Structure of 99799-09-4
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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
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CAS No. : | 99799-09-4 |
Formula : | C8H14O3 |
M.W : | 158.20 |
SMILES Code : | O=C(O)CC1CCC(O)CC1 |
MDL No. : | MFCD13659403 |
InChI Key : | ALTAAUJNHYWOGS-UHFFFAOYSA-N |
Pubchem ID : | 12702257 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H315-H319 |
Precautionary Statements: | P264-P280-P302+P352-P337+P313-P305+P351+P338-P362+P364-P332+P313 |
Num. heavy atoms | 11 |
Num. arom. heavy atoms | 0 |
Fraction Csp3 | 0.88 |
Num. rotatable bonds | 2 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 2.0 |
Molar Refractivity | 41.39 |
TPSA ? Topological Polar Surface Area: Calculated from |
57.53 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.35 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.57 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
1.01 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.69 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
0.74 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.87 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.05 |
Solubility | 14.2 mg/ml ; 0.0896 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-1.35 |
Solubility | 7.05 mg/ml ; 0.0446 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-0.28 |
Solubility | 83.6 mg/ml ; 0.528 mol/l |
Class? Solubility class: Log S scale |
Soluble |
GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg |
High |
BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg |
Yes |
P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) |
No |
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) |
No |
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) |
No |
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) |
No |
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) |
No |
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) |
No |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-6.86 cm/s |
Lipinski? Lipinski (Pfizer) filter: implemented from |
0.0 |
Ghose? Ghose filter: implemented from |
None |
Veber? Veber (GSK) filter: implemented from |
0.0 |
Egan? Egan (Pharmacia) filter: implemented from |
0.0 |
Muegge? Muegge (Bayer) filter: implemented from |
1.0 |
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat |
0.56 |
PAINS? Pan Assay Interference Structures: implemented from |
0.0 alert |
Brenk? Structural Alert: implemented from |
0.0 alert: heavy_metal |
Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<1.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
2.25 |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
25% | EXAMPLE 50 (trans)-2-(4-Hydroxy-cyclohexyl)-N-[4-methoxy-7-(tetrahydro-pyran-4-yl)-benzothiazol-2-yl]-acetamide Using 4-methoxy-7-(tetrahydro-pyran-4-yl)-benzothiazol-2-ylamine and <strong>[99799-09-4](4-hydroxy-cyclohexyl)-acetic acid</strong>, the title compound was prepared in the same manner as described for N-[4-methoxy-7-(tetrahydro-pyran-4-yl)-benzothiazol-2-yl]-2-(tetrahydro-pyran-4-yl)-acetamide and obtained as white crystals (25% yield). Mp 120-145 C., MS: m/e=405(M+H+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
150 mg | With potassium hydroxide; In methanol; water; at 60.0℃; for 6.0h; | A mixture of potassium hydroxide (326 mg) and methyl 2-(4-hydroxycyclohexyl)acetate (D8, 500 mg) in methanol (20 mL) and water (20 mL) was stirred at 60C for 6 hours. After cooling to RT, the reaction mixture was concentrated and acidified with HC1 solution (2 M) to adjust the pH valute to 1, and then extracted with EA (50 mL). The organic layer was dried over Na2 SO4, filtered and concentrated in vacuo to afford the title compound (150 mg) as white solid. MS (ESI): C8H,403requires 158; found 159 [M+HJ. |
3 g | With water; potassium hydroxide; In methanol; at 80.0℃; for 6.0h; | Description 32-(4-Hydroxycyclohexyl)acetic acid (D3) The mixture of potassium hydroxide (2.61 g) and methyl 2-(4-hydroxycyclohexyl)acetate (D2, 4 g) was dissloved in MeOH (30 mL) and water (30 mL). The reaction mixture was stirred for 6 hours at 80C. The reaction mixture was concentrated and acidified with 2 M HC1 (aq.) to pH = 1, then extrated with DCM (2x50 mL). The organic layer was dried with anhydrous sodium sulfate.Filtered, the filtrate was concentrated to afford the title compound (3 g) as yellow solid. MS (ESI):C8H1403 requires 158; found 157 [IVI-H]. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
48 mg; 18 mg | With HATU; In N,N-dimethyl-formamide; at 20.0℃; for 6.0h; | Examples 61&62N-(5-chloro-3-(((S)-4-(cyclopentanecarbonyl)-3-methylpiperazin-1-yl)methyl)-2-methylphenyl)-2-((ls,4R)-4-hydroxycyclohexyl)acetamide & N-(5-chloro-3-(((S)-4-(cyclopentanecarbonyl)-3-methylpiperazin-1-yl)methyl)-2-methylphenyl)-2-((lr,4S)-4- hydroxycyclohexyl)acetamide (E61 & E62) 2-(4-Hydroxycyclohexyl)acetic acid (D3, 150 mg) and HATU (361 mg) were added to the (S)-(4-(3-amino-5-chloro-2-methylbenzyl)-2-methylpiperazin-1 -yl)(cyclopentyl)methanone (D157, 332mg) solution in DMF (20 mL), the reaction mixture was continued to stir for 6 hours at RT. Water(20 mL) was added and extracted with EtOAc (50 mL), the organic layer was dried over Na2SO4.Filtered, the filtrated was concentrated and the residue was purified by preparative HPLC to affordthe two compounds (48 mg and 18 mg) as white solid. Isomer 1: ?H NMR (500 MHz, DMSO-d6):9.35 (s, 111), 7.38 (s, 1H), 7.15 (s, 1H), 4.54 (brs, 0.5H), 4.47 (d, J= 4.4 Hz, 1H), 4.19 (d, J 10.1 Hz, 1H), 3.75 (d, J= 12.9 Hz, 0.511), 3.45-3.36 (m, 2ff), 3.36-3.33 (m, 1ff), 3.17 (t, J 12.1 Hz, 0.5H), 2.97-2.86 (m, 1H), 2.81-2.68 (m, 1.511), 2.60 (d, J= 9.5 Hz, 111), 2.21 (d, J= 6.9 Hz, 2H),2.16 (s, 3H), 2.14-1.45 (m, 15H), 1.29-0.95 (m, 7H). MS (ESI): C27H.40C1N3O3 requires 489; found490 [M+H]. Isomer 2: ?H NMR (500 MHz, DMSO-d6): 9.37 (s, 1H), 7.38 (d, J= 1.6 Hz, 1H),7.15 (s, 1H), 4.54 (brs, 0.511), 4.30 (d, J- 3.2 Hz, 1H), 4.20 (d, J= 8.5 Hz, 1H), 3.79-3.70 (m,1.5H), 3.46-3.36 (m, 211), 3.18 (t, J 11.7 Hz, 0.5H), 2.91 (quin, J=? 7.4 Hz, 1H), 2.81-2.68 (m,1.5H), 2.65-2.57 (m, 1H), 2.26 (d,J 7.3 Hz, 2H), 2.17 (s, 311), 2.13-1.38 (m, 19H), 1.27-1.05 (m,311). MS (ESI): C27H40C1N3O3 requires 489; found 490 {M+Hj. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With HATU; In N,N-dimethyl-formamide; at 20.0℃; for 18.0h; | Description 204(S)-tert-butyl 4-(5-chloro-3-(5-fluoro-6-methylnicotinamido)-2-methylbenzyl)-2-methylpiperazine-1-carboxylate (D204)NHF N.0A solution of (S)-tert-butyl 4-(3 -amino-5-chloro-2-methylbenzyl)-2-methylpiperazine-1 -carboxylate (D159, 913 mg), 5-fluoro-6-methylnicotinic acid (Dl 13, 400 mg), HATU (980 mg)and DIPEA (0.45 0 mL) in DCM (100 mL) was stirred at RT for 18 hours. The mixture wasconcentrated under vacuum to afford the title compound (1.2 g) as red oil which was used directlyfor next step without further purification. |
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