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Nateglinide

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Name

Nateglinide

EINECS N/A
CAS No. 105816-04-4 Density 1.104 g/cm3
PSA 66.40000 LogP 3.65180
Solubility N/A Melting Point 137-141 °C
Formula C19H27NO3 Boiling Point 527.6 °C at 760 mmHg
Molecular Weight 317.428 Flash Point 272.9 °C
Transport Information N/A Appearance white crystalline powder
Safety 24/25-36 Risk Codes 22
Molecular Structure Molecular Structure of 105816-04-4 (Nateglinide) Hazard Symbols HarmfulXn
Synonyms

Nateglinide [INN];Fastic;trans-N-((4-(1-Methylethyl)cyclohexyl)carbonyl)-D-phenylalanine;A 4166;Starlix;Nateglinide(105816-04-4 );Nateglinide,105816-04-4;Starsis (TN);(2R)-3-phenyl-2-[[(1S,3S)-3-propan-2-ylcyclohexanecarbonyl]amino]propanoic acid;D-Phenylalanine,N-[[trans-4-(1-methylethyl)- cyclohexyl]carbonyl]-;Starsis;(-)-N-(trans-4-Isopropylcyclohexanecarbonyl)-D-phenylalanine;Nateglynide;Nateglinide intermediate;Nateglinide-H;AY 4166;D-Phenylalanine, N-((4-(1-methylethyl)cyclohexyl)carbonyl)-, trans-;

Article Data 14

Nateglinide Synthetic route

105746-47-2

N-<(trans-4-Isopropylcyclohexyl)carbonyl>-D-phenylalanine methyl ester

105816-04-4

nateglinide

Conditions
ConditionsYield
Stage #1: N-<(trans-4-Isopropylcyclohexyl)carbonyl>-D-phenylalanine methyl ester With water; sodium hydroxide In methanol at 25 - 30℃; for 5h;
Stage #2: With hydrogenchloride In water pH=2.0 - 2.5;
80.8%
With sodium hydroxide In methanol Yield given;
Stage #1: N-<(trans-4-Isopropylcyclohexyl)carbonyl>-D-phenylalanine methyl ester With sodium hydroxide In acetone at 20 - 25℃; for 2h;
Stage #2: With hydrogenchloride In water at 10℃; for 1h; pH=2 - 3; Product distribution / selectivity;
7077-05-6

trans-4-isopropylcyclohexane-1-carboxylic acid

673-06-3

D-(R)-phenylalanine

541-41-3

chloroformic acid ethyl ester

A

21488-23-3

N-(ethoxycarbonyl)-(D)-phenylalanine

B

105816-04-4

nateglinide

C

2-[2-[(trans-4-isopropylcyclohexanecarbonyl)amino]-3-phenylpropionylamino]-3-phenylpropionic acid

Conditions
ConditionsYield
Stage #1: trans-4-isopropylcyclohexane-1-carboxylic acid; chloroformic acid ethyl ester With triethylamine In acetone at -10 - -5℃; for 1.25h;
Stage #2: D-(R)-phenylalanine With 4-methyl-morpholine; triethylamine In water; acetone at -10 - -5℃;
A n/a
B 80%
C n/a
1245809-48-6

C17H24O4S

673-06-3

D-(R)-phenylalanine

105816-04-4

nateglinide

Conditions
ConditionsYield
In dichloromethane at 25 - 30℃; for 18.5h;75%
673-06-3

D-(R)-phenylalanine

100597-38-4

4-iso-propylcyclohexanecarbonyl chloride

105816-04-4

nateglinide

Conditions
ConditionsYield
With sodium hydroxide; sulfuric acid65%
With sodium hydroxide; sulfuric acid In n-heptane; ethyl acetate65%
With potassium hydroxide In water; acetone
84855-54-9

trans-4-iso-propylcyclohexylcarbonyl chloride

N,O-bis trimethylsilyl D-phenylalanine

105816-04-4

nateglinide

Conditions
ConditionsYield
In acetonitrile at -5 - 0℃; for 3.58333 - 3.66667h; Heating / reflux;
7077-05-6

trans-4-isopropylcyclohexane-1-carboxylic acid

105816-04-4

nateglinide

Conditions
ConditionsYield
Multi-step reaction with 2 steps
1: 1) N-hydroxysuccinimide, dicyclohexylcarbodiimide / 1) CHCl3, 3 h, 2) CHCl3, 25 deg C, 1 d
2: 2N NaOH / methanol
View Scheme
21685-51-8

D-phenylalanine methyl ester

105816-04-4

nateglinide

Conditions
ConditionsYield
Multi-step reaction with 2 steps
1: 1) N-hydroxysuccinimide, dicyclohexylcarbodiimide / 1) CHCl3, 3 h, 2) CHCl3, 25 deg C, 1 d
2: 2N NaOH / methanol
View Scheme
Multi-step reaction with 2 steps
1.1: benzotriazol-1-ol / dichloromethane / 0.25 h / 25 °C / Inert atmosphere
1.2: 3.25 h / 0 - 15 °C
2.1: sodium hydroxide / acetone / 2 h / 20 - 25 °C
2.2: 1 h / 10 °C / pH 2 - 3
View Scheme
175284-00-1

p-menthan-7-oic acid methyl ester

105816-04-4

nateglinide

Conditions
ConditionsYield
Multi-step reaction with 3 steps
1: 1) NaH, 2) 2N aq. NaOH / 1) 150 deg C, 2 h, 2) MeOH, 20 deg C, 10 min
2: 1) N-hydroxysuccinimide, dicyclohexylcarbodiimide / 1) CHCl3, 3 h, 2) CHCl3, 25 deg C, 1 d
3: 2N NaOH / methanol
View Scheme
594837-86-2

C19H26NO3(1-)*K(1+)

105816-04-4

nateglinide

Conditions
ConditionsYield
With hydrogenchloride In water at 15 - 20℃; pH=2.0 - 3.0; Product distribution / selectivity;
594837-85-1

C19H26NO3(1-)*Na(1+)

105816-04-4

nateglinide

Conditions
ConditionsYield
With hydrogenchloride; water at 25℃; for 0.5h; pH=2 - 3; Product distribution / selectivity;

Nateglinide Specification

The CAS registry number of Nateglinide is 105816-04-4. The systematic name is N-{[trans-4-(propan-2-yl)cyclohexyl]carbonyl}-D-phenylalanine. In addition, the molecular formula is C19H27NO3 and the molecular weight is 317.42. What's more, it belongs to the meglitinide class of blood glucose-lowering drugs. It is a drug for the treatment of type 2 diabetes. And it can be used as an amino-acid derivative that stimulates insulin secretion. Besides, it also can be used as an antidiabetic.

Physical properties about this chemical are: (1)ACD/LogP: 2.35; (2)ACD/LogD (pH 5.5): 2; (3)ACD/LogD (pH 7.4): 1; (4)ACD/BCF (pH 5.5): 5; (5)ACD/BCF (pH 7.4): 1; (6)ACD/KOC (pH 5.5): 27; (7)ACD/KOC (pH 7.4): 1; (8)#H bond acceptors: 4; (9)#H bond donors: 2; (10)#Freely Rotating Bonds: 6; (11)Polar Surface Area: 66.4 Å2; (12)Index of Refraction: 1.536; (13)Molar Refractivity: 89.612 cm3; (14)Molar Volume: 287.347 cm3; (15)Polarizability: 35.525 ×10-24cm3; (16)Surface Tension: 44.58 dyne/cm; (17)Density: 1.105 g/cm3; (18)Flash Point: 272.869 °C; (19)Enthalpy of Vaporization: 84.443 kJ/mol; (20)Boiling Point: 527.578 °C at 760 mmHg.

When you are using this chemical, please be cautious about it as the following:
This chemical is harmful if swallowed. During using it, wear suitable protective clothing and you should avoid contact with skin and eyes.

You can still convert the following datas into molecular structure:
(1)SMILES: O=C(N[C@H](Cc1ccccc1)C(O)=O)[C@H]2CC[C@@H](CC2)C(C)C
(2)InChI: InChI=1/C19H27NO3/c1-13(2)15-8-10-16(11-9-15)18(21)20-17(19(22)23)12-14-6-4-3-5-7-14/h3-7,13,15-17H,8-12H2,1-2H3,(H,20,21)(H,22,23)/t15-,16-,17-/m1/s1
(3)InChIKey: OELFLUMRDSZNSF-BRWVUGGUBB

The toxicity data is as follows:

Organism Test Type Route Reported Dose (Normalized Dose) Effect Source
dog LD oral > 2gm/kg (2000mg/kg) GASTROINTESTINAL: NAUSEA OR VOMITING Yakuri to Chiryo. Pharmacology and Therapeutics. Vol. 25(Suppl,
rat LD oral > 2gm/kg (2000mg/kg) SENSE ORGANS AND SPECIAL SENSES: PTOSIS: EYE

BEHAVIORAL: SOMNOLENCE (GENERAL DEPRESSED ACTIVITY)

GASTROINTESTINAL: "HYPERMOTILITY, DIARRHEA"
Yakuri to Chiryo. Pharmacology and Therapeutics. Vol. 25(Suppl,

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