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

Exatecan CAS Registry Number: 171335-80-1 依喜替康

CAS Name: (1S,9S)-1-Amino-9-ethyl-5-fluoro-1,2,3,9,12,15-hexahydro-9-hydroxy-4-methyl-10H,13H-benzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinoline-10,13-dionePercent Composition: C 66.20%, H 5.09%...
Literature References: Topoisomerase I inhibitor; synthetic analogue of camptothecin, q.v. Prepn: H. Terasawa et al., EP 495432 (1992 to Daiichi); of mesylate: S. Kamihara et al., EP 737686; eidem, US 6552197 (1996, 2003 both to Daiichi). HPLC determn in mouse plasma: T. Oguma et al., Biol. Pharm. Bull. 24, 176 (2001). Clinical pharmacokinetics and evaluation in advanced leukemia: F. J. Giles et al., Clin. Cancer Res. 8, 2134 (2002); in advanced solid malignancies: M. A. Garrison et al., ibid. 9, 2527 (2003); in breast cancer: F. J. Esteva et al., Cancer 98, 900 (2003); in gastric cancer: J. A. Ajani et al., Invest. New Drugs 23, 479 (2005).

HNE CAS Registry Number: 18286-49-2 (E-form); 29343-52-0 (undefined)

CAS Name: (2E)-4-Hydroxy-2-nonenal
Additional Names: 4-HNE
Percent Composition: C 69.19%, H 10.32%, O 20.48%
Literature References: Toxic aldehyde formed during lipid peroxidation in response to oxidative stress. Reacts primarily with the amino acids His or Lys to form an adduct which may alter protein function. Increased levels of the HNE-adduct are seen in Alzheimer's disease and after ozone exposure. Identification of cytotoxic activity of lipid oxidative products: E. Schauenstein, H. Esterbauer, Monatsh. Chem. 94, 164 (1963). Prepn: H. Esterbauer, W. Weger, ibid. 98, 1994 (1967). Synthesis: H. W. Gardner et al., Lipids 27, 686 (1992). Quantitative analysis by uv, GC/MS, HPLC: M. Kinter in Free Radicals N. A. Punchard, F. J. Kelly, Eds. (IRL Press, Oxford, UK, 1996) pp 133-145. Cytotoxicity: A. Benedetti et al., Biochim. Biophys. Acta 620, 281 (1980). Structural definition of adduct sites: D. V. Nadkarni, L. M. Sayre, Chem. Res. Toxicol. 8, 284 (1995); by MS: M. S. Bolgar, S. J. Gaskell, Anal. Chem. 68, 2325 (1996). Ozone-induced formation: A. Kirichenko et al., Toxicol. Appl. Pharmacol. 141, 416 (1996). Role in Alzheimer's disease: R. J. Mark et al., J. Neurochem. 68, 255 (1997); L. M. Sayre et al., ibid. 2092.

Picrotoxinin CAS Registry Number: 17617-45-7 木防己苦毒宁

CAS Name: (1aR,2aR,3S,6R,6aS,8aS,8bR,9R)-Hexahydro-2a-hydroxy-8b-methyl-9-(1-methylethenyl)-3,6-methano-8H-1,5,7-trioxacyclopenta[ij]cycloprop[a]azulene-4,8(3H)-dione
Percent Composition: C 61....
Literature References: Toxic component of picrotoxin, q.v. Prepn from picrotoxin: Horrmann, Ber. 45, 2090 (1912). Structure: Conroy, J. Am. Chem. Soc. 73, 1889 (1951); 79, 5550 (1957); Craven, Tetrahedron Lett. no. 19, 21 (1960). Total synthesis: E. J. Corey, H. L. Pearce, J. Am. Chem. Soc. 101, 5841 (1979). Structure-activity relationship: C. H. Jarboe et al., J. Med. Chem. 11, 729 (1968). Review: Porter, Chem. Rev. 67, 441 (1967).

Cytisine CAS Registry Number: 485-35-8 金雀花碱

CAS Name: (1R)-1,2,3,4,5,6-Hexahydro-1,5-methano-8H-pyrido-[1,2-a][1,5]diazocin-8-one
Additional Names: baptitoxine; sophorine; ulexine
Trademarks: Cytiton (USSR)
Percent Composition: C 6...
Literature References: Toxic principle in seed of Laburnum anagyroides Medik. and other Leguminosae. Extraction: Ing, J. Chem. Soc. 1931, 2200; Späth, Galinovsky, Ber. 65, 1526 (1932); 66, 1338 (1933); Lecoq, Bull. Soc. Chim. Fr. 10, 153 (1943). Structure: Ing, J. Chem. Soc. 1932, 2778. Synthesis: Bohlmann et al., Angew. Chem. 67, 708 (1955); Van Tamelen, Baran, J. Am. Chem. Soc. 77, 4944 (1955). Absolute configuration: Okuda et al., Chem. Ind. (London) 1961, 1751. Pharmacological properties: R. B. Barlow, L. J. McLeod, Br. J. Pharmacol. 35, 161 (1969).

Atractyloside CAS Registry Number: 17754-44-8 二钾(2R,4R,4aR,6aR,7S,9S,11bR)-4-羧基-7-羟基-11b-甲基-8-甲基苯乙烯-水氢-6a,9-甲基环庚-2-基 2-O-(3-甲基丁醇)-3,4-二-O-磺胺-α-D-葡萄吡喃苷

CAS Name: (2b,4a,15a)-15-Hydroxy-2-[[2-O-(3-methyl-1-oxobutyl)-3,4-di-O-sulfo-b-D-glucopyranosyl]oxy]-19-norkaur-16-en-18-oic acid dipotassium salt
Additional Names: potassium atractylate; atra...
Literature References: Toxic principle isolated from the thistle Atractylis gummifera L., Compositae: M. Lefranc, Compt. Rend. 67, 954 (1868). Structure and stereochemistry of the aglycone, atractyligenin: F. Piozzi et al., Tetrahedron Suppl. 8 II, 515 (1966); total synthesis of (±)-form: A. K. Singh et al., J. Am. Chem. Soc. 109, 6187 (1987). Structure and stereochemistry of atractyloside: eidem, Gazz. Chim. Ital. 97, 935 (1967). Toxicity studies: G. Cascio et al., Boll. Soc. Ital. Biol. Sper. 44, 253 (1968). Review: Atractyloside: Chemistry, Biochemistry, and Toxicology, R. Santi, S. Luciani, Eds. (Piccin Medical Books, Padova, Italy, 1978) 136 pp.

Platyphylline CAS Registry Number: 480-78-4 阔叶千里光碱

CAS Name: (1a)-1,2-Dihydro-12-hydroxysenecionan-11,16-dione
Additional Names: platifillin
Percent Composition: C 64.07%, H 8.07%, N 4.15%, O 23.71%
Literature References: Toxic pyrrolizidine alkaloid from Senecio platyphyllus DC. and other Senecio spp., Compositae: Orékhov, Tiedebel, Ber. 68, 650 (1935); Orékhov et al., ibid. 1886; Konovalova, Orékhov, ibid. 69, 1908 (1936); Bull. Soc. Chim. Fr. [5] 4, 2037 (1937); Allen, Am. J. Pharm. 117, 110 (1945). Structure: Dry et al., J. Chem. Soc. 1955, 63. Comprehensive reviews of platyphylline and other pyrrolizidine alkaloids: L. Bull et al., The Pyrrolizidine Alkaloids (North-Holland, Amsterdam, 1968) 293 pp; F. L. Warren in The Alkaloids vol. 12, R. H. F. Manske, Ed. (Academic Press, New York, 1970) pp 245-331.

Monocrotaline CAS Registry Number: 315-22-0 单响尾蛇毒蛋白

CAS Name: (13a,14a)-14,19-Dihydro-12,13-dihydroxy-20-norcrotolanan-11,15-dione
Additional Names: crotaline; MCTPercent Composition: C 59.06%, H 7.13%, N 4.30%, O 29.50%
Literature References: Toxic pyrrolizidine alkaloid isolated from Crotalaria spp. Isoln: R. Adams, E. F. Rogers, J. Am. Chem. Soc. 61, 2815 (1939); R. B. Tinker, W. M. Lauter, Econ. Bot. 10, 254 (1956); C. C. J. Culvenor, L. W. Smith, Aust. J. Chem. 16, 239 (1963). Structure: R. Adams et al., J. Am. Chem. Soc. 74, 5612 (1952). Stereochemistry: D. J. Robins, D. H. G. Crout, J. Chem. Soc. C 1969, 1386. Crystal structure: H. Stoeckli-Evans, Acta Crystallogr. B35, 231 (1979). Stereoselective synthesis: H. Niwa et al., Tetrahedron 48, 10531 (1992). ELISA measurment: M. A. Bober et al., Toxicon 27, 1059 (1989). Toxicology: P. M. Newberne et al., Toxicol. Appl. Pharmacol. 18, 387 (1971); R. A. Roth et al., ibid. 60, 193 (1981). Review of carcinogenicity studies: IARC Monographs 10, 291-302, 333-342 (1976). Comprehensive reviews: L. Bull et al., The Pyrrolizidine Alkaloids (North-Holland, Amsterdam, 1968) 293 pp; D. J. Robins, Fortschr. Chem. Org. Naturst. 41, 115-203 (1982). Review of pulmonary toxicity: D. W. Wilson et al., Crit. Rev. Toxicol. 22, 307-325 (1992).

Pentachloroethane CAS Registry Number: 76-01-7 五氯乙烷

Additional Names: Pentalin
Percent Composition: C 11.87%, H 0.50%, Cl 87.63%
Literature References: Toxicity data: G. S. Barsoum, K. Saad, Q. J. Pharm. Pharmacol. 7, 205 (1934).

Diethyl Carbitol® (Union Carbide) CAS Registry Number: 112-36-7 二乙二醇二乙醚

CAS Name: 1,1'-Oxybis(2-ethoxy)ethane
Additional Names: diethylene glycol diethyl ether
Percent Composition: C 59.23%, H 11.18%, O 29.59%
Literature References: Toxicity data: H. F. Smyth et al., J. Ind. Hyg. Toxicol. 23, 259 (1941).

Methyl Cellosolve® Acetate (Carbide and Carbon Chem.) CAS Registry Number: 110-49-6 2-甲氧基乙酸乙酯

CAS Name: 2-Methoxyethanol acetate
Additional Names: ethylene glycol monomethyl ether acetate
Percent Composition: C 50.84%, H 8.53%, O 40.63%
Literature References: Toxicity data: H. F. Smyth et al., J. Ind. Hyg. Toxicol. 23, 259 (1941). Series of articles on toxicology: Environ. Health Perspect. 57, 1-275 (1984).