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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

Atrasentan CAS Registry Number: 173937-91-2 (2R,3R,4S)-4-(1,3-苯并二氧戊环-5-基)-1-[2-(二丁基氨基)-2-氧代乙基]-2-(4-甲氧基苯基)吡咯烷-3-羧酸

CAS Name: (2R,3R,4S)-4-(1,3-Benzodioxol-5-yl)-1-[2-(dibutylamino)-2-oxoethyl]-2-(4-methoxyphenyl)-3-pyrrolidinecarboxylic acid
Additional Names: trans,trans-2-(4-methoxyphenyl)-4-(1,3-benzodiox...
Literature References: Endothelin (ET) antagonist with selectivity for the ETA subtype. Prepn: M. Winn et al., WO 9606905; eidem, US 5767144 (1996, 1998 both to Abbott); eidem, J. Med. Chem. 39, 1039 (1996). Synthesis: S. J. Wittenberger, M. A. McLaughlin, Tetrahedron Lett. 40, 7175 (1999). HPLC determn in pharmaceutical formulations: J. A. Morley et al., J. Pharm. Biomed. Anal. 19, 777 (1999); in plasma: P. D. Bryan et al., Biomed. Chromatogr. 15, 525 (2001). In vitro inhibition of ovarian carcinoma: D. Salani et al., Clin. Sci. 103, Suppl. 48, 318S (2002). Clinical pharmacokinetics and dynamics: M. C. Verhaar et al., Br. J. Clin. Pharmacol. 49, 562 (2000); and safety: M. A. Carducci et al., J. Clin. Oncol. 20, 2171 (2002). Clinical evaluation in prostate cancer: M. Fisher, Clin. Prostate Cancer 1, 79 (2002). Review of clinical development in prostate cancer: A. Jimeno, M. Carducci, Expert Opin. Invest. Drugs 13, 1631-1640 (2004).

p-Chlorobenzotrifluoride CAS Registry Number: 98-56-6 4-氯三氟甲苯

CAS Name: 1-Chloro-4-(trifluoromethyl)benzene
Additional Names: (4-chlorophenyl)trifluoromethane; 4-chloro-a,a,a-trifluorotoluene; PCBTF
Trademarks: Oxsol 100 (Occidental Chemical)
Percen...
Literature References: Environmentally friendly solvent. Prepn: H. S. Booth et al., J. Am. Chem. Soc. 57, 2066 (1935). Mass spectrum: F. Belsito et al., Ann. Chim. 69, 259 (1979). Photochemical reactivity: M. Khan et al., Atmos. Environ. 33, 1085 (1999). Use as chemical intermediate: E. R. Lavagnino et al., Org. Prep. Proced. Int. 11, 23 (1979); M. Beller, A. Zapf, Synlett 1998, 792. GLC/MS determn in fish: M. P. Yurawecz, J. Assoc. Off. Anal. Chem. 62, 36 (1979). Toxicology: P. E. Newton et al., Inhalation Toxicol. 10, 33 (1998). Review: C. H. Hare, Mod. Paint Coat. 88, 30-36 (1998).

Citramalic Acid CAS Registry Number: 2306-22-1

CAS Name: 2-Hydroxy-2-methylbutanedioic acid
Additional Names: 2-methylmalic acid; 2-hydroxy-2-methylsuccinic acid; a-hydroxypyrotartaric acid
Percent Composition: C 40.55%, H 5.44%, O 54.01...
Literature References: Enzymatic synthesis: Barker, Blair, Biochem. Prep. 9, 21 (1962). Chemical synthesis: Barker, ibid. 25; J. B. Wilkes, R. G. Wall, J. Org. Chem. 45, 247 (1980). Stereoselective synthesis: E. G. J. Staring et al., Rec. Trav. Chim. 105, 374 (1986).

L -Asparaginase CAS Registry Number: 9015-68-3 L-天门冬酰胺酶

Additional Names: L-Asparagine amidohydrolase; colaspase; L-asnase; EC 3.5.1.1Trademarks: Crasnitin (Bayer); Elspar (Merck Co.); Kidrolase (RPR); Leunase (Kyowa)
Literature References: Enzyme which catalyzes the hydrolysis of L-asparagine to L-aspartic acid and ammonia. Inhibits the growth of tumor cells requiring exogenous asparagine. Widely distributed; occurs in bacteria, fungi, yeasts, plants, animal tissues and guinea pig serum. Commonly obtained from E. coli and Erwinia sp. Asparaginase from E. coli has a mol wt of ~136,000 and is composed of four identical subunits. Identification of antitumor activity: J. D. Broome, Nature 191, 1114 (1961); idem, J. Exp. Med. 118, 99 (1963). Purif, chemical properties of asparaginase from E. coli: D. H. Ho et al., J. Biol. Chem. 245, 3708 (1970). Structural studies: A. C. Greenquist, J. C. Wriston, Arch. Biochem. Biophys. 152, 280 (1972). Amino acid sequence: T. Maita et al., J. Biochem. 76, 1351 (1974). Pharmacology and clinical effects: R. H. Adamson, S. Fabro, Cancer Chemother. Rep. Part 1 52, 617 (1968); R. L. Capizzi et al., Annu. Rev. Med. 21, 433 (1970). Reviews: R. L. Capizzi, Leuk. Lymphoma 10, Suppl., 147-150 (1993); M. J. Keating et al., ibid. 153-157.

Factor X CAS Registry Number: 9001-29-0 人抗血友病因子 C

CAS Name: Blood-coagulation factor X
Additional Names: Stuart-Prower factor; Stuart factor; Prower factor
Literature References: Enzyme which is activated by a complex of factors IX, VIII, calcium ions and phospholipid, or by factor VII and tissue factor in the intrinsic and extrinsic pathways of blood coagulation resp. Non-physiological activators are trypsin and a specific protein from Russel's viper venom: see Fujikawa et al., Biochemistry 11, 4892 (1972). Active factor X apparently acts upon factor V, q.v. in the presence of calcium ions and lipid to form a complex which activates the conversion of prothrombin to thrombin. Present in both plasma and serum because neither increases nor decreases during clotting. Presumably synthesized in the liver because level is reduced with coumarin drugs and in liver disease. Isoln and characterization of bovine factor X: eidem., ibid. 4882. Factor Xa is a serine protease which, in the presence of factor V, Ca2+ ions and phospholipids, activates prothrombin. Severe deficiency causes hemorrhagic state resembling hemophilia. Mild deficiency may result in easy bruising. In severe cases deep muscular and joint hemorrhages occur. Improved purification and bibliography of earlier isoln procedures: Bajaj, Mann, J. Biol. Chem. 248, 7729 (1973). Comparison of the molecular forms generated by the different methods of activation: Radcliffe, Barton, ibid. 6788. Review: Graham, Hougie in Thombolytic Activity and Related Phenomena, I. S. Wright et al., Eds. (Schattauer-Verlag, Stuttgart, 1961) pp 416-420; C. M. Jackson, Thromb. Diath. Haemorrh. Suppl. 57, 197-216 (1974). Reviews on prepn, physical properties and function in the coagulation process: K. Fujikawa, E. W. Davie, Methods Enzymol. 45B, 89 (1976); J. Jesty, Y. Nemerson, ibid. p 95.

Isoascorbic Acid CAS Registry Number: 89-65-6 D-异抗坏血酸

CAS Name: D-erythro-Hex-2-enonic acid g-lactone
Additional Names: D-araboascorbic acid; erythorbic acid; isovitamin C; saccharosonic acid; glucosaccharonic acid; D-erythro-3-ketohexonic acid la...
Literature References: Epimer of L-ascorbic acid. Has one-twentieth of the vitamin C activity of L-ascorbic acid. Prepd by treating methyl 2-keto-D-gluconate with sodium methoxide: Maurer, Schiedt, Ber. 66, 1054 (1933); 67, 1239 (1934); Ohle et al., ibid. 67, 324 (1934); Baird et al., J. Chem. Soc. 1934, 63; Reichstein et al., Helv. Chim. Acta 17, 516 (1934). Synthesis from sucrose: Heimann, Reiff, Pharm. Zentralhalle 93, 97 (1954). Production by Penicillium spp: Takahashi et al., Nature 188, 411 (1960); US 3052609 (1962 to Sankyo); Bull. Agric. Chem. Soc. Jpn. 24, 533 (1960), C.A. 55, 1788 (1961). Conformation: Matsui et al., Agric. Biol. Chem. 27, 185 (1963).

Ursodiol CAS Registry Number: 128-13-2 熊去氧胆酸

CAS Name: (3a,5b,7b)-3,7-Dihydroxycholan-24-oic acid
Additional Names: 17b-(1-methyl-3-carboxypropyl)etiocholane-3a,7b-diol; 3a,7b-dioxycholanic acid; ursodeoxycholic acid
Trademarks: Actiga...
Literature References: Epimeric with chenodiol, q.v., with respect to the hydroxyl group at C7. Found in bear bile (combined with taurine). Isoln: Shoda, J. Biochem. (Tokyo) 7, 505 (1927). Structure: Kaziro, Z. Physiol. Chem. 185, 151 (1929); 197, 206 (1931); Iwasaki, ibid. 244, 181 (1936). Toxicity data: M. Ardenne, P. G. Reitnauer, Arzneim.-Forsch. 20, 323 (1970). Effect on cholesterol and bile acid metabolism: G. S. Tint et al., Gastroenterology 91, 1007 (1986). Clinical trial in primary biliary cirrhosis: R. E. Poupon et al., N. Engl. J. Med. 324, 1548 (1991). Review of pharmacology, toxicology, efficacy: A. Ward et al., Drugs 27, 95-131 (1984). Brief review of clinical effects and comparison with chenodiol: H. Fromm, Gastroenterology 87, 229-233 (1984).

Epitiostanol CAS Registry Number: 2363-58-8 硫雄甾醇

CAS Name: (2a,3a,5a,17b)-2,3-Epithioandrostan-17-olTrademarks: Thiodrol (Shionogi)
Percent Composition: C 74.45%, H 9.87%, O 5.22%, S 10.46%
Literature References: Episulfide deriv of androstane, q.v. Prepn: GB 977599; T. Komeno, US 3230215 (1964, 1966 both to Shionogi); K. Takeda et al., Tetrahedron 1965, 329; P. D. Klimstra et al., J. Med. Chem. 9, 693 (1966). Antitumor effect in mice: A. Matsuzawa, T. Yamamoto, Cancer Res. 37, 4408 (1977). Teratogenicity study: T. Minesita et al., Oyo Yakuri 7, 723 (1973), C.A. 80, 116474p (1974). Toxicity study: eidem, ibid. 805, C.A. 80, 66865u (1974). Use in treatment of breast cancer: M. Fujimoro et al., Cancer 31, 789 (1973).

Ravuconazole CAS Registry Number: 182760-06-1 立福康唑

CAS Name: 4-[2-[(1R,2R)-2-(2,4-Difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl]-4-thiazolyl]benzonitrile
Additional Names: (2R,3R)-3-[4-(4-cyanophenyl)thiazol-2-yl]-2-(2,4-di...
Literature References: Ergosterol biosynthesis inhibitor. Prepn (stereochemistry unspecified): T. Naito et al, EP 667346; eidem, US 5648372 (1995, 1997 both to Eisai); of optically acitve form: A. Tsuruoka et al., Chem. Pharm. Bull. 46, 623 (1998). Chiral synthesis: Y. Kaku et al., ibid. 1125. In vitro comparative antifungal spectrum: J. C. Fung-Tomc et al., Antimicrob. Agents Chemother. 42, 313 1998. Antifungal activity in candidosis: K. V. Clemons, D. A. Stevens, ibid. 45, 3433 (2001); in aspergillosis: W. R. Kirkpatrick et al., J. Antimicrob. Chemother. 49, 353 (2002). Clinical evaluation in onychomycosis: A. K. Gupta et al., J. Eur. Acad. Dermatol. Venereol. 19, 437 (2005). Review of development and therapeutic potential: S. Arikan, J. H. Rex, Curr. Opin. Invest. Drugs 3, 555-561 (2002).

Difenoconazole CAS Registry Number: 119446-68-3 苯醚甲环唑

CAS Name: 1-[[2-[2-Chloro-4-(4-chlorophenoxy)phenyl]-4-methyl-1,3-dioxolan-2-yl]methyl]-1H-1,2,4-triazole
Additional Names: cis,trans-3-chloro-4-[4-methyl-2-(1H-1,2,4-triazol-1-ylmethyl)-1,3-di...
Literature References: Ergosterol biosynthesis inhibitor. Prepn: A. Hubele, P. Riebli, GB 2098607 (1982 to Ciba-Geigy). Properties and antifungal activity: W. Ruess et al., Brighton Crop Prot. Conf. - Pests Dis. 1988, 543. Field studies: A. J. Leadbeater et al., ibid. 917; A. B. Bassi, Jr. et al., Br. Crop Prot. Counc. Monogr. 57, 91 (1994). Uptake and translocation in crops: H. Dahmen, T. Staub, Plant Dis. 76, 523 (1992).