TW212801B - - Google Patents

Description

V. Description of the invention (1) The present invention is characterized by the fact that [3 Η, 7 η] «zozo [3, 4-a] at steep, its preparation method and the pharmaceutical composition containing them. More to be determined, the present invention is based on the compound of formula (1):

S (please idle ^ memorize the meal on the back and then write this page). The staff of the Central Standards Bureau of the Ministry of Economic Affairs prints and burns the cooperative. Among them: R is (qD alkyl; Ri is free or carboxylated, alkane glass) Group or radon group. Or as in the formula -C0NH (CH2> q _HRaRb group, wherein <1 is an integer 2 to 4; Ra is radon, Cfk alkyl, benzyl; Rb is hydrogen or (Ci-C6) alkyl , Or Ra and Rb together with the cyanide atom to form pyrrolidin-1-yl, hexahydro W; pyridin-1-yl, isop-4-yl, 4-thio-OSS-4-yl, (C1-C4) Alkyl hexahydropyridyl-buyl; 1 to 2 is ({: 3- ^ 7) alkyl, ", / 9 or 7-pyridyl, optionally substituted phenyl or bicyclic (where benzene ring and Containing one or more inclination S from 0, the atoms are mixed together, the Wen is connected via benzene); It is a free or salted carboxyl group or alkane carbonyl group; D is 5- or 6- with 1_3 sickle nitrogen atom Bezachen, which may be ® or 2-tilt amine group, mono- (Ci-Ce alkyl) group, mono- (c3-c7 alkenyl) group, *-· wood paper ruler Λ Valve Threshold Jiahuan (CNS) A · 1 gauge f each (210 X:】 97 public exchange) Λ 6 Β6 212801 V. Description of the invention (2) (Please read the notes on the back (Write this page) Mono- (c3-c7 alkynyl) amine, di- (Ci-h alkyl) amine, (Ci-C6 alkyl)-(C3-C7 alkenyl) amine, hexahydropyridine -1-yl, moxi-4-yl, pyrrolidin-1-yl. In this context, "optionally substituted phenyl" means phenyl substituted with 1-3 substituents selected from the following groups: ((^-(: 6) alkyl such as methyl, ethyl, propyl, isopropyl, 3-butyl; (Ci-cy alkanoyl such as methyl, ethoxy, or propoxy ; (Ci-C4) alkylthio groups such as methylthio, ethyl «group: benzene gas group; 4-hydroxybenzene m group; phenylthio group; 4-hydroxyphenyl group; halogen atom (ambient, bromine or fluorine); Cyano, azide, nitro, amine; (Ci-Ce) amide group; trihaloacetamide group such as trifluoroethyl amine group; methyl- or tri «methyl-sulfonyl amine group; benzene- Or p-toluenesulfonamide; trihalomethyl such as trichloro- or trifluoromethyl; dihalomethoxy such as difluoromethyl m; trifluoromethoxy; free or salted carboxyl groups; (Ci- C 4) Alkyl chlorocarbonyl group. The preferred mono- or poly-substituted phenyl groups are those with the following substituents: 2-gas, printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs * * SR, 4-tired, 2, 3--tired, 2_ articles, 2-cut -3-first, 2-ίβ group, 3 * &quot; nitro, 3-nitro-4-phenoxy, 4- Nitro, 4-nitro-3-phenoxy, 2-trifluoromethyl-, 3-trifluoromethyl-, 3- «yl, 3-methyloxy, 2-amino, 3-amino , 4-amino, 2-methanesulfonamido, 3-methanesulfonamido, 4-methanesulfonamido, 3-methanesulfonamido-4-benzyl, 4-methanesulfonamide Yl-3-phenylamino, 4-«-2,3-diazepine, 3-carboxy-4-hydroxy, 3-hydroxy-4-carboxy, and combinations thereof. When R2S (C3-C7) oxalyl is preferred, it is preferably propyl, pentyl or cyclohexyl. When 1 ^ or P3 is an alkyl carbonyl group, it is preferably ((^-(: 4) alkyl ester, allyl-coated paper. Applicable to the Chinese standard? Standard (CNS) A! Regulations 丨 each X 297 male; f) 4 Λ (ιΗ (; 212801 V. Description of the invention (3) Ester, propargyl ester, benzyl ester, p-methoxybenzyl ester, diphenylmethyl ester, triphenylmethyl ester or trichloroethyl Ester. When R2 is Shuangchen and one of the Benzene and 5- or 6-members is conjugated, it is preferably benzene; and -1,3-dioxol-4-yl, 1,4- Benzodiazepine-6-yl, 1,4-benzodiazepine-5-yl, benzofuran-4-yl, benzofuran-4-yl. ^ Preferred examples of D There are pyridin-2-yl, pyrimidin-4-yl, piperidin-2-yl or 1,3,5-tris-2-yl, which can be substituted with 1 or 2 amine groups, mono- (Ci- Ce -alkyl) amino, 2-propenylamino, 2-propynylamino, propylamino, isopropyl leg, or dialkylamino such as dimethylamino, diethyl Amino group, ethyl-2-propenylamino group, etc. Other preferred D are: pyridin-2-yl, [2,6 _2 (diethylamino) diurethane-4-every-, [2 , 6-® (2-propanyl-based) -i-4-_yl], [2,6-¾ (amino) pyrimidin-4-yl] [2,6-Second (pyrrolidinyl-bromo) -pyridin-4-yl], [4,6-Second (2-propenylamino) -1,3,5-tris-2-yl], [4,6-Two (diethylamino) -1,3,5-tris-2-yl], [4,6-Two (pyrrolidin-: 1-yl) -1,3,5- Trim-2-yl], [3,6-II (diethylamino) tft pyridin-2-yl], [3, 6- II (tt pyridin-1-yl) lit pyridin-2-yl ], [3,6-Two (2-propenylamino) ladian_2-yl]. The particularly preferred compound (I) printed by the employee consumer cooperative of the Central Standards Bureau of the Ministry of Economic Affairs is ^ and ^ is alkane carboxyl , Especially methoxycarbonyl, ethylcarbonyl, isopropyl, 2-propylenecarbonyl and 3-butoxycarbonyl, or Ri is -C0HH (CH2) q-NRaRb and q, Ra and Rb are as before Definitions, and R3 is an alkyl carbonyl group as defined above; "2 is an optionally substituted phenyl or (C3-C 7) alkane group as defined above; and R is a paper standard applicable to the domestic standard (.CNS) Jiajiange (210 X 297 Gonglian) '-5 A6 212801 _B6_ V. Description of the invention (4) The base. When there is an acidic or _ sex group in the compound of formula (I), it can be used in medicine Acceptable bell or acidification. The resulting non-toxic salts, as well as single para-isomers, racemates and diastereomers, or their complexes are included in the present invention. More specifically, the compounds of formula (I) are in 3- and The 7-position contains two asymmetric sulfon atoms, the same supply and the geometric configuration of phase I are defined by the following (la) and (lb) respectively: (^ Call to read the precautions on the back and then write this page)

(la) -Identical side (lb) -The compound printed by the Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs (la) compound is referred to hereinafter as Tong inverted-[3H, 7H] Kuangzo [3, 4-a] Pyridine, or abbreviated as [3 Η, 7 Η] «« zo [3, 4-a] pyridine. The compound of formula (I b) will be referred to as p-employed- [3H, 7H] thiazolo [3,4-a] pyridine, and the mixture of diastereoisomers will be represented by (s, a)-[3H, 7H ] Thiazolo [3, 4-a] ttt pyridine said. The compound of formula (I a) and the compound of formula (I b) obtained from racemic dihydropyridine are racemic mixtures. The optically active compound (I a) is defined as (R) -or (S). The paper size is applicable to China ’s 0 standard (CNS> A4 specifications (210 X 297 public goods) 6 212801 Λ «; Bfi V. Description of the invention (5) -Toggle- [3 Η, 7 Η] &lt; «azolo [3, 4-a] pyridine, or abbreviated as (R) or (S)-[3 Η, 7 Η] thiazolo [3 , 4-a] pyridine; compound (I b) is called (1〇- or (S)-pie Royal | [3 Η, 7 Η] zazolo [3, 4-a] pyridine. The formula of the present invention (I) The compound is prepared by the following method: Let Michael of formula (Ua) or-(I b) be affected:

Hal 'C:

： C Η-C ： -C-C〇2R ^ (Ila C〇2r4 (Hb) [where Hal is a halogen atom (helium, bromine or sulfonate), and R4 is (Ci-CJ 院 基) and the formula ( I) 1,4-dihydropyridine reaction:

R! Ch2s-r5 Η (III) ----------------- 1 '------ ¾ ------. Employee consumption of Central Bureau of Standards, Ministry of Economic Affairs Cooperative Society Seal ii [where 1 {and 1 ^ 2 are as defined above; h 'and its definition are WR1 & R3, and are not free or carboxyl groups; R5 is hydrogen or the formula c (= NH) -NH2 or c (= ΝΗ )-ΗΗ2 · H + P- group (wherein P- is an inorganic or organic acid such as hydrochloric acid, rabronic acid, acetic acid, betulinic acid, phenylacetate, tartaric acid or 0, 〇'-dibenzyl tartaric acid Counter ion)]. The paper if &lt; · and Ttii is used in "Η'ί: Zuo Zhun (CNS) A.1 Gongge (210 X 297 public) 7 Ministry of Economic Affairs Central Standards Bureau Negative Work Consumer Cooperative Printing and Burning Λ 6 B6_ V. Description of invention (3 ) The reaction of the compound of formula (I) and the compound of formula (m) is usually carried out in the presence of a suitable sickle in an emotional solution to obtain the compound of formula (Ic):

(Wherein R, R'i, R2. R'3 and R4 are as defined above) The compound of formula (Ic) is in the form of a mixture of two / pival diastereoisomers, with the pival diastereomers predominant . The resulting compound of formula (Ic) is then separated into mono-diastereomers, or the following conventional reactions convert them to compounds of formula (I): a) Hydrolysis of the carboxyl group to the «carboxyl group of« , And then convert it into peroximine, fermented chloride, mixed anhydride or other known reactive carboxyl derivatives; conventional hydrolysis step »contains, for example, with ammonium formate, Pd / C and triphenylene Hydrolysis of allyl carbonyl; age-hydrolyzed methyl carbonyl or ethoxycarbonyl; hydrolysis of the third 3-butoxycarbonyl group with trimethylsilyl sulfide, etc .; b) acid or its derivative derived from a). Formula H2N- (CH2) q- c) The free or carboxylated carboxyl group or its corresponding mixed anhydride or carboxyester group can be converted into a primary enzyme (CH20H); a suitable raw material agent includes dialkylene or fumazine or _ soil Jin Yizhi's boron «chemicals; clothing and paper are also suitable for Zhongyuanyuan Jiazheng (CNS) A 4 丨 see grid (210 X 2 public goods) 8 -------------- --- for ------ installed ------ ordered (know the notes on the back of 汸 first and then write this page) Λ 6 E36 V. Description of the invention (7) d) from c) Fermentation reacts with thiocarbendazole to stimulate amines of formula (iv) :

HN

N-D (IV) reaction, and converted into the compound of formula (I) of the invention. e) reduction of the aromatic nitro group that may be present in the compound of formula (Ic) to obtain an amine group; f) the halide of the amine group obtained from e) and carboxylic acid, alkylsulfonic acid or arylsulfonic acid or The anhydride reacts and falls asleep. The corresponding amides and sulfonamides are obtained; S) Salting and / or separation of optical, geometric or diastereoisomers according to conventional methods. The reaction of the compound of formula U) with the compound of formula (H) involves the formation of an intermediate of formula (Va) or (Vb): R.

2. A ^ 2_ CVa) 'Hal

The Ministry of Economic Affairs, Central Bureau of Standards, Employee and Consumer Cooperatives printed bismuth 'C〇2R4 n ^^ CH2S-CH = CH-C〇2R4 H CVb) These intermediates were directly converted into compounds of formula (I c) without separation. For example, Mitchell's condyle of formula (I) is known or can be prepared by conventional methods; some of them are commercially available. More to be determined, the paper of the compound of formula (H) has once again been used in the general home-made standard (CN'S) A.1 specification (210 X 297 g; Λ () 212801 V. Description of the invention (s) : A) propynoic acid ester; b) a-haloacrylate (obtained by the addition reaction of acrylic acid ester and halogen, obtained by dehydrohalogenation). For example, the 1,4-dihydro ft pyridine of formula (I) is known in "087/00836 (12.02.1987), or they can be split according to the method described in the international patent application. The compound of formula (I) can be used in the form of racemate and pure para-isomer. The useful cleavage method for the pure paraisomer of the compound of formula U) involves optical analysis of the isothiourea a formed with the optically active acid according to the method described in EP90102951.2 (15.02, 1990). Hexahydrogen as in formula (IV) is described in W087 / 01706 (26.03, 1987). The compounds of the present invention have been found to be effective in preventing and / or reducing excessive responsiveness of the respiratory tract and in treating inflammation associated with acute and subchronic inflammation of bronchial mucosa. The responsiveness of the bronchial encounter is a symptom of bedlessness of gas, which is usually doubled by the abnormal potential contraction and sensitivity of the bronchial mucosa. Bronchial fluency is delayed, and / or mildew is induced by external irritants such as inhalation of tobacco races, dirt, allergens, and endocrine secretions, which can cause an acute gas crisis. The status of excessive anti-plaque printing of the bronchus by the β-Consumer Cooperative Society of the Ministry of Economic Affairs of the Ministry of Economic Affairs can be simulated by experimental chess. It includes the infusion of PAF (600ju g / JL) into a male guinea pig with a human weight of 400 ~ 450g. He was kept under artificial anesthesia and under anesthesia of urethane and pancuroniu bromide. PAF, which is one of the most important media in the course of airway inflammation, causes an encounter response to various special substances (bronchoconstriction) after 1 hour of infusion. The activity of the compound of the present invention in the above-mentioned _experimental chess pattern is used to induce PAF paper size a with H3S Home Press Standard (CNS) f.1 regulation (210 X 297 public goods) _

0 V 0 V A6 B6

212S0I V. Description of the invention (9) The preventive power of over-reactivity is said to be known by measuring the increase in lung inspiratory pressure (pulmonary inhalation S according to Naun. Schmied.

Arch. E x p e r. Pathol. Pharmacol. 19 1, 7 1, 1 970,

(Measured by the improved procedure described by Konzett and Rossler). Administration of 2-50 // g / kg of the compound of the present invention 10 minutes before PAF administration shows a protective effect of holding for at least 4 to 6 hours. This causes PAF-induced excessive anti-inverse reduction. The pharmacological effect depends on the dose. The activity of some representative compounds of the present invention in the PAF-induced overreaction assay is shown in Table 1 below. (Please read the precautions on the back of the window before filling in this page) Compound Table Tianzhu E Liquor's PAF-induced over-reactive dose (mg / kg), duodenal injection reduced by %%. Consumer Cooperative Seal-30 9 2 30 3 4% 30 4 5% 30 29% model test, that is, eta 1., A .-a .Rev. Respir. 1 3 7; (1 9 8 8) ; 5 8-5 7 7). The later reaction is waiting if! Is in the egg Example 1 Example 2-Compound 1 Ben Shi Example 2-Compound 2 Example 2-Compound 3 D ί 夂 纸 怅 尺 连连》 1 as a family standard (CNS) Narrow 4 «Grid (210 X 37)) 11 Huanzheng — 21280i A6 Ιί _B6_ V. Description of the invention (9>) In albumin aerosol sensitized guinea pig bronchoalveolar lavage fluid (BAL) Increased red blood cells. The compound of the present invention is effective in reducing the number of inosine leukocytes in BAL (measured 72 hours after evoked response with ovalbumin). The activity of a representative compound of the present invention in this test is shown in Table 2 below. _2_ Ovalbumin-sensitized guinea pig post-reactive compound dose U g / kg), Oral infiltration of eosinotic leukocytes __ _ Inhibition% _ Example 1 7 5 5 0% From the above display, it can be seen that the compounds of the present invention can be used for treatment Asthma in humans and obstructive diseases of the respiratory tract, as well as treatment of inflammatory inflammation. In the desired therapeutic use, the compound of the present invention can be administered in the form of a pharmaceutical composition, which can be prepared with excipients and conventional techniques, for example, Remington Pharmaceutical Science Handbook (Mack Publishing Company, New York, USA, 17th Edition , 1985) suitable for intramuscular, intravenous, oral, spray and rectal dosage forms. The daily dose will depend on various factors, such as the severity of the disease and the condition of the patient: for a patient weighing 70 kg, the dose of the compound of formula (I) is usually 1 to 50 mg, administered once or several times a day. 1 The paper size is used in the Zhongwei National Float Standard (CNS> Tian 4 specifications (210 X? 97 佂 兮) t 1 (Λ (please read the precautions on the back before filling out this page). Install. .ΤΓ. — Line. Printed by S Industry and Consumer Cooperatives of Shenyang Bureau of Standards, Ministry of Economics «. Λ 6 B6 2l2B〇i V. Description of invention (10) (Please read the note on the back first and then write this page). -Methyl-5-methylcarbonyl-3-ethylcarbonyl-4- (3-nitrophenyl) -1,4-dihydropyridin-2-yl) methyl] isocarbazide cyanide (20g) Suspend in MeOH (200ffl) suspension, under inert gas atmosphere, room temperature and stirring, add methyl propionate (4.2bJL) and aqueous NaOH solution (35S :, 10.8 JL). Test thin I completely dissolved After that, a crystalline precipitate was formed, and DMF (40%) was added to re-dissolve the precipitate. Xie Ji stirred for another 12 hours, during which a second precipitate was formed, which was filtered to obtain 14.6g of 2- (3- (5 -methyl-6- Methane carbonyl-7- (3-nitrophenyl) -8-ethane carbonyl) [3H, 7H] -benzozo [3, 4-a] pyridyl) methyl acetate, b. P · 1 5 8-1 6 0. Preparation Example 2 Under vigorous stirring, 1 liter of hydrogen sulfonate sodium run and aqueous solution were dropped into 50 g of (7R) -S-[(6-methyl-5-methanecarbonyl-3-ethyl Oxycarbonyl-4- (3-nitrophenyl) -1,4-dihydrottt-pyridin-2-yl) methyl] isoparaben-D-(—)-phenylacetate suspended in 1 liter of AcOEt In the suspension, at the end of the addition, remove the aqueous phase, dry the organic phase through the sale of alkali acid and evaporate the solvent under reduced pressure (the temperature is kept below 40T). Printed by the Staff Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs Residual (7R) -S-[(6-Methyl-5-methylcarbonyl-3-ethylcarbonyl-4- (3-nitrophenyl) -1,4-dihydrottt-pyridin-2-yl ) Methyl isothioacid gland (37g) is dissolved in 150g of methylenzyme, and methyl 9-propionate is added rapidly under mechanical agitation and unique atmosphere, followed by 35XHaOH aqueous solution immediately (11.3 meaning) The splashing of the product occurred almost immediately. After 15 minutes, 37X hydrochloric acid was added to the reaction mixture to make it acidic pH, and then the crystalline solid was filtered out and After drying, 40.2g (7R) -3-[(6-methyl-5-methylcarbonyl-3-ethylethanecarbonyl-4- (3-nitrophenyl) -1,4-dihydropyridine «- 2-base) A "« base] acrylic coat paper ruler and general-purpose medium ® Yinjiahuan (CNS) Jiayue Luo (210 X 297 public exchange)-12 Λ6 2128G, five 'invention description (u) (*- '' '' ^ Read ._: '^ And the note' 4 ^-&quot; '! Recode ^ this page) Methyl acid ester. Under stirring and inert gas atmosphere, add 12.801 1,3-diazabicyclo [5.4.0] deca- 7-ene (DBU) to 40.2g (7R) -3-[(6-methyl -5-Methoxycarbonyl-3-ethyl gas carboxy-4- (3-nitrophenyl) -1,4-dihydropyridin-2-yl) methanyl] methyl acrylate dissolved in 110ml of anhydrous DMF . The koji ore was stirred for another 18 hours, and then the reaction mixture 1 was cooled with water / ice, and 373; hydrochloric acid was added to the acidic pH value. The crystal precipitation is separated by filtration to obtain 35.7 S (7R) -2- (3- (5-methyl-6-methylcarbonyl-7- (3-¾ylphenyl) -8-ethanecarbonyl )-[3 Η, 7 Η] thiazolo [3, 4-a] pyridyl) methyl acetate. N. P. 1 2 6-1 2 8 Ό 〇 Split Example 3 Under stirring, 6.4g (7R) -2- (3- (5-Methyl-6-methoxycarbonyl-7- (1u. 3-nitrophenyl) -8-ethoxycarbonyl) [3H, 7H] benzozo [3.4 -a] pyridyl) methyl acetate was added to LiBr (3.8g) and sodium borohydride (1.75g) fit floated in a suspension of diethylene glycol methyl alcohol (10 · Wen), the suspension was previously Keep at room temperature for 30 minutes. Heat the reaction mixture to 50 ° C for 1 hour, printed by the Beigong Consumer Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs.

It was then poured into water and acidified with 1N hydrochloric acid. After taking with AcOEt (3xl5 ·!), The combined organic extracts were washed with water (5X20BJI), dried over sodium sulfate and the solvent was distilled off under reduced pressure to obtain 4.8g (7R) -2- (3 -(5-Methyl-6-methoxycarbonyl-7- (3-nitrophenyl) -8- (ethoxycarbonyl) [3H, 7 Η] &gt; «Zolo [3, 4-a] pyridine Base)-ethyl yeast,. P. 5 8-6 2 ”, [a] D = 51.9 ° (C = 0.21, soluble in EtOH). Example 4 of preparation method According to the method described in Preparation Examples 2 and 3, prepare the following 2-([3H, 7Η] · «Wood paper and Mao Yuzhong BKK family Zuoping (CN—S) A.1 regulations (210 X 297 public loan) 13 2128C #! Printed by the employee consumer cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs ? Generation five, description of the invention (12) oxazolo [3,4-a] pyridin-3-yl) ethanol: 5-methyl-6-methyloxycarbonyl-7- (3-aminophenyl) -8-ethyl Gas carbonyl, 5-methyl-6-methyl gas carbonyl-7-ethylhexyl-8-ethoxykinyl, 5-methyl-6-allyl gas carboxy-7- (3-nitrophenyl) -8 -Ethoxycarbonyl, 5-methyl-6-allyloxycarbonyl-7- (3-chlorophenyl) -8-ethoxycarbonyl, 5-methyl-6-allyloxycarbonyl-7-chenhexyl- 8-ethane gas 1 carbonyl. Example 1 Under S inert inert gas, 1.74g thiocarbonyldiimidazole was added to 3.5g (7R) -2- (3- (5-methyl-6-methoxypyridyl-7- (3-nitrophenyl) -8-ethoxycarbonyl) [3H, 7H] benzozo [ 3,4-a] pyridine) ethanol was dissolved in a solution of 20b anhydrous THF. After 5 hours, H- [3,6-II (diethylamino) pyridin-2-yl] hexahydrogen 1ft (2.65 g) The solution dissolved in 15nJLTHF was added dropwise to the reaction mixture, stirred at room temperature for more than 1 hour, then 701 »water was added to the reaction mixture and extracted repeatedly with AcOEt (3x 20π 义). The combined organic extracts Wash with water (3X10), dry with sodium sulfate and evaporate the solvent under reduced pressure. Residue (6.7 g) »Silicon Condensation Chromatography (20 0 g | S silica); Dissolving agent: Dichloromethane / Formazan 98/2) purification, to obtain 4.3g (7R) -H- (3,6-two (diethylamine) tft pyridin-2-yl) -Ν'- (2- (3- (5-methyl -6-Methoxycarbonyl-7- (3-nitrophenyl) -8-ethoxycarbonyl) [3H, 7H] «« oxazolo [3,4-a] pyridine P-yl) ethoxythiocarbonyl) hexa鰲 唞 · n. P · Anoate 1 6 9-1 7 11:, [oc] D = + 4.4 ° (C = 0.2 in ethyl yeast). Example 2 Follow the steps described in Example 1 , Prepare the following (([3H, 7H] thiazolo [3,4-a] tf t-pyridinyl) ethoxylated carbonyl) hexahydropyridine; (read the notes before the smelting-matters and then write this page) This paper is used in the Chinese as standard (CNS) A J specifications (210 X 297 public translation) 14 21280.: \ 6 B6 V. Description of the invention (13) (7R) -N- (2,6-Second (pyrrolidin-1-yl) ohdian-4-yl) -Η,- (2- (3-(5-methyl-6-methylcarbonyl-7- (3-nitrophenyl) -8-ethanecarbonyl) .m.p., Sulfate, 1 6 2-1 6 5 t :, (4, 6-Two (pyrrolidin-1-yl) -1,3, 5 -trifluoro-2-yl) -Η,-(2- (3- (5-methyl-6- Methane carbonyl-7- (3-nitrophenyl) -8-ethane carbonyl 1H NMR (200 MHz) S 1.26 (t, 3H), 1.95 (m, 8H), 2.34 (m, 2H), 2.59 ( s, 3H), 3 .55 (m, 14H), 3.67 (s, 3H), 3.85 (m, 2H), 4.14 (m, 4H), 4.2 (d, lH), 4.65 (d, lH); 5.18 (s, lH), 5.5 (m, lH); 7.41 (t, ΙΗ), 7.6 (d; lH), 1 3.05 (m, 2H), Η- (2,6-II (pyrrolidinyl-butyl) Feeding-4-yl) -N,-(2- (3- (5-methyl- (please read the precautions on the back of 汸 before filling out this page) Printed by R Industry and Consumer Cooperatives, Central Bureau of Standards, Ministry of Economic Affairs 6- Methane carbonyl-7- (3-chlorophenyl) -8-ethane carbonyl 1H NMR (200 MHz) S 1.25 (t, 3H); 1.93 (m, 8H), 2.35 (m, 2H), 2.6 (s, 3H), 3.55 (m, 14H), 3.67 (s, 3H), 3.85 (m, 2H), 4.15 (m, 4H), 4.2 (d, lH), 4.65 (d, lH), 4.87 (s, iH), 5.19 (S, 1H), 5.51 7.21 (m, 4H), 1 &lt;-( 3,6-Two (diethylamino) pyridin-2-yl) -1 &lt; '-(2- (3- (5-methyl-6-methoxycarbonyl-7- (3-chlorobenzene Radical) -8-ethane gas carbonyl), 1H NMR (200 MHz) 6 0.97 1.1 (t, 6H), 1.25 (t, 3H), 2.35 (m, 2H), 2.6 (s, 3H), 2.98 (q, 4H), 3.53 (m; 10H), 3.68 (s, 3H), 3.84 (m, 2H), 4.14 (m, 4H), 4.22 (d, lH); 4.66 (d, lH); 5.17 (s, lH ), 5.51 (m, lH), 6.07 (d, lH), 7.1 (d, lH), 7.22 (m, 4H), N- (4,6-II (ttt pyrrolidin-1-yl) -1, 3,5-tris-2-yl) -N,-(2- (3- (. This paper ruler Λϋ uses the Chinese 0 Jiazheng (CNS) A 4 specifications (210 X 297 public: $) 15 B6 280 5. Description of the invention (14) 5-methyl-6-methyl gas carbonyl-7- (3-chlorophenyl) -8-ethane gas carbonyl), 1H NMR (200 MHz) &lt; 5 1.25 (t, 3H) , 1.93 (m, 8H), 2.36 (m, 2H), 2.59 (s, 3H), 3.53 (ra; 14H), 3.65 (s, 3H), 3.85 (ra, 2H), 4.13 (m, 4H), 4.22 (d, lH), 4.67 (d, lH), 5.17 (s, lH), 5.52 (m, lH), 7.21 (m, 4H), (2, 6- Two (pyrrolidinyl-pyridyl) pyrimidin-4-yl,)-N ·-(2-(3- (5-methyl-methylcarbonylcarbonyl-7-cyclohexyl-8-ethoxycarbonyl), lh NMR (200 MHz) 8 〇. '98 (m, 6H), 1.25 (t, 3H), 1.49 (m, 5H), 1,94 (m, 8H), 2.35 (m, 2H), 2.6 (s, 3H), 3.54 (m, 14H), 3.68 (s, lH), 3.85 (m, 2H), 3.91 (d, lH); 4.13 (m, 4H), 4.19 (d, lH), 4.64 (d, lH ), 5.87 (s, lH), 5.51 (m, 1H), (3, 6-Two (diethylamino) pyridin-2-yl) -N '-(2- (3- (5-methyl- 6- A «carbonyl-7-Chenhexyl-8-B« carbonyl), (please read the back-end notes first-mand ^ and then write this page) Printed by the Ministry of Economic Affairs Bureau of Central Standards Bureau Pongong Consumer Cooperative H NMR (200 MHz) S 0.98 (m, 12H), 1.05 (t, 6H), 1.25 (t, 3H), 1.51 (m, 5H), 2.35 (m, 2H); 2.61 (s; 3H), 2.98 (q , 4H), 3.53 (m, 10H), 3.66 (s, 3H), 3.84 (m, 2H), 3.91 (d, lH), 4.14 (m, 4H), 4.22 (d, lH), 4.66 (d; lH); 5.51 6.06 (d, lH), 7.1 (d, 1H), N-(4.6 · 2- (ttpyridine-1-m) -i, 3,5-tris-2-yl ) -N,-(2- (3 5-methyl-6-methyloxycarbonyl-7-chenhexyl-8-ethoxycarbonyl), NMR (200 MHz) 6 1.01 (m, 6H), 1.25 (t , 3H), 1.4 9 (m, 5, H), 1.94 (m, 8H), 2. .35 (m, 2H), 2.6 (s, 3H), 3.53 (m, 14H), 3.65 i (s, 3H), 3.84 (m, 2H), 3.91 (d,! H), 4.13 (m, 4H), 4,19 (d, lH), 4.64 (d, lH), 5.52 Clothing paper is again applicable to Chinese national standards ( CNS) A 4 specifications (210 X 297 mm) 16 V. Description of the invention (15) Ν- (2, 6-Two ("t pyrrolidin-1-yl) pyrimidin-4-yl) -Ν'- (2 -(3- (5-methyl-6-allyloxycarbonyl-7- (3-nitrophenyl) -8-ethoxycarbonyl), 1H NMR (200 MHz) ^ 1.25 (t, 3H), 1.93 (m, 8H), 2.31 (m, 2H), 2.59 (s, 3H), 3.55 (m, 14H), 3.85 (m, 2H); 4.13 (m, 4H), 4.2 (d, lH), 4.61 ( m, 2H), 4.65 (d, lH), 4.84 (S, 1H), 5.22 (m, 3H), 5.49 5.9 (m, lH), 7.41 7.61 (d, lH), 8.05 (m, 2H), N -(3,6-Two (diethylamino) pyridine «-2-yl) -Ν ·-(2- (3- (5-methyl-6-propanoxycarbonyl-7- (3-nitro Phenyl) -8-ethoxycarbonyl>, (please read 1? Back to the notes # item write this page) (XH NMR (200 MHz) b 0.97 (t, 6H), 1.04 (t, 6H), 1.25 (t, 3H), 2! .33 (m, 2H), 2.61 (s, 3H), 2.98 (q, 4H), 3.52 (m, 10H), 3.84 (m, 2H), 4.13 (m, 4H ), 4.21 (d, lH), 4.61 (m, 2H), 4. 66 (d, lH), 5.22 (m, 3H), 5. 49 5.9 6.06 (d, lH), 7.1 (d, lH), 7.42 (t, lH), 7.6 (d, lH), 8.05 (m, 2H), «-(4,6-Two (1«: pyrridine -1-yl) -1,3,5-tris-2-yl)-^-(2- (3- (Packing-booking_ Printed by the Ministry of Economic Affairs, Central Standards Bureau, Zhengong Consumer Cooperative 5_Methyl_ 6-allyloxycarbonyl-7- (3-nitrophenyl) -8-ethoxycarbonyl), 1H NMR (200 MHz) ^ 1.25 (t, 3H), 1.94 (m, 8H), 2.33 (m, 2H), 2.59 (s, 3H), 3.53 (m, 14H), 3.84 (m, 2H), 4.14 (ra, 4H), 4.19 (d, lH), 4.62 (m, 2H), 4.64 (d , lH), 5.22 (m, 3H), 5.49 (m, lH), 5-91 (m, lH), 7.42 7.61 (d, lH), i 3.05 (m, 2H), N- (2,6- Two (ttt pyrrolidin-1-yl) piperidin-4-yl) -Ν ·-(2- (3- (5-methyl-this "Zhang scales use Chinese national standards" (CN5) T4 specifications (210x297 Male *) «I. 7. 20, OQ ^ k (U) 17 2i28〇i Λ 6 Β6 V. Description of the invention (16) 6-allyl gas carbonyl ~ 7- (3-gas phenyl) -8-B Gas carbonyl), LH NMR (200 MHz) S 1.25 (t; 3H), 1.93 (m, 8H); 2.33 (m, 2H), 2.6 (s, 3H), 3.54 (m, 14H); 3.83 (m, 2H), 4.13 (γτ \, 4Η), 4.2 (d, lH), 4.6 (m, 2H), 4.65 (d, lH), 4.86 (S, ΙΗ), 5.21 (m, 3H), 5.48 (m, 1H), 5.89 (m, 1H), 7.21 (m, 4Η), N- (3, 6- 1C (diethylamino) pyridin-2-yl) -N,-(2- (3- (5-methyl-6-allyl gas carbonyl-7- (3-aminophenyl) -8-ethoxy Glassy), LH NMR (200 MHz) ^ i 0.96 (t, 6H), 1.03 (t, 6H), 1.25 (t, 3H), 2.33 (m, 2H), 2.58 (s, 3H), 2.98 (q, 4H), 3.51 (m, 10H), 3.83 (ra, 2H), 4.13 (m, 4H), 4.19 (d, lH), 4.62 (m, 2H), 4.64 (d, lH), 5.22 (m, 3H), 5.48 (m, lH), 5.89 (m, lH), 6.06 (d, lH), 7.11 (d, lH), 7.23 (m, 4H), H- (4,6-Two (Ft pyrrolidine-butyl) -1,3,5-tris-2-yl) 4 '-(2- (3- (5-methyl-6-allyloxycarbonyl-7- (3-cyano Phenyl) -8-ethoxycarbonyl), (first read ^, note on the back and then write this page) Printed by the Staff Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs ^ -H NMR (200 MHz) δ 1.26 (t , 3H), 1.93 (m, 8H), 2.33 (nt, 2H), 2.57 (s, 3H), 3.53 (m, 14H), 3.84 (m, 2H); 4.14 (m, 4H), 4.21 (d, lH), 4.62 (m, 2H), 4.66 (d, lH), 5.23 (m; 3H), 5.48 (m, lH), 5.88 (m, lH), 7.22 (m, 4H), N- (2, 6-Two Oft Pyridin-1-yl) Rhinidine-4-yl) -ir-(2- (3- (5- (6-Methyl 6-allyl carbonyl-7-cuthexyl-8-ethoxycarbonyl) , 1H NMR (200 MHz) 5 0.98 ( m, 6H); 1.26 (t, 3H), 1.51 clothing and paper, and Di Zhongzhong Zuojia (CNS) A.1 rules and regulations (210 X 297 gong) 18 BC V. Description of the invention (17) ( m, 5H), 1.94 (m, 8H), 2.33 (m, 2H), 2.59 (S, 1H), 3.53 (m, 14H), 3.83 (m, 2H), 3.91 (d, lH), 4.13 (ra , 4H), 4.19 (d, lH), 4.61 (m, 2H), 4.64 (d, 1H), 4.86 (s; lH), 5.22 (m, 2H), N- (3,6- 5.48 (m, 1H), 5.88 (m, 1H), II (diethylamino) pyridin-2-yl) -'- (2- (3- (5-methyl-6allylcarbonylcarbonyl-7-cyclohexyl-8 -Ethane carbonyl), -'H NMR (200 MHz) 6 &quot;: L.01 (m, 12H), 1.05 (t, 6H), 1.26 (t, 3Η), 1.49 (m, 5H), 2.33 (m , 2H), 2:59 (s, 3H), 2.97 (q, 4H), 3.52 (m, 10H), 3.83 (m, 2H), 3.9 (d, 1H), 4.12 (m, 4H), 4.2 (d, lH), 4.6 (m, 2H), 4.65 (d, lH), 5.21 (m, 2H), 5.48 (m, lH), 5.9 (m, 1H), 6.06 (d, lH), 7.11 (-also ask *; 3 note on the back &quot; item then write this page) (d, 1H), N-(4,6-¾ v Θ syndrome-1-yl) -1,3 , 5-trimethyl-2-yl) -H '-(2- (3 5-methyl-6-allylcarbonyl-7-cyclohexyl-8-ethoxycarbonyl), 1H NMR (200 MHz) 6 0.98 (m, 6H), 1.25 (t, 3H), 1.49 (m, 5H), 1.93 (m, 8H), 2. 33 (m, 2H), 2.59 (S, 3H), 3.55 (m, 14H), 3.83 (m; 2H), 3.89 (d, lH), 4.13 (m, 4H), 4.19 (d, lH), 4.59 (m, 2H), 4.64 (d, lH), 5.21 (m, 2H), 5.48 5.87. Example 3 a) Under stirring and vigorous gas "atmosphere", 0.25gl0XPd / C, 0.37g ammonium formate and 15ng triphenylshaven was added to lg N- [2,6-di (Ift pyridin-1-yl) pyrimidin-4-yl] -Ν '[2- (3- (5-methyl-6-allyl gas Carbonyl-7- (3-nitrophenyl) -8-ethoxycarbonyl) [3H, 7H] &gt; «oxazolo [3,4-a] ttt pyridyl) ethyl gas thiocarboxy] hexahydropyridine In the solution of "Er Erban", then the reaction mixed paper is appropriately called Zhongjia Zuozheng (CNS) A'1 specification (2U> X 297 Gongzi)-19--installation-Central Standard of Economy and Economy Printed by the Bureau ’s Consumer Cooperatives Λ () _R6_ V. Description of the invention (18) (-first &quot; -Contrary? Xiang Zaicheng wrote this page) The compound was refluxed for 6 hours. After that, the reaction mixture was filtered through celite, diluted with AcOEt (10uJL) and washed repeatedly with water (3x5nJl). The resulting organic phase was dried over sulfuric acid and the solvent was evaporated under reduced pressure to obtain a residue (0.9g), which was chromatographed by vaporized silica gel (30g vaporized silica; dissolving agent: hexane / AcOEt 6/4). 0.8 g of H-l2,6-II (pyrrolidinyl-bromo) piperidin-4-yl] -Ν '-[2- (3- (5-lyl-6-carboxy-7- (3-nitro Phenyl) -8-ethoxycarbonyl) [3H, 7H] thiazolo [3,4-a] pyridyl) acetylene carbonyl] hexahydropyridine. b) Add 0.135g of carboxydiimidazole to 0.8g of N- [2,6-Ⅱ («; pyridine-butyl) pyrimidin-4-yl] -fT- [2- (3- (5-Methyl-6-carboxy-7- (3-¾ylphenyl) -3-ethoxycarbonyl) [3H, 7H] thiazolo [3,4-a] pyridyl) ethanesulfur Carbonyl] hexahydropyridine dissolved in 5BJLTHF solution. After 3 hours, add 0.65nJl 2- (N-t «i) printed by the Ministry of Economic Affairs, Central Bureau of Standards, Employee and Consumer Cooperatives ****, and then stir in Myanmar for another 5 hours. The mixture was then diluted with 15n water and extracted with AcOEt (3X5iJl). The combined organic extracts were washed with water, dried over sodium sulfate and the solvent was distilled off under reduced pressure. The residue (lg) «« silica gel chromatography (30g vaporized silica; dissolving agent: hexane / AcOEt 8/2) and purified, to obtain 0.82g N- [2,6-II (Ift pyridine-1 -Yl) pyrimidin-4-yl] -N '-[2- (3- (5-methyl-6- (2- (N-ftfc pyrrolidine) ethylaminecarbonyl) -7- (3-nitrobenzene Group) -8-ethoxy glassy group) [3H, 7H] «« oxazolo [3,4-a] pyridyl) ethoxythiocarbonyl] hexahydropyridine, 1H NMR (200 MHz) b 1.25 (t, 3H), 1.84 (m, 4H), 1 • 95 (m, 8H); 2.33 (m, 2H), 2.59 (s, 3H), 2.8 (m, 6H); 3 -51 (m, 16H), 3.84 (m, 2H), 4.13 (m, 4H), 4.19 (d, lH), 4.64 (d, lH), 4.84 (S, 1H), 5.21 (S, 1H), 5.48 (m; 1H), 7.2 (b, lH) 7 7.41 (t, lH), 7.6 (d, lH), 8.03 (m, 2H). The table paper scale is applicable to 0 Chinese standards (CNS) A4 specifications (210 X 297 mm) 20

Bfa

aiaBQ 5. Description of the invention (19) Example 4 According to the method described in Example 1, the (6-allyloxycarbonyl) [3H, 7H] benzozo [3,4-a] described in Example 2 Pyridine, to prepare the following (6- (2- (N-pyrrolidinyl) ethylamine carbonyl) [3H, 7H] thiazolo [3,4-a] pyridyl) ethane gas carbonyl) hexahydropyridine: (Read first * ;; Note on the back then write this page) Two (diethylamino) ¾ pyridine-2-yl),-(2- (3- (5-methyl-7 triyl) -8-ethoxycarbonyl), 1H NMR (200 0.98 (t, 6H), 1.03 (t, 6H), 1.26 (t, 3H), 1.85 2.33 (m, 2H), 2.59 (S, 3H), 2.85 ( m, 10H), 3.51 3.83 (m, 2H), 4.13 (m, 4H), 4.19 (d, lH), 4.64 5.19 (s, lH), 5.5 (m, lH), 6.07 (d, lH) , 7.11 7. L8 (b,! H), 7.41 (t, lH), 7.6 (d, lH), 8.03 Binding — Binding_ Central Ministry of Economic Affairs Bureau of Staff Consumer Cooperatives-(m, 2H), only-( 4,6-Two (1 »pyridine-: 1-yl)-: 1,3,5-tris-2-yl)-« '-(2- (3-5-methyl-7- (3 -Nitrophenyl) -8-ethoxycarbonyl), 1 «NMR (200 MHz) S 1.26 (t, 3H), 1.84 (m, 4H), 1.96 (m, 8H), 2.33 (ra, 2H), 2.58 (s, 3H), 2.81 (πι, βΗ), 3.52 (rn, 16H), 3.83 (m, 2H), 4.11 (m, 4H), 4.18 (d, lH), 4.63 (d, lH), 5.19 (S, 1H), 5.5 7.15 (b, lH), 7.42 (t, lH), 7.59 (d, lH), 8.05 (m, 2H), N- (2,6-Second (ttt pyrrolidin-1-yl) pyridin-4-yl) -N,-(2- (3- (5-methyl-based paper standard applicable medium valve S homework standard (CNS) A 4 specifications (210 X 297 mm) 31 212601 V. Description of the invention (20) -7- (3-chlorophenyl) -8-ethane gas carboxyl), 1h NMR (200 MHz) S 1. 26 (t; 3H), 1.84 (m, 4H), 1.95 (m, 8H), 2.35 (m, 2H), 2.59 (s, 3H), 2.82 (m, 6H), 3.52 (m, 16H) ; 3.83 (m, 2H), 4.13 (m, 4H), 4.19 (d, lH), 4.64 (d, lH), 4.86 (s, ΙΗ), 5.18 (S, 1H), 5.48 7.23 (m, 5H) , N- (3,6-II (diethylamino) pyridine-2-yl) -N,-(2- (3- (5-methyl-7- (3-aminophenyl) -8-ethyl Gas carbonyl), 1h NMR (200 MHz) 5 0.96 (t, 6H), 1.04 (t, 6H) (1.26 (t, 3H), 1.83 (m, 4H), 2.33 (m, 2H), 2.59 (s, 3H), 2.79 (m, 6H), 2.99 (q, 4H), 3.51 (m, 12H), 3.83 (ra, 2H), 4.13 (m, 4H), 4.21 (d; 1H), 4.66 (d, lH ), 5.21 (s, 1H), 5.48 (m, 1H), 6:06 (d,! H), 7.11 (d; lH), 7.23 (m, 5H), (please read the notes on the back of Qi first Write this page again) i. Binding. Ordering. Printed by the Central Standards Bureau WK Industry and Consumer Cooperative 1 ^-(4,6-Wu ((11; Gedian-1_Base) _. 1,3,5-Sanshu-2-yl) _ ^ 1 '-( 2- (3- (5-Methyl-7- (3-Aminophenyl) -8-ethoxycarbonyl), MMR (200 MHz) S 1.25 (t, 3H), 1.84 1.95 (m, 8H), 2.33 (ra, 2H), 2.59 (s, 3H), 2.8 (m; 6H); 3.5 (m; 16H), 3.83 (m, 2H), 4.15 (m, 4H), 4.2 (d, lH), 4.65 ( d, lH), 5.21 (S, 1H), 5.5 (m, lH), 7.23 (m, 5H), N- (2,6-¾ (¾ pyrrolidin-1-yl) piperidin-4-yl) -H,-(2- (3- (5-methyl7-cyclohexyl-8-ethoxycarbonyl)), this paper is again applicable to the Chinese National Standard (CNS) A 4 specifications (210 X 297 public: $) 22 .Line. Λ6 B6 2l2d〇 ^-V. Description of the invention (21), 1R NMR (200 MHz) ^ 0.99 (m7 6H), 1,26 (t, 3H), 1.51 (m; 5H); 1.84 (m, 4H), 1.95 (m, 8H), 2. 33 (m, 2H), 2.6 (s, 3H), 2.81 (m, 6H), 3.51 (m, 16H), 3.83 (m, 2H), 3.91 (d, lH), 4.13 (m, 4H), 4.19 (d, 1H), 4.64 (d, lH), 4.86 (S, 1H), 5.5 7.2 (b, lH), H- (3, 6-Two (Diethylamino) pyridine-2-yl) -N '_ (2-(3-(5 -methyl-7 cyclohexyl-8-ethanecarbonyl)), * (Please read the precautions on the back first Write this page)

1H NMR (200 MHz) S 1 (m, 12H), 1.05 (t, 6H), 1.25 (t, 3H), 1.5 (m, 5H), 1.83 (m; 4H), 2.33 (rn, 2H), 2.59 (s, 3H), 2.8 (m, 6H), 2.98 (q, 4H), 3.51 (m, 12H), 3.83 (m, 2H), 3.91 (d, lH), 4,13 (m, 4H), 4.2 (d, lH), 4.65 (d, lH); 5.48 6.06 (d, lH), 7.1 (d, lH), 7.16 (b, lH),-installed. 'ΤΓ. 许 （4,6-Two ( Pyrrolidine-: 1-yl) -1,3,5-tris-2-yl)-«'-(2- (3- (5 -methyl-7 -trihexyl-8-ethanecarbonyl)), 1 1h NMR (200 MHz) S 0.98 (m, 6H), 1.25 (t, 3H), 1.51 (m, 5H), 1.83 (m, 4H), 1.94 (m, 8H), 2.34 (tn, 2H ), 2.59 (s, 3H), 2.8 (m, 6H), 3.51 (m, 16H), 3.83 (ra, 2H), 3.9 (d, lH), 4.13 (m, 4H), 4.19 (d, lH) , 4.64 (d, lH), 5.5 (m, lH), 7.2 (b, 1H). Applicable paper size standard is in 1¾¾ National Standard (CNS) A.1 specification (210 X 297 g; Ϊ) 23 Central Ministry of Economic Affairs The Bureau of Standards printed the SR.

Claims (1)

(Please read the precautions on the back before filling out this page) Blanket Ministry of Economy Central Standards Bureau employee consumption cooperation thorium printing-where: R is (C1-C4) courtyard; Ri is free or salted carboxyl group, q-C4-alkane Gas carbonyl, allyloxycarbonyl, or a group such as -C Ο N Η-C Η 2-C Η 2-; 1? 2 is ((^ -〇7) cycloalkyl, ",) 8 or 7- Pyridyl, phenyl substituted by halogen or nitro such as 2-atmosphere, 3-atmosphere, 4-atmosphere, 2,3-di-trim, 2-gas, 2-gas-3-atmosphere, 2-nitro Group, 3-nitro group, 4-nitro group, or 4-gas-2,3-ditriphenyl group; R3 is free or salted carboxyl group or 4-C4-homooxycarbonyl group; D is 1-3. 5- or 6-membered heterocyclic ring of nitrogen atom, which can be substituted with 1 or 2 amine groups, mono- (q-C6 alkyl) amine group, mono- (C3-C7 alkenyl) leg group,, Di- (qk alkyl) amino group, (q-c6 alkyl)-(c3-c7 alkenyl) amine group, hexahydropyridine-butyl group, mol-4-yl group,% pyridine-1-yl group, As well as its pharmaceutically acceptable salts, single palmate isomers, racemates and diastereomeric coating papers, it is also applicable to the gS family f? Quasi (CNS) A 4 regulations (21ΰ X 297 father loan &gt; ^ B7 C7 D7 VI. Application for a patent garden (please read the precautions on the back before filling in this page) 2. Compounds as described in item 1 of the patent application, where D is selected from the group containing the following groups: [2,6- Two (diethylamino) pyrimidin-4-yl], [2,6-two (2-propenylamino) pyrimidin-4-yl], [2,6-two (amino) pyrimidine-4-yl Group], [2,6 -2 (tft pyridin-1-yl) pyrimidine Γ 4-yl], [4,6 -2 (2-propenylamino) -1,3, 5-trison-2 -Yl], [4,6 ·. II (diethylamino) -1,3,5-tris-2-yl], [4, 6- II (pyrrolidin-1-yl) -1, 3, 5-tris-2-yl], [3,6-two (diethylamino) «pyridin-2-yl], [3,6-two (pyrrolidin-: 1-yl) pyridine- 2-yl], [3,6-two (2-propenylamino) pyridin-2-yl]. 3. If the compound of patent application item 1 or 2, wherein & and 1? 3 are both q -Cf alkane carbonyl, or! ^; ^ (: ΟΝΗ-(: Η2-(: Η2-Ν ^), R2 is as defined above, and R is methyl. 4. A kind of anti-asthmatic and anti-inflammatory activity on the respiratory tract The chemical composition, which contains one or more formulas as described in Item 1 of the patent scope ( I) Compounds and appropriate excipients. Printed by the Central Standards Bureau of the Ministry of Economy, Industry, and Consumer Cooperatives. "This paper XJt is used in the Chinese S3 home standard (CNS) A 4 current format (210 X 297 Gongluo> 〇