JPS5936614A - Antilipemic agent - Google Patents

Abstract

PURPOSE:An antilipemic agent, containing a specific thienyloxazolylacetic acid derivative as an active constituent, and having improved reducing action on cholesterol in blood serum, reducing action on triglyceride in the blood serum and inhibitory action on agglutination of blood platelets without side effects, e.g. hepatic functin disorder. CONSTITUTION:An antilipemic agent containing a thienyloxazolylacetic acid derivative expressed by formula I (ring A is phenyl or halogen-substituted phenyl; R<1> is H or lower alkyl) or a pharmacologically acceptable salt thereof e.g. ethyl 2-[2-(4-fluorophenyl)-5-(3-thienyl)-4-oxazolyl]acetate, as an active constituent. The compound is obtained by subjecting a 3-benzoylaminopropionic acid derivative expressed by formula II (R<2> is lower alkyl) to the ring closing reaction through dehydration in the presence of a dehydrating agent in a solvent to form the aimed compound expressed by formula I (R<1> is lower alkyl). The daily dose thereof is preferably 5-15mg/kg body weight expressed in terms of the active constituent.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to an antilipemic agent, and more specifically, it is represented by the general formula (where Term 8 represents a phenyl group or a halogen-substituted phenyl group, and Hi represents a hydrogen atom or a lower alkyl group). The present invention relates to an antilipemic agent containing the following chenyloxazolyl acetic acid derivative or a pharmacologically acceptable salt thereof as an active ingredient.

Hyperlipidemia is thought to be a major cause of arteriosclerosis, and for the treatment and prevention of hyperlipidemia, drugs such as dextran sulfate and synfibrate [chemical name:
2-(4-chlorophenoxy)-2-methylpropionic acid 1. ▽3-propanediyl ester], nicomol (▽chemical name: 2.▽2.▽6.▽6-tetrakis (
nicotinoyloxymethyl)cyclohexyl], tallofibrate [chemical name: 2-(4-chlorophenoxy]-2-methylpropionic acid ethyl ester), and vitamin E/nicotinate, etc. It is used.

The present inventors have conducted various studies in order to develop better antilipemic agents. As a result, the chenyloxazolyl acetic acid derivative represented by the general formula CI) has an excellent serum cholesterol lowering effect and serum triglyceride lowering effect. In addition, compound CI) has no side effects such as liver dysfunction, and also has platelet aggregation inhibitory effects.
Discovered that this compound is extremely useful as an antilipidemic agent.

The present invention has now been completed. That is, the present invention provides %
: /L/An antilipemic agent comprising an oxazolyl acetic acid derivative (I) or a pharmacologically acceptable salt thereof as an active ingredient.

Examples of the chenyl oxazolyl acetic acid derivatives according to the present invention include, for example, in the general formula (I), where the chenyl group is a 2-chenyl group or a 3-chenyl group; , bromophenyl group, halogen-substituted phenyl group such as iodophenyl group;
Examples include compounds which are lower alkyl groups such as butyl group, isobutyl group, n-pentyl group, and inpentyl group.

Among these, preferred compounds include general formula CI)
i is ring 8f) (▽phenyl group, 4-fluorophenyl group, 2-chloro'phenyl group, 3-chlorophenyl group or 4-gelorophenyl group, and R1 is a hydrogen atom, methyl group, ethyl group, isopropyl group) f<, n−
▽Compounds that are a phthyl group or an n-pentyl group are mentioned. More preferred compounds include general formula CI) in which ring 8 is a phenyl group, 4-fluorophmenyl group, or 4-fluorophmenyl group.
It is a chlorophenyl group, and R1 is a hydrogen atom, an ethyl group,
Examples include compounds in which the chenyl group is a 3-chenyl group in the general formula CI), and the compound is an n-butyl group or an n-pentyl group. Examples include compounds in which R1 is a lophenyl group and R1 is an ethyl group or an n-pentyl group.

In the compound (I) according to the present invention, when R1 is a hydrogen atom, (, t, ffl:b, pjltrN
*qa, r-6,1, *l, can also be used in the form of a true salt. Such salts include, for example, alkali metal salts such as sodium salts and potassium salts; alkaline earth metal salts such as calcium salts and magnesium salts;
Examples include salts with basic amino acids such as lysine, ornithine, and arginine; and ammonium salts.

When compound (I) or a salt thereof is used as a medicine, it can be administered orally or parenterally. When compound (I) or a salt thereof is administered orally, it can be made into tablets, powders, capsules, granules, etc., and they can be shaped into conventional shapes.

For example calcium carbonate, calcium phosphate, corn starch, potato starch 1 sand 11i.

It may contain lactose, talc, magnesium stearate, etc. In the case of oral administration, it may be administered as a liquid preparation such as an aqueous or oily suspension, solution, syrup, or elixir. Furthermore, when administering parenterally, for example, injections,
Suppositories, etc., and injectable preparations are given in the form of solutions or suspensions, and are prepared using distilled water for injection, essential oils (e.g., peanut oil, corn oil, etc.) or non-aqueous solvents. (For example, polyethylene glycol, polypropylene glycol, lanolin, coconut oil, etc.) may be contained. The daily dosage of compound (I) or a salt thereof according to the present invention varies depending on the route of administration, patient's age, weight, medical condition, etc., but is usually 1 to 20 TR9/K per day. , Toriwake 5-151ng/Kg
I like it.

The 1,000-enyloxazole derivative (I) according to the present invention is:

A 3-benzoylaminopropionic acid derivative represented by the general formula (81▽▽ (where R2 represents a lower alkyl group and term 8 has the same meaning as above) is subjected to multiple dehydration ring-closing reactions to obtain the general formula (▽▽ (R2 and ring 8 have the same meanings as above).

▽bl The compound (■) obtained by the above fal method is hydrolyzed to give a chenyloxazolyl acetic acid derivative represented by the general formula (however, term 8 has the same meaning as above), or ( c) ▽Compound (I-b) obtained by the above (bl method)
It can be produced by esterifying to obtain a chenyloxazolyl acetate derivative represented by the general formula (wherein R3 represents a lower alkyl group and term 8 has the same meaning as above).

The dehydration ring closure reaction of compound (II) is carried out using a dehydrating agent (for example (f), phosphorus oxychloride, thionyl chloride,
-5° to 100° in the presence of phosphorus pentachloride, phosphoric anhydride, etc.)
It can be suitably carried out at a temperature of 0.degree. C., particularly 00 to 10.degree.

Hydrolysis of compound C▽I-a) results in compound (I-a)
This can be carried out by treating with an acid (for example, a mineral acid such as hydrochloric acid or sulfuric acid) or an alkali (for example, an alkali gold hydroxide rR such as sodium hydroxide or potassium hydroxide) in a suitable solvent. This reaction proceeds suitably at 00 to 100°C, especially at 10▽ to 30°C. As the reaction solvent, for example, a mixed solvent of water and T-kanol (eg, methanol, ethanol, propanol, etc.), tetrahydrofuran, dioxane, formic acid, or acetic acid can be suitably used.

Esterification of compound (I-b) is carried out by combining a reactive derivative (e.g., acid halide, mixed acid anhydride, etc.) at the carboxyl group of compound (I-b) with R”OH▽ (where R3 has the same meaning as above). alkanols represented by
-pentanol, impentanol, etc.). For example, compound (I
-b) When using the corresponding acid halide as the reactive derivative, the reaction is carried out in a suitable solvent (e.g. methylene chloride, chloroform, acetic acid ethyl ester, tetrahydrofuran, benzene, dioxane, dimethylformaldehyde, etc.) with a deoxidizing agent. (For example, triethylamine, tributylamine, pyridine, etc.) The reaction can be suitably carried out at -10°C to 20°C in the presence or absence.

In addition, esterification of compound (I-b) can be performed by esterifying compound (▽I-
b) and an alkanol represented by R”OH▽ (where Hl has the same meaning as above) in a suitable solvent (e.g., tetrahydrofuran, dioxantoluene, chloroform, etc.) with a dehydrating agent (e.g., 2-iodide). Chloro-1
-Methylpyridinium.

The reaction can be carried out by reacting at 00 to 30°C in the presence of 2-bromo-1-methylpyridinium iodide, dicyclohexylcarbodiimide, etc.). In addition, when using 2-chloro-1-methylpyridinium iodide or 2-bromo-1-methylpyridinium iodide as a dehydrating agent, this reaction is carried out in the presence of a deoxidizing agent (for example, triethylamine, tributylamine, pyridine, etc.). It is preferable to carry out the

Esterification of further compound CI-b)
) and alkanols represented by R30H▽▽ (where RS has the same meaning as above) with an acid (for example, P-
50 in the presence of toluenesulfonic acid, hydrochloride, sulfuric acid, etc.)
Should the reaction be carried out at ~100°C?

Alternatively, compound (I-b) may be mixed with a suitable solvent (for example, ▽).

Alkyl halides (e.g., methyl iodide, ethyl iodide, etc.) in the presence of an appropriate base (pyridine, triethylamine, etc.)
It can also be carried out by reacting with n-propyl bromide, n-propyl iodide, n-butyl bromide, n-pentyl chloride, etc.) at 50° to 100°C.

Incidentally, the raw material compound (In) for the above reaction can be produced by the method shown in the following reaction formula.

do. In addition, in the present specification, the lower alkyl group has a carbon number of 1 to 5.
The alkyl group of is represented by h.

Experimental example] (▽IJI quality deterioration effect) Sample content: 0.05 when the sample was mixed with powdered rat feed
<) - The mixture was administered to SD male rats (body weight: 120 to 1
40f! , 5 animals per group) were allowed to feed freely for one week, then blood was collected from the tail under ether anesthesia, and serum cholesterol levels were measured using the ZaK method (▽Amar, J.
CIin, Patho1. , Vol, 2▽4
.

P, 1307 (1954)), serum triglyceride levels were determined by the Van Handel-Zilvaremit method (▽J, Lab.

& Clim, Mad, , Vo1, 55. P, 152 (
1957)). On the other hand, the liver was removed and the liver weight was removed. From these results, relative liver weight increase rate, serum cholesterol decrease rate, and serum triglyceride decrease rate were determined using the following formulas. The results of lipid lowering effect are below @1
As shown in the table. Also. Regarding liver relative weight increase rate,
Clofibrate had 12 beaks, but all of the compounds of the present invention had 0 beaks.

Experimental Example 2 (Platelet aggregation inhibitory effect) SD male rats anesthetized with ether (body weight = 250-3
00F) was collected from the abdominal aorta, 9 volumes of the blood was mixed with 1 volume of a 3.8 width trisodium citrate aqueous solution, centrifuged (▽500XV, 5 minutes), and the supernatant was collected. Collect the fluid and perform platelet rich plasma (hereinafter referred to as PRP).
was prepared. Furthermore.

The remaining blood was centrifuged (100×g, 10 minutes) and the supernatant was collected and referred to as platelet-poor plasma (hereinafter referred to as PPP).

] was prepared. Dilute PRE▽ with ppp and PRP platelet count is 8▽-▽1▽0 X 1▽0▽aalls/m
It was prepared so that al. The P prepared above was placed in the cell of a platelet aggregometer (Cienco, DP-24 Fu D type).
Take a mixture of R▽P 2▽0▽0 pl and sample solution 25141 (final concentration: 100μVtnl) and heat at 37°C.
, 1] After preincubation for 2 minutes at 0▽0 rpm, the method of Holmsen et al.
Completed, Vo1.186. P, 254 (▽1969)
] Collagen suspension* (▽10(1▽/m
Z) 25μe was added to cause platelet aggregation. Platelet aggregation ability was measured using the Bourne method [Nature, Vol.
．． ] 9▽4 *Page 927 (1969): According to I, the platelet aggregation inhibition rate was determined by the following formula, and the inhibition rate was less than 10% (-), and the inhibition rate 10< or more (+).
It was determined that The results are shown in Table 2 below.

Actual sample example 3 (Platelet aggregation inhibitory effect) The sample was suspended in #0.25<carboxymethylcellulose sodium salt 1▽0.0▽1<TWeon 8▽0 solution.

The suspension was transferred to SD male rats (body weight: 200-240F).
, 4 animals per group) by oral administration (dose=100"?/[▽
l) L, ta. One hour after administration of the sample, blood was collected from the abdominal aorta under anesthesia. After blood collection.

It was treated in the same manner as in Experimental Example 2. After measuring the platelet aggregation ability, the platelet aggregation inhibition rate was calculated using the following formula. The results are shown in Table 3.

Reference example 1 3-(4-fluorobenzoylamino)Φ-3-[3-
chenylcarbonylpropionate ethyl ester 40
y is dissolved in 150 - of dimethylformamide, 24.6 g of phosphorus oxychloride is gradually added dropwise into the solution at 0° to 5°C, and the mixture is stirred at the same temperature for 4 hours and then at room temperature overnight. After the reaction is complete, the mixture is poured into water, made neutral with sodium bicarbonate, and extracted with ethyl acetate.

The extract is washed with water, dried, and the solvent is distilled off under reduced pressure.

By recrystallizing the residue from ethanol, 2-(2
-(4-fluorophenyl)-5-(3-chenyl)-
Mu-oxazolyl)acetic acid, r-thyl ester 32.47
get. Yield: 85.5・≦M, P, 112°-113
℃ I R▽pNujol (▽(3-,) : 1▽7▽
3▽0▽ax Reference Examples 2 to 7 The compound shown in Tg is obtained by the same treatment as in Reference Example 1.

+2>2-1m2-phenyl-5-(3-chenyl)-
4-oxazolyl]ethyl acetate ester M, P,
90°-91℃ IRνN: Koni▽ (▽ci”): 1▽7▽2▽0
, ▽1▽6▽2▽0(31▽▽2▽−▽(▽2▽−▽
(▽4-chlorophenyl)-5-(3-chenyl]-4
-oxazolyl]acetic acid ethyl ester M, P・12▽7°−▽1▽2▽8℃IR siege (
cg7▽):1730.1630(4) 2▽-C
▽2▽-▽(▽4-chlorophenyl)-5-<31chenyl)-4-oxazolyl]acetic acid methyl ester M, P, 127°-128°C I R▽▽νN: 1 (▽cfri: 1740. 16
23+512-(2-chenyl-5-(2-chenyl)
-4-oxazolyl]acetic acid methyl ester M, P, 82
°-83℃ IRvNu”▽(ai”): 1725.1618▽ax +61 ▽2-C▽2-(▽4-fluorophenyl)-
5-(2-chenyl,)-4-o+sa/▽IJru]
Acetic acid ethyl ester 1, P・ 116°−1▽1▽7℃ IRνPx1 (▽Ca+”): 1▽7▽2▽0 *
1▽6▽2▽0(7) 2▽- C▽2▽-▽(▽
4-chlorophenyl)-5-(2-chenyl)-4-oxazolyl]acetic acid ethyl ester M, P, 119°-120°C IRy"jol(ti"): 1730-1620▽ax Reference example 8 2, -(2 -(4-fluorophenyl)-5-(3-chenyl)-4-oxazolyl]acetic acid ethyl ester 27
．． 45▽ to methanol 7▽0▽0 rrJ and water 100-
Potassium hydroxide is dissolved in a mixture of 10.9!
Add F and stir at room temperature for 17 hours. After the reaction is complete, the mixture is concentrated under reduced pressure to remove the solvent. After adding water to the residue, the pH was adjusted to pH▽2 with concentrated hydrochloric acid, and the mixture was extracted with ethyl acetate. The extract was washed with water, dried, and then the solvent was distilled off under real pressure. By recrystallizing the residue from ethanol.

22.37% of 2-(2-(4-fluorophenyl)-5-(3-chenyl)-4-oxazolyl]acetic acid are obtained.
Yield: 89 M, P, 207°-209°C IRνNujO1 (▽c*Q: l 7▽2▽0dakea
x Reference Example 9~(▽11▽-1▽▽) By treating in the same manner as in Reference Example 8, the compound shown below is obtained.

L91 ▽2▽- C▽2▽-▽(▽4-fluorophenyl)-5-(2-chenyl]-4-oxazolyl]acetic acid M, P, 208°-209°C I R▽▽I/Nuj 01 ( i”) 2 1
▽7 ▽20m &
▽ (▽cm””): 1▽7▽2▽5 (11-1)
2▽- C▽2▽-▽(▽4-chlorophenyl)-
5-(3-chenyl)-4-oxazolyl]acetic acid M, P
, 218°-219°C I R▽v”j” (▽Ql”): 1▽7▽2▽0
▽ 118 Stir at room temperature for 3 hours. After the reaction is completed, the reaction mixture is concentrated under reduced pressure to remove the solvent. By washing the residue with cold ethanol and ether, *▽l▽(1-(
▽4-chlorophenyl)-5-(▽3-chenyl)-4
-oxazolyl]acetic acid sodium salt 2.9y is obtained.
Yield: 90%, P, ) 250°C IR sea iρ1 (01”): 1593 Reference example 12 2-(2-(4-fluorophenyl)-5-(3-chenyl)-4-oxazolyl E vinegar m Ethyl ester 2.7
9 to xo1 water-potassium oxide/methanol solution IQrn
1 and stirred at room temperature for 17 hours. After the reaction is complete,
By filtering the precipitated product and washing with cold ethanol and ether, 2-C2-(4-fluorophenyl)-5
-(3-chenyl)-4-oxazolyl]potassium acetate salt 2.4F is obtained. Yield: 80% M, P, >250℃ I R▽v”▽J” (▽(g”): 1▽5▽8▽
0▽ax Reference Example 13 2-(2-(4-chlorophenyl)-5-(3-chenyl)-4-oxazolyl]acetic acid 2y was dissolved in toluene 2-, thionyltalolide 32 was added to the solution, and 1
Stir at night. The reaction mixture was concentrated under reduced pressure and the residue was
Add 30-pentanol and stir at room temperature for 4 hours. After concentrating the mixture under reduced pressure to distill off n-pentanol.

The residue is extracted with acetic acid, %m. Carbonated water extract; na)
After washing with an aqueous IJum solution and water and drying, the solvent is distilled off under reduced pressure. By recrystallizing the residue from ethanol, 2-(2-(4-chlorophenyl)-5-(3-
(chenyl)-4-oxazolyl)acetic acid n-pentyl ester1. :l▽I got it.

Yield: 49 width} J, P, 86°-8▽7℃ I RuN, :jcx▽(ai▽) :1730 @
1625 Reference Examples 14-16 By treating in the same manner as in Reference Example 13, the compounds shown below are obtained.

+14) 2-(2-phenyl-5-(3-chenyl)-
4-Oxazolyl]acetic acid isopropyl ester▽ ItP, 62°-▽6▽3℃ I R▽▽飄c▽ (▽Ca+-”): 1▽7▽2
▽5 r 1▽6▽3▽1(15) 2-[2-phenyl-5-(3-chenyl)-4-oxazolyl]acetic acid n-
Butyl ester M, P, 71▽-72℃ IRvNujol(cf”) :] 725▽.1▽6
30▽ax i1612-(2-phenyl-5-(3-chenyl▽)
-4-oxazolyl]acetic acid n-pentyl ester▽ M, P▽, 61▽-62 °C IRνNu”▽ (▽rm”): 1▽7▽2▽5
+ I Ei 2▽5▽aX Reference example 17 2-C2-C4-chlorophenyl)-5-(3-chenyl)-4-oxazolyl]acetic acid 2.69 was added with potassium hydroxide 0. ▽5▽4 F-containing 50% methanol aqueous solution 20〃
After stirring the mixture at room temperature for 3 hours, the mixture is concentrated under reduced pressure and the solvent is distilled off. After adding 6.47 g of oxalyl chloride to the residue and stirring overnight, the mixture is concentrated under reduced pressure and excess oxalyl chloride is distilled off. Add 20 tnl of inpropanol to the remaining residue and incubate at room temperature for 5 tnl.
Stir for some time. After the reaction is complete, the mixture is concentrated under pressure to remove the solvent. The residue is extracted with acetic acid, extracted with H; and washed with an aqueous solution of sodium bicarbonate and water. 'The extract is dried and concentrated under reduced pressure to remove the solvent.

By recrystallizing the remaining residue from ethanol, 2-(2
7(4-chlorophenyl)-5-(3-chenyl)-4
-oxazolyl]acetic acid isopropyl ester 1.61 is obtained. Yield: 55 M, P, 118°-119°C IR▽vNuj0▽ (▽Cl+▽): 1▽
7▽2▽5, ▽1▽6▽3▽0 Reference Examples 18 to 19 By treating in the same manner as in Reference Example 17, the compounds shown below are obtained.

(18) 2▽-C▽2▽-▽(▽4▽-▽fluorophenyl)-5-(3-chenyl)-4-oxazolyl]acetic acid n-butyl ester M, P, 31°-82°C I R ▽νNuj01(ci”): 1730.16
30▽, 1610▽ax (IgI2▽- C▽2▽-▽(▽4-fluorophenyl)-5(3-chenyl)-4-oxazolyl]acetic acid n
-Pentyl ester M, P, 78°-80°C I R▽v”, 1°1Ccm”): 1730.163
0.1610+llaX Reference Example 20 2-C2-C4-fluoro7ale)-5-(3-chenyl)-4-oxazolyl)acetic acid IP.

2-gelol iodide 1-methyl-bilisoum 0.9.3
f! and 0.22% of impropanol were dissolved in 40% of tetrahydrofuran, and 0.22% of triethylamine was added to the solution. ▽6
▽6 Drop Fl. The mixture is stirred at room temperature for 18 hours. After the reaction is completed, water is added to the reaction mixture, and the mixture is concentrated under reduced pressure to distill off tetrahydrofuran. The remaining residue is removed with ethyl acetate, and the extract is washed successively with a 20% aqueous citric acid solution, an aqueous sodium bicarbonate solution, and water. After drying the extract, the solvent was distilled off and the residue was recrystallized from ethanol to obtain 2-1G2-(4-fluorophenyl) -▽5▽-▽(▽3-▽chenyl). -4-oxazolyl]acetic acid isopropyl ester o, a5sEi?
Ill.

Yield: ÷4.6 LP, 108°-110°C IRν”, !:1(▽ai▽): 1730▽.1▽
630, ▽1605 Reference Example 21 2-[2-[4
-chlorophenyl 1▽-▽5▽- (▽3-chenyl)
-4-oxazolyl]-acetic acid n-butyl ester is obtained.

Reference Examples 22 to 23 The following compounds were obtained by treating in the same manner as in Reference Example 1.

(22) 2-C2-(2-chlorophenyl)-5-(3
-Chenyl-4-oxacylinoliacetate ethyl ester M, P, 73°-▽7▽5℃ I R▽▽V Nu”▽ (▽an▽): 1▽7
▽2▽5 #] 6▽2▽0▽ax (2312-1:2-(3-chlorophenyl)-5-(
3-chenyl▽)-4-oxazolyl]ethyl acetate varnish T▽ M, P, 128°-1▽30℃ I R▽▽νNujo1(d-l): 310t)
, 1730, 1630°▽ax ▽600 Reference Examples 24-25 The following compound was obtained by treating in the same manner as in Reference Example 8.

(24) 2-(Hc(2-chlorophenyl)-5-(
3-chenyl)-4-oxazolyl]acetic acid M, P, 16
3°-165℃ IR▽νN”01(ci”): 1▽728, ▽1
▽630(25)2-(2-(3-chlorophenyl-5)
-(3-chenyl)4-oxazolyl]acetic acid 1, P.

▽ ▽ 4°− ▽ 9▽7℃ ■ ▽ , Nujol ( am) :　　　1▽710▽. 1▽630　▽． 1600 agents patent attorney During ~ Shima Positive -1・), same 1・(j・Re′v1 12 stitches IN, yj, 1

Claims (1)

[Claims] 1. A chenyloxazolyl acetic acid derivative represented by the general formula (wherein, ring A represents a phenyl group or a halogen-substituted phenyl group, and R1 represents a hydrogen atom or a lower alkyl group) or its pharmacology An antilipemic agent containing vine salt as an active ingredient. 2. The antilipemic agent according to claim 1, wherein in the general formula (I), ring A is a carphenyl group, a chlorophenyl group, or a fluorophenyl group. 3. In general formula CI), ring A is a phenyl group, 4
-Fluorophenyl M, 2-chlorophenyl group. The antilipemic agent according to claim 1, which is a 3-chlorophenyl group or a 4-chlorophenyl group. 4. The antilipemic agent according to claim 1, 2, or 3, wherein in general formula (I), R1 is a hydrogen atom. 5. The antilipemic agent according to claim 1, 2, or 3, wherein in general formula (i), R1 is a lower alkyl group. 6. In general formula (I), ring A is a phenyl group, 4-
Fluorophenyl group, 2-chlorophenyl group. The antilipemic agent according to claim 1, which is a 3-chlorophenyl group or a 4-chlorophenyl group, and R1 is a hydrogen atom, a methyl group, an ethyl group, an isopropyl group, an n-butyl group, or an n-pentyl group. .