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

Cinacalcet CAS Registry Number: 226256-56-0 西那卡塞

CAS Name: (aR)-a-Methyl-N-[3-[3-(trifluoromethyl)phenyl]propyl]-1-napthalenemethanamine
Additional Names: (R)-N-(3-(3-(trifluoromethyl)phenyl)propyl)-1-(1-napthyl)ethylaminePercent Composition:...
Literature References: Calcimimetic. Prepn: B. C. Van Wagenen et al., US 6211244 (2001 to NPS Pharmaceuticals). Review of pharmacology and mechanism of action: M. Wada, N. Nagano, Nephrol. Dial. Transplant. 18, Suppl. 3, iii13-iii17 (2003); of clinical development: N. Franceschini et al., Expert Opin. Invest. Drugs 12, 1413-1421 (2003). Clinical trial in secondary hyperparathyroidism: G. A. Block et al., N. Engl. J. Med. 350, 1516 (2004).

BAPTA CAS Registry Number: 85233-19-8 1,2-双(2-氨基苯氧基)乙烷-N,N,N',N'-四乙酸

CAS Name: N,N'-[1,2-Ethanediylbis(oxy-2,1-phenylene)]bis[N-(carboxymethyl)glycine]
Additional Names: 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid
Percent Composition: C 55.46%, H...
Literature References: Calcium (Ca2+) chelator derived from EGTA. Ca2+ binding causes a shift in the uv absorbance and fluorescence of the molecule. Parent compound of second generation fluorescent imaging agents such as Indo-1, Fura-2, q.q.v. Prepn: R. Y. Tsien, Biochemistry 19, 2396 (1980). Dissociation constants: R. Pethig et al., Cell Calcium 10, 491 (1989). Use as chelator: P. W. Marks, F. R. Maxfield, Anal. Biochem. 193, 61 (1991). Binding constants and fluorescence with heavy metals: A. Yuchi et al., Bull. Chem. Soc. Jpn. 66, 3377 (1993). Prepn of 19F-forms and use for intracellular Ca2+ measurement: G. A. Smith et al., Proc. Natl. Acad. Sci. USA 80, 7178 (1983); L. A. Levy et al., Am. J. Physiol. 252, C441 (1987). NMR determn of Ca2+ in brain by 5F-BAPTA: H. S. Bachelard et al., J. Neurochem. 51, 1311 (1988).

Terodiline CAS Registry Number: 15793-40-5 特罗地林

CAS Name: N-(1,1-Dimethylethyl)-a-methyl-g-phenylbenzenepropanamine
Additional Names: N-tert-butyl-1-methyl-3,3-diphenylpropylamine; N-(1-methyl-3,3-diphenylpropyl)-tert-butylamine; 4,4-dipheny...
Literature References: Calcium antagonist with anticholinergic and vasodilatory activity. Prepn and use in treatment of angina: GB 923942; S. Carlsson, US 3371014 (1963, 1968 both to AB Recip). Pharmacokinetics: B. Karlen et al., Eur. J. Clin. Pharmacol. 23, 267 (1982). Series of articles on pharmacology and clinical efficacy in urinary frequency and motor urge incontinence: Scand. J. Urol. Nephrol. Suppl. 87, 1-61 (1984). Clinical trial in urinary incontinence: U. Ulmsten et al., Am. J. Obstet. Gynecol. 153, 619 (1985).

Fendiline CAS Registry Number: 13042-18-7 缺甲心可定

CAS Name: g-Phenyl-N-(1-phenylethyl)benzenepropanamine
Additional Names: N-(3,3-diphenylpropyl)-a-methylbenzylamine; N-(1-phenylethyl)-3,3-diphenylpropylamine
Percent Composition: C 87.57%, ...
Literature References: Calcium blocking agent. Prepn: BE 621300; Harsányi et al., US 3262977 (1962, 1966 both to Chinoin); eidem, J. Med. Chem. 7, 623 (1964); Klosa, J. Prakt. Chem. 34, 312 (1966). Prepn and studies of the labelled compound: Volford, Harsányi, J. Labelled Compd. 9, 219 (1973). Structure-activity studies: Leszkovszky et al., Acta Physiol. Acad. Sci. Hung. 29, 283 (1966). Pharmacologic properties: W. R. Kukovetz et al., Arzneim.-Forsch. 26, 1321 (1976); A. Fleckenstein et al., ibid. 27, 562 (1977). Pharmacokinetics and tolerance: R. Weyhenmeyer et al., ibid. 37, 58 (1987). Use in ischemic heart disease: Z. Antaloczy, I. Preda, Ther. Hung. 27, 71 (1979). Assessment of Ca2+-antagonist effects: M. Spedding, Arch. Pharmacol. 318, 234 (1982).

Perhexiline CAS Registry Number: 6621-47-2 哌克昔林

CAS Name: 2-(2,2-Dicyclohexylethyl)piperidine
Additional Names: 1,1-dicyclohexyl-2-(2-piperidyl)ethane; perhexilene
Percent Composition: C 82.24%, H 12.71%, N 5.05%
Literature References: Calcium blocking agent. Prepn: GB 1025578 (1966 to Richardson-Merrell), C.A. 65, 2229f (1966). Pharmacology: Hudak et al., J. Pharmacol. Exp. Ther. 173, 371 (1970). Clinical studies: Winsor, Clin. Pharmacol. Ther. 11, 85 (1970). Toxicity study: Causa, Perri, Arzneim.-Forsch. 21, 114 (1971). Series of articles: Postgrad. Med. J. Suppl. 49, 8-132 (1973). Book: Antiarrhythmic Action and the Puzzle of Perhexiline, E. M. Vaughan Williams, Ed. (Academic Press, New York, 1980) 143 pp.

Lidoflazine CAS Registry Number: 3416-26-0 利多氟嗪

CAS Name: 4-[4,4-Bis(4-fluorophenyl)butyl]-N-(2,6-dimethylphenyl)-1-piperazineacetamide
Additional Names: 4-[4,4-bis(p-fluorophenyl)butyl]-1-piperazineaceto-2',6'-xylidide; 1-[4,4-di(4-fluoroph...
Literature References: Calcium blocking agent. Prepn: NL 6507312; H. K. F. Hermans, W. K. Schaper, US 3267104 (1965, 1966, both to Janssen). Crystal structure: G. Germain et al., Acta Crystallogr. 33B, 1971 (1977). Tissue specificity of calcium-blocking properties: J. M. Van Neuten, D. Wellens, Arch. Int. Pharmacodyn. Ther. 242, 329 (1979). Cardioprotective effects: W. Daenen, W. Flameng, Angiology 32, 543 (1981). Effects in angina: F. L. Gobel et al., Circulation 65, 1 Pt. 2, 127 (1982); W. Shapiro et al., ibid. 143.

Bepridil CAS Registry Number: 64706-54-3 苄普地尔

CAS Name: b-[(2-Methylpropoxy)methyl]-N-phenyl-N-(phenylmethyl)-1-pyrrolidineethanamine
Additional Names: 1-[2-(N-benzylanilino)-1-(isobutoxymethyl)ethyl]pyrrolidine; 1-isobutoxy-2-pyrrolidino-...
Literature References: Calcium channel blocker with antianginal and antiarrhythmic properties. Prepn: R. Y. Mauvernay et al., DE 2310918; eidem, US 3962238; reissued with structure correction: N. Busch et al., US RE 30577 (1973, 1976, 1981 all to CERM). See also: R. Y. Mauvernay et al., DE 2802864 (1978 to CERM), C.A. 89, 179852s (1978). Cardiovascular pharmacology in dogs: M.-T. Michelin et al., Therapie 32, 485 (1977). Mechanism of action studies: S. Vogel et al., J. Pharmacol. Exp. Ther. 210, 378 (1979); C. Labrid et al., ibid. 211, 546 (1979). Clinical comparison of hemodynamic and coronary changes: J. P. Merillon et al., Therapie 36, 123 (1981). Clinical evaluation in angina: M. K. Sharma et al., Am. J. Cardiol. 61, 1210 (1988).

Diltiazem CAS Registry Number: 42399-41-7 地尔硫卓

CAS Name: (2S-cis)-3-(Acetyloxy)-5-[2-(dimethylamino)ethyl]-2,3-dihydro-2-(4-methoxyphenyl)-1,5-benzothiazepin-4(5H)-one
Additional Names: (+)-cis-5-[2-(dimethylamino)ethyl]-2,3-dihydro-3-hydro...
Literature References: Calcium channel blocker with vasodilating activity. Prepn (unspec stereochem): H. Kugita et al., DE 1805714; eidem, US 3562257 (1969, 1971 both to Tanabe Seiyaku); eidem, Chem. Pharm. Bull. 19, 595 (1971). Resolution of optical isomers: H. Inoue et al., Yakugaku Zasshi 93, 729 (1973), C.A. 79, 66331w (1974). Stereospecific synthesis: K. Igarashi, T. Honma, DE 3415035; eidem, US 4552695 (1984, 1985 both to Shionogi). Structure-activity studies: Sato et al., Arzneim.-Forsch. 21, 1338 (1971); T. Nagao et al., Chem. Pharm. Bull. 21, 92 (1973). Pharmacology and toxicity: eidem, Jpn. J. Pharmacol. 22, 467 (1972). Metabolism: Meshi et al., Chem. Pharm. Bull. 19, 1546 (1971). Review of synthesis and pharmacology: H. Inoue, T. Nagao, Chron. Drug Discovery 3, 207-238 (1993). Comprehensive description: D. J. Mazzo et al., Anal. Profiles Drug Subs. Excip. 23, 53-98 (1994). Review of pharmacology and efficacy in angina: M. Chaffman, R. N. Brogden, Drugs 29, 387-454 (1985); in hypertension: M. R. Weir, J. Clin. Pharmacol. 35, 220-232 (1995). Comparative clinical trial in prevention of complications of hypertension: L. Hansson et al., Lancet 356, 359 (2000).

Aranidipine CAS Registry Number: 86780-90-7 阿雷地平

CAS Name: 1,4-Dihydro-2,6-dimethyl-4-(2-nitrophenyl)-3,5-pyridinedicarboxylic acid methyl 2-oxopropyl ester
Additional Names: (±)-methyl 2-oxopropyl 1,4-dihydro-2,6-dimethyl-4-(2-nitrophen...
Literature References: Calcium channel blocker. Prepn: S. Ohno et al., FR 2514761; eidem, US 4446325 (1983, 1984 both to Maruko Seiyaku); idem et al., Chem. Pharm. Bull. 34, 1589 (1986). Pharmacology and receptor binding studies: K. Miyoshi et al., Eur. J. Pharmacol. 238, 139 (1993). Determn by GC-MS in plasma and urine: Y. Umeno et al., J. Chromatogr. 434, 123 (1988); by HPLC in plasma: Y. Iida et al., ibid. 571, 277 (1991). Cardiovascular profile: A. Kanda et al., J. Cardiovasc. Pharmacol. 22, 167 (1993). Clinical pharmacology: S. Suzuki et al., Arzneim.-Forsch. 43, 1152 (1993). Toxicity studies: S. Nakano et al., Yakuri to Chiryo 21, S931 (1993), C.A. 119, 131216 (1993).

Clentiazem CAS Registry Number: 96125-53-0 克仑硫卓

CAS Name: (2S,3S)-3-(Acetyloxy)-8-chloro-5-[2-(dimethylamino)ethyl]-2,3-dihydro-2-(4-methoxyphenyl)-1,5-benzothiazepin-4(5H)-one
Additional Names: (+)-(2S,3S)-8-chloro-5-[2-(dimethylamino)ethyl...
Literature References: Calcium channel blocker; 8-chloro derivative of diltiazem. Prepn: M. Takeda et al., EP 127882; eidem, US 4567175 (1984, 1986 both to Tanabe); H. Inoue et al., J. Med. Chem. 34, 675 (1991). Cardiovascular pharmacology: H. Narita et al., Arzneim.-Forsch. 38, 515 (1988). Clinical pharmacokinetics: A. K. Shah et al., J. Clin. Pharmacol. 33, 354 (1993). Clinical evaluation in hypertension: S. Kawakita et al., Clin. Cardiol. 14, 53 (1991).