其它产品项目整合

项目整合的本质是一项集合成方法学、反应工程学与过程分析技术于一体的系统工程。其核心逻辑可以概括为以下几点：源头优选：利用如N-硝胺化学等底层方法学突破，从分子层面颠覆传统高成本、高污染路线。过程强化：依托连续流技术，攻克有机金属试剂应用、光化学反应放大等“不可能”任务，实现高危工艺的本质安全。系统集成：整合“反应-淬灭-分离”全流程，利用微流控与在线分析技术，消除批次间的差异，实现药品制造的连续化与智能化。当前，中间体工艺研发正在经历从“经验驱动”向“数据驱动”的转变。AI辅助路线设计、自动化高通量筛选与连续制造平台的结合，将使得“分子结构与最优工艺路径”之间的映射关系逐渐清晰。未来的竞争优势，将属于那些能够将底层化学创新与先进工程技术进行无缝整合的研发体系。
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其它产品项目整合

Etoposide CAS Registry Number: 33419-42-0 依托泊苷

CAS Name: 9-[(4,6-O-Ethylidene-b-D-glucopyranosyl)oxy]-5,8,8a,9-tetrahydro-5-(4-hydroxy-3,5-dimethoxyphenyl)furo[3',4':6,7]naphtho[2,3-d]-1,3-dioxol-6(5aH)-one
Additional Names: 4'-demethylepip...
Literature References: DNA topoisomerase II inhibitor. Semi-synthetic deriv of podophyllotoxin, related structurally to teniposide, q.q.v. Prepn: C. Keller-Juslén et al., US 3524844 (1970 to Sandoz); idem et al., J. Med. Chem. 14, 936 (1971). Teratogenicity and cytogenicity study: S. M. Sieber et al., Teratology 18, 31 (1978). Review of pharmacokinetics and assay methods: P. I. Clark, M. L. Slevin, Clin. Pharmacokinet. 12, 223-252 (1987). Comprehensive description: J. J. M. Holthuis et al., Anal. Profiles Drug Subs. 18, 121-151 (1989). Review of pharmacology and clinical experience: J. D. Hainsworth, F. A. Greco, Ann. Oncol. 6, 325-341 (1995); S. Joel, Cancer Treat. Rev. 22, 179-221 (1996).

Apomorphine CAS Registry Number: 58-00-4 阿扑吗啡

CAS Name: (6aR)-5,6,6a,7-Tetrahydro-6-methyl-4H-dibenzo[de,g]quinoline-10,11-diol
Additional Names: 6ab-aporphine-10,11-diol
Percent Composition: C 76.38%, H 6.41%, N 5.24%, O 11.97%
Literature References: Dopamine (D1 and D2) receptor agonist. Synthetic opiate obtained by treating morphine with concd HCl: A. Matthiessen, C. R. A. Wright, Proc. R. Soc. London Ser. B 17, 455 (1869). Structure: R. Pschorr et al., Ber. 35, 4377 (1902). Configuration: H. Corrodi, E. Hardegger, Helv. Chim. Acta 38, 2038 (1955). Total synthesis of (±)-form: J. L. Neumeyer et al., J. Pharm. Sci. 59, 1850 (1970); of (+)- and (-)-forms: V. J. Ram, J. L. Neumeyer, J. Org. Chem. 46, 2830 (1981). Toxicity data: J. Z. Ginos et al., J. Med. Chem. 18, 1194 (1975). Clinical evaluation in impotence: J. P. W. Heaton et al., Urology 45, 200 (1995). Historical review: J. L. Neumeyer et al., in Apomorphine and Other Dopaminomimetics vol. 1, G. L. Gessa, G. U. Corsini, Eds. (Raven, New York, 1981) p 1-17. Comprehensive description: F. J. Muhtadi, M. S. Hifnawy, Anal. Profiles Drug Subs. 20, 121-166 (1991). Review of pharmacology and clinical efficacy in Parkinson's disease: D. Muguet et al., Biomed. Pharmacother. 49, 197-209 (1995); in erectile dysfunction: F. Giuliano, J. Allard, Int. J. Impotence Res. 14, Suppl. 1, S53-S56 (2002).

Dopastin CAS Registry Number: 37134-80-8 2-丁胺,N-[(2S)-2-(羟基亚硝基氨基)-3-甲基丁基]-, (2E)-

CAS Name: (2E)-N-[(2S)-2-(Hydroxynitrosoamino)-3-methylbutyl]-2-butenamide
Additional Names: N-(2-nitrosohydroxylamino-3-methylbutyl)crotonamide
Percent Composition: C 50.22%, H 7.96%, N 19....
Literature References: Dopamine b-hydroxylase inhibitor isolated from a culture filtrate of a bacterium of the Pseudomonas genus. Prodn, isoln and characterization: Iinuma et al., Agric. Biol. Chem. 38, 2093 (1974). Structure and synthesis: Iinuma et al., ibid. 2099. Biochemical and biological studies: Iinuma et al., ibid. 2107.

Fenoldopam CAS Registry Number: 67227-56-9 芬洛多潘

CAS Name: 6-Chloro-2,3,4,5-tetrahydro-1-(4-hydroxyphenyl)-1H-3-benzazepine-7,8-diol
Additional Names: 6-chloro-7,8-dihydroxy-1-p-hydroxyphenyl-2,3,4,5-tetrahydro-1H-3-benzazepinePercent Composi...
Literature References: Dopamine D1-receptor agonist. Prepn: J. Weinstock, DE 2751258; idem, US 4197297 (1978, 1980 both to SmithKline); J. Weinstock et al., J. Med. Chem. 23, 973 (1980). HPLC determn in urine and plasma: V. K. Boppana et al., J. Chromatogr. 317, 463 (1984). Clinical pharmacology: R. M. Stote et al., Clin. Pharmacol. Ther. 34, 309 (1983); R. M. Carey et al., J. Clin. Invest. 74, 2198 (1984). Hemodynamic effects in hypertension: H. O. Ventura et al., Circulation 69, 1142 (1984); M. P. Caruana et al., Br. J. Clin. Pharmacol. 24, 721 (1987). Clinical evaluation in congestive heart failure: G. S. Francis et al., Am. Heart J. 116, 473 (1988).

Blonanserin CAS Registry Number: 132810-10-7 布南色林

CAS Name: 2-(4-Ethyl-1-piperazinyl)-4-(4-fluorophenyl)-5,6,7,8,9,10-hexahydrocycloocta[b]pyridineTrademarks: Lonasen (Dainippon)
Percent Composition: C 75.17%, H 8.23%, F 5.17%, N 11.43%
Literature References: Dopamine D2 and serotonin 5-HT2 receptor antagonist. Prepn: K. Hino et al., EP 385237; eidem, US 5021421 (1990, 1991 both to Dainippon). HPLC determn in plasma: M. Matsuda et al., J. Pharm. Biomed. Anal. 15, 1449 (1997). X-ray crystal structure: K. Suzuki et al., Anal. Sci. 18, 1289 (2002). In vitro receptor binding study and in vivo pharmacology in animals: M. Oka et al., J. Pharmacol. Exp. Ther. 264, 158 (1993). Evaluation in mouse models of schizophrenia: T. Nagai et al., NeuroReport 14, 269 (2003). Review of development and clinical experience: C. E. Heading, Curr. Opin. Cent. Peripher. Nerv. Syst. Invest. Drugs 2, 79-84 (2002).

Pramipexole CAS Registry Number: 104632-26-0 普拉克索

CAS Name: (S)-4,5,6,7-Tetrahydro-N6-propyl-2,6-benzothiazolediamine
Additional Names: (S)-2-amino-4,5,6,7-tetrahydro-6-(propylamino)benzothiazole
Percent Composition: C 56.83%, H 8.11%, N 19...
Literature References: Dopamine D2-receptor agonist. Prepn of racemate: G. Griss et al., EP 186087; eidem, US 4886812 (1986, 1989 both to Thomae); of enantiomers: C. S. Schneider, J. Mierau, J. Med. Chem. 30, 494 (1987). Pharmacology: J. Mierau, G. Schingnitz, Eur. J. Pharmacol. 215, 161 (1992). Clinical safety and pharmacodynamics: J. C. Schilling et al., Clin. Pharmacol. Ther. 51, 541 (1992). Clinical trial in Parkinson's disease: K. Kieburtz et al., J. Am. Med. Assoc. 278, 125 (1997).

Cabergoline CAS Registry Number: 81409-90-7 卡麦角林

CAS Name: (8b)-N-[3-(Dimethylamino)propyl]-N-[(ethylamino)carbonyl]-6-(2-propenyl)ergoline-8-carboxamide
Additional Names: 1-ethyl-3-(3'-dimethylaminopropyl)-3-(6'-allylergoline-8'b-carbonyl)ur...
Literature References: Dopamine D2-receptor agonist. Prepn: P. Salvati et al., BE 888243; eidem, US 4526892 (1981, 1985 both to Farmitalia Carlo Erba). Prepn and bioactivity: E. Brambilla et al., Eur. J. Med. Chem. 24, 421 (1989). Clinical pharmacology: C. Ferrari et al., J. Clin. Endocrinol. Metab. 63, 941 (1986). Veterinary trial as abortifacient in dogs: K. Post et al., Theriogenology 29, 1233 (1988). Clinical evaluation to prevent puerperal lactation: G. B. Melis et al., Obstet. Gynecol. 71, 311 (1988); in hyperprolactinemic disorders: C. Ferrari et al., J. Clin. Endocrinol. Metab. 68, 1201 (1989). Clinical trial in Parkinson's disease: J. T. Hutton et al., Neurology 46, 1062 (1996).

Lisuride CAS Registry Number: 18016-80-3 稠环乙脲

CAS Name: N'-[(8a)-9,10-didehydro-6-methylergolin-8-yl]-N,N-diethylurea
Additional Names: 9-(3,3-diethylureido)-4,6,6a,7,8,9-hexahydro-7-methylindolo[4,3-f,g]quinoline; 1,1-diethyl-3-(D-6-methy...
Literature References: Dopamine D2-receptor agonist. Prepn: V. Zikan, M. Semonsky, Collect. Czech. Chem. Commun. 25, 1922 (1960); eidem, Pharmazie 23, 147 (1968). Pharmacology and toxicity: Z. Votava, I. Lamplova, Physiol. Bohemoslov. 12, 37 (1963), C.A. 59, 9221d (1963).

Alpiropride CAS Registry Number: 81982-32-3 阿吡必利

CAS Name: 4-Amino-2-methoxy-5-[(methylamino)sulfonyl]-N-[[1-(2-propenyl)-2-pyrrolidinyl]methyl]benzamide
Additional Names: (±)-N-[(1-allyl-2-pyrrolidinyl)methyl]-4-amino-5-(methylsulfamoyl...
Literature References: Dopamine D2-receptor antagonist structurally similar to sulpiride, q.v. Prepn: J. Perrot, M. Thominet, EP 47207; eidem, US 4550179 (1982, 1985 both to Soc. d'Etudes Sci. Ind. l'Ile-de-France). Dopamine receptor binding study: P. Sokoloff et al., Arch. Pharmacol. 327, 221 (1984). HPLC determn in plasma and urine: F. Bressolle et al., J. Chromatogr. 343, 443 (1985). Pharmacokinetics and metabolism in humans: F. Bressolle et al., J. Pharm. Clin. 4, 261 (1985). Preliminary study in experimentally induced migraine: A. Bès et al., Int. J. Clin. Pharmacol. Res. 6, 189 (1986).

Itopride CAS Registry Number: 122898-67-3 伊托必利

CAS Name: N-[[4-[2-(Dimethylamino)ethoxy]phenyl]methyl]-3,4-dimethoxy benzamide
Additional Names: N-[p-[2-(dimethylamino)ethoxy]benzyl]veratramide
Percent Composition: C 67.02%, H 7.31%, N 7...
Literature References: Dopamine D2-receptor antagonist with anticholinesterase activity. Prepn: Y. Itoh et al., EP 306827; eidem, US 4983633 (1989, 1991 both to Hokuriku Pharm.); J. Sakaguchi et al., Chem. Pharm. Bull. 40, 202 (1992). Pharmacology: Y. Iwanaga et al., Jpn. J. Pharmacol. 56, 261 (1991). Toxicity studies: M. H. Barker et al., Yakuri to Chiryo 21, 1685, 1669 (1993). Metabolism study: T. Mushiroda et al., Drug Metab. Dispos. 28, 1231 (2000). HPLC determn in serum and clinical pharmacokinetics: S. S. Singh et al., J. Chromatogr. B 818, 213 (2005). Clinical study in postoperative ileus: R. Gürlich et al., Chir. Gastroenterol. Interdiszip. 20, 61 (2004); in dyspepsia: D. N. Amarapurkar, P. Rane, J. Indian Med. Assoc. 102, 735 (2004).