127168-88-1

Basic information

• Product Name: 5-METHOXY-2,3-DIHYDRO-1H-ISOINDOLE
• Synonyms: 5-METHOXY-2,3-DIHYDRO-1H-ISOINDOLE;5-METHOXYISOINDOLINE;5-METHOXY-2,3-DIHYDRO-1H-ISOINDOL;m90100;5-METHOXYISOINDOLINE HCL;1H-Isoindole,2,3-dihydro-5-Methoxy-;5-methoxyisoindoline 5-methoxy-2,3-dihydro-1h-isoindole;2,3-Dihydro-5-methoxy-1H-isoindole
• CAS NO: 127168-88-1
• Molecular Formula: C₉H₁₁NO
• Molecular Weight: 149.19
• Product Categories: Heterocycles series
• Mol File: 127168-88-1.mol

Chemical Properties

• Boiling Point: 254℃
• Flash Point: 95℃
• Appearance: /
• Density: 1.076
• Vapor Pressure: 0.018mmHg at 25°C
• Refractive Index: 1.546
• Storage Temp.: 2-8°C(protect from light)
• PKA: 9.56±0.20(Predicted)
• CAS DataBase Reference: 5-METHOXY-2,3-DIHYDRO-1H-ISOINDOLE(CAS DataBase Reference)
• NIST Chemistry Reference: 5-METHOXY-2,3-DIHYDRO-1H-ISOINDOLE(127168-88-1)
• EPA Substance Registry System: 5-METHOXY-2,3-DIHYDRO-1H-ISOINDOLE(127168-88-1)

Safety Data

• Hazardous Substances Data: 127168-88-1(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
5-METHOXY-2,3-DIHYDRO-1H-ISOINDOLE is used as a reagent for the synthesis of PDK inhibitors, which are designed to target glucose and fat levels in type 2 diabetes. These inhibitors help regulate the metabolic pathways involved in glucose and fat metabolism, thereby improving the overall management of the disease.
Used in Anticancer Applications:
In the field of cancer research, 5-METHOXY-2,3-DIHYDRO-1H-ISOINDOLE is utilized in the preparation of C20' ureas based on 20'amino-vinblastine. These compounds are specifically designed to combat vinblastine-resistant cancer cell lines, offering a potential therapeutic alternative for patients with drug-resistant tumors.
By understanding the molecular structure and properties of 5-METHOXY-2,3-DIHYDRO-1H-ISOINDOLE, researchers can continue to explore its potential applications in the development of new drugs and therapies for various medical conditions, including type 2 diabetes and cancer.

InChI:InChI=1/C9H11NO/c1-11-9-3-2-7-5-10-6-8(7)4-9/h2-4,10H,5-6H2,1H3

Synthetic route

4-methoxyphthalimide (50727-04-3) → 5-methoxy-2,3-dihydro-1H-isoindole (127168-88-1)

Conditions	Yield
Stage #1: 4-methoxyphthalimide With borane-THF In tetrahydrofuran at 0℃; for 16h; Heating / reflux; Stage #2: With hydrogenchloride In tetrahydrofuran; methanol; water for 3h; Heating / reflux;	47%
Stage #1: 4-methoxyphthalimide With borane-THF In tetrahydrofuran at 0℃; for 16h; Heating / reflux; Stage #2: With hydrogenchloride In tetrahydrofuran; methanol at 0℃; for 3h; Heating / reflux;	47%
With borane In tetrahydrofuran at 0℃; for 16h; Heating / reflux;	47%

N-benzylisoindolin-5-yl methyl ether (127168-89-2) → 5-methoxy-2,3-dihydro-1H-isoindole (127168-88-1)

Conditions	Yield
With Pd(OH)2/C; ammonium formate In methanol Reflux;
Stage #1: N-benzylisoindolin-5-yl methyl ether With hydrogen; acetic acid; palladium on carbon In methanol under 2327.23 Torr; for 23h; Stage #2: With sodium hydroxide; water In methanol

5-methoxy-2-[(4-methylphenyl)sulfonyl]isoindoline (1025424-06-9) → 5-methoxy-2,3-dihydro-1H-isoindole (127168-88-1)

Conditions	Yield
With hydrogen bromide; phenol In propan-1-ol; water at 100℃; for 2h;

3,4-dimethylanisole (4685-47-6) → 5-methoxy-2,3-dihydro-1H-isoindole (127168-88-1)

5-methoxy-2,3-dihydro-1H-isoindole (127168-88-1) → 5-hydroxy-isoindoline hydrobromide

Conditions	Yield
With hydrogen bromide In water at 100℃;	95%
With hydrogen bromide In water for 16h; Heating / reflux;	93%
With hydrogen bromide In water for 16h; Heating / reflux;	93%

5-methoxy-2,3-dihydro-1H-isoindole (127168-88-1) → 5-hydroxyisoindoline (54544-67-1)

Conditions	Yield
With hydrogen bromide at 100℃; for 2h;	80%

4-bromophenyl chloroformate (7693-44-9) + 5-methoxy-2,3-dihydro-1H-isoindole (127168-88-1) → 4-bromophenyl 5-methoxyisoindoline-2-carboxylate (1620228-48-9)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In dichloromethane at 0 - 20℃; for 1h;	63%

2-(4-(4-oxo-3,4-dihydrophthalazin-1-yl)phenyl)acetic acid (1620226-65-4) + 5-methoxy-2,3-dihydro-1H-isoindole (127168-88-1) → 4-(4-(2-(5-methoxyisoindolin-2-yl)-2-oxoethyl)phenyl)phthalazin-1(2H)-one (1620222-40-3)

Conditions	Yield
With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; for 2h;	59%

tert-butyl 4-((1H-indazol-5-yl)amino)-2-chloro-5H-pyrrolo[3,4-d]pyrimidine-6(7H)-carboxylate + 5-methoxy-2,3-dihydro-1H-isoindole (127168-88-1) → tert-butyl 4-((1H-indazol-5-yl)amino)-2-(5-methoxyisoindolin-2-yl)-5H-pyrrolo[3,4-d]pyrimidine-6(7H)-carboxylate

Conditions	Yield
With triethylamine In 1-methyl-pyrrolidin-2-one at 150℃; for 1h;	48.9%

2,6-Dichloropyrimidine (3934-20-1) + 5-methoxy-2,3-dihydro-1H-isoindole (127168-88-1) → 2-(2-chloropyrimidin-4-yl)-5-methoxyisoindoline

Conditions	Yield
With sodium carbonate In ethanol at 90℃; for 12h;	47.8%

(4-bromophenyl)(2-chloropyrimidin-4-yl)amine (260046-09-1) + 5-methoxy-2,3-dihydro-1H-isoindole (127168-88-1) → N-(4-bromophenyl)-2-(5-methoxyisoindolin-2-yl)pyrimidin-4-amine

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In acetonitrile at 90℃; for 17h;	42.9%
With N-ethyl-N,N-diisopropylamine In acetonitrile at 90℃; for 17h;	42.9%

2-chloropyrimidin-4-amine (7461-50-9) + 5-methoxy-2,3-dihydro-1H-isoindole (127168-88-1) → 2-(5-methoxyisoindolin-2-yl)pyrimidin-4-amine

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In acetonitrile at 90℃; for 16h;	35.4%
With N-ethyl-N,N-diisopropylamine In acetonitrile at 90℃; for 16h;	35.4%

N-(2-chloro-5,6-dimethylpyrimidin-4-yl)-1H-indazol-5-amine + 5-methoxy-2,3-dihydro-1H-isoindole (127168-88-1) → N-(2-(5-methoxyisoindolin-2-yl)-5,6-dimethylpyrimidin-4-yl)-1H-indazol-5-amine

Conditions	Yield
With potassium carbonate In acetonitrile at 90℃; for 72h;	30%
With potassium carbonate In acetonitrile at 90℃; for 72h;	30%

tert-butyl 4-((1H-indazol-5-yl)amino)-2-chloro-5,6-dihydropyrido[3,4-d]pyrimidine-7(8H)-carboxylate + 5-methoxy-2,3-dihydro-1H-isoindole (127168-88-1) → tert-butyl 4-((1H-indazol-5-yl)amino)-2-(5-methoxyisoindolin-2-yl)-5,6-dihydropyrido[3,4-d]pyrimidine-7(8H)-carboxylate

Conditions	Yield
With triethylamine In 1-methyl-pyrrolidin-2-one at 150℃; for 1h;	29.6%

N-(2,5-dichloropyrimidin-4-yl)-1H-indazol-5-amine (1257302-89-8) + 5-methoxy-2,3-dihydro-1H-isoindole (127168-88-1) → N-(5-chloro-2-(5-methoxyisoindolin-2-yl)pyrimidin-4-yl)-1H-indazol-5-amine

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In acetonitrile at 90℃; for 12h;	29.1%

N-(2-chloro-5-methylpyrimidin-4-yl)-1H-indazol-5-amine (1257302-90-1) + 5-methoxy-2,3-dihydro-1H-isoindole (127168-88-1) → N-(2-(5-methoxyisoindolin-2-yl)-5-methylpyrimidin-4-yl)-1H-indazol-5-amine

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 110℃; for 12h;	27%

N-(2-chloro-6-methylpyrimidin-4-yl)-1H-indazol-5-amine + 5-methoxy-2,3-dihydro-1H-isoindole (127168-88-1) → N-(2-(5-methoxyisoindolin-2-yl)-6-methylpyrimidin-4-yl)-1H-indazol-5-amine

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 110℃; for 12h;	21.4%

2-chloro-N-(1H-indazol-5-yl)-5,7-dihydrofuro[3,4-d]pyrimidin-4-amine + 5-methoxy-2,3-dihydro-1H-isoindole (127168-88-1) → N-(1H-indazol-5-yl)-2-(5-methoxyisoindolin-2-yl)-5,7-dihydrofuro[3,4-d]pyrimidin-4-amine

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In acetonitrile at 90℃; for 20h;	17.2%

2-chloro-5-fluoro-N-(indazoline-5-yl)-4-pyrimidineamine (575474-16-7) + 5-methoxy-2,3-dihydro-1H-isoindole (127168-88-1) → N-(5-fluoro-2-(5-methoxyisoindolin-2-yl)pyrimidin-4-yl)-1H-indazol-5-amine

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In acetonitrile at 90℃; for 12h;	12.1%

N-(1H-indazol-5-yl)-2-(methylsulfonyl)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-4-amine + 5-methoxy-2,3-dihydro-1H-isoindole (127168-88-1) → N-(1H-indazol-5-yl)-2-(5-methoxyisoindolin-2-yl)-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-4-amine

Conditions	Yield
With triethylamine In 1,4-dioxane at 150℃; for 2h; Microwave irradiation; Sealed tube;	7.23%

trans-2-(1-(4-(N-tert-butoxycarbonyl)amino)cyclohexyl)acetaldehyde (215790-29-7) + 5-methoxy-2,3-dihydro-1H-isoindole (127168-88-1) → {4-[2-(5-methoxy-1,3-dihydro-isoindol-2-yl)-ethyl]-cyclohexyl}-carbamic acid tert-butyl ester (437650-81-2)

Conditions	Yield
With NaBH(OAc)2 In 1,2-dichloro-ethane at 20℃; for 16h;

5-methoxy-2,3-dihydro-1H-isoindole (127168-88-1) → 5-cyano-2,3-dihydro-1H-isoindole (263888-58-0)

Conditions	Yield
Multi-step reaction with 5 steps 1: 80 percent / aq. HBr / 2 h / 100 °C 2: 40 percent / Et3N / CH2Cl2 / 16 h / 20 °C 3: 70 percent / Et3N / CH2Cl2 / 6 h / -20 - 20 °C 4: 90 percent / Pd(PPh3)4 / dimethylformamide / 4 h / 100 °C 5: 90 percent / TFA / CH2Cl2 / 0.5 h / 40 °C View Scheme

5-methoxy-2,3-dihydro-1H-isoindole (127168-88-1) → 5-methanesulfonyloxy-2,3-dihydro-1H-isoindole (263888-60-4)

Conditions	Yield
Multi-step reaction with 4 steps 1: 80 percent / aq. HBr / 2 h / 100 °C 2: 40 percent / Et3N / CH2Cl2 / 16 h / 20 °C 3: 70 percent / Et3N / CH2Cl2 / 16 h / 20 °C 4: 90 percent / TFA / CH2Cl2 / 0.5 h / 40 °C View Scheme

5-methoxy-2,3-dihydro-1H-isoindole (127168-88-1) → tert-butyl 5-hydroxyisoindoline-2-carboxylate (226070-47-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: 80 percent / aq. HBr / 2 h / 100 °C 2: 40 percent / Et3N / CH2Cl2 / 16 h / 20 °C View Scheme

5-methoxy-2,3-dihydro-1H-isoindole (127168-88-1) → tert-butyl 5-cyanoisoindoline-2-carboxylate (263888-56-8)

Conditions	Yield
Multi-step reaction with 4 steps 1: 80 percent / aq. HBr / 2 h / 100 °C 2: 40 percent / Et3N / CH2Cl2 / 16 h / 20 °C 3: 70 percent / Et3N / CH2Cl2 / 6 h / -20 - 20 °C 4: 90 percent / Pd(PPh3)4 / dimethylformamide / 4 h / 100 °C View Scheme

5-methoxy-2,3-dihydro-1H-isoindole (127168-88-1) → 5-methanesulfonyloxy-1,3-dihydro-isoindole-2-carboxylic acid tert-butyl ester (263888-59-1)

Conditions	Yield
Multi-step reaction with 3 steps 1: 80 percent / aq. HBr / 2 h / 100 °C 2: 40 percent / Et3N / CH2Cl2 / 16 h / 20 °C 3: 70 percent / Et3N / CH2Cl2 / 16 h / 20 °C View Scheme

5-methoxy-2,3-dihydro-1H-isoindole (127168-88-1) → 4-[2-(5-methoxy-1,3-dihydro-isoindol-2-yl)-ethyl]-cyclohexylamine (437651-98-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: NaBH(OAc)2 / 1,2-dichloro-ethane / 16 h / 20 °C 2: 90 percent / TFA / CH2Cl2 / 0.5 h / 40 °C View Scheme

5-methoxy-2,3-dihydro-1H-isoindole (127168-88-1) → 5-trifluoromethanesulfonyloxy-1,3-dihydro-isoindole-2-carboxylic acid tert-butyl ester (263888-57-9)

Conditions	Yield
Multi-step reaction with 3 steps 1: 80 percent / aq. HBr / 2 h / 100 °C 2: 40 percent / Et3N / CH2Cl2 / 16 h / 20 °C 3: 70 percent / Et3N / CH2Cl2 / 6 h / -20 - 20 °C View Scheme

5-methoxy-2,3-dihydro-1H-isoindole (127168-88-1) → 2-[2-(4-amino-cyclohexyl)-ethyl]-2,3-dihydro-1H-isoindole-5-carbonitrile (437652-04-5)

Conditions	Yield
Multi-step reaction with 7 steps 1: 80 percent / aq. HBr / 2 h / 100 °C 2: 40 percent / Et3N / CH2Cl2 / 16 h / 20 °C 3: 70 percent / Et3N / CH2Cl2 / 6 h / -20 - 20 °C 4: 90 percent / Pd(PPh3)4 / dimethylformamide / 4 h / 100 °C 5: 90 percent / TFA / CH2Cl2 / 0.5 h / 40 °C 6: NaBH(OAc)2 / 1,2-dichloro-ethane / 16 h / 20 °C 7: 90 percent / TFA / CH2Cl2 / 0.5 h / 40 °C View Scheme

5-methoxy-2,3-dihydro-1H-isoindole (127168-88-1) → methanesulfonic acid 2-[2-(4-amino-cyclohexyl)-ethyl]-2,3-dihydro-1H-isoindol-5-yl ester (437652-01-2)

Conditions	Yield
Multi-step reaction with 6 steps 1: 80 percent / aq. HBr / 2 h / 100 °C 2: 40 percent / Et3N / CH2Cl2 / 16 h / 20 °C 3: 70 percent / Et3N / CH2Cl2 / 16 h / 20 °C 4: 90 percent / TFA / CH2Cl2 / 0.5 h / 40 °C 5: NaBH(OAc)2 / 1,2-dichloro-ethane / 16 h / 20 °C 6: 90 percent / TFA / CH2Cl2 / 0.5 h / 40 °C View Scheme

5-methoxy-2,3-dihydro-1H-isoindole (127168-88-1) → {4-[2-(5-cyano-1,3-dihydro-isoindol-2-yl)-ethyl]-cyclohexyl}-carbamic acid tert-butyl ester (437651-10-0)

Conditions	Yield
Multi-step reaction with 6 steps 1: 80 percent / aq. HBr / 2 h / 100 °C 2: 40 percent / Et3N / CH2Cl2 / 16 h / 20 °C 3: 70 percent / Et3N / CH2Cl2 / 6 h / -20 - 20 °C 4: 90 percent / Pd(PPh3)4 / dimethylformamide / 4 h / 100 °C 5: 90 percent / TFA / CH2Cl2 / 0.5 h / 40 °C 6: NaBH(OAc)2 / 1,2-dichloro-ethane / 16 h / 20 °C View Scheme

5-methoxy-2,3-dihydro-1H-isoindole (127168-88-1) → methanesulfonic acid 2-[2-(4-tert-butoxycarbonylamino-cyclohexyl)-ethyl]-2,3-dihydro-1H-isoindol-5-yl ester (437650-82-3)

Conditions	Yield
Multi-step reaction with 5 steps 1: 80 percent / aq. HBr / 2 h / 100 °C 2: 40 percent / Et3N / CH2Cl2 / 16 h / 20 °C 3: 70 percent / Et3N / CH2Cl2 / 16 h / 20 °C 4: 90 percent / TFA / CH2Cl2 / 0.5 h / 40 °C 5: NaBH(OAc)2 / 1,2-dichloro-ethane / 16 h / 20 °C View Scheme

Upstream product

• 127168-89-2 N-benzylisoindolin-5-yl methyl ether 
• 50727-04-3 4-methoxyphthalimide 
• 1025424-06-9 5-methoxy-2-[(4-methylphenyl)sulfonyl]isoindoline 
• 4685-47-6 3,4-dimethylanisole 

Downstream Products

• 437650-81-2 {4-[2-(5-methoxy-1,3-dihydro-isoindol-2-yl)-ethyl]-cyclohexyl}-carbamic acid tert-butyl ester 
• 54544-67-1 5-hydroxyisoindoline 
• 437652-01-2 methanesulfonic acid 2-[2-(4-amino-cyclohexyl)-ethyl]-2,3-dihydro-1H-isoindol-5-yl ester 
• 437651-10-0 {4-[2-(5-cyano-1,3-dihydro-isoindol-2-yl)-ethyl]-cyclohexyl}-carbamic acid tert-butyl ester 
• 437650-82-3 methanesulfonic acid 2-[2-(4-tert-butoxycarbonylamino-cyclohexyl)-ethyl]-2,3-dihydro-1H-isoindol-5-yl ester 
• 630407-39-5 5-methoxy-2-methylisoindoline 
• 508237-23-8 5-(3,4-Dimethoxybenzylamino)-2-(2-furyl)-8-(5-methoxyisoindolin-2-ylmethyl)[1,2,4]triazolo[1,5-c]pyrimidine 
• 888724-82-1 1-(5-methoxyisoindolin-2-yl)-6-[4-(3-trifluoromethylphenyl)piperazin-1-yl]hexan-1-one 
• 905269-98-9 C₂₀H₂₀F₃NO₅S 
• 1620228-49-0 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl 5-methoxyisoindoline-2-carboxylate 
• 1620228-48-9 4-bromophenyl 5-methoxyisoindoline-2-carboxylate 
• 1233145-41-9 6-methoxy-2-methylisoindolin-5-amine 

Relevant articles and documents

PHARMACEUTICAL COMPOUNDS

The invention provides a compound for use in medicine, the compound being a compound of the formula (VI0) or a salt, solvate, tautomer or N-oxide thereof: wherein the bicyclic group: is selected from the structures C1, C5 and C6: wherein n is 0, 1, 2 or 3; R1 is hydrogen, hydroxy, or O—Rz; R2a is hydroxy, methoxy or O—Rz; provided that at least one of R1 and R2a is O—Rz; Rz is Lp-Rp1; SO3H; a glucuronide residue; a mono-, di- or tripeptide residue; or Lp is a bond, C═O, (C═O)O, (C═O)NRp1 or S(O)xNRp1; x is 1 or 2; Rp1 is hydrogen or a an optionally substituted C1-25 hydrocarbyl group containing 0, 1 or 2 carbocyclic rings and 0, 1, 2, 3, 4, 5 or 6 carbon-carbon multiple bonds, provided that Rp1 is not hydrogen when Lp is a bond, C═O or (C═O)O; and provided also that O—Rz does not contain an O—O moiety; and excluding compounds wherein R1 is hydroxy and R2a is methoxy; Rp2 and Rp3 are the same or different and each is a group Rp1; and R3, R4a, R8 and R10 are defined in the claims. The compounds of formula (VI0) are pro-drugs of parent compounds wherein R1 and/or R2a are hydroxy, wherein the parent compounds have Hsp90 inhibiting activity.

Discovery of (2,4-Dihydroxy-5-isopropylphenyl)-[5-(4-methylpiperazin-1- ylmethyl)-1,3-dihydroisoindol-2-yl]methanone (AT13387), a novel inhibitor of the molecular chaperone Hsp90 by fragment based drug design

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Arylpiperazine Derivatives and their Use as Selective Dopamine D3 Receptor Ligands

The invention concerns compounds of general formula (I), a method for preparing same, as well as their use as therapeutic agent.

PHARMACEUTICAL COMBINATIONS

The invention provides combinations comprising (or consisting essentially of) one or more ancillary compound(s) and a compound of the formula (I): or salts, tautomers, solvates and N-oxides thereof; wherein R1 is hydroxy or hydrogen; R2 is hydroxy; methoxy or hydrogen; provided that at least one of R1 and R2 is hydroxy; R3 is selected from hydrogen; halogen; cyano; optionally substituted C1-5 hydrocarbyl and optionally substituted C1- 5 hydrocarbyloxy; R4 is selected from hydrogen; a group -(O)n-R7 where n is 0 or 1 and R7 is an optionally substituted acyclic C1-5 hydrocarbyl group or a monocyclic carbocyclic or heterocyclic group having 3 to 7 ring members; halogen; cyano; hydroxy; amino; and optionally substituted mono- or di-C1-5 hydrocarbyl-amino; or R3 and R4 together form a monocyclic carbocyclic or heterocyclic ring of 5 to 7 ring members; and NR5R6 forms an optionally substituted bicyclic heterocyclic group having 8 to 12 ring members of which up to 5 ring members are heteroatoms selected from oxygen, nitrogen and sulphur. The combinations have activity as Hsp90 inhibitors.

PHARMACEUTICAL COMBINATIONS

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PHARMACEUTICAL COMBINATIONS

The invention provides combinations comprising (or consisting essentially of) one or more ancillary compound(s) and a compound of the formula (I): or salts, tautomers, solvates and N-oxides thereof; wherein R1 is hydroxy or hydrogen; R2 is hydroxy; methoxy or hydrogen; provided that at least one of R1 and R2 is hydroxy; R3 is selected from hydrogen; halogen; cyano; optionally substituted C1-5 hydrocarbyl and optionally substituted C1-5 hydrocarbyloxy; R4 is selected from hydrogen; a group -(O)n-R7 where n is 0 or 1 and R7 is an optionally substituted acyclic C1-5 hydrocarbyl group or a monocyclic carbocyclic or heterocyclic group having 3 to 7 ring members; halogen; cyano; hydroxy; amino; and optionally substituted mono- or di-C1-5 hydrocarbyl-amino; or R3 and R4 together form a monocyclic carbocyclic or heterocyclic ring of 5 to 7 ring members; and NR5R6 forms an optionally substituted bicyclic heterocyclic group having 8 to 12 ring members of which up to 5 ring members are heteroatoms selected from oxygen, nitrogen and sulphur. The combinations have activity as Hsp90 and/or glycogen synthase kinase-3 and/or cyclin dependent kinase and/or aurora kinase inhibitors.

PHARMACEUTICAL COMPOUNDS

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Design, synthesis, and evaluation of fused heterocyclic analogs of SCH 58261 as adenosine A2A receptor antagonists

SCH 58261 is a reported adenosine A2A receptor antagonist which is active in rat in vivo models of Parkinson's Disease upon ip administration. However, it has poor selectivity versus the A1 receptor and does not demonstrate oral activity. Quinoline analogs have improved upon the selectivity and pharmacokinetics of SCH 58261, but were difficult to handle due to poor aqueous solubility. We report the design and synthesis of fused heterocyclic analogs of SCH 58261 with aqueous solubility as well as improved A2A receptor binding selectivity and pharmacokinetic properties. In particular, the tetrahydronaphthyridine 4s has excellent A2A receptor in vitro binding affinity and selectivity, is active orally in a rat in vivo model of Parkinson's Disease, and has aqueous solubility of 100 μM at physiological pH.

ISOINDOLE DERIVATIVES

This invention relates to compounds of formula (I) or pharmaceutically acceptable salts thereof, a process of making these compounds, pharmaceutical compositions containing one or more of these compounds or their salts, and their use for the treatment of schizophrenia, bipolar disorder, or other central nervous system disorders.

COMPOUND INHIBITING DIPEPTIDYL PEPTIDASE IV

The invention aims to provide a dipeptidyl peptidase IV inhibitor which is satisfactory in respect of activity, stability and safety and has an excellent action as a pharmaceutical agent. The invention is directed to a compound represented by the following general formula or a pharmaceutically acceptable salt thereof: wherein R1 and R2 each represents hydrogen, an optionally substituted C1-6 alkyl group, or -COOR5 whereupon R5 represents hydrogen or an optionally substituted C1-6 alkyl group, or R1 and R2, together with a carbon atom to which they are bound, represent a 3- to 6-membered cycloalkyl group, R3 represents hydrogen or an optionally substituted C6-10 aryl group, R4 represents a hydrogen or a cyano group, D represents -CONR6-, -CO- or -NR6CO-, R6 represents hydrogen or an optionally substituted C1-6 alkyl group, E represents -(CH2)m- whereupon m is an integer of 1 to 3, -CH2OCH2-, or -SCH2-, n is an integer of 0 to 3, and A represents an optionally substituted bicyclic heterocyclic group or bicyclic hydrocarbon group.