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

Gramicidin S CAS Registry Number: 113-73-5 短杆菌肽 S

Additional Names: Gramicidin S (Soviet); gramicidin C (Soviet)
Percent Composition: C 63.13%, H 8.12%, N 14.73%, O 14.02%
Literature References: Cyclic decapeptide antibiotic produced by a strain of Bacillus brevis. Isoln: Gause et al., Compt. Rend. Acad. Sci. USSR 43, 217 (1944), C.A. 39, 1195 (1945); Gause, Brazhnikova, Lancet 247, 715 (1944). More closely related to tyrocidines in biological and chemical properties than to true gramicidins, q.q.v. Structure: Synge, Biochem. J. 39, 363 (1945); Consden et al., ibid. 40, xliii (1946); 41, 596 (1947); Battersby, Craig, J. Am. Chem. Soc. 73, 1887 (1951); Erlanger, Goode, Nature 174, 840 (1954). Synthesis and absorption spectrum: Schwyzer, Sieber, Helv. Chim. Acta 40, 624 (1957); Waki, Izuniya, Bull. Chem. Soc. Jpn. 40, 1687 (1967). Solid phase synthesis: Losse, Neubert, Tetrahedron Lett. 1970, 1267; M. Ohno et al., J. Am. Chem. Soc. 93, 5251 (1971). Improved synthesis via a linear pentapeptide: Y. Minematsu et al., Tetrahedron Lett. 1980, 2179; via a linear decapeptide: T. Mukaiyama et al., Chem. Lett. 1981, 1367. Industrial procedure: GB 836725 (1960 to Ciba). Review: Y. A. Ovchinnikov, V. T. Ivanov, "The Cyclic Peptides: Structure, Conformation, and Function" in The Proteins vol. V, H. Neurath, R. L. Hill, Eds. (Academic Press, New York, 3rd ed., 1982) pp 547-555.

Aplidine CAS Registry Number: 137219-37-5 去氢代代宁B

CAS Name: N-[1-(1,2-Dioxopropyl)-L-prolyl]-didemnin A
Additional Names: dehydrodidemnin B; DDB
Trademarks: Aplidin (PharmaMar)
Percent Composition: C 61.66%, H 7.90%, N 8.83%, O 21.61%
Literature References: Cyclic depsipeptide analog of the didemnins, q.v., isolated from the marine tunicate, Aplidum albicans. Induces rapid apoptotic death with or without previous cell cycle arrest. Isoln and synthesis: K. Rinehart, A. M. Lithgow-Bertelloni, WO 9104985 (1991 to PharmaMar); G. Jou et al., J. Org. Chem. 62, 354 (1997). Antiproliferative effects on Ehrlich carcinoma: J. L. Urdiales et al., Cancer Lett. 102, 31 (1996); cytotoxic effect on acute lymphoblastic leukemia cells: E. Erba et al., Br. J. Cancer 89, 763 (2003). Mechanism of action study: idem et al., ibid. 86, 1510 (2002). Degradation kinetics in solution: J. C. M. Waterval et al., J. Chromatogr. B 754, 161 (2001). 2D-NMR conformational analysis in solution: F. Cárdenas et al., J. Org. Chem. 68, 9554 (2003). LC/MS/MS determn in plasma: J. Yin et al., Rapid Commun. Mass Spectrom. 17, 1909 (2003). In vitro toxicity on hematopoietic progenitors and stem cells: S. G. Gomez et al., Exp. Hematol. 31, 1104 (2003). Clinical pharmacokinetics and evaluation in advanced malignancies: S. Faivre et al., J. Clin. Oncol. 23, 7871 (2005).

Nefiracetam CAS Registry Number: 77191-36-7 奈非西坦

CAS Name: N-(2,6-Dimethylphenyl)-2-oxo-1-pyrrolidineacetamide
Additional Names: 2-(2-oxo-1-pyrrolidinyl)-N-(2,6-dimethylphenyl)acetamide; 2-oxo-1-pyrrolidineaceto-2',6'-xylidide; 2-oxo-1-pyrrol...
Literature References: Cyclic deriv of g-aminobutyric acid. Prepn: H. Betzing et al., DE 2924011; eidem, US 4341790 (1980, 1982 both to Nattermann). Cognition enhancing effects in rats: T. Sakurai et al., Jpn. J. Pharmacol. 50, 47 (1989). HPLC determn in serum and urine: Y. Fujimaki et al., J. Chromatogr. 575, 261 (1992). Clinical pharmacokinetics: eidem, Xenobiotica 23, 61 (1993). Series of articles on pharmacology and toxicology: Arzneim.-Forsch. 44, 193-259 (1994).

Daptomycin CAS Registry Number: 103060-53-3 达托霉素

Trademarks: Cidecin (Cubist); Cubicin (Cubist)
Percent Composition: C 53.36%, H 6.28%, N 14.69%, O 25.67%
Literature References: Cyclic lipopeptide antibiotic derived from a fermentation product of Streptomyces roseosporus; disrupts plasma membrane function in gram-positive bacteria. Prepn: B. J. Abbott et al., US 4537717 (1985 to Eli Lilly); M. Debono et al., J. Antibiot. 41, 1093 (1988). Mechanism of action study: N. E. Allen et al., Antimicrob. Agents Chemother. 31, 1093 (1987); and structure determn: D. Jung et al., Chem. Biol. 11, 949 (2004). Comparative in vitro antibacterial spectrum: I. A. Critchley et al., J. Antimicrob. Chemother. 51, 639 (2003). Clinical pharmacokinetics: J. R. Woodworth et al., Antimicrob. Agents Chemother. 36, 318 (1992). Clinical trial in skin infections: R. D. Arbeit et al., Clin. Infect. Dis. 38, 1673 (2004). Review of pharmacology and clinical evaluations: F. P. Tully et al., Expert Opin. Invest. Drugs 8, 1223-1238 (1999); L. P. Kotra Curr. Opin. Anti-Infect. Invest. Drugs 2, 185-205 (2000).

N-Nitrosopyrrolidine CAS Registry Number: 930-55-2 N-亚硝基吡咯烷

CAS Name: 1-Nitrosopyrrolidine
Additional Names: NPYR; NO-PYR
Percent Composition: C 47.99%, H 8.05%, N 27.98%, O 15.98%
Literature References: Cyclic nitrosamine that occurs in food products and tobacco smoke. Prepn: F. C. Peterson, Ber. 21, 290 (1888). Carcinogenicity studies: H. Druckrey et al., Z. Krebsforsch. 69, 103 (1967); M. Greenblatt et al., J. Natl. Cancer Inst. 48, 1687 (1972); IARC Monographs 17, 313 (1978). Mechanism of mutagenicity: L. I. Hecker et al., Mutat. Res. 62, 213 (1979). Metabolism: R. C. Cottrell et al., Adv. Exp. Med. Biol. 136B, 1165 (1982).

Emodepside CAS Registry Number: 155030-63-0 艾默德斯

CAS Name: Cyclo[(aR)-a-hydroxy-4-(4-morpholinyl)benzenepropanoyl-N-methyl-L-leucyl-(2R)-2-hydroxypropanoyl-N-methyl-L-leucyl-(aR)-a-hydroxy-4-(4-morpholinyl)benzenepropanoyl-N-methyl-L-leucyl-(2R)...
Literature References: Cyclic octadepsipeptide that binds to presynaptic latrophilin receptors in nematodes. Semisynthetic derivative of PF1022A, a fungal metabolite of Mycelia sterilia. Prepn: H. Nishiyama et al., WO 9319053; eidem, US 5514773 (1993, 1996 both to Fujisawa). In vivo anthelmintic activity: A Harder, G. von Samson-Himmelstjerna, Parasitol. Res. 87, 924 (2001); H. Zahner et al., Int. J. Parasitol. 31, 1515 (2001). Review of mechanism of action studies: A. Harder et al., Parasitol. Res. S1-S10 (2005).

Capreomycin CAS Registry Number: 11003-38-6 卷曲霉素

Trademarks: Capastat (Lilly)
Literature References: Cyclic peptide antibiotic similar to viomycin; produced by Streptomyces capreolus NRRL 2773; Herr et al., 140th Am. Chem. Soc. Meet. (Chicago, Sept. 1961), Abstracts of Papers, p 49C; Chem. Eng. News 39, 57 (Sept. 18, 1961); GB 920563; US 3143468 (1963, 1964 both to Lilly). Mixture of capreomycins IA, IB, IIA, and IIB in the approx percentages, 25%, 67%, 3%, 6%, resp.: Herr, Redstone, Ann. N.Y. Acad. Sci. 135, 940 (1966). Activity studies: Sutton et al., ibid. 947; Lucchesi, Antibiot. Chemother. 16, 27 (1970). Proposed structure: Bycroft et al., Nature 231, 301 (1971). Revised structure and total synthesis: T. Shiba et al., Tetrahedron Lett. 1976, 3907; S. Nomoto et al., Tetrahedron 34, 921 (1978). Structure of IA and IB: eidem, J. Antibiot. 30, 955 (1977). Toxicity study: Welles et al., Ann. N.Y. Acad. Sci. 135, 960 (1966).

Bicozamycin CAS Registry Number: 38129-37-2 二环霉素

Additional Names: Bicyclomycin; aizumycin; 8,10-diaza-6-hydroxy-5-methylene-1-(2-methyl-1,2,3-trihydroxypropyl)-2-oxabicyclo[4.2.2]decan-7,9-dione; antibiotic 5879Trademarks: Bacfeed (Fujisawa) Literature References: Cyclic peptide antibiotic substance. Prepn by fermentation of Streptomyces sapporensis: T. Miyoshi et al., DE 2150593; H. Imanaka et al., US 3923790 (1972, 1975 both to Fujisawa). Isoln and characterization: T. Miyoshi et al., J. Antibiot. 25, 569 (1972). Isoln from S. aizunensis and identity with antibiotic 5879: S. Miyamura et al., ibid. 26, 479 (1973). Bicyclomycin has a unique chemical structure which bears no relation to any group of known antibiotics. Structural elucidation: T. Kamiya et al., ibid. 25, 576 (1972). Crystal and molecular structure: Y. Tokuma et al., Bull. Chem. Soc. Jpn. 47, 18 (1974). In vitro and in vivo activity studies: M. Nishida et al., J. Antibiot. 25, 582 (1972). Metabolism: eidem, ibid. 594. Mechanism of action: N. Tanaka et al., ibid. 29, 155 (1976); N. Tanaka in Antibiotics vol. 5(pt. 1), E. Hahn, Ed. (Springer, New York, 1979) p 18. Synthetic approaches: L. V. Dunkerton, R. M. Ahmed, Tetrahedron Lett. 21, 1803 (1980); R. M. Williams, ibid. 22, 2341 (1981); S. Nakatsuka et al., ibid. 4973; J. H. Hoare, P. Yates, Chem. Commun. 1981, 1126. Total synthesis of (±)-bicyclomycin: S. Nakatsuka et al., Tetrahedron Lett. 24, 5627 (1983); of (+)-bicyclomycin: R. M. Williams et al., J. Am. Chem. Soc. 106, 5749 (1984); eidem, ibid. 107, 3253 (1985). Review of synthetic, mechanistic and biological studies: R. M. Williams, C. A. Durham, Chem. Rev. 88, 511-540 (1988).

Decamethylcyclopentasiloxane CAS Registry Number: 541-02-6 环五聚二甲基硅氧烷

Additional Names: D5
Percent Composition: C 32.39%, H 8.16%, O 21.58%, Si 37.87%
Literature References: Cyclic siloxane. Isolated from the hydrolysis product of dimethyldichlorosilane: W. Patnode, D. F. Wilcock, J. Am. Chem. Soc. 68, 358 (1946). HPLC determn and GC-MS characterization of metabolites in urine: S. Varaprath et al., Drug Metab. Dispos. 31, 206 (2003). Physicochemical properties: M. Palczewska-Tulinska, P. Oracz, J. Chem. Eng. Data 50, 1711 (2005).

L -Pyroglutamic Acid CAS Registry Number: 98-79-3 L-焦谷氨酸

CAS Name: 5-Oxo-L-proline
Additional Names: 5-oxo-2-pyrrolidinecarboxylic acid; 2-pyrrolidone-5-carboxylic acid; glutimic acid; glutiminic acid; a-aminoglutaric acid lactam; glutamic acid lacta...
Literature References: Cyclized internal amide of L-glutamic acid found in vegetables, fruits, grasses, and molasses. Easily prepd from L-glutamic acid by autoclaving with an equal wt of water at 135-140°: Dearborn, Stekol, US 2528267; purification: Blish, US 2738353 (1950, 1956, both to International Minerals and Chem.). Review: Orlowski, Meister, in The Enzymes vol. 4, P. D. Boyer, Ed. (Academic Press, New York, 3rd ed., 1971) pp 123-151; C. Moret, M. Briley, Trends Pharmacol. Sci. 9, 278-279 (1988).