovirus infection or influenza infection.
• the infectious disease is a fungal infection.
• the infectious disease is a bacterial infection.
• J) Biological control agent - bacteria genus: Actinomycetes, Agrobacterium, Arthrobacter, Alcaligenes, Aureobacterium, Azobacter, Bacillus, Beijerinckia, Bradyrhizobium, Brevibacillus, Burkholderia, Chromobacterium, Clostridium, Clavibacter, Comamonas,
• the user applies the composition according to the invention usually from a predosage device, a knapsack sprayer, a spray tank or a spray plane.
• the agrochemical composition is made up with water and/or buffer to the desired application concentration, it being possible, if appropriate, to add further auxiliaries, and the ready-to-use spray liquor or the agrochemical composition according to the invention is thus obtained.
• 50 to 500 liters of the ready-to-use spray liquor are applied per hectare of agricultural useful area.
• 100 to 400 liters of the ready-to-use spray liquor are applied per hectare.
• the invention provides a kit for greenhouse application of a ready-to-use composition of the invention.
• the invention provides a mixture comprising a provided compound (component 1) and at least one active substance selected from the fungicides given in group F) (component 2).
• the fungicides of group F) are selected from the group consisting of dithianon, fentin salts, such as fentin acetate, fosetyl, fosetyl-aluminium, H 3 PO 3 and salts thereof, chlorthalonil, dichlofluanid, thiophanat-methyl, copper acetate, copper hydroxide, copper oxychloride, copper sulfate, sulfur, cymoxanil, metrafenone and spiroxamine.
• Trichophyton megninii Trichophyton mentagrophytes, Trichophyton rubrum, Trichophyton schoenleinii, Trichophyton tonsurans, and/or Trichophyton verrucosum
• Tinea favosa which may be caused by one or more of Microsporum gypseum and/or Trichophyton schoenleinii
• Tinea barbae which may be caused by one of more of Trichophyton rubrum
• Trichophyton mentagrophytes var granulosum Trichophyton verrucosum
• Microsporum canis and Trichophyton mentagrophytes var erinacei, are treatable by the administration of a provided compound or composition thereof.
• a provided compound or composition thereof can be topically administered once per day for a period of time from 1 week to 8 weeks, from 1 week to 4 weeks, for 1 week, for 2 weeks, for 3 weeks, for 4 weeks, for 5 weeks, for 6 weeks, for 7 weeks, or for 8 weeks.
• Example 23 Synthesis of 3-(l-ethyl-2-oxopiperidin-3-yl)-l-((R)-2-(5-fluoro-2- methoxyphenyl)-2-((tetrahydro-2H-pyran-4-yl)oxy)ethyl)-5-methyl-6-(2H-l,2,3-triazol-2- yl)thi -d]pyrimidine-2,4(lH,3H)-dione, 1-23,
• Example 43 Synthesis of l-((R)-2-(5-fluoro-2-methoxyphenyl)-2-(2-methoxy- ethoxy)ethyl)-5-methyl-3-((S)-l-methyl-2-oxopyrrolidin-3-yl)-6-(lH-pyrazol-l-yl)thieno[2,3- d]pyrimidine-2 4(lH,3H)-dione, 1-43

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• Health & Medical Sciences (AREA)
• Chemical & Material Sciences (AREA)
• Organic Chemistry (AREA)
• Life Sciences & Earth Sciences (AREA)
• General Health & Medical Sciences (AREA)
• Animal Behavior & Ethology (AREA)
• Pharmacology & Pharmacy (AREA)
• Medicinal Chemistry (AREA)
• Public Health (AREA)
• Veterinary Medicine (AREA)
• Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
• General Chemical & Material Sciences (AREA)
• Chemical Kinetics & Catalysis (AREA)
• Engineering & Computer Science (AREA)
• Hematology (AREA)
• Bioinformatics & Cheminformatics (AREA)
• Obesity (AREA)
• Diabetes (AREA)
• Wood Science & Technology (AREA)
• Environmental Sciences (AREA)
• Zoology (AREA)
• Agronomy & Crop Science (AREA)
• Pest Control & Pesticides (AREA)
• Plant Pathology (AREA)
• Dentistry (AREA)
• Child & Adolescent Psychology (AREA)
• Epidemiology (AREA)
• Oncology (AREA)
• Communicable Diseases (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
• Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
• Peptides Or Proteins (AREA)
• Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
• Agricultural Chemicals And Associated Chemicals (AREA)
• Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)

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• 2016
  • 2016-10-25 AR ARP160103255A patent/AR106472A1/es unknown
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  • 2016-10-26 US US15/334,955 patent/US10179793B2/en not_active Expired - Fee Related
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  • 2016-10-26 CA CA3003275A patent/CA3003275A1/en not_active Abandoned
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